Geneology International

Tag: disease

  • Statement on the fourteenth meeting of the International Health Regulations (2005) Emergency Committee regarding the coronavirus disease (COVID-19) pandemic

    Statement on the fourteenth meeting of the International Health Regulations (2005) Emergency Committee regarding the coronavirus disease (COVID-19) pandemic

    The WHO Director-Standard has the satisfaction of transmitting the Report of the fourteenth conference of the Worldwide Well being Polices (2005) (IHR) Unexpected emergency Committee pertaining to the coronavirus 2019 sickness (COVID-19) pandemic, held on Friday 27 January 2023, from 14:00 to 17:00 CET.

    The WHO Director-Common concurs with the tips made available by the Committee pertaining to the ongoing COVID-19 pandemic and decides that the event proceeds to constitute a general public well being crisis of global worry (PHEIC). The Director-Typical acknowledges the Committee’s views that the COVID-19 pandemic is in all probability at a transition issue and appreciates the advice of the Committee to navigate this transition meticulously and mitigate the possible damaging penalties.

    The WHO Director-Basic deemed the tips delivered by the Committee pertaining to the proposed Short term Suggestions. The established of Short term Recommendations issued by the WHO Director-General is introduced at the close of this assertion.

    The WHO Director-Normal expresses his honest gratitude to the Chair and Customers of the Committee, as nicely as to the Committee’s Advisors.

    ===

    Proceedings of the conference

    The WHO Director-Common, Dr Tedros Adhanom Ghebreyesus, welcomed Associates and Advisors of the Unexpected emergency Committee, who ended up convened by videoconference. He mentioned that this 7 days marks the 3-yr anniversary of the perseverance of the COVID-19 PHEIC in January 2020. Though the planet is in a much better position than it was during the peak of the Omicron transmission just one yr in the past, additional than 170 000 COVID-19-linked fatalities have been described globally in just the previous eight months. In addition, surveillance and genetic sequencing have declined globally, making it a lot more tricky to observe regarded variants and detect new kinds. Wellbeing systems are presently battling with COVID-19 and caring for sufferers with influenza and respiratory syncytial virus (RSV), health and fitness workforce shortages, and fatigued wellbeing personnel. Vaccines, therapeutics, and diagnostics have been and stay important in avoiding critical condition, preserving life and having the pressure off wellness systems and wellness staff globally. However, the COVID-19 reaction remains hobbled in far too a lot of international locations not able to deliver these applications to the populations most in need to have, older individuals and well being personnel. He thanked the Chair, Associates, and Advisors of the Committee for their work.

    The Place of work of Legal Counsel’s consultant briefed the Committee Customers and Advisors on their roles, responsibilities, and mandate less than the applicable content of the IHR. The Ethics Officer from the Section of Compliance, Danger Administration, and Ethics reminded Users and Advisers of their obligation of confidentiality as to the meeting conversations and the get the job done of the Committee, as very well as their person accountability to disclose to WHO in a timely way any pursuits of a personalized, specialist, money, mental or professional mother nature that might give increase to a perceived or immediate conflict of curiosity. No conflicts of desire for the attending Members and Advisors ended up recognized. 

    The meeting was handed above to the Chair of the Crisis Committee, Professor Didier Houssin, who introduced the targets of the conference: to offer sights to the WHO Director-Common on no matter whether the COVID-19 pandemic carries on to represent a PHEIC, and to critique momentary tips to States Functions. 

    The WHO Secretariat offered a global overview of the present-day position of the COVID-19 pandemic. The latest swift hazard assessment carries on to characterize the world wide risk of COVID-19 to human wellbeing and its ongoing transmission as large. The WHO Secretariat introduced on the pursuing: worldwide COVID-19 epidemiological condition at this time circulating SARS-CoV-2 variants of concern, which includes descendent lineages of these variants unexpectedly early seasonal return of influenza and RSV in some locations, which is burdening some currently overstressed wellbeing devices standing of global vaccination and hybrid immunity and new vacation-linked health and fitness measures, which includes tests and vaccination demands, implemented in response to the the latest wave of COVID-19 cases after policy alterations.

    The WHO Secretariat expressed issue about the ongoing virus evolution in the context of unchecked circulation of SARS-CoV-2 and the substantial lower in Member States’ reporting of facts relevant to COVID-19 morbidity, mortality, hospitalization and sequencing, and reiterated the great importance of well timed knowledge sharing to guideline the ongoing pandemic response.

    WHO proceeds to work closely with nations on all elements of the COVID-19 response, such as for strengthening the administration of COVID-19 in longer-time period disorder management plans. The WHO Secretariat precisely highlighted its support to States Get-togethers to: keep a number of part surveillance programs  implement sentinel surveillance making use of a coordinated world wide technique to characterize acknowledged and emerging variants bolster COVID-19 clinical treatment pathways offer common updates to the COVID-19 pointers boost access to therapeutics, vaccines and diagnostics and carry on to conduct Unity scientific studies which offer important facts about seroprevalence globally.

    WHO is urging nations: to continue to be vigilant and keep on reporting surveillance and genomic sequencing facts to suggest properly specific risk-primarily based general public wellness and social actions (PHSM) where essential to vaccinate populations most at danger to minimize severe ailment and deaths and to carry out common hazard communication, answering inhabitants issues and partaking communities to boost the knowing and implementation of countermeasures.

    The Committee was informed that, globally, 13.1 billion doses of COVID-19 vaccines have been administered, with 89{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} of wellbeing personnel and 81{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} of more mature grownups (in excess of 60 many years) obtaining concluded the primary sequence. Major progress has also been produced in: establishing successful medical countermeasures making worldwide potential for genomic sequencing and genomic epidemiology and in comprehending how to handle the infodemic in the new informational eco-technique like social media platforms.

    Deliberative Session

    The Committee regarded as the successes and challenges in the course of the PHEIC. The Committee acknowledged the do the job of WHO, Member States and partners, in accomplishing significant world-wide progress around the very last three yrs.

    Nevertheless, Committee Associates expressed problem about the ongoing possibility posed by COVID-19, with a even now large variety of deaths when compared to other respiratory infectious disorders, the insufficient vaccine uptake in reduced- and middle-revenue nations around the world, as perfectly as in the best-risk groups globally, and the uncertainty connected with emerging variants. They identified that pandemic exhaustion and lessened community perception of risk have led to substantially lowered use of public well being and social steps, these as masks and social distancing. Vaccine hesitancy and the continuing distribute of misinformation continue on to be extra hurdles to the implementation of critical public wellness interventions. At the exact time, the long-term systemic sequelae of article-COVID affliction and the elevated chance of put up-an infection cardiovascular and metabolic illness will possible have really serious unfavorable on-going effect on inhabitants, and care pathways for these kinds of patients are minimal or not readily available in many international locations.

    The Committee acknowledged that, although the Omicron sub-lineages at present circulating globally are hugely transmissible, there has been a decoupling in between an infection and critical disorder when compared to previously variants of problem. Having said that, the virus retains an potential to evolve into new variants with unpredictable attributes. The Committee expressed a will need for enhanced surveillance and reporting on hospitalizations, intense care unit admissions, and fatalities to improved understand the present-day effect on wellness devices and to appropriately characterize the scientific attributes of COVID-19 and post COVID-19 condition.

    Persistent health workforce shortages and tiredness and competing priorities, including other disease outbreaks, carry on to stretch wellness techniques in a lot of nations. The Committee emphasised the great importance of sustaining capacities created all through the COVID-19 reaction and continuing to strengthen wellbeing system resilience.

    Position of the PHEIC

    The Committee agreed that COVID-19 stays a risky infectious illness with the potential to bring about sizeable destruction to health and wellbeing methods. The Committee discussed no matter if the continuation of a PHEIC is expected to preserve worldwide notice to COVID-19, the potential destructive repercussions that could crop up if the PHEIC was terminated, and how to transition in a risk-free fashion.

    The Committee acknowledged that the COVID-19 pandemic may be approaching an inflexion place. Obtaining bigger degrees of population immunity globally, either as a result of infection and/or vaccination, might limit the impression of SARS-CoV-2 on morbidity and mortality, but there is minor doubt that this virus will remain a forever recognized pathogen in individuals and animals for the foreseeable long run. As such, long-term public well being motion is critically essential. While eliminating this virus from human and animal reservoirs is very not likely, mitigation of its devastating impression on morbidity and mortality is achievable and should really continue to be a prioritized objective.

    Relocating ahead past the PHEIC demands a focused motivation of WHO, its Member States and intercontinental organizations to producing and utilizing sustainable, systematic, extended-time period avoidance, surveillance, and regulate action options. WHO’s direction, created with aid from pertinent specialized and advisory groups, should really be steady, and really should help States Functions in having steps and running the implications of this transition.

    The Committee, consequently, recommended that WHO, in consultation with associates and stakeholders, should really build a proposal for choice mechanisms to keep the global and nationwide concentrate on COVID-19 just after the PHEIC is terminated, which includes if required a doable Evaluate Committee to suggest on the issuance of standing suggestions beneath the IHR.

    The Committee also requested the WHO Secretariat to supply an evaluation relating to the regulatory implications for building and authorising vaccines, diagnostics, and therapeutics if the PHEIC ended up to be terminated in the coming months.

    The Committee also inspired WHO to assess and, if important, to accelerate the integration of COVID-19 surveillance into the World-wide Influenza Surveillance and Reaction Process.

    ===

    Momentary Recommendations issued by the WHO Director-General to all States Get-togethers

    1. Retain momentum for COVID-19 vaccination to attain 100{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} protection of superior-priority groups guided by the evolving SAGE recommendations on the use of booster doses. States Events really should system for integration of COVID-19 vaccination into part of everyday living-course immunization programmes. Normal data assortment and reporting on vaccine protection ought to consist of equally principal and booster doses. (International COVID-19 Vaccination Tactic in a Switching Entire world: July 2022 update Up to date WHO SAGE Roadmap for prioritizing uses of COVID-19 vaccines January 2023 Interim assertion on the use of further booster doses of Unexpected emergency Use Shown mRNA vaccines from COVID-19 Very good exercise assertion on the use of variant-that contains COVID-19 vaccines Behavioural and social drivers of vaccination: instruments and realistic assistance for obtaining superior uptake.)
    2. Increase reporting of SARS-CoV-2 surveillance information to WHO. Superior info are desired to: detect, evaluate, and watch emerging variants discover sizeable changes to COVID-19 epidemiology and comprehend the burden of COVID-19 in all regions. States Parties are encouraged to use an integrated tactic to respiratory infectious illness surveillance that leverages the World wide Influenza Surveillance and Response system. Surveillance should incorporate information and facts from consultant sentinel populations, party-based mostly surveillance, human wastewater surveillance, sero-surveillance, and animal-human-environmental surveillance. WHO should carry on to operate with Member States to make sure suitable potential and protection of COVID-19 surveillance are in area to recognise swiftly any significant variations in the virus and/or its epidemiology and medical impact such as hospitalization, so that WHO can result in suitable worldwide alerting as important. ( Public wellbeing surveillance for COVID-19 )
    3. Enhance uptake and ensure lengthy-expression availability of health-related countermeasures. States Functions ought to improve obtain to COVID-19 vaccines, diagnostics and therapeutics, and look at preparing for these health-related countermeasures to be authorized outside the house of  Emergency Use Listing processs and inside usual nationwide regulatory frameworks. (Therapeutics and COVID-19: residing guideline COVID-19 Medical Care Pathway)
    4. Preserve powerful national response ability and prepare for long term activities to keep away from the prevalence of a worry-neglect cycle. States Get-togethers must take into consideration how to bolster nation readiness to answer to outbreaks such as attention to overall health workforce potential, infection avoidance and command, and financing for respiratory and non-respiratory pathogen preparedness and response. (WHO COVID-19 plan briefs Strengthening pandemic preparedness scheduling for respiratory pathogens: policy quick)
    5. Go on operating with communities and their leaders to address the infodemic and to properly apply threat-centered community overall health and social steps (PHSM). Possibility conversation and community engagement should be tailored to local contexts and deal with mis- and dis-information and facts that erodes believe in in health care countermeasures and PHSM. States Events really should strengthen the public, media, and communities’ being familiar with of the evolving science to persuade proof-informed action and policies. States Functions should really continue on to observe specific and general public reaction to the implementation of PHSM and the uptake and acceptability of COVID-19 vaccines, and implement actions, together with conversation procedures, to help appropriate utilization.  (WHO risk communications methods Criteria for employing and altering PHSM in the context of COVID-19.)
    6. Continue to alter any remaining intercontinental travel-linked steps, dependent on danger evaluation, and to not have to have evidence of vaccination towards COVID-19 as a prerequisite for worldwide travel. (Interim posture paper: factors pertaining to evidence of COVID-19 vaccination for worldwide travellers Plan criteria for implementing a threat-primarily based technique to international journey in the context of COVID-19).
    7. Carry on to help investigation for enhanced vaccines that decrease transmission and have broad applicability, as effectively as analysis to have an understanding of the complete spectrum, incidence and impact of publish COVID-19 ailment, and to create suitable built-in care pathways.

       

  • Role of Alternative Medical Systems in Adult Chronic Kidney Disease Patients: A Systematic Review of Literature

    Role of Alternative Medical Systems in Adult Chronic Kidney Disease Patients: A Systematic Review of Literature

    Chronic kidney disease (CKD) is one of the leading causes of death globally, which affects 13.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} of the world’s population [1]. With deterioration in renal function, this leads to the onset of CKD-related complications, such as uremia, anemia, and electrolyte disorders [2]. These complications often manifest as symptoms ranging from pruritus, pain, and insomnia to muscle cramps. This in turn has negative implications on patients’ quality of life [3,4]. Importantly as CKD patients approach end-stage renal disease (ESRD), the prevalence and severity of such symptoms increase [5].

    Despite medical breakthroughs and the advent of new therapies in the past decades, optimal treatments for some of the symptoms resulting from CKD-related complications remained unclear, possibly due to their complex pathophysiology. A case in point is uremic pruritus, which is found in around 20{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} of pre-dialysis CKD patients and 40{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} of ESRD patients [6]. Although prevalent treatments include the use of emollients, gabapentin, and antihistamines, data related to their efficacy were often derived from small studies and their use is limited by adverse effects [7].

    The use of alternative medical systems (AMS) which forms a key pillar of complementary and alternative medicine (CAM) has increased in the past 20 years [8]. AMS is defined as “entire systems of health theory and practice that developed separately from conventional medicine” [9]. Notably, around 18{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} of dialysis patients have utilized some form of AMS [10,11]. In addition, prescription of AMS therapies such as traditional Chinese medicine (TCM) by professional practitioners often aids in minimizing the risk of side effects, hence increasing their appeal as potential therapeutic alternatives [11].

    Prior studies have shown that AMS is effective in reducing symptoms such as pain, nausea, and fatigue in non-CKD patient populations. For instance the use of TCM formulas, such as Liu Junzi Tang and Xiao Banxia Plus Fuling have demonstrated efficacy in treating cancer-related pain and chemotherapy-related nausea and vomiting [12]. In addition, Chinese herbs such as Curcuma longa and Panax ginseng among patients with malignancies have shown efficacy in promoting apoptosis of cancer cells and inhibiting tumor metastasis [13]. Another study showed that a multi-modal Ayurvedic treatment approach was effective in reducing knee osteoarthritis symptoms, such as pain and stiffness, and improving function [14]. With increasing research supporting the use of AMS, this has led to a rise in healthcare institutions adopting and providing such integrated services which are supported by insurance coverage [15].

    Among CKD patients, multiple studies have also been conducted to assess the efficacy of AMS in the treatment of CKD-related conditions and symptoms such as uremic pruritis and anemia. For instance, a study that assessed the efficacy of homeopathy verum among CKD patients showed a reduction in pruritus symptoms by 49{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} after 30 days of treatment [16]. Another study that evaluated the use of TCM patients with glomerulonephritis showed improvement in hemoglobin after 24 weeks of therapy [16,17].

    Existing reviews which have assessed the role of AMS are currently limited to specific indications, such as uremic pruritus [18], use of subtypes of AMS in specific CKD subgroups, such as consumption of Chinese herbal medicine in diabetic kidney disease [19], and specific AMS therapies, such as use of Astragalus [20,21]. This review aimed to summarize and evaluate the broad roles and efficacy of AMS as potential alternative therapeutic options for CKD patients. Findings from the review will aid physicians in gaining a better understanding of the efficacy of AMS for CKD patients, which can aid in facilitating purposeful discussions with patients who are using or considering these therapies.

    Methods

    Protocol and Registration

    The protocol for this study was registered on Open Science Framework (https://osf.io/ymks8/) and was composed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Synthesis without Meta-Analysis (SWiM) reporting guidelines [22,23].

    Information Sources and Search

    A literature search was conducted in MEDLINE, Embase, Scopus, CENTRAL, CINAHL, and PsycINFO. There was no start date restriction, and studies up to April 2022 were included. Key terms related to CKD, randomized controlled trials (RCT), and AMS were included in the searches. The search terms were adapted from other systematic reviews and the full search strategy is available in Appendix 1 [18,24-26].

    Eligibility Criteria

    With regards to inclusion criteria, full-text articles in English language which involved RCTs evaluating the use of AMS in adult CKD patients (>18 years old) were included. As defined by the National Center for Complementary and Integrative Health (NCCIH), AMS is a broad category encompassing a variety of medical modalities and refers to an entire system of theory and practice which developed separately from conventional medicine [15]. In this review, we included TCM, naturopathy, homeopathy, and ayurvedic medicine. Non-RCTs, case series, other systematic reviews, and meta-analyses were excluded.

    Description of Main Types of AMS

    TCM: TCM is a system of medical practice which originated in China and adopts a holistic approach to the medical treatment of a patient based on “syndrome differentiation.” It focuses on the integrity of the human body by emphasizing the intimate relationship between the body and its social and natural environment, as well as dynamic balance of movement [27]. The basic tenet of TCM is based on the flow and balance of vital energy, Qi, which flows through channels in the body called meridians that connect various organs and tissues [28]. Diseases are believed to be brought about by the imbalance of Qi. Hence, by restoring balance via acupoints or intake of herbs, TCM seeks to promote individual wellness and prevent diseases [29].

    Naturopathy: Naturopathy is a form of medical practice which is rooted in vitalism and folk medicine and, promotes natural and self-healing ideologies [30]. The unique attribute of naturopathic medicine lies in the reprioritization of the order of therapeutics with increased emphasis on preventive behaviors, lifestyle modifications, nutrition, and exercise, over medical or surgical interventions [31].

    Homeopathy: Homeopathy entails the therapeutic administration of substances derived from plants, minerals, or animals that produce effects that correspond to the clinical manifestation of diseases [32]. Its practice is centered on two following theories: “like cures like” and “law of minimum dose.” “Like cures like” refers to the belief that diseases can be treated with substances that produce similar symptoms in healthy individuals, and “law of minimum dose” refers to the belief that the lower the dose the greater its therapeutic efficacy [32].

    Ayurvedic medicine: Ayurvedic medicine is one of the oldest alternative medical systems which involves the use of therapeutics derived predominantly from plants, animals, minerals, diet, exercise, and lifestyle changes. Its therapies are centered on the principle of “Panchakarma,” which comprises five karmas (actions) to rejuvenate and remove toxins from one’s body [33].

    Study Selection and Data Collection Process

    Citations retrieved from the six databases were extracted into Endnote X9 software (Philadelphia, PA: Clarivate) and duplicated citations were removed. During the initial article screening, two independent reviewers (WY and SW) reviewed the titles and abstracts of articles to select relevant articles. Thereafter, the full texts of the identified articles were evaluated. All discrepancies during the article screening process were resolved by discussion with a third reviewer (JJ). Hand-searching of references within identified articles was also performed to enhance the comprehensiveness of the search. A standardized Microsoft Excel data collection form was used for data extraction, and details related to the study characteristics, studied indications of intervention, efficacy, and safety were collected.

    Management of Missing Data

    For studies with missing data, authors were contacted for clarification to enhance the comprehensiveness of this review. Missing information that could not be retrieved after two email reminders were labeled as unavailable.

    Risk of Bias in Individual Studies

    The Cochrane Risk of Bias tool version 2.0 (Oxford, England: Cochrane) was utilized in the assessment of the included RCTs [34]. Two independent reviewers (Teo and Chu) performed the risk of bias assessment (Appendix 2). The instrument comprises of the following five domains: risk of bias arising from the randomization process, deviations from intended interventions, missing outcome data, outcome measurement, and selection of reported results. Using the responses derived from the five domains, the overall risk of bias for the individual studies was rated as “low,” “some concerns,” or “high” risk of bias.

    Assessment of Heterogeneity

    Clinical and methodological heterogeneity of included studies were analyzed to evaluate if meta-analyses could be performed for specific interventions in this study. Clinical heterogeneity describes variation in characteristics of study participants, intervention, or outcomes while methodological heterogeneity describes variation in study design and risk of bias. This was performed by two independent reviewers (Yeam and Seng). In view of the clinical and methodological heterogeneity across the included studies, a narrative review of the RCTs was conducted.

    Synthesis of Data

    With regard to the efficacy of AMS interventions, the response rates and any changes in patients’ quality of life were recorded. Additionally, the safety profile of each intervention was evaluated and the reported prevalence, severity, and outcomes of adverse effects were tabulated. The adverse events reported in included studies were categorized using the Common Terminology Criteria for Adverse Events (CTCAE) [35].

    Summary Measures

    Descriptive statistics were utilized to summarize the characteristics of all included studies. The principal summary measures evaluated in this study were the studied indications, efficacy of each AMS, and safety profile of each AMS.

    Results

    Study Selection

    Out of 14,583 retrieved citations, 33 full-text articles were included in this review. The inclusion and exclusion criteria for the studies are shown in Figure 1. The percentage of agreement of articles between the reviewers was 94.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} and all disagreements were resolved after discussion.

    Role of Alternative Medical Systems in Adult Chronic Kidney Disease Patients: A Systematic Review of Literature
    Figure
    1:
    Flow chart for the inclusion of articles in this systematic review.

    Study Characteristics

    Types of AMS studied: Table 1 shows the characteristics of included studies. Among the four main types of AMS, TCM was the most studied (n=20, 60.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [3,7,17,36-52], followed by Ayurveda (n=6, 18.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [53-58], naturopathy (n=5, 15.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [59-63], and homeopathy (n=2, 6.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [16,64].

    Study (year of publication) Study design Number of patients in treatment and control arm Indication for use of intervention Treatment Comparator Country Patient population Mean age of patients (SD) Gender (male) ({fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c})
    Traditional Chinese medicine (n=20)
    Li et al. (2015) [41] Double-blinded parallel arm T1:66, C1:32, T2:56, C2:26 Renal function 8 g TSF granules and ARB BID x 24 weeks 8 g placebo TID and ARB BID x 24 weeks China Non-dialysis CKD patients T1:59.5 (10.1), C1:56.7 (9.3), T2:58.9 (9.0), C2:60.8 (10.0) T1:54.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C1:53.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, T2:58.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C2:53.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Ma et al. (2013) [43] Parallel arm T:25, C:20 Renal function 150 mL ZSTL solution BID x 3 months 10 mg benazepril QD x 3 months China Early DN patients T:57, C:57 T:40{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:40{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Wang et al. (2012) [17] Double-blinded parallel arm T1:192, T2:191, C:189 Renal function T1: TCM granules BID x 24 weeks, T2: TCM granules BID and 10mg benazepril QD x 24 weeks 10 mg benazepril QD and TCM placebo TID x 24 weeks China CKD stage 3 T1:47.3 (10.9), T2:49.3 (11.4), C:49.0 (10.5) T1:54.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, T2:47.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:47.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Yu et al. (2017) [50] Single-blinded parallel arm T:28, C:25 Renal function Acupuncture at Li4, ST36 and K13 acupoint QD x 3 months Sham acupuncture QD x 3 months China CKD stage 2-4 T:58.5, C:61.0 T:89.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:88.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Zhao et al. (2020) [52] Double-blinded parallel arm T:171, C:172 Renal function Herbal granules TID x 6 months Placebo granules x TID 6 months China CKD stage 3 T:51.89 (13.12), C:52.03 (12.62) T:62.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:70.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Xiang et al. (2016) [47] Parallel arm T:51, C:51 Renal function QDDHGa tablets BID x 12 weeks ARB tablets (minimum dosage) China DN patients T:57.21 (13.20), C:58.16 (11.59) T:24{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:22{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Xu et al. (2016) [49] Double-blinded parallel arm T:91, C:86 Renal function 500 mg GS-Rb1 (ginseng extract) QD x 6 months  Placebo tablets QD x 6 months China CKD stage 2-3 T:59.2 (8.5), C:58.4 (7.5) T:72.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:70.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Chen et al. (2013) [37] Parallel arm T:95, C:95 Proteinuria 9.6 g of Shenqi particle TID x 48 weeks Routine care China Non-dialysis CKD patients T:49 (14), C:53 (12) T:36.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:68.42{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Ge et al. (2013) [39] Parallel arm T:34, C:31 Proteinuria  40 mg TWHF TID x 3 months followed by 20 mg TWHF TID x 3 months 80 mg valsartan BID x 6 months China DN patients T:51.9 (9.8), C:51.0 (8.9) T:58.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:54.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Li et al. (2020) [42] Double-blinded parallel arm T:735, C:735 Proteinuria Huangkui capsule TID x 12 months Losartan potassium tablet QD and placebo capsules TIW x 12 months China CKD stage 1-3a T:37.7 (10.9), C:37.1 (10.4) T:48.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:46.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Zhang et al. (2014) [51] Parallel arm T1:133, T2:136, C:135 Proteinuria T1: Huangkui capsule TID x 6 months, T2: Huangkui capsule TID and Losartan potassium tablet QD x 6 months  Losartan tablet potassium QD x 6 months  China Non-dialysis CKD patients T1:37.3 (12.5), T2:37.1 (11.1), C:38.1 (12.7) T1:50.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, T2:47.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:53.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Xiong et al. (2020) [48] Parallel arm T:62, C:62 Proteinuria 60 mg TWHF and 160 mg valsartan QD x 24 weeks 160 valsartan QD x 24 weeks China Non-dialysis CKD patients T:50.3 (11.8), C:49.6 (12.3) T:69.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:72.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Che-Yi et al. (2005) [36] Double-blinded parallel arm T:20, C:20 Uremic pruritus Acupuncture at Quchi (L11) acupoint TIW x 1 month Sham acupuncture TIW x 1 month China ESRD T:62.4 (9.1), C:63.2 (7.5) T:45.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:50.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Gao et al. (2002) [38] Double-blinded parallel arm T:34, C:34 Uremic pruritus Acupuncture at Quchi (L11) and Zusanli (ST 36) acupoint BIW x 1 month Sham acupuncture BIW x 1 month China ESRD 43.6 59.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Nahidi et al. (2018) [7] Single-blinded parallel arm T:15, C:11 Uremic pruritus Acupuncture at various acupoints TIW x 6 weeks Sham acupuncture TIW x 6 weeks Iran HD T:54.7 (11.4), C:41.4 (16.2) T:60{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:73{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Ono et al. (2015) [3] Parallel arm T:23, C:17 Fatigue, insomnia, itchiness, and pain Acupuncture QIW x 2 months Routine care Japan HD T:70.0 (9.6), C:67.3 (13.0) NI
    Su et al. (2009) [44] Parallel arm T:31, C:30 QoL Infrared stimulation of Qihai (RN6), Kuamyuan (RN4) and Chungchi (RN3) TIW x 3 months Heat pad therapy to acupoints TIW x 3 months China ESRD T:61.07 (13.9), C:58.6 (12.6) T:51.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:56.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Wang et al. (2019) [45] Single-blinded parallel arm T:40, C:40 Wnt/β-catenin signaling pathway Qingshen granules TID x 3 months Placebo granules TID x 3 months China CKD stage 3-5 T:52.1 (10.4), C:54.9 (9.2) T:55{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:48{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Wang et al. (2020) [46] Parallel arm T:136, C:146 Immune function Qingshen granules TID x 3 months Routine care China CKD stage 3-5 T:54.0 (10.5), C:51.8 (12.0) T:55.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:57.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Li et al. (2009) [40] Parallel arm T:32, C:32 Vascular endothelial function TBN tablets (gingko extract) TI x 8 weeks Routine care China Early DN patients T:66.5 (71.1), C:67.2 (7.2) T:53.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:50{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Ayurveda (n=6)
    Alam et al. (2020) [53] Parallel arm T:70, C:66 Renal function Sativa oil QD and alpha-keto amino acid tablets TID x 3 months Alpha-keto amino acid tablets TID x 3 months India CKD stage 3-4 T:49.2, C:48.8 T:58.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:51.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Fallahzadeh et al. (2012) [54] Double-blinded parallel arm T:30, C:30 Renal function 140 mg silymarin tablet QD x 3 months Placebo tablet QD x 3 months Iran Non-dialysis CKD patients T:55.9 (8.3), C:57.6 (7.5) T:50{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:43.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Hoseini et al. (2019) [55] Parallel arm T:22, C:22 Renal function Camel milk BID x 3 months Routine care Iran CKD stage 3-4 56.7 (11.8) 52.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Khajehdehi et al. (2011) [56] Double-blinded parallel arm T:28, C:28 Renal function 140 mg silymarin TID x 3 months Placebo tablet TID x 3 months Iran Non-dialysis CKD patients T:55.9 (8.3), C:57.6 (7.5) T:50{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:43.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Makhlough et al. (2010) [57] Double-blinded parallel arm T:17, C:17 Uremic pruritus 0.03{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} capsaicin ointment QID x 4 weeks Placebo ointment QID x 4 weeks Iran ESRD 57 (18.6) 41.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Pingali et al. (2020) [58] Double-blinded parallel arm T1:18, T2:18, C:19 Hyperuricemia T1:500 mg of beleric capsule taken QD T2: 1000 mg of beleric capsule taken QD C:40 mg of febuxostat taken QD India CKD stage 2-3 T1:53.2 (8.9), T2:50.8 (8.8), C:51.0 (9.8) T1:72.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, T2:77.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:73.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Naturopathy (n=5)
    Khan et al. (2014) [60] Double-blinded parallel arm T:80, C:80 Malnutrition  Alpha-keto amino acid tablets TID x 3 months Placebo tablets TID x 3 months India Non-dialysis CKD patients T:45.0, C:45.0 T:59.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:57.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Prakash et al. (2004) [61] Double-blinded parallel arm T:21, C:19 Malnutrition  Keto amino acid tablets QD x 9 months Placebo tablets QD x 9 months India CKD stage 3-4 T:52.8 (14.1), C:55.9 (17.6) T:55.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:43.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Sedaghattalab et al. (2021) [62] Double-blinded parallel arm T:22, C:23 Inflammation Watercress extract QD x 1 month Placebo extract QD x 1 month Iran HD T:58.9 (16), C:63.1 (13) NI
    Zare et al. (2019) [63] Double-blinded parallel arm T:19, C:21 Inflammation Garlic extract tablets TIW x 2 months Placebo tablets TIW x 2 months Iran PD T:56.0 (16.1), C:52.8 (18.8) T:42.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:42.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Boldaji et al. (2019) [59] Crossover trial T:22, C:19 Hypertension, stress, and inflammation Pomegranate juice TIW x 2 months Routine care Iran ESRD 47.8 (13.3) 61{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Homeopathy (n=2)
    Cavalcanti et al. (2003) [16] Double-blinded parallel arm T:11, C:9 Uremic pruritus Homeopathic verum medicationb administered Placebo medication administered Brazil HD T:47, C:57 T:64{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:56{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Silveira et al. (2019) [64] Double-blinded parallel arm T:18, C:14 Renal function Brazilian green propolis pills BID x 3 months Placebo pills BID x 3 months Brazil CKD stage 1-5 T:52.8 (14.1), C:55.9 (17.6) T:55.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, C:43.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Table
    1: Characteristics of included AMS intervention studies.

    aQDDHG is composed of Huang Qi, Danshen, Dihuang, Shanyao, and Gan Cao.

    bDosage and frequency vary from patient to patient.

    ARB: angiotensin receptor blockers; DN: diabetic neuropathy; ESRD: end-stage renal disease; TBN: tianbaoning; TSF: tangshen formula; TWHF: Tripterygium wilfordii Hook F; ZSTL: zishentongluo; QoL: quality of life; QD: once a day; TIW: thrice a week; TID: thrice a day; CKD: chronic kidney disease; QIW: four times a week; HD: hemodialysis; T: test group; C: control group; T1: test group 1; T2: test group 2; C1: control group 1; C2: control group 2

    Overview of study design and patient characteristics in included studies are as follows: the majority of the studies were conducted in Asia (n=31, 93.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), whereas most of the studies were performed in China (n=18, 54.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}). Out of all reviewed studies, 20 (60.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) were blinded to randomized controlled trials. The sample size was greater than 50 patients in 21 (63.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) trials (Table 1). Non-dialysis patients were recruited in seven studies (21.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), whereas ESRD patients were recruited in five studies (15.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}). The average duration of follow-up for all studies was 4.9 months (Table 2).

    Study (year of publication) Indication for use of intervention Treatment (dose and duration if available) Comparator (dose and duration if available) Tool(s) used to assess outcomes Outcome Improvement symptoms (yes / no) Percentage reductiona/improvement in symptoms (if available) Follow-up duration
    Traditional Chinese medicine (n=20)
    Li et al. (2015) [41] Renal function 8 g TSF granules TID and ARB BID x 24 weeks 8 g placebo TID and ARB BID x 24 weeks WHOQOL-BREF, DQOL UAER (μg/min) (pre vs post): 105.39±77.29 vs 88.37±108.46, p=0.021 Yes -16.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (UAER) 6 months
    24 h urinary protein (g/24 h) (pre vs post): 1.12±0.75 vs 0.91±0.90, p=0.017 -18.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (24 h urinary protein)
    Ma et al. (2013) [43] Renal function 150 mL ZSTL solution BID x 3 months 10 mg benazepril QD x 3 months Radioimmunoassay, ELISA HbA1c ({fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) (baseline vs mean change from baseline): 10.68 (8.48, 13.96) vs -4.29 (-5.85, -2.79), p<0.05. Yes -40.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (HbA1c) 9 months
    UAER (μg/min) (baseline vs mean change from baseline): 211.52 (164.58, 243.89) vs -106.99 (-121.29, -85.55), p<0.05 -50.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (UAER)
    SCr (μmol/L) (baseline vs mean change from baseline): 87.17 (70.59, 110.25) vs -3.33 (-11.02, 2.15), p<0.05 -3.82{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (SCr)
    CCR (mL/min) (baseline vs mean change from baseline): 139.86 (129.58, 149.52) vs -9.22 (-13.42, -5.82), p <0.05 -6.59{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (CCR)
    Wang et al. (2012) [17] Renal function T1: TCM granuleb BID x 24 weeks. T2: TCM granuleb BID and 10 mg benazepril QD x 24 weeks. 10 mg benazepril QD and TCM placebo TID x 24 weeks MDRD study equation, TCM assessing sheets eGFR (mL/min/1.73 m2) (pre vs post): T1: 45.26±10.12 vs 48.46±15.90, p<0.05. T2: 44.68±9.82 vs 48.31±17.50, p<0.05. Yes 7.07{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (eGFR; T1), 8.12{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (eGFR; T2) 6 months
    24 h proteinuria (mg/24 h) (pre vs post): T1: 725.98 vs 990.00, p<0.05. T2: 590.00 vs 453.50, p<0.05 36.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (proteinuria; T1), -21.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (proteinuria; T2)
    Urinary albumin/creatinine (mg/gCr) (pre vs post): T2: 0.30 vs 0.22, p<0.05 -26.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (urinary albumin/creatinine; T2)
    Hb (g/L) (pre vs post): T1: 127.31±18.47 vs 129.57±21.82, p<0.05 17.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (Hb; T1)
    Yu et al. (2017) [50] Renal function Acupuncture at Li4, ST36 and K13 acupoint QD x 3 months Sham acupuncture QD x 3 months NI SCr levels (mg/dL) (T vs C): baseline: 1.45 vs 1.67, p=0.1298. Post-intervention: 1.41 vs 1.65, p=0.0489. 3-month follow-up: 1.32 vs 1.81, p=0.0467 Yes -2.76{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (SCr; pre vs post), -9.00{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (SCr; pre- vs 3 months follow-up) 6 months
    eGFR (mL/min/1.73m2) (T vs C): Baseline: 51.85 vs 42.50, p=0.0855. Post-intervention: 54.50 vs 43.60, p=0.0470. 3-month follow-up: 59.90 vs 40.80, p=0.0191 5.11{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (eGFR; pre vs post), 15.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (eGFR; pre-intervention vs 3 months follow-up)
    hs-CRP (mg/dL) (T vs C): Baseline: 1.10 vs 0.79, p=0.4361. Post-intervention: 0.80 vs 0.90, p=0.8773 -27.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (hs-CRP pre vs post)
    Zhao et al. (2020) [52] Renal function Herbal granulec TID x 6 months Placebo granules x TID 6 months Dye-binding method, Cerebrospinal fluid protein test kit, Determiner L CRE kit SCr (μmol/L) (pre vs weeks 16, 20 and 24): 148.42±35.90 vs 130.19±29.79, 130.08±30.57, 130.78±32.55, p<0.05 Yes -12.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (SCr; pre vs 16 weeks), -12.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (SCr; pre vs 20 weeks), -11.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (SCr; pre vs 24 weeks) 6 months
    Xiang et al. (2016) [47] Renal function QDDHG tablets BID and ARB (minimum dosage) x 12 weeks ARB tablets (minimum dosage) Guidelines for clinical research of Chinese medicine Albumin (mg/24h) (within treatment group, baseline vs 4 vs 8 vs 12 week): 85.30 (66.00, 176.30) vs 61.50 (49.00, 110.20), p<0.05 vs 51.00 (37.00, 90.00), p<0.05 vs 41.40 (29.00, 68.00), p<0.05 Yes -27.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (Albumin; 4 weeks), -40.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (Albumin; 8 weeks), -43.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (Albumin; 12 weeks) 3 months
    Proteinuria (g/24h) (within treatment group, baseline vs 4 vs 8 vs 12 week): 0.20 (0.10, 0.30) vs 0.10 (0.10, 0.20), p<0.05 vs 0.10 (0.10, 0.20), p<0.05 vs 0.10 (0.10, 0.20), p<0.05 -50{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (Proteinuria; 4, 8, 12 weeks)
    Albumin/creatinine (mg/mol) (within treatment group, baseline vs 4 vs 8 vs 12 week): 20.70 (11.00, 30.50) vs 16.30 (8.10, 25.00), p<0.05 vs 15.00 (7.20, 20.60), p<0.05 vs 10.10 (5.60, 17.00), p<0.05 -21.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (albumin/creatinine; 4 weeks), -27.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (albumin/creatinine; 8 weeks), -51.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (albumin/creatinine; 12 weeks)
    Xu et al. (2016) [49] Renal function 500 mg GS-Rb1 (ginseng extract) QD x 6 months  Placebo tablets QD x 6 months ELISA Creatinine and urea level (T vs C): 6 months, p<0.01. 12 months, p<0.01 Yes – 12 months
    Oxidative stress markers (T vs C): 6 months, p<0.01. 12 months, p<0.05
    TNF-a level (T vs C): 6 months, p<0.05
    Chen et al. (2013) [37] Proteinuria 9.6 g of Shenqi particle TID x 48 weeks Routine care MDRD study equation Proteinuria (g/d) (pre vs post): 5.34±2.74 vs 2.04±2.15, p<0.001 Yes -61.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (proteinuria) 12 months
    eGFR (mL/min/1.73 m2) (pre vs post): 84.6±27.0 vs 100.7±37.5, p=0.001 19.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (eGFR)
    Ge et al. (2013) [39] Proteinuria 40 mg TwHF TID x 3 months, 20 mg TwHF TID x 3 months. 160 mg valsartan capsules QD x 6 months Trichloroacetic acid method, Jaffe reaction, MDRD study equation, high-performance liquid chromatography Urinary protein (g/24 h) (pre vs 1 month, pre vs 3 months, pre vs 6 months): 4.99±2.25 vs 3.23±2.57, p<0.01. 4.99±2.25 vs 2.83±1.57, p<0.01. 4.99±2.25 vs 2.99±1.81, p<0.01 Yes -35.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (urinary protein; 1 months), -43.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (urinary protein; 3 months), -40.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (urinary protein; 6 months) 6 months
    eGFR (mL/min/1.73 m2) (pre vs 6 months): 43.07±21.65 vs 38.71±23.66, p<0.05 -10.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (eGFR; 6 months)
    Li et al. (2020) [42] Proteinuria Huangkui capsule TID x 12 months Losartan potassium tablet QD and placebo capsules TIW x 12 months NI Proteinuria (mg/24 h) (pre vs post): 1238.9±667.4 vs 1008.8±1104.7, p<0.001 Yes -18.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (proteinuria) 12 months
    Zhang et al. (2014) [51] Proteinuria T1: Huangkui capsule TID x 6 months. T2: Huangkui capsule TID and Losartan potassium tablet QD x 6 months. Losartan tablet potassium QD x 6 months Biuret method, sarcosine oxidase assay Proteinuria within T1 (pre vs 12 vs 24 weeks): 1045±420 vs 762±533, p<0.001 vs 537±409, p<0.001 Yes T1: -27.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (pre vs 12 weeks), -48.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (pre vs 24 weeks) 6 months
    Proteinuria within T2 (pre vs 12 vs 24 weeks): 1073±439 vs 783±658, p<0.001 vs 529±509, p<0.001. T2: -27.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (pre vs 12 weeks), -50.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (pre vs 24 weeks).
    Xiong et al. (2020) [48] Proteinuria 60 mg TWHF and 160 mg valsartan QD x 24 weeks 160 valsartan QD x 24 weeks CKD-EPI equation Proteinuria (g/24 h) (T vs C, PP analysis): 3.16±0.62 vs 4.28±0.85, p<0.001 Yes PP: -26.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (proteinuria)  6 months
    Serum albumin (g/L) (T vs C, PP analysis): 37.65±4.31 vs 33.59±4.56, p<0.001 PP: 12.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (serum albumin)
    Proteinuria (g/24 h) (T vs C, ITT analysis): 3.36±0.83 vs 4.52±1.06; p<0.001 ITT: -25.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (proteinuria)
    Serum albumin (g/L) (T vs C, ITT analysis): 36.91±4.42 vs 34.67±4.75, p=0.008 ITT: 6.46{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (serum albumin)
    Che-yi et al. (2005) [36] Uremic pruritus Acupuncture at Quchi (L11) acupoint TIW x 1 month Sham acupuncture TIW x 1 month Validated questionnaire Pruritus scores (pre vs post vs 3 months follow-up): 38.2±4.8 vs 17.3±5.5 vs 16.5±4.9, p<0.001 Yes -54.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (pruritus scores; pre- vs post-intervention), -56.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (pruritus scores; pre-intervention vs 3 months follow-up) 3 months
    Gao et al. (2002) [38] Uremic pruritus Acupuncture at Quchi (L11) and Zusanli (ST 36) acupoint BIW x 1 month Sham acupuncture BIW x 1 month NI Number of patients (complete alleviation vs improvement vs no effect): 24 (70.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) vs 9 (26.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) vs 1 (2.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) Yes – 3 months
    Nahidi et al. (2018) [7] Uremic pruritus 30 minutes of acupuncture, for six weeks, at the following acupoints: Sp6, Sp10, Lv3, Li4, Li11. 30 minutes of sham acupuncture, for 6 weeks. VAS Pruritus scores (pre vs post): 9.87±0.35 vs 3.93±2.85, p<0.001 Yes -60.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (pruritus scores) 6 weeks
    Ono et al. (2015) [3] Fatigue, insomnia, itchiness, and pain Acupuncture QIW x 2 months Routine care VAS, EQ-5D Headache score (pre vs post): 17.1±26.1 vs 6.2±13.5, p<0.05. Yes -63.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (headache score)  3 months
    Blurred vision score (pre vs post): 33.4±32.7 vs 17.0±22.2, p<0.05. -49.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (blurred vision score) 
    Dizziness score (pre vs post): 13.0±21.4 vs 1.4±6.3, p<0.05. -89.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (dizziness score) 
    Ear buzzing (pre vs post): 17.9±27.2 vs 8.0±14.7, p<0.05 -55.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (ear buzzing)
    Cervical pain (pre vs post): 37.7±39.1 vs 25.3±29.7, p<0.05 -32.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (cervical pain) 
    Stiff shoulders (pre vs post): 29.9±28.6 vs 12.5±21.6, p<0.05 -58.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (stiff shoulders) 
    Back pain (pre vs post): 38.5±33.7 vs 9.3±18.1, p<0.05 -58.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (back pain)
    Lower limb pain (pre vs post): 29.4±36.4 vs 17.1±23.3, p<0.05 -41.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (lower limb pain) 
    Numbness in upper limb (pre vs post): 18.9±30.4 vs 4.0±29.5, p<0.05 -78.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (numbness in upper limb) 
    Numbness in lower limb (pre vs post): 21.9±34.9 vs 11.0±26.2, p<0.05 -49.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (numbness in lower limb) 
    Itchiness (pre vs post): 38.7±40.7 vs 29.3±31.5, p<0.05 -24.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (itchiness)
    Difficulty in sleeping (pre vs post): 34.8±36.9 vs 12.8±22.5, p<0.05 -63.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (difficulty in sleeping)
    Utility in treatment group (pre vs post): 0.66±0.15 vs 0.76±0.17, p<0.05 15.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (utility)
    Su et al. (2009) [44] QoL Infrared stimulation of Qihai (RN6), Kuamyuan (RN4) and Chungchi (RN3) TIW x 3 months Heat pad therapy to acupoints TIW x 3 months Heart rate variability analyser, WHOQOL-BREF questionnaire LF activity (pre vs post): 49.99±79.08 vs 131.71±214.36, p=0.01 Yes 163{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (LF activity) 3 months
    Fatigue index (pre vs post): 133.90±20.43 vs 121.71±32.68, p=0.02 -9.10{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (fatigue index)
    Psychological domain (pre vs post): 18.16±4.30 vs 19.39±0.72, p=0.02 6.77{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (psychological domain)
    Environmental domain (pre vs post): 29.87±4.04 vs 32.00±4.85, p=0.00. 7.13{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (environmental)
    Wang et al. (2019) [45] Wnt/β-catenin signaling pathway Qingshen granules TID x 3 months Placebo granules TID x 3 months ELISA Effective rates of TCM symptom (T vs C): 80{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} vs 60{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, p=0.024 Yes – 3 months
    eGFR (mL/min) (T vs C): 15.9±3.2 vs 14.0±4.0, p=0.019 17.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (eGFR)
    HIF-1𝛼 (ng/mL) (T vs C): 0.66±0.16 vs 1.39±0.17, p≤0.001 -61.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (HIF-1𝛼)
    Wnt1 (pg/mL) (T vs C): 314.2±85.8 vs 382.8±85.3, p=0.001 -16.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (Wnt1)
    𝛽-catenin (pg/mL) (T vs C): 416.5±13.6 vs 462.1±15.1, p ≤0.001 -10.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (𝛽-catenin)
    𝛼-SMA (KU/L) (T vs C): 20.5±3.1 vs 23.5±4.1, p≤0.001 -20.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (𝛼-SMA)
    E-cadherin (ng/mL) (T vs C): 2166.9±398.6 vs 2370.7±468.0, p=0.039 -15.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (E-cadherin)
    Wang et al. (2020) [46] Immune function Qingshen granules TID x 3 months Routine care Flow cytometry, ELISA CD4+/CD8+ T cell (pre vs post): 1.98±0.86 vs 1.58±0.72, p<0.05. Yes -20.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (CD4+/CD8+ T cell) 3 months
    Th17 cell (pre vs post): 2.51±1.05 vs 1.70±0.83, p<0.01. -32.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (Th17)
    NF-κB p65 (pre vs post): 36.84±12.96 vs 24.86±1.97, p<0.05 -32.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (NF-κB p65)
    IL-17 (pre vs post): 28.62±13.53 vs 19.78±12.25, p<0.05 -30.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (IL-17)
    IL-6 (pre vs post): 77.13±20.54 vs 58.42±18.25, p<0.05 -24.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (IL-6)
    TNF-α (pre vs post): 110.34±23.76 vs 75.49±22.80, p<0.01 -31.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (TNF-α)
    TRAF6 (pre vs post): 4.94±1.82 vs 2.85±1.53, p<0.01 -42.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (TRAF6)
    FN (pre vs post): 93.42±20.36 vs 62.86±19.35, p<0.01 -32.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (FN)
    Col-IV (pre vs post): 36.85±14.58 vs 24.36±13.36, p<0.01 -33.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (Col-IV)
    Total effective rate (T vs C): 79.41{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} vs 67.12{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, p<0.05. –
    Li et al. (2009) [40] Vascular endothelial function TBN tablets (gingko extract) TID x 8 weeks Routine care Chemical colorimeter, Radioimmunoassay, ELISA, Siemens Sequoia 512 color Doppler ultrasonography UAER (μg/min) (pre vs post): 153.30±63.28 vs 85.15±36.82, p<0.01 Yes -44.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (UAER) 3 months
    SCr (μmol/L) (pre vs post): 120.76±17.83 vs 105.67±18.13, p<0.01 -12.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (SCr)
    NO (μmol/L) (pre vs post): 50.16±24.64 vs 70.65±28.71, p<0.01 40.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (NO)
    vWF ({fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) (pre vs post): 182.05±64.13 vs 128.56±48.98, p<0.01 -29.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (vWF)
    BAID responsive change ({fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) (pre vs post): 4.91±2.31 vs 6.78±3.89, p<0.01 38.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (BAID responsive change)
    Ayurveda (n=6)
    Alam et al. (2020) [53] Renal function Sativa oil QD and alpha-keto amino acid tablets TID x 3 months Alpha-keto amino acid tablets TID x 3 months Hemogram, renal function test, serum electrolyte test Hb{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (g/dL) (pre vs post): 8.84±1.31 vs 10.24±1.10, p<0.001 Yes 15.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (Hb{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) 3 months
    24-h TUV (mL/day) (pre vs post): 1250.69±303.74 vs 1660.14±258.78, p<0.001 32.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (TUV)
    eGFR (mL/min) (pre vs post): 22.71±7.28 vs 42.42±17.38, p<0.001 86.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (eGFR)
    Fallahzadeh et al. (2012) [54] Renal function 140 mg silymarin tablet QD x 3 months Placebo tablet QD x 3 months Jaffé method, ELISA MDA assay, MDRD study equation, nephelometry, high-performance liquid chromatography, mercury sphygmomanometer Urinary TNF-α (pg/mg) (change from baseline): -3.45 (-5.44 to -1.46), p<0.05 Yes – 2 months
    Urinary MDA (nmol/mg) (change from baseline): -1.5 (-2.87 to -0.13, p<0.05
    Serum MDA (μmol/L) (change from baseline): -3.43 (-6.02 to -0.83), p<0.05
    Hoseini et al. (2019) [55] Renal function Camel milk BID x 3 months Routine care MDRD eGFR (pre vs post): 26.9±7.39 vs 31.45±8.99, p=0.001 Yes 16.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (eGFR) 3 months
    SCr levels (pre vs post): 2.58±0.71 vs 2.2±0.48, p=0.01 -14.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (SCr)
    BUN (pre vs post): 60.31±22.61 vs 44.38±14.29, p=0.0001 -26.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (BUN)
    Khajehdehi et al. (2011) [56] Renal function 140 mg silymarin TID x 3 months Placebo tablet TID x 3 months ELISA Proteinuria (mg/24h) (pre vs post, patients with type 2 diabetic nephropathy): 4328.7±3038.2 vs 2354.7±1800.1, p=0.001 Yes -45.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (proteinuria) 2 months
    IL-8 (pg/mL) (pre vs post, patients with type 2 diabetic nephropathy): 99.1±97.9 vs 43.6±55.0, p=0.002 -56.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (IL-8)
    TGF-β (pg/mL) (pre vs post, patients with overt type 2 diabetic nephropathy): 522.3±189.2 vs 397.3±55.2, p=0.006 -23.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (TGB-β)
    IL-8 (pg/mL) (pre vs post, patients with overt type 2 diabetic nephropathy): 41.4±50.3 vs 30.6±75.2, p=0.02 -26.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (IL-8)
    Makhlough et al. (2010) [57] Uremic pruritus 0.03{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} capsaicin ointment QID x 4 weeks Placebo ointment QID x 4 weeks Uremic pruritus scoring questionnaire by Duo Pruritus score (T vs C): 2.5±2.5 vs 7.2±5.5, p<0.05 Yes -84.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (pruritus score)  
    Pingali et al. (2020) [58] Hyperuricemia T1:500 mg of beleric capsule taken QD. T2: 1000 mg of beleric capsule taken QD 40 mg of Febuxostat taken QD Jaffe method, MDRD Study equation, Salbutamol challenge test, Ellman’s method, Chrono-log light transmittance aggregometry, Spectrometry, Colorimetric detection with Griess reagents SCr (pre vs post): group B: 1.86±0.32 vs 1.64±0.29, p≤0.005. Group C: 2.06±0.26 vs 1.56±0.24, p≤0.0001 Yes -11.70{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}±9.00 (SCr, group B), -24.42{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}±8.14 (SCr, group C). 6 months
    eGFR (pre vs post): group B: 39.13±6.57 vs 45.96±11.14, p≤0.005. Group C: 34.78±5.34 vs 48.93±11.46, p≤0.0001 16.96{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}±14.87 (eGFR, group B), 40.39{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}±20.98 (eGFR, group C)
    Serum uric acid (pre vs post): Group B:8.10±0.67 vs 6.46±0.34, p≤0.0001. Group C: 8.54±0.64 vs 5.63±0.37, p≤0.0001 19.84{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}±6.43 (serum uric acid, group B), 33.88{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}±4.95 (serum uric acid, group C)
    Naturopathy (n=5)
    Khan et al. (2014) [60] Malnutrition Alpha-keto amino acid tablets TID x 3 months Placebo tablets TID x 3 months Blood tests Hb{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (g/dL) (T vs C): 9.39±0.87 vs 8.91±1.48, p<0.05 Yes 19.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (Hb{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) 3 months
    FBG (mg/dL) (T vs C): 104.00±8.46 vs 113.78±14.31, p<0.001 -20.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (FBG)
    Blood urea (mg/dL) (T vs C): 66.07±19.29 vs 79.78±24.79, p<0.001 -38.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (blood urea)
    SCr (mg/dL) (T vs C): 2.83±1.10 vs 3.33±1.37, p<0.05 -39.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (SCr)
    24 h TUP (g/day) (T vs C): 2.06±0.61 vs 2.43±0.97, p<0.01 -38.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (TUP)
    24 Hour TUV (mL/day) (T vs C): 1943.23±204.1 vs 1736.76±176.04, p<0.001 33.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (TUV)
    GFR (mL/min) (T vs C): 29.4±3.68 vs 23.3±1.63, p<0.001 49.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (GFR)
    Prakash et al. (2004) [61] Malnutrition Keto amino acid tablets QD x 9 months Placebo tablets QD x 9 months 99mTc-DTPA plasma sample method GFR (mL/min/ 1.73 m2) (pre vs post within C): 28.6±17.6 vs 22.5±15.9, p=0.015. Progress of renal failure prevented. – 9 months
    Serum total proteins (g{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) (pre vs post within C): 7.04±0.66 vs 6.56±0.83, p=0.038
    Mid-arm circumference (cm) (pre vs post within C): 28.0±4.4 vs 27.3±4.8, p=0.048
    Sedaghattalab et al. (2021) [62] Inflammation Watercress extract QD x 1 month Placebo extract QD x 1 month Blood tests, TBA reaction assay, Colorimetric kits, Spectrophotometer BUN (mg/dL) (pre vs post): 40.6±11.2 vs 34.6±15.1, p<0.04. Yes -14.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (BUN) 1 month
    Calcium (mg/dL) (pre vs post): 8.8±1.32 vs 10.4±2, p<0.001 18.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (calcium)
    Total oxidant status (μM) (pre vs post): 11.3±3.3 vs 6.9±2.4, p<0.001 -38.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (total oxidant status)
    Sulfhydryl protein (mmol/L) (pre vs post): 13.1±5.3 vs 7.4±4.3, p<0.001 -43.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (sulfhydryl protein)
    MDA (mmol/L) (pre vs post): 1.6±0.13 vs 0.42±0.27, p<0.001 -73.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (MDA)
    Superoxide dismutase (U/mL) (pre vs post): 29.3±6.3 vs 37.1±8.4, p<0.001 26.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (superoxide dismutase)
    Zare et al. (2019) [63] Inflammation Garlic extract tablets TIW x 2 months Placebo tablets TIW x 2 months Human homocysteine kits, ELISA IL-6 (pg/mL) (pre vs post): 2.2 (0.8, 6.4) vs 0.7 (0.6, 1.2), p<0.001 Yes -68.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (IL-6) 2 months
    CRP (mg/L) (pre vs post): 13.0 (5.0, 14.0) vs 2.0 (1.0, 9.0), p<0.001 -84.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (CRP)
    ESR (mm) (pre vs post): 50.7±28.5 vs 35.4±21.7, p=0.021. -30.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (ESR)
    Boldaji et al. (2019) [59] Hypertension, stress, and inflammation Pomegranate juice TIW x 2 months Routine care Mini nutritional assessment MDA (μmol L-1) (pre vs post): 0.88±0.01vs 0.77±0.01, p<0.001 Yes -12.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (MDA) 2 months
    Total antioxidant capacity (mmol L-1) (pre vs post): 0.40±0.08vs 0.49±0.11, p<0.001 22.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (total antioxidant capacity)
    IL-6 (ng L-1) (pre vs post): 3.00±1.48 vs 2.09±1.25, p<0.0001 -30.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (IL-6)
    Homeopathy (n=2)
    Cavalcanti et al. (2003) [16] Uremic pruritus Homeopathic verum medicationd administered Placebo medication administered Validated scale Pruritus score (pre vs 15 vs 30 vs 45 vs 60 days): 65±25 vs 46±29, p=0.002 vs 41±30, p=0.002 vs 42±29, p=0.002 vs 38±33, p=0.004 Yes -29.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (pruritus score, pre vs 15 days), -36.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (pruritus score, pre vs 30 days), -35.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (pruritus score, pre vs 45 days), -41.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (pruritus score, pre vs 60 days) 60 days
    Silveira et al. (2019) [64] Renal function Brazilian green propolis pills BID x 3 months Placebo pills BID x 3 months Immunoturbidimetry, ELISA Proteinuria (mg/24 h) (T vs C, baseline vs 12 months): 695 (95{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} CI, 483 to 999) vs. 1403 (95{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} CI, 1031 to 1909); p=0.004 Yes -27.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} (proteinuria) 12 months
    Table
    2: Assessment of outcomes and efficacy of different AMS interventions.

    aPercentage reduction in symptoms is computed using (mean score at baseline – mean score post-treatment at end of study)/(mean score at baseline) for the treatment group.

    bTCM granules are formulated based on four TCM syndrome patterns (Qi Yin/Xue deficiency, blood stasis in the kidney, wind-dampness interfering in the kidney, and endoretention of damp heat) for the treatment of CKD.

    cHerbal granules consist of ten herbs: Huangqi, Danggui, Huzhang, Liuyuexue, Tufuling, Niuxi, Shiwei, Dahuang, Jixuecao, and Huangjing.

    dDosage and frequency vary from patient to patient.

    99mTc-DTPA: 99 m technetium diethylenetri-aminepenta-aceticacid; ARB: angiotensin II receptor blockers; BAID: brachial arterial inner diameter; BIW: twice a week; BUN: blood urea nitrogen; CCR: creatinine clearance rate; CKD-EPI: chronic kidney disease-epidemiology collaboration; DQOL: diabetes quality of life; eGFR: estimated glomerular filtration rate; ESR: erythrocyte sedimentation rate; ELISA: enzyme-linked immunosorbent assay; EQ-5D: EuroQol-5 dimension; FBG: fasting blood glucose; GS-RB1: Ginsenoside Rb1; HbA1c: haemoglobin A1c; ITT: intention to treat; LF: low frequency; MDA: malondialdehyde; MDRD: modification of diet in renal disease; NI: no information; PP: per protocol; QD: once a day; QDDHG: Qidan Dihuang Grain; SCr: serum creatinine; TBN: Tianbaoning; TCM: traditional Chinese medicine; TIW: thrice a week; TSF: Tangshen formula; TwHF: Tripterygium Wilfordii Hook F; TUP: total urine protein; TUV: total urine volume; UAER: urinary albumin excretion rate; VAS: visual analog scale; WHOQOL-BREF: World Health Organization Quality of Life-100 Questionnaire; ZSTL: Zishentongluo; Hs-CRP: high-sensitivity c-reactive protein; ITT: intention to treat; QIW: four times a week; HIF-1α: hypoxia-inducible factor 1-alpha; Wnt1: Wnt family member 1; α-SMA: alpha smooth muscle actin; TNF-α: tumor necrosis factor alpha; TRAF6: tumor necrosis factor receptor associated factor 6; FN: Fibronectin

    Tools used for outcomes assessments of symptoms during interventions are as follows: the most frequently utilized tools were the abbreviated version of the World Health Organization Quality of Life-100 Questionnaire (n=2) and visual analog scale (n=2).

    Risk of bias within studies: Out of all included studies, 14 (42.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) studies were assessed to be of “low” risk of bias, nine (27.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) and 10 (30.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) studies were scored as “some concerns” and “high” risk of bias, respectively.

    Results of Individual Studies

    Traditional Chinese medicine: The most commonly utilized interventions in the studies were herbal treatments (n=14, 70{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [17, 37-43, 45-49, 51, 52] followed by acupuncture (n=6, 30{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [3,7,36,38,44,50]. For acupuncture treatment, five studies used conventional acupuncture [3,7,36,38,50] while one study used infrared stimulation of acupoints [44]. The common acupoints administered during conventional acupuncture treatment were Li11 (n=3, 60{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), ST36 (n=2, 20{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), and Li4 (n=2, 20{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}). The frequency of acupuncture ranged from once a week to once a day, whereas the duration of studies lasted between six weeks to six months. Uremic pruritus (n=3, 60{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) was the most commonly studied indication, with reductions in pruritus score observed between 54.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} and 60.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} [7,36,38]. Infrared stimulation was used on RN6, RN4, and RN3 thrice a week for three months [44]. The indication studied was quality of life (QoL). According to QoL scores that were evaluated using the EQ-5D questionnaire, utility increased by 15.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}.

    Herbal treatments include six single-herb (n=6, 42.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [39-42,48,49,51] and eight multi-herbs formula granules (n=8, 57.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [17,37,41,43,45-47,52]. Common single-herb treatments used are Huangkui (n=2, 33.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) and TWHF (n=2, 33.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}). The frequency of treatment was once to three times a day, for two to 12 months. Proteinuria was the most studied indication (n=4, 66.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), where the various treatments reduced proteinuria between 27.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} and 61.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} [39,42,48,51]. Common herbs used in the multi-herb formula granules studies included Huang Qi (n=6, 75{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), Danggui (n=4, 50{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), Salvia miltiorrhiza (n=3, 37.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), and Poria (n=3, 37.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}). The most commonly studied indication was improvement in renal function (n=5, 62.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [17,41,43,47,52]. Serum creatinine decreased (2.76-12.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) and eGFR increased (7.07-15.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) across the various treatments.

    Ayurveda: The included studies evaluated both plant-based (n=3, 50{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [53,54,56] and animal-based (n=3, 50{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) treatments [55,57,58]. The most common treatment studied was plant-based silymarin tablets (n=2, 33.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) while that for clinical indication was improvement in renal function (n=4, 66.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [53-56]. The eGFR increased between 16.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} and 86.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} across the various treatments [53-56].

    Naturopathy: Keto amino acids were the most studied naturopathic treatment (n=2, 40{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}). Common indications studied included anemia and glucose control, where hemoglobin and fasting blood glucose levels in subjects improved by 19.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} and 20.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, respectively [60,61]. The use of watercress and garlic extract was also studied for inflammation, where the total oxidant status and IL-6 levels were shown to improve by 38.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} and 68.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, respectively.

    Homeopathy: Homeopathic verum was studied for relief of uremic pruritus with improvement in pruritus score between 29.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} and 41.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} [16]. For Brazilian green propolis pills, it was studied for proteinuria where a 27.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} reduction in proteinuria was noted [64].

    Safety Profile of AMS Interventions

    The adverse events reported by all included studies are shown in Table 3. Adverse events reported were of grade 1 (n=13, 39.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), grade 2 (n=8, 24.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), and grade 3 (n=6, 18.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) severity. There were no life-threatening consequences or death related to adverse effects (grades 4 and 5) reported.

    Study (year) N (T) Treatment Reported adverse effects based on Common Terminology Criteria for Adverse Effects (CTCAE) v5.0a,b,c Onset of adverse effects (if available) Management and outcomes of patients
    Grade 1 ({fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) Grade 2 ({fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) Grade 3 ({fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c})
    Traditional Chinese medicine (n=19)
    Chenet al. (2013) [37] 95 9.6 g of Shenqi particle TID x 48 weeks NI Interstitial pneumonia (n=1, 1.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) Lung infection (n=5, 5.26{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); liver injury (n=3, 3.15{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NI NI
    Geet al. (2013) [39] 34 40 mg Tripterygium Wilfordii Hook F TID x 3 months Vomiting (n=13, 38.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) Hyperkalaemia (n=8, 23.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); Leukopenia (n=1, 2.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); Photosensitive dermatitis (n=3, 8.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NA NI Patient with decreased white blood cell withdrawn from the study
    Liet al. (2020) [42] 735 Huangkui capsule TID x 12 months NA NA Upper respiratory tract infections (n=21, 2.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NI NI
    Zhanget al. (2014) [51] T1:133 T2:136 T1: Huangkui capsule TID x 6 months T2: Huangkui capsule TID and Losartan potassium tablet QD x 6 months  Elevated cholesterol (T1: n=5, 3.76{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}; T2: n=4, 2.94{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) Upper respiratory tract infections (T1: n=4, 3.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}; T2: n=4, 2.94{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) Liver injury (T1: n=3, 2.26{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NI NI
    Xionget al. (2020) [48] 62 60 mg Tripterygium Wilfordii Hook F and 160 mg valsartan QD x 24 weeks Itchy skin (n=4, 6.45{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); nausea (n=3.22{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); rash (n=1, 1.61{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NA Liver dysfunction (n=12, 19.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); leukopenia (n=1, 1.61{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NI NI
    Liet al. (2015) [41] 122 8 g Tangshen Formula granules and angiotensin receptor blockers BID x 24 weeks NA Anaemia (n=2) Acute myocardial infarction (n=5) NI NI
    Maet al. (2013) [43] 25 150 mL zishentongluo solution BID x 3 months NA NA NA NA NA
    Wanget al. (2012) [17] T1:192 T2:191 T1: TCM granules BID x 24 weeks T2: TCM granules BID and 10 mg benazepril QD x 24 weeks Dry cough (T2: n=2, 1.04{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); Gastrointestinal symptoms (T1: n=7, 3.64{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}; T2: n=3, 1.57{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) Anaemia (T1: n=7, 3.64{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}; T2: n=6, 3.14{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) Liver injury (T1: n=2, 1.04{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}; T2: n=5, 2.61{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); hyperkalaemia (T1 n=7, 3.64{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}; T2 n=18, 9.42{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NI NI
    Yuet al. (2017) [50] 28 Acupuncture at Li4, ST36 and K13 acupoint QD x 3 months Mild pain, bleeding and bruising in some patients  NA NA NI Symptoms resolved spontaneously without any treatment
    Zhaoet al. (2020) [52] 171 Herbal granules TID x 6 months Mild abnormal liver function test (n=5, 2.92{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); Mild discomfort (n=2, 1.17{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NA   NI NI
    Xianget al. (2016) [47] 51 QDDHGb tablets BID x 12 weeks Insomnia (n=1, 1.96{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NA NA NI NI
    Xuet al. (2016) [49] 91 500 mg GS-Rb1 (ginseng extract) QD x 6 months  NA NA NA NI NI
    Che-yiet al. (2005) [36] 20 Acupuncture at Quchi (L11) acupoint TIW x 1 month Elbow soreness (n=2; 10.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NA NA NI Symptoms resolved spontaneously after 1 day.
    Gaoet al. (2002) [38] 34 Acupuncture at Quchi (L11) and Zusanli (ST 36) acupoint BIW x 1 month NA NA NA NA NA
    Nahidiet al. (2018) [7] 15 Acupuncture at various acupoints TIW x 6 weeks NA NA NA NA NA
    Onoet al. (2015) [3] 23 Acupuncture QIW x 2 months NA NA NA NA NA
    Suet al. (2009) [44] 31 Infrared stimulation of Qihai (RN6), Kuamyuan (RN4) and Chungchi (RN3) TIW x 3 months NA NA NA NA NA
    Wanget al. (2019) [45] 41 Qingshen granules TID x 3 months NA NA NA NA NA
    Wanget al. (2020) [46] 136 Qingshen granules TID x 3 months NA NA NA NA NA
    Liet al. (2009) [40] 32 Tianbaoning tablets (gingko extract) TID x 8 weeks NA NA NA NA NA
    Ayurveda (n=6)
    Alamet al. (2020) [53] 70 Sativa oil QD and alpha-keto amino acid tablets TID x 3 months NA NA NA NA NA
    Fallahzadehet al. (2012) [54] 30 140 mg silymarin tablet QD x 3 months Nausea and vomiting (n=3, 10{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); headache (n=2,6.67{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NA NA NI NI
    Hoseiniet al. (2019) [55] 22 Camel milk BID x 3 months NA Abdominal pain (n=1, 4.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NA NI NI
    Khajehdehiet al. (2011) [56] 28 140 mg silymarin TID x 3 months NA NA NA NA NA
    Makhlough et al. (2010) [57] 17 0.03{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} capsaicin ointment QID x 4 weeks NA Severe skin burning (n=1, 2.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NA NI NI
    Pingaliet al. (2020) [58] 18 1000 mg of beleric capsule taken QD Mild gastrointestinal intolerance (n=2, 11.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NA NA NA NA
    Naturopathy (n=5)
    Khanet al. (2014) [60] 80 Alpha-keto amino acid tablets TID x 3 months Nausea (n=5, 6.25{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); diarrhoea (n=5, 6.25{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NA NA NA NA
    Prakashet al. (2004) [61] 21 Keto amino acid tablets QD x 9 months NA NA NA NI NI
    Sedaghattalabet al. (2021) [62] 22 Watercress extract QD x 1 month NA NA NA NA NA
    Zareet al. (2019) [63] 19 Garlic extract tablets TIW x 2 months NA NA NA NI NI
    Boldajiet al. (2019) [59] 22 Pomegranate juice TIW x 2 months Stomach discomfort (n=1, 4.54{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) NA NA NI NI
    Homeopathy (n=2)
    Cavalcantiet al. (2003) [16] 11 Homeopathic verum medicationc administered NA NA NA NA NA
    Silveiraet al. (2019) [64] 18 Brazilian green propolis pills BID x 3 months NA NA NA NA NA
    Table
    3: Adverse effects reported with AMS usage.

    aThe adverse effects were graded based on Common Terminology Criteria for Adverse Effects (CTCAE).

    bQDDHG is composed of Huang Qi, Danshen, Dihuang, Shanyao, and Gan Cao.

    cDosage and frequency vary from patient to patient.

    Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local, or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: death related to adverse effects; AE: adverse events; BID: twice a day; C: control arm; NA: not applicable; QD: once a day; T: treatment arm; TID: thrice a day; TIW: thrice a week

    Adverse effects associated with traditional Chinese medicine: the use of acupuncture is associated with mild pain, bleeding, bruising, and elbow soreness (grade 1) [36,40]. These symptoms resolved spontaneously without additional treatment. For single-herb treatments, TWHF treatment was associated with vomiting (38.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, grade 1), itchy skin (6.45{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, grade 1), nausea (3.22{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, grade 1), and rash (1.61{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, grade 1) [39,48]. Grade 2 adverse events associated with its use included hyperkalemia (23.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), leukopenia (2.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), and photosensitive dermatitis (8.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), while grade 3 adverse effects included liver dysfunction (19.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) and severe leukopenia (1.61{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}). Subjects who developed leukopenia were withdrawn from the study.

    For Huangkui treatment, adverse effects observed included elevated cholesterol (2.94-3.76{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) (grade 1), upper respiratory tract infection (2.94-3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) (grade 2 and grade 3), and liver injury (2.26{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) (grade 3) [42,51]. The use of Shenqi particles was associated with interstitial pneumonia (1.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, grade 2), lung infection (5.26{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, grade 3), and liver injury (3.15{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, grade 3) [37]. Anemia (grade 2) and acute myocardial infarction (grade 3) were observed for subjects using Tangshen formula granules [41]. The use of QDDHG tablets was associated with insomnia (1.96{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, grade 1) [47].

    Adverse effects associated with ayurveda: Silymarin treatment was associated with nausea and vomiting (10{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}), as well as headache (6.67{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [54,56]. Beleric capsule treatment was associated with mild gastrointestinal intolerance (11.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) [58]. Adverse effects from both studies were of grade 1 severity. Abdominal pain (4.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, grade 2) was observed with the treatment of camel milk [55].

    Adverse effects associated with naturopathy: All adverse effects reported for naturopathy treatments are of grade 1 severity (Table 3). They include nausea (6.25{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) and diarrhea (6.25{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) with the use of alpha-keto amino acid [60], as well as stomach discomfort (4.54{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) with the use of pomegranate juice [59].

    Adverse effects associated with homeopathy: No adverse effects were reported with the use of homeopathy (Table 3).

    Summary of Efficacy and Safety Profile of AMS Interventions

    Table 4 shows a summary related to the efficacy and safety profiles of AMS interventions.

    Type of AMS Common doses and treatment regimens and duration of therapy Indications Percentage reduction in CKD symptoms (if available) Adverse effects reported ({fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c})
    TCM (n=20) [3,7,17,36-52] Herbal Renal function 2.76{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to 51.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} Elbow soreness (10{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); liver injury and dysfunction (1.04-19.40{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); dry cough, pneumonia, and upper respiratory infections (1.04-5.26{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); hyperkalemia (3.64-23.50{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); vomiting (38.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); leukopenia and anemia (1.61-2.90{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); photosensitive dermatitis, itchy skin, and rash (1.65-8.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); gastrointestinal symptoms, nausea, and vomiting (1.57-38.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); insomnia (1.96{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c})
    Herbal granules TID x 6 months; QDDHG tabletsa BID x 12 weeks; 500 mg GS-Rb1 QD x 6 months; 8 g TSF granules and ARB BID x 24 weeks; 150 mL ZSTL solution BID x 3 months; TCM granules BID x 24 weeks
    Acupuncture
    Acupuncture at Li4, ST36 and K13 acupoint QD x 3 months
    Herbal Proteinuria -61.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to -18.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    9.6 g of Shenqi particle TID x 48 weeks; 40 mg TWHF TID x 3 months followed by 20 mg TWHF TID x 3 months; Huangkui capsule TID x 12 months; 60 mg TWHF and 160 mg valsartan QD x 24 weeks
    Acupuncture Uremic pruritus -60.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to -54.7{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Acupuncture at Quchi (L11) acupoint TIW x 1 month; acupuncture at Quchi (L11) and Zusanli (ST 36) acupoint BIW x 1 month; acupuncture at various acupoints TIW x 6 weeks
    Acupuncture QIW x 2 months Fatigue, insomnia, itchiness, and pain -89.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to 15.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Infrared stimulation of Qihai (RN6), Kuamyuan (RN4) and Chungchi (RN3) TIW x 3 months QoL -9.10{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to 163{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Qingshen granules TID x 3 months Wnt/β-catenin signaling pathway -61.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to 17.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Qingshen granules TID x 3 months Immune function 42.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to -20.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    TBN tablets (gingko extract) TI x 8 weeks Vascular endothelial function 44.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to 40.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Ayurveda (n=6) [53-58] Plant-based Renal function -56.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to 86.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} Nausea, vomiting, and headache (6.67-10{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); abdominal pain (4.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) severe skin burning (2.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c})
    Sativa oil QD and alpha-keto amino acid tablets TID; 140 mg silymarin TID x 3 months; 140 mg silymarin tablet QD x 3 months
    Animal-based
    Camel milk BID x 3 months
    0.03{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} capsaicin ointment QID x 4 weeks Uremic pruritus -84.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    1000/500 mg of beleric capsule taken QD Hyperuricemia -24.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to 40.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Naturopathy (n=5) [59-63] Alpha-keto amino acid tablets TID x 3 months; Keto amino acid tablets QD x 9 months Malnutrition 39.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to 49.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} Nausea (6.25{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); diarrhea (6.25{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}); stomach discomfort (4.45{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c})
    Watercress extract QD x 1 month; garlic extract tablets TIW x 2 months Inflammation -73.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to 26.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Pomegranate juice TIW x 2 months Hypertension, stress, and inflammation -30.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to 22.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Homeopathy (n=2) [16,64] Homeopathic verum medicationb administered x 60 days; Brazilian green propolis pills BD x 3 months Uremic pruritus -41.5{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} to -29.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} –
    Renal function -27.6{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}
    Table
    4: Summary of efficacy and safety profile of AMS indicated for CKD symptoms.

    aQDDHG is composed of Huang Qi, Danshen, Dihuang, Shanyao, and Gan Cao.

    bDosage and frequency vary from patient to patient.

    Percentage reduction in symptoms is computed using (mean score at baseline – mean score post-treatment at end of study)/(mean score at baseline) for the treatment group.

    99mTc-DTPA: 99 m technetium diethylenetri-aminepenta-aceticacid, BAID: brachial arterial inner diameter, BID: twice a day, ELISA: enzyme-linked immunosorbent assay, GS-Rb1: Ginseng extract, MDRD: Modification of Diet in Renal Disease, QoL: Quality of life, TBN: Tianbaoning, TID: thrice a day, TIW: thrice a week, TwHF: Tripterygium Wilfordii Hook F, ZSTL: zishentongluo

    Discussion

    To the best of our knowledge, this is the first review that has summarized findings related to the therapeutic uses of AMS for CKD patients in RCTs. Among the four classes of AMS, TCM was the most studied class which has demonstrated efficacy in improving CKD-related symptoms and outcomes [3,7,36-52]. Among the TCM interventions evaluated, Huangkui, TWHF, and acupuncture have shown efficacy in reducing proteinuria and relieving uremic pruritus symptoms. The therapeutic basis of TCM for CKD is rooted in the restoration of vital energy and nourishment of blood, dispelling of heat and reduction of dampness, and regulation of Yin and Yang in the body [65]. In Western medicine, this is seen in a reduction in inflammation and oxidative stress, as well as boosting micro-circulation and enhancement of metabolism [52]. For example, Huangkui, also known as Abelmoschus manihot, reduces proteinuria by removing oxygen radicals, improving the circulation, and clearance of immune complexes as well as reducing inflammation and renal tubular epithelial injury [66]. It is also noted that triptolide, the key constituent of TWHF, suppresses the nuclear factor kappa b (NF-κB) signaling pathway and prevents the trigger of T lymphocytes and some inflammatory cytokines (TNF-α, IL-1β, IL-6, and IFN-γ), in addition to its podocyte-protective capabilities [67-70]. Notably, two of the included studies demonstrated that a combination of TCM and Western medicine, such as the intake of Huangkui capsule and losartan tablet to alleviate proteinuria, is more efficacious than taking TCM or Western medicine alone. This adds to existing evidence on potential applications of TCM alongside conventional medical therapy. Among patients on TWHF, regular checks of potassium and liver enzymes should be performed due to the risk of hyperkalemia and raised liver enzymes.

    With regards to the use of acupuncture, it results in the release of endogenous opiate-like substances that have been proposed to dull the peripheral and central perception of itching [71]. Stimulation of acupoints via far infrared (FIR) treatments has also been revealed to boost skin microcirculation, lessen emotional anxiety and promote excretion of waste products by improving the autonomic nervous system [44,72-76]. Enhanced circulation via a stronger autonomic nervous system is postulated to relieve CKD-related symptoms as the development of renal failure is attributed to poor circulation in the field of TCM [73,77]. Currently, renowned hospitals in the United States such as the Mayo Clinic and Duke University Medical Center have started providing acupuncture, along with other treatments. With growing evidence related to the efficacy and safety of TCM, there has been greater receptivity from medical doctors related to applications and use of TCM in clinical practice [78]. It is however important to note that TCM is not without any side effects. For example, the use of Huangkui should be cautioned in patients with hyperlipidemia or liver disease as its use has been associated with elevated lipid levels and liver injury. On the other hand, acupuncture appears to be relatively safe with mild side effects, such as elbow soreness. More studies related to TCM are required to further assess their long-term safety profile, and they should be prescribed with careful consideration of each patient’s health condition.

    For Ayurveda, silymarin was one of the most studied interventions which demonstrated efficacy in improving renal function. Ayurvedic therapies are derived predominantly from plants, animals, minerals, exercise, and lifestyle changes. They are believed to rejuvenate and remove toxins from one’s body. In conventional medicine, the therapeutic effects of ayurveda for CKD are ascribed to their anti-inflammatory and anti-oxidant properties. For instance, silymarin has shown efficacy in in vitro studies in attenuating inflammatory stress in renal tissue by suppressing the NF-κB signaling pathway and hence TNF production [79-85]. Other Ayurvedic treatments, such as the application of capsaicin ointment, were also found to alleviate uremic pruritus. Topical capsaicin, a natural alkaloid derived from red chili pepper, has been discovered to relieve uremic pruritus by binding specifically to type C sensory neurons and resulting in the release of substance P, as well as suppressing its synthesis, transport, and storage thereafter [57]. Relatively few side effects were observed for the Ayurvedic therapies discussed above. Despite the promising benefits associated with Ayurvedic treatments, it is currently less globally recognized as compared to TCM [86]. Further research is necessary to evaluate their efficacy and safety profile to improve their acceptance in clinical practice as adjunctive treatments, in particular for CKD patients.

    For naturopathy, its unique attribute lies in the reprioritization of the order of therapeutics, with increased emphasis on non-invasive treatments, such as lifestyle modifications and nutrition, over medical or surgical interventions. In this review, one of the more studied interventions is the use of ketoanalogues of essential amino acids (KAs). The addition of KAs to a low-protein diet has been shown to improve renal function and uremia. Notably, while lowering protein intake may improve renal function in CKD patients by altering immunologic events and reducing hypertrophy and hyperfiltration in the remaining nephrons, it may result in malnutrition [87-89]. However, the supplementation of KAs not only averts malnutrition by ensuring adequate consumption of amino acids but also alleviates uremia [61]. The absence of amino nitrogen in KAs allows them to become transaminated by taking nitrogen from non-essential amino acids and hence, reducing the production of urea via re-using the amino group [90,91]. Relatively few and mild adverse effects were observed for the included naturopathic therapies, rendering them attractive treatment options. Additionally, as naturopathic treatments are usually non-invasive, they can be easily combined with conventional medications. Of note, 28 health systems, hospitals, and cancer treatment centers in the United States currently have at least one licensed naturopathic physician at their premises [92]. With increasing research evaluating the efficacy and safety profile of naturopathic treatments, its role as potential adjunctive treatment for CKD patients is also likely to expand in the future.

    Lastly, homeopathy has also shown efficacy in improving CKD-related symptoms and outcomes. Homeopathy entails the therapeutic administration of substances derived from plants, minerals, or animals which produce effects that correspond to the clinical manifestation of diseases. In this review, the use of Brazilian green propolis pills and homeopathic verum medication were found to improve renal function and alleviate uremic pruritus, respectively. Brazilian green propolis was reported to improve renal function via a few mechanisms. Firstly, it decreases proteinuria via its ability to reduce urinary oxidative stress and macrophage infiltration into the kidneys [93]. Secondly, chrysin, a flavonoid in propolis has been shown to decrease podocyte apoptosis in patients with diabetic nephropathy and lessen glomerular injury [94]. Lastly, propolis has also been shown to decrease blood pressure via acetylcholine-induced vasodilation and from its antioxidant properties [93,95-97]. With regard to the safety of homeopathic treatment, no adverse effects were reported across included studies. However, the practice of homeopathy is relatively restricted, with 36{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} of states in the United States requiring homeopathic practitioners to either be licensed Western medicine or Naturopathic practitioners [32]. Consequently, more research is necessitated to validate the efficacy and safety of homeopathic treatment as adjunctive therapy for CKD patients.

    Limitations

    The following limitations should be considered in conjunction with this review. Firstly, due to the clinical and methodological heterogeneity of the studies, meta-analyses were not performed. As the pool of evidence for AMS trials for CKD patients grows, subsequent reviews should consider conducting meta-analyses for the efficacy of AMS treatments for CKD patients. In addition, there could have been exclusion of potentially applicable studies even though an extensive search strategy was used. To prevent this, the references of included studies were also hand-searched as part of our search strategy. Another limitation of the study relates to the inclusion of only articles in English language. Researchers should consider the inclusion of studies in other languages such as Chinese and Tamil in future reviews. Finally, although results of the included studies were reported normalized Z scores, care should be taken when interpreting these values and comparing the efficacy of various AMS classes. This is due to considerable diversity in types of outcomes evaluated and comparator arms and tools adopted for evaluation of outcomes. Overall, it is hoped that with greater standardization of study outcomes for AMS therapies in future studies, these normalized Z scores can enable more purposeful comparisons of the efficacy of the different AMS classes.

  • 9 Tips For Lowering Your Risk of Heart Disease

    9 Tips For Lowering Your Risk of Heart Disease

    Among Americans, heart disease is the leading cause of death. Someone has a heart attack every 40 seconds in the US. While heart disease statistics are scary, heart disease, generally speaking, is preventable for those who don’t have preexisting heart conditions. 

    However, there are challenges and several risk factors that can’t be changed, including family history, sex or age. Additionally, some people don’t have access to heart-healthy foods and others don’t have the opportunity to see a doctor and get insights about their current health status. 

    For the most part, however, the average person can significantly reduce their risk of heart disease with simple lifestyle changes, like the nine steps detailed here.

    Health tips don’t end here. Check out tips to help you quit drinking alcohol, a dietary supplement that doubles as a sleep aid, and the best food for lowering blood pressure. 

    a close-up of runner's shoes

    These lifestyle changes can significantly boost your heart health.


    Getty Images

    Health Tips logo

    1. Take a daily walk

    Decades of research support cardiovascular exercise as a first defense against heart disease. Walking is an easy, simple way to get cardio exercise in, and you can do it pretty much anywhere outdoors or indoors with a treadmill. 

    Studies show that walking can prevent heart disease risk despite being a less intense modality than other forms of cardio exercise, such as hiking, jogging or cycling. Plus, research suggests that more people stick to a walking plan over time versus other types of exercise, which makes walking more effective in the long run (no exercise is effective if you don’t keep it up). 

    And you can always make your walk harder if you want to improve your health even further. 

    Related: Best Treadmill for 2022

    2. Strength train a few times each week

    Most research on heart health and exercise has focused on aerobic exercise like walking. An emerging body of research points to resistance training as another way to reduce your risk of heart disease. In fact, a 2018 study found that lifting weights for less than one hour a week could reduce your risk for a heart attack or stroke by up to 70{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} — independent of aerobic exercise, making these results even more significant.  

    According to Johns Hopkins Medicine, this profound effect probably has something to do with the way weightlifting changes your body composition. Lifting weights helps you build muscle and lose fat. Excess body fat is a major risk factor for heart disease, so any exercise that helps you reduce body fat is helpful. 

    You don’t need a gym or fancy equipment to start strength training. Bodyweight exercises, such as air squats, push-ups and lunges, provide the same strengthening benefits at home.

    3. Eat heart-healthy foods

    Many delicious foods have a direct link to improved heart health. In general, a diet rich in whole grains, fruit, vegetables, lean protein and healthy fats from nuts, seeds, fish and oils promotes heart health. If you don’t have access to fresh produce, frozen and canned fruits and veggies work just as well (just be mindful of salt intake when eating canned foods). 

    4. Limit foods linked to heart disease

    On the flip side, several foods have direct links to heart disease. To reduce your risk of heart disease, limit high-fat and high-sugar foods such as potato chips and store-bought desserts. Highly processed foods, including most fast food, processed meats (think hot dogs and cured meats) and boxed snacks like Twinkies and crackers, also contain ingredients harmful to your heart. 

    Specifically, look out for trans fats (hydrogenated oils) and high-fructose corn syrup, two common key ingredients that aren’t great for your heart. Trans fats increase “bad” cholesterol and triglycerides in your blood, while high-fructose corn syrup is a driver of several heart disease risk factors and comorbidities. 

    Side note: Don’t be afraid of saturated fat on its own, as research has debunked the myth that saturated fat alone leads to heart disease. Many healthy foods, such as avocados and cheese, contain saturated fats. Processed foods are often high in saturated fat, but it’s more so the trans fats and refined carbohydrates to look out for. 

    5. Quit smoking

    It’s common knowledge by now that smoking is just plain bad for health. Your heart is no exception. According to the Food and Drug Administration, cigarette smoking is a leading cause of cardiovascular disease, including heart attacks and strokes. 

    Smoking impairs your cardiovascular system in a few ways: It leads to plaque buildup in your arteries, changes your blood chemistry and thickens blood, and permanently damages your heart muscle and blood vessels. The National Heart, Lung and Blood Institute says that even an occasional cigarette can cause substantial damage. 

    6. Limit alcohol intake

    We’re not here to tell you that you can’t enjoy your favorite cocktail or crack a cold one on game day, but we’d be remiss if we didn’t mention the consequences of excess alcohol consumption. Drinking too much is generally bad for all your body systems. 

    In regard to heart health specifically, alcohol has been linked to various cardiovascular diseases, including hypertension, coronary artery disease, peripheral artery disease and stroke. However, the exact relationships vary greatly depending on the quantity and pattern of consumption. 

    The American Heart Association maintains that drinking in moderation is OK, but once you inch past that mark (one drink per day for women and two for men), things take a turn for the worse. And, no, the link between red wine and heart health isn’t all that clear. 

    7. Keep stress levels low

    More research is needed to understand exactly how stress contributes to heart disease, but scientists have observed a relationship between stress and heart health. For starters, high levels of chronic stress can trigger unhealthy coping habits, such as smoking, drinking alcohol or eating lots of high-fat or high-sugar food. Stress also undermines your body’s ability to rest and sleep. 

    Researchers have even identified a specific and unusual sort of heart attack called takotsubo cardiomyopathy, also known as stress cardiomyopathy and “broken heart syndrome.” This condition has been linked to emotional trauma, but many patients with this condition exhibit no identifiable cause. 

    So, don’t underestimate the impact of stress on your heart. While stress is inevitable and unavoidable at times, it helps to have a handful of stress-relief tactics to rely on in times of extreme duress. 

    8. Prioritize sleep

    If there were a miracle drug, sleep would probably be it, with exercise coming in a close second. Scientists have positioned sleep deprivation as a risk factor for heart disease because of inverse relationships between sleep duration and cardiovascular diseases: It seems the less sleep you get, the higher your risk for cardiovascular events. 

    Insomnia and sleep apnea have also been linked to heart disease, and sleep duration and quality seem to have a direct effect on blood pressure. Indirectly, sleep deprivation causes people to make poorer food choices and lack motivation to exercise, both of which increase the risk for heart disease. 

    Read more: Why You Should Skip Your Workout If You Didn’t Get Enough Sleep

    9. See your doctor and keep up with health records

    If you’re able to, schedule a yearly checkup with your doctor to make sure all’s in order. 

    Getting a blood panel that checks for cholesterol, triglycerides, blood sugar and other important health markers can help you keep close tabs on your heart health. If you don’t have a primary care doctor, call your nearest urgent care or walk-in clinic to see if it offers basic blood tests. At the very least, checking your blood pressure with an at-home monitor gives you some indication of how you’re doing. Keep track of your health records so you can identify any changes or patterns over time.

    If any indication of heart disease arises, don’t be afraid to ask your doctor any questions. Make sure you understand what the numbers mean, what changes you might need to make to your lifestyle, and if you’ll need any medications. Being an advocate for your own health gets you far. 

    Want more health tips? Read here how to naturally cure an upset stomach, 8 tips to help you quit smoking and how 15 minutes a day can make you more fit. 

    The information contained in this article is for educational and informational purposes only and is not intended as health or medical advice. Always consult a physician or other qualified health provider regarding any questions you may have about a medical condition or health objectives.

  • A New Study Links COVID-19 With This Debilitating Disease

    A New Study Links COVID-19 With This Debilitating Disease

    New investigation posted in the Nature Cardiovascular Investigation journal has joined postural orthostatic tachycardia syndrome (POTS for short) with COVID-19 an infection.

    The examine confirms the relationship between the two diseases, which had been observed by several cardiologists, together with Aneesh Tolat, MD, a cardiac electrophysiologist with the Hartford Health care Heart & Vascular Institute.

    Dr. Tolat points out POTS and its potential link to COVID.

    > Connect with the Coronary heart & Vascular Institute

    What is POTS and how is it dealt with?

    POTS affects a part of the nervous program that regulates involuntary capabilities like coronary heart level, blood pressure, respiration, digestion and sexual arousal. It is normally additional widespread in females among the ages of 15 and 50.

    Indicators of the disease include:

    • Quick coronary heart charge
    • Lower blood force
    • Fainting
    • Lightheadedness

    Therapy for these with POTS is largely self-care this kind of as expanding fluid ingestion, blood pressure treatment, IV fluids and compression stockings, says Dr. Tolat.

    > Linked: Is There a Url Among COVID-19 and Atrial Fibrillation?

    Vaccine connection

    The researchers analyzed facts on close to 300,000 individuals in California who gained just one dose of COVID vaccine or had the virus. Most of all those vaccinated received a Pfizer or Moderna mRNA vaccine.

    They found a modest raise in POTS soon after vaccination, exclusively dose a single, but established the threat was five moments higher for all those infected with COVID. This underscores the worth of vaccine, which the Centers for Sickness Command and Avoidance a short while ago credited with preserving additional than 18.5 million individuals in the U.S. out of the healthcare facility and conserving much more than 3.2 million lives.

    “The information is apparent. Much more individuals who ended up unvaccinated and obtained COVID obtained POTS,” Dr. Tolat suggests.

    > Want extra well being information? Text MoreLife to 31996 to sign up for text alerts

    A challenge to diagnose

    POTS can be hard to diagnose simply because it shares signs and symptoms with a number of other wellbeing disorders, together with dehydration. Until finally this point, health professionals experienced no crystal clear cause to join it with COVID.

    “Inflammation is possible a variable, but the precise induce for POTS is not known,” he clarifies, adding that swelling might also be the website link concerning the condition and COVID vaccination, as pointed out by the investigation.

    When to see a medical professional

    If you see any indicators of POTS, talk with your main treatment medical professional.

  • An Overview of Parkinson’s Disease: Curcumin as a Possible Alternative Treatment

    An Overview of Parkinson’s Disease: Curcumin as a Possible Alternative Treatment

    After Alzheimer’s disease, Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease [1]. A PD diagnosis can be devastating for the person who has it and the family, who often would also be the caregivers. Moreover, despite the surgical and pharmacological interventions, the patient’s physical and mental health declines from a certain period after the onset of the disease.

    PD is characterized by loss of dopamine due to dysfunctional dopaminergic neurons and can be classified as a hypokinetic disorder. Dopamine is not only directly involved in movement and cognition but also plays a broad role in many other nervous system processes. Therefore, the loss of dopamine can lead to a broad range of sometimes severe neuropsychological symptoms, including motor defects, cognitive impairment, and depression. The PD progression is divided into six stages, each associated with a distinct area in the CNS. The first stage appears due to the lesions/dysfunction in the lower medulla oblongata. It includes subtle symptoms like unilateral resting tremors and changes in facial expression. The second stage ensues with damage to the raphe’s lower nuclei, which manifests as motor symptoms affecting walking and posture. Stage 3 of the disease progresses to the substantia nigra, and patients begin to progress to motor symptoms such as difficulty balancing. The temporal mesocortex is affected in the fourth stage, followed by neocortical temporal fields. Many daily tasks are not possible, and even walking may need assistance. Finally, the cortex will be involved in stage 6, and patients are almost completely immobile and can have psychological manifestations such as hallucinations [2]. Although there are distinct stages of PD after diagnosis, initial symptoms of the disease (bradykinesia, resting tremor, and postural instability) are not present until approximately 70{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}-80{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} of dopaminergic neurons have been damaged [3]. Due to this fact, PD is considered a disease with a long latency period as the diagnosis is not likely to occur for years after the initial damage. It is, therefore, essential to diagnose PD as early as possible. The physical progression of the disease through the CNS is accompanied by a drastic worsening of symptoms and a decrease in treatment effectiveness [2].

    Oxidative stress leading to dopaminergic neuron dysfunction in the substantia nigra has been considered the most plausible cause of PD [4,5]. Reactive oxygen species (ROS) can activate the caspase cascade in mitochondria, resulting in the cell’s death [6]. Heavy metal poisoning, for example, often results in the accumulation of these toxins in the nigra material, resulting in reactive oxidative harm [2].

    In addition, alpha-synuclein aggregation is a common finding in PD. These aggregations are harmful to dopaminergic neurons and may cause the formation of Lewy bodies (LB) and eventual necrosis [4]. The formation of LB can trigger a cascade of events. In a non-pathological state, LB aggregates are usually scavenged by a proteasome complex or lysosome. However, defects in these scavenging pathways are common in PD, which causes a further spread of aggregates [2]. LB are considered a defining pathological characteristic of PD and are also commonly found in dementia. It has been assumed that the initial alpha-synuclein travels through the vagus nerve, the major parasympathetic unit, from the enteric nervous system [2].

    A cytochrome P450 2D6-deficient individual is nearly 2x more likely to develop PD in the presence of pesticides [2]. The normal function of this cytochrome is to metabolize pesticides, and the deficiency leads to the build-up of toxins. In addition, the presence of any ROS is likely to increase the risk of developing PD [2]. 

    Antioxidants, natural sources, have recently gained popularity in combating the effects of ROS. The Zingiberaceae family contains the rhizome turmeric (Curcuma longa). For centuries, it has been used in India, China, and Southeast Asia for flavoring, food processing, coloring, and as traditional medicine [7]. Turmeric has long been used to treat rheumatism, eye infections, and liver problems [8]. Curcumin, turmeric’s active ingredient, has antioxidant, anti-apoptotic, and anti-inflammatory properties that protect tissues from the harmful effects of ROS [9]. The phenol moiety, which donates a proton to ROS, is thought to be responsible for curcumin’s antioxidant properties [8]. Curcumin also protects against A53T α-synuclein aggregation and monoamine oxidase B, becoming a compound of interest in treating neurodegenerative disorders such as PD [10,11]. Curcumin has been found to protect nigrostriatal dopaminergic neurons from damage in animal models. Curcumin had protective effects on alpha7-nicotinic acetylcholine receptors after administration of 6-hydroxydopamine (6-OHDA) in rats with a curcumin dose of 200 mg/kg [12]. Curcumin restored nigrostriatal dopamine neurons to 87.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} and 84.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} after low-dose 11-methyl-4-phenyl-1, 2, 3,6-tetrahydropyridine (MPTP) administration, compared to 49.1{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} in the MPTP group [3]. The use of tyrosine hydroxylase (TH) immunohistochemistry to determine dopamine denervation in coronal parts of the brain [12] further confirmed these findings [3].

    The measurement of accurate biomarkers has become highly significant due to the long latent time between the onset of dopaminergic neuronal failure and PD symptom onset. Biomarkers to monitor the potential diagnosis of PD include neurochemical biomarkers and neuroimaging biomarkers. There are various risk factors associated with an increased likelihood of developing PD. A family genomic PD occurs earlier, but this accounts for only 10{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}-15{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} of all PD cases [2]. This indicates that a significant environmental factor plays a role in the pathology of PD. Any environmental factor that causes dopaminergic cell death may be considered a risk factor for developing PD. 

    Prevalence of PD in different ethnic groups

    PD is a global condition affecting people of all races and ethnicities. However, Wright et al. examined ethnic disparities and proposed that the prevalence of PD is higher in Caucasians than in African and Asian populations. As a result, there are known differences in PD incidence between Caucasians and Asians. Wright Willis et al. [13] found that Caucasian Americans had a higher incidence of PD than African Americans and Asians in a population-based study of Medicare recipients over 65 in the United States. In a study, Pringsheim et al. [14] observed a substantial difference in the prevalence of PD between Asia (646/100,000) and North America, Europe, and Australia (1601/100,000) in the population aged 70-79 years. According to these age-based studies, there is a variation in the prevalence of PD in different races at different ages.

    Wright Willis et al. [13] support their claim with data from a population-based survey of over 65-year-olds in the United States conducted between 1995 and 2005, including over 450,000 PD cases per year. According to the findings, the prevalence of age-standardized PD (per 100,000) in white males was 2168.18 (95.64), 1036.41 (86.01) in blacks, and 1138.56 (46.47) in Asians. In a meta-analysis of the prevalence of PD by Pringsheim et al. [14], a significant difference in prevalence by geographical location and age (70-79 years of age) between 1985 and 2010 is noted. The results reported a prevalence of 1,601/100,000 in individuals from North America, Europe (including France, Italy, Spain, the Netherlands, and Germany), Australia, and South America (including Brazil, Uruguay, Argentina, and Bolivia), compared to a prevalence of 646/100,000 in individuals from Asia (including India, Taiwan, Hong Kong, Korea, China, Japan, Singapore, and Saudi Arabia) (P < 0), thus concluding that the prevalence of PD was much lower in Asia than in Europe, North America, and Australia. However, there is still a large variability in results in existing studies, so there is still much debate. This is due to other factors such as geographical location, cultural beliefs, and practices.

    The data reported by Wright Willis et al. [13] and Pringsheim et al. [14] show that the highest prevalence of PD is in the white population, as with most existing studies. However, it is important to note [15] that other factors beyond ethnicity affect the prevalence of PD. They proposed that geographic area, rather than race, may be a more important determinant of PD prevalence. For example, the prevalence of PD in Black Africans in sub-Saharan Africa (40/100,000) is much lower than in people of African descent in the United States. In addition, the results of age-based studies may also be confused by cultural beliefs. For example, Dotchin and Walker [15] reported that many Chinese Americans viewed Parkinsonian symptoms as a consequence of aging, leading to delayed diagnosis. This could be a point of argument that PD prevalence is the same across ethnic groups. Nagashayana et al. [16] reported that the use of Ayurveda in Indian people impacts the presentation of PD symptoms and could potentially improve the outcome of the disease. Therefore, cultural practices also have a significant role in the prevalence of PD. In addition, Ben-Joseph et al. [17] noted that there is little public evidence of differences in the prevalence of PD in different ethnic groups that accommodate health inequalities, cultural practices, and geographical location. It is, therefore, imperative to note that while there is still evidence that PD claims are more prevalent in Caucasians than in the rest of the world, it is not yet sufficient in its bulk to make a firm conclusion. These differences among races should also alert healthcare providers when they are evaluating patients of different ethnicities as the appearance and presentation of disease may be variant. Providers must be cognizant of these variations to prevent missed diagnoses.

    However, we cannot say that the difference is due exclusively to these two factors; we must also consider sociocultural differences. According to Dotchin and Walker [15], many Chinese Americans believe that Parkinsonian symptoms are a result of aging. This illustrates that different societies have different meanings of disease. As a result, there is a delay in diagnosis, and, as a result, the findings of age-based research are muddled. Furthermore, there are documented inequalities in access to advanced healthcare based on race and ethnicity [17]. As a result, the medical community needs to accept and investigate allopathic treatment practices as viable for treating conditions like PD. This is because they can have a higher uptake in some populations, reducing symptom incidence and disease progression. Nagashayana et al. [16], for example, found that the use of Ayurveda in Indians affects the presentation of PD symptoms and could potentially enhance the disease’s outcome. This variation may be a result of the additional benefits of curcumin. 

    Current allopathic treatments for PD 

    Unfortunately, there is currently no curative treatment for PD. There are, however, a variety of ways to treat the symptoms and improve one’s quality of life. Currently, both medications are designed to compensate for dopamine deficiency by either increasing dopamine levels, acting as dopamine agonists, or inhibiting dopamine metabolism. Common medicines include levodopa (L-dopa, L-3,4-dihydroxyphenylalanine), selegiline/rasagiline, entacapone/tolcapone, rapamycin, and adenosine A2A antagonists [2]. Surgery is a potential treatment, but it is used as a last resort when other methods are exhausted.

    For this reason, it is only used in patients with highly advanced PD who are no longer able to manage their symptoms with drugs. Surgical intervention is a deep stimulation of the subthalamic nucleus of the brain [2]. Since advanced PD does not respond to levodopa, gene therapy for PD has been a developing area of research over the last decade. Target genes include aromatic amino acid decarboxylase (AADC) and glutamic acid decarboxylase (GAD) [2]. All of the traditional allopathic PD therapies have been designed to treat symptoms. Since they are less effective in treating advanced PD, we believe that a holistic approach could provide a better prognosis for these patients.

    Levodopa

    Tyrosine-based levodopa is a precursor to dopamine and is one of the most effective treatments for PD. Levodopa is converted to dopamine by the enzyme dopa decarboxylase.

    However, this could be problematic because the enzyme could have decarboxylated orally administered levodopa before it reaches the CNS and would, therefore, not have been able to cross the blood-brain barrier. Carbidopa or benserazide is administered in conjunction with levodopa to ensure that it is not decarboxylated before the blood-brain barrier is crossed and the CNS is reached. Carbidopa and benserazide are classified as peripheral decarboxylation inhibitors. Carboxylated levodopa, combined with these inhibitors, can reach the CNS and decarboxylated to dopamine by serotonergic neurons [18,19]. 

    Monoamine Oxidase (MAO) Inhibitors

    MAO is the oxidative deamination and neurotransmitter degradation enzyme responsible for catecholamine families. Selegiline and rasagiline are included in this class. The dopamine metabolism can result in neuronal damage in dopaminergic neurons as a byproduct of oxidative deamination caused by the growth of ROS. However, those neurons are also protected against other ROS damage from dopamine metabolites by inhibiting the degradation of dopamine and not only by increasing dopamine function throughout the CNS [20].

    Catechol o Methyltransferase (COMT) Inhibitors

    COMT is a brain enzyme responsible for the inactivation of levodopa via methylation. Entacapone and tocapone inhibit COMT and thus prevent the inactivation of levodopa. These drugs may allow the levodopa dose to be effective for a more extended period of time [2,18].

    Autophagy Upregulators

    Part of the pathophysiology of PD is the accumulation of protein aggregates and LB. Autophagy refers to a cell’s ability to destroy dysfunctional or pathogenic components. Rapamycin is a drug that can enhance the autophagy of neurons by inhibiting kinase mTOR (mammalian target of rapamycin). Therefore, the potential treatment of PD could be considered as reducing the accumulation of protein aggregates in the subthalamic nucleus [21].

    Adenosine A2A

    Adenosine A2A is a CNS receptor that antagonizes dopaminergic neurotransmission [22]. Adenosine A2A receptor antagonists such as caffeine have shown remarkable results in laboratory studies with transgenic mice and, more recently, in humans. Transgenic mice with mutant alpha-synuclein have been protected from PD if their adenosine A2A gene has also been removed [23]. Istradefylline has shown tremendous promise in reducing “OFF” time in PD patients. “OFF” time is considered to be the period during which PD patients return their motor symptoms and dyskinesia. Generally, “OFF” time increases the longer the patient has PD, more specifically, the longer the patient has been treated with levodopa [22,24]. Therefore, the combination of istradefylline and levodopa therapy is likely to reduce “OFF” time in advanced PD patients effectively. 

    Deep Brain Stimulation (DBS)

    DBS is considered only when PD symptoms are extremely advanced and can no longer be controlled adequately with oral medication. Generally, DBS targets the subthalamic nucleus through an electrical stimulator using radiologically guided intracranial electrodes [25]. The diseased neuronal pathways would be either excited or inhibited by this electrical excitement. The release of dopamine could be activated through this process [25]. However, the risk of post-DBS infection and waiting time for treatment are high for PD surgery [2].

    Gene Therapy

    Patients with PD have shown a decrease in AADC, leading to less conversion of levodopa (L-DOPA) to dopamine. Because of this, the upregulation of this gene combined with sufficient levodopa intake would be beneficial for PD symptoms [2]. GABA is a neurotransmitter inhibitor. GAD helps GABA-ergic neurons produce more GABA. The lack of dopamine in PD triggers a chain of events that result in unnecessary muscle contractions and motor symptoms. These symptoms could be reduced by the upregulation of GAD and the subsequent increase in the inhibitory GABA neurotransmitter [26]. 

    An alternative approach: curcumin and its neuroprotective effects 

    Curcumin’s Mode of Action

    Curcumin’s protective properties start with its ability to cross the blood-brain barrier due to its lipophilic nature [27]. Curcumin has various protective properties in the brain, including protection against toxic metals and ROS. Toxic metal ions can interfere improperly with tissues in the brain, causing neurological damage. Curcumin, as a flavonoid, has antioxidant properties that are potentially stronger than typical antioxidants such as vitamins C and E [3]. The brain is more susceptible to oxidative damage than other body tissues because it absorbs a higher percentage of oxygen (around 20{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}) than other tissues. With too much oxygen, the formation of ROS such as peroxide accumulates over time, resulting in lower mitochondrial density, lower overall ATP output, and a decreased ability to sustain intracellular ion concentrations, ultimately leading to neuron death. Curcumin’s ability to donate an H ion from the beta-diketone moiety is thought to be responsible for its anti-ROS properties [28]. Curcumin protects mitochondria and neurons from the damaging effects of ROS by donating an H ion. The development of LB is related to the onset of PD. Alpha-synuclein oligomers clump together to form LB. Curcumin has been shown to prevent alpha-synuclein oligomer aggregation [28]. 

    Protecting Effects of Curcumin in Animal Atudies

    In one study, intrastriatal 6-OHDA injections were administered to rats to induce parkinsonism. One group received 200 mg/kg of curcumin over four weeks, but not the other. A reverse response to cognitive impairment was used to determine. Average control groups over the 30-minute test averaged 8.9 ± 5 turns. The rats treated with 6-OHDA had, on average, 257.8 ± 23.4, which was considerably superior to control. There has been a significant reduction in turns with just 126.9 ± 23.8 turns in the group administered with 6-OHDA and curcumin during the 30-minute test. Following the experiment, TH antibodies stained the brains of the test animals. The staining density was used to determine the amount of fibers that produced dopamine left after each treatment.

    In contrast to the control group, the curcumin rat kept 32.46{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} ± 4.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} of its fibers (98.29{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} ± 5.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}). In the group with 6-OHDA without curcumin, the control was only 7.14{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} ± 3.2{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} [29]. In another animal study, MPTP administration of parkinsonism was applied to rats. MPTP was given to the first group only, MPTP + 1 mg/kg of curcumin to the second group, and MPTP + 2 mg/kg of curcumin to the third group. All test groups were assessed the total movement distance in 10 minutes. The group treated with MPTP alone had a 32.0{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} decrease in movement over control. The MPTP + 1 mg/kg curcumin-treated trial group only saw a 59.4{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} increase, with MPTP + 2 mg/kg curcumin movement increasing by 136{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} over the control group. The experiment involved taking brain sections and the analysis of TH antibody expression. The group without curcumin but administered MPTP experienced an increase to 42.9{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} from the control of TH expression. The MPTP + 1 mg/kg group of curcumin has increased to 60.3{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c}, and the MPTP + 2 mg/kg of curcumin has increased to 74.8{fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} compared to the control group. The dose-dependent response of curcumin has become clear in this study [30].

    Limitations of the study

    The differences in the prevalence of PD among different ethnicities are reported in many studies. Researchers have found that genetic factors, geographical location, and cultural practices all play a significant role in the presentation, diagnosis, and management of this complex disease. Though we speculate curcumin consumption as a significant determinant of the observed differences in the prevalence of PD, future studies directly comparing the dosage with the prevalence of PD would provide unequivocal evidence for the protective role of curcumin in PD. Current allopathic treatments are discussed in Table 1.

    Allopathic Treatment Mechanism of Action Adverse Effects
    Levodopa Dopamine precursor (given with carbidopa to decrease peripheral metabolism) Hallucinations, anxiety, depression, cardiac arrhythmias
    MAO inhibitors Inhibition of dopamine metabolism and deamination Serotonin syndrome and hypertensive crisis when used with serotonergic drugs
    COMT inhibitors Inhibition of dopamine inactivation and methylation Tolcapone can lead to hepatic necrosis
    Autophagy upregulators Enhance neuronal ability to degrade dysfunctional proteins Pancytopenia (decrease in RBC, WBC, and platelet counts)
    Adenosine A2A Blockade of dopaminergic inhibition Hallucinations, muscle spasms, insomnia, nausea, vomiting
    Deep brain stimulation Electrical stimulation of the subthalamic nucleus Seizures, infection at site of entry, stroke, headache
    Gene therapy Upregulation of AADC, leading to increased conversion of L-DOPA to dopamine Immune reactions
    Table
    1: Current Allopathic Treatments for Parkinson’s Disease.

    MAO: monoamine oxidase; COMT:  Catechol o methyltransferase; RBC: red blood cells; WBC: white blood cells; A2A: adenosine A2A antagonists; AADC: aromatic amino acid decarboxylase; L-DOPA: levodopa.

  • LUCID Partners With Japanese Pharmaceutical Company to Develop Personalized Music Treatment for Alzheimer’s Disease | News

    LUCID Partners With Japanese Pharmaceutical Company to Develop Personalized Music Treatment for Alzheimer’s Disease | News

    TORONTO–(Business enterprise WIRE)–Jun 2, 2022–

    12.7 million People aged 65 and more mature are projected to have Alzheimer’s dementia by 2050. LUCID and JT are now partnering on the advancement of a prescription electronic therapeutic for Alzheimer’s sickness.

    Alzheimer’s is far more than just memory loss – neuropsychiatric signs and symptoms can consist of nervousness, aggression and persona changes. These indicators aren’t just heartbreaking, they are marketing the burnout of caregivers. Cure is a lot more required than ever.

    “People living with Alzheimer’s should have dignity in this stage of their everyday living,” stated Zach McMahon, CEO and co-founder of LUCID. “They are entitled to a procedure that is equally successful and can enrich high-quality of lifestyle for them and their caregivers.”

    Before this year, LUCID’s initially randomized controlled clinical demo demonstrated scientific evidence in the reduction of acute stress within grown ups with moderate panic. With the support of JT, LUCID will translate their details-driven clinical insights into the development of a electronic therapeutic to reduce agitation and stress and anxiety in dementia care, to begin with with Alzheimer’s.

    “Music interventions can ease these psychiatric symptoms and spark joy,” McMahon explained. “We’re dedicated to providing new care paradigms in an proof-dependent way.”

    Now, with funding from JT, LUCID will conduct study and growth of the digital therapeutic that will be identified as LUC-101. Sheridan College’s Centre for Elder Investigate is also involved in the enhancement of LUC-101 through a Normal Sciences and Engineering Investigate Council of Canada (NSERC) initiative to assistance gerontological analysis and style and design.

    LUCID will take a leadership place to deliver the electrical power of new music as drugs to individuals and caregivers globally. With LUC-101, LUCID strives to supply the added benefits of personalized tunes treatment for Alzheimer’s whilst reducing the general cost and barrier to entry by AI technologies and cloud-enabled programs.

    About LUCID

    LUCID develops therapeutic new music ordeals for mental health. By unlocking the electrical power of neuroscience and device finding out, LUCID’s AI curates new music encounters that are optimized for specific emotional results. They aim to present individualized, evidence-dependent, and available solutions in mental health treatment. LUCID is working in the direction of the clinical validation of songs as drugs.

    LUCID’s newest clinical demo is The Result of Tunes & Auditory Defeat Stimulation on Stress and anxiety. For much more information, please take a look at www.thelucidproject.ca.

    About JT

    JT, Japan Tobacco Inc., has a pharmaceutical business enterprise which focuses on investigation and development, producing and income of prescription prescription drugs. For a lot more information, you should check out https://www.jt.com/about/division/pharma/index.html.

    Look at source variation on businesswire.com:https://www.businesswire.com/information/property/20220602005912/en/

    Call: Kendall Saretsky

    [email protected]

    Key phrase: JAPAN NORTH The us CANADA ASIA PACIFIC

    Industry Key word: Analysis OTHER Well being Normal Overall health Entertainment PHARMACEUTICAL Mental Overall health Engineering Medical TRIALS SCIENCE Audio Option Medicine OTHER Technological know-how Health and fitness

    Supply: LUCID

    Copyright Company Wire 2022.

    PUB: 06/02/2022 04:09 PM/DISC: 06/02/2022 04:09 PM

    http://www.businesswire.com/news/residence/20220602005912/en

    Copyright Small business Wire 2022.