|Year : 2022 | Volume
| Issue : 1 | Page : 3
Applying the guidelines to standardize the behavior of clinicians in the treatment of chronic kidney disease with Chinese patent medicine
Qingli Cheng1, Ping Li2
1 Department of Nephrology, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Centre for Geriatric Diseases, Beijing, China
2 Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China
|Date of Submission||26-Dec-2021|
|Date of Decision||10-Feb-2022|
|Date of Acceptance||22-Feb-2022|
|Date of Web Publication||27-Apr-2022|
Dr. Ping Li
Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Cheng Q, Li P. Applying the guidelines to standardize the behavior of clinicians in the treatment of chronic kidney disease with Chinese patent medicine. Integr Med Nephrol Androl 2022;9:3
|How to cite this URL:|
Cheng Q, Li P. Applying the guidelines to standardize the behavior of clinicians in the treatment of chronic kidney disease with Chinese patent medicine. Integr Med Nephrol Androl [serial online] 2022 [cited 2022 Aug 16];9:3. Available from: https://journal-imna.com//text.asp?2022/9/1/3/344230
The 2012 National chronic kidney disease (CKD) epidemiological survey reported that the prevalence of CKD in China was 10.8%. It is estimated that there are approximately 120 million Chinese adult CKD patients, with those in CKD stages 3–5 at considerable risk for the rapid deterioration of renal function.
Currently, the standard treatment of CKD includes adequate control of the primary disease; changes in lifestyle (including a low-salt, low-fat, and low-protein diet); control of risk factors such as hypertension, hyperglycemia, and hyperlipemia; and prevention of overactivity of the renin–angiotensin system. Unfortunately, treatment does not guarantee the maintenance of renal function, and a small number of patients may demonstrate rapid progression to a point where dialysis becomes necessary.
Fearing a loss of work or freedom of movement, many patients with CKD in China are reluctant to begin dialysis prematurely and look for other alternative treatments to delay renal function deterioration. Chinese patent medicines (CPMs) have been widely used by patients with CKD, particularly outpatients in stable conditions. CPMs have become an indispensable supplementary addition to the integrated treatment of CKD and are trusted and used by many CKD patients in China. However, at present, inappropriate application of CPMs is common in the clinical practice. It is well known that syndrome differentiation and treatment form the basis of Traditional Chinese Medicine (TCM). Most doctors trained in Western medicine are not familiar with this principle of TCM, yet more than 70% of CPMs are prescribed by such doctors. Similarly, the abuse of CPMs is not uncommon. These problems have an obvious effect on the efficacy of CPMs and may even lead to adverse reactions in CKD patients. In view of this, the State Administration of TCM approved a special project to be implemented by the China Association of Chinese Traditional Medicine. The China-Japan Friendship Hospital and the Chinese PLA General Hospital were responsible for establishing and formalizing “Clinical Guideline for the Treatment of CKD Stages 3–5 (nondialysis-dependent) with CPMs (2020)”.
The formulation of the guideline was quite different from that of other domestic expert consensus or clinical practice guidelines in China. First, there was no foreign information available for reference. Second, only a small number of randomized controlled trials (RCTs) on CPMs exist. Third, formulation of the guideline was asked to be in full accordance with the WHO Handbook for Guideline Development. To conduct this special task, the State Administration of TCM required that the guideline be formulated following the principle of “evidence-based as the priority, consensus as a supplement, and experience as a reference.”
To better develop the guideline, clinical questions about the prescription of CPMs were compiled into a questionnaire by 58 well-known nephrologists in China, whose educational backgrounds included TCM, Western medicine, and integrative medicine. Ultimately, five questions were proposed:(1) Can CPMs reduce the risk of end-stage renal disease, improve kidney function, and delay CKD progression in patients with CKD stages 3–5 (nondialysis-dependent)? (2) Can CPMs reduce urinary protein excretion in patients with CKD stages 3–5 (nondialysis-dependent)? Can CPMs control risk factors such as hematuria and hypertension in patients with CKD stages 3–5 (nondialysis-dependent)? Can CPMs improve anemia, calcium and phosphate metabolic disorders, metabolic acidosis, and other complications in patients with CKD stages 3–5 (nondialysis-dependent)? (5) Can CPMs improve clinical symptoms and quality of life in patients with CKD stages 3–5 (nondialysis-dependent)?
Based on the above clinical questions, a questionnaire was administered to 46 nephrologists with more than 10 years of clinical work experience. Experts from tertiary hospitals in regions throughout China were consulted. After several rounds of discussion and consideration of dozens of options, nine CPMs were selected for the treatment of CKD stages 3–5 (nondialysis-dependent). These included Niaoduqing particles, Shen shuaining capsules, Shenkang injections, Haikun shenxi capsules, Bailing capsules, Jinshuibao capsules, Huangkui capsules, Shenyan Kangfu tablets, and Shengxuening tablets.
During discussions, extraction of relevant data, risk bias assessment, and meta-analysis were performed after identification of search strategies and establishment of inclusion and exclusion criteria of the relevant literature. Studies that met the following criteria were included: (a) patients had been diagnosed with renal insufficiency, had CKD stages 3–5 (nondialysis-dependent), or had an average serum creatinine level >120 μmol/L; (b) the intervention group received treatment using CPMs in combination with Western medicine; (c) treatment timeframe was >8 weeks for oral medication or 4 weeks for intravenous medication; (d) study results mentioned end-stage renal disease risk, quality of life, serum creatinine, estimated glomerular filtration rate, urine protein excretion, blood pressure, hematuria, anemia, calcium and phosphorus metabolism disorders, or acidosis and included all pre- and postintervention trial data; and (e) the study was a randomized controlled clinical trial. Exclusion criteria for the literature included studies in which the design could not independently evaluate the efficacy of CPMs, studies whose results reported only the efficacy of the treatment without mentioning specific laboratory indicators, studies in which the method of randomization used was inappropriate, and studies with previously published content (in these cases, only the earliest publication of the content was retained). With a combination of the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach and expert consensus, specific recommendations for various CPMs were established.
The guideline gives detailed information regarding the benefits, side effects, indications, and precautions related to the use of the nine specified CPMs in the treatment of patients with CKD stages 3–5 (nondialysis-dependent). Due to insufficient literature and a lack of consensus from experts, no recommendations were made regarding the use of CPMs for the treatment of hematuria, hypertension, and complications such as disorders of calcium and phosphate metabolism, metabolic acidosis, and hypercoagulable states.
It is worth mentioning that the guideline was funded by the State Administration of TCM without any manufacturer sponsorship or direct conflicts of interest. Since the release of the guideline, the China Association of Chinese Traditional Medicine has undertaken several activities to promote awareness of the guideline and to encourage the implementation of the guideline in clinical practice. At present, most nephrologists in larger or teaching hospitals do refer to the guideline when prescribing CPMs for patients with CKD stages 3–5 (nondialysis-dependent). However, the promotion of the guideline and their integration into standardized medical training needs to be strengthened by primary hospitals, grassroots clinics, and specialists other than nephrologists, especially community general practitioners who write a large number of prescriptions.
During the development of the guideline, we found that CPMs have a long-standing history of use in the treatment of CKD. Many patients benefit from treatment, resulting in symptom improvement, or the maintenance of and possible reduction in serum creatinine levels. However, there is still a relative lack of high-quality evidence supporting the use of CPMs in the treatment of patients with CKD stages 3–5 (nondialysis-dependent). Most of the reviewed clinical trials involving CPMs have problems relating to either nonstandard study design or low methodological quality. For example, the study sample size was not large enough to avoid small sample size estimation bias, the study duration was too short, no mention was made of how randomization of patients was concealed, no blinding techniques were used, no data were reported for case withdrawals or patients lost to follow-up, or no intentionality analysis was performed, to mention but a few. Long-term clinical studies with “hard endpoints” (objective clinical outcomes such as end-stage renal failure or death) are rare. A lack of such literature directly affects the reliability of the meta-analysis results as well as the quality of the evidence. Consequently, when the GRADE criteria were used in the revision of the guideline, all of the recommended CPMs received low or very low evidence quality scores. We anticipate more high-quality clinical studies involving the use of CPMs in the future with the aim of improving evidence ratings for the next update of the guideline.
Treatment based on syndrome differentiation and improvement in a patient's quality of life is the cornerstone and greatest advantage of TCM and CPMs. However, most clinical studies involving treatment with CPMs did not include a relevant TCM syndrome corresponding to the condition of the patients involved in the study. Moreover, changes in symptom severity and quality of life were also rarely reported in these studies. As a result, the clinical practice guideline for the use of CPMs in the treatment of CKD stages 3–5 (nondialysis-dependent) lacks evidence related to the improvement of TCM symptoms and quality of life. Future RCTs should be aimed at establishing this link.
Finally, it should be emphasized that clinicians should still follow relevant international or national clinical guidelines when diagnosing and treating patients with CKD stages 3–5 (nondialysis-dependent). The use of the CPMs mentioned in this report should merely complement modern standardized medical treatment.
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