Research for CKD prevention and control
Chronic kidney disease (CKD) is the 8th leading cause of death in <st1:country-region w:st="on">Taiwan</st1:country-region>. ESRD patients here account for only 0.15% of the total population but spend more than 7.2% of the annual national health insurance budget for dialysis care. Health care expenditure for ESRD patients has become a huge burden on our society. To mitigate the severity of our problems of end-stage renal disease, Department of Health (DOH) assigned Bureau of Health Promotion (BHP) in 2006 to coordinate the relevant organizations of DOH (Food and Drug Administration, Bureau of Medical Affairs, National Health Insurance Task Force, Committee on Chinese Medicine and Pharmacy, Bureau of National Health Insurance) and jointly promote the chronic kidney disease (CKD) prevention and control researches.
First, we collect relevant information and make proposal to apply the National Science and Technology Development Grant for one-year pilot study of CKD research. The followed four-year researches use the regular government budget. When the proposal has been adopted, we start to establish CKD Project Management Office, Steering Committee and Advisory Committee to strenghten the comming planning, ssupervision and implementation. Under the consensus for CKD research from of the specialists and representatives from DOH, we made projects for the prevention and control of chronic kidney disease, which is a prototype of the framework. The four main projects (PART I: Research about CKD prevention and control) as follows:
PART I: Research about CKD prevention and control
This part included four projects. The Project 1「A research proposal to set up an integrated national data bank and monitoring system and to establish the indicators and risk factors for chronic kidney disease in Taiwan」included (1) By de-coding and re-coding processes (with the assistance of the Bureau of National Health Insurance), we will establish an integrated national data bank combining clinical datasets in the Dialysis Registry System of the Taiwan Society of Nephrology, the National Health Insurance Archives in the National Health Research Institutes, and the CKD data bank in the Institute of Biomedical Sciences of the Academia Sinica. (2) By collaborating with the major teaching hospitals of <st1:country-region w:st="on">Taiwan</st1:country-region>, we will build up a cohort for long-term epidemiological studies. The sample size of this designed cohort is 5,000. Basic demographics, information, and CKD-related biomarkers will be collected. (3) Descriptive analysis, logistic regression and Cox proportional hazard models will be used to analyze data. A data release policy and data application mechanism will be developed to disseminate processed datasets to researchers for further studies.
The Project 2「Prevention and treatment of chronic kidney disease in Taiwan – Development of early diagnostic techniques and setup of local therapeutic guidelines and standards」, we will address these issues in three sub-studies. The first sub-study try to find biomarker(s) that are potential for early diagnosis and/or prediction of progression of CKD; the second sub-study will use inulin clearance to derive a formular of estimated GFR for Taiwanese, and set a comprehensive CKD staging; the sub-project 2-2 will study (1) the optimal time for initiating dialysis for ESRD patients, (2) the factors predicting recovery from acute exacerbation and the guidline for treatment, and (3) the advising mechanisms for non-doing or withdraw long-term dialysis. All these studies will be performed in a multicentered project. Three medical centers in which CKD researches have been conducted for many years will provide a large cohort and share the data collected from their own hospitals. We expect that the results will provide an excellent guidline for CKD care, achieve cost-effectiveness of dialysis therapy and better life quality of ESRD patients.
The Project 3「Construct shared-care system and establish the management model of chronic kidney disease patients」，the goal of sub-project 3-1 is (1) to compare the mortality, biochemical data, rehabilitation status, and cost effectiveness between PD and HD by collecting the national data from the Taiwan Society of Nephrology. A cross-sectional analysis will be performed in the first year and a longitudinal analysis will be done in the second and third year. (2) To study the quality of life in incident PD or HD patients. These results will offer the government further evidence to promote PD and provide the more appropriate choice of dialysis modality and rehabilitation plans for patients. The goals of sub-project 3-2 are to confirm the correlation between oxidative stress and cardiovascular disease in CKD patients and to validate the feasibility and the benefits of anti-oxidant therapy. Sub-project 3-3 is “Construture and Evalustion the Model of Chronic Kidney Diseases Treatment with Multiple-Professional and Multiple-Disciplinary”. The purpose of this study is to explore the outcome of patients who are in the single division or the combined care. The main goal of sub-project 3-4 is to explore the special needs and critical factors influencing the social and psychological development of children with CKD and ESRD. In the sub-project 3-5 are will set up the management model of caring CKD cases and test the model。During the first one-year pilot study, we will set up the management model of caring CKD cases and implement the model. The comming four-year rearch, we will: (1) enroll more than 20,000 participants to the shared-care system, and establish the quality control indexes. (2) try to establish the individual support system and add it to the scoring system of quality control. We hope that the established caring model can be promoted nationalwide, and reduce the ESRD incidence in <st1:country-region w:st="on">Taiwan</st1:country-region>.
The Project 4「Study on medical payments for chronic kidney disease and kidney transplant systems」consists of two studies. The first study will explore health care expenditures at different stage of CKD, Cost efficiency analysis (CEA) and Cost utility analysis (CUA) for different treatments, disease progression, and survival time for different dialysis modes. The second study will investigate the ethical legal and related policy concerning kidney transplant, and will examine the needs and opinions of the general public, families, and medical personnel regarding kidney transplant.
PART II: Research about Chinese herbal medicine
This part included three projects. The Project 1 「The safety evaluation of nephrotoxicity induced by Chinese herbal medicines」: The main purpose of this project is to explore the nephrotoxicity of top 20 Chinese herbal medicines which was selected from NHI data in <st1:country-region w:st="on">Taiwan</st1:country-region>. The nephrotoxicity was evaluated in vitro by various kidney cell lines and in vivo by SD rats with 7 biomarkers of nephrotoxicity recommended by US FDA and histopathological evaluation. Not only the nephrotoxicity of popular Chinese medicines was evaluated, but also the screening plate form of nephrotoxicity of drugs was constructed by this project.
Project 2 「Study of platform of combination therapy for CKD with Chinese herb and conventional medicine」: as the re-defining the role of Chinese herbal medicine in kidney disease, to discuss the three sub-projects. The main results: In the cell model, found that some crude extracts from single herbs, such as Angelica, Tithonia diversifolia, Astragalus and Ginseng have effect on the anti-inflammation and anti-fibrosis, and two types of Chinese herbal medicine (formulas), Chi-Sheng-Shen-Chi-Wan and Chih-Po-Ti-Huang-Wan have significant effect on anti-inflammation and anti-fibrosis. In animal models found that some crude extract, such as Angelica, Tithonia diversifolia, Astragalus and Ginseng have significant effect on nephritis, and one of them, Angelica methanol layer, have therapeutic effect by regulating the immune response and angiogenesis. Another, Chih-Po-Ti-Huang-Wan has retarded the severity of diabetes. Chih-Po-Ti-Huang-Wan and Chi-Sheng-Shen-Chi-Wan improve membranous glomerulonephritis proteinuria. After three months of treatment in clinical cases, we found three types of Chinese medicine formulas do not harm the case of renal function. Chi-Sheng-Shen-Chi-Wan and Chih-Po-Ti-Huang-Wan can reduce the cases of inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and C-reactive protein (CRP) production significantly. The study also established the structure and model of combination therapy with medicine and Chinese herbal medicine.
Project 3 「The epidemiological study and database building on Chinese herbal medication for patients with chronic kidney disease」. The objectives of this project are to conduct research on the epidemiology of Chinese herbal medication usage, and to establish a pilot intelligence platform in collecting a group of cohort information consisting of their utilization of Chinese herbal medication and risk factors related to CKD/ESRD. We used the claims data of a nationally representative cohort of NHI enrollees in 2000 and 2005 (the Longitudinal Health Insurance Database 2000 and 2005) to conduct a case control study. After adjusting available confounding factors (age, sex, hypertension, diabetes, and consumption of non-steroid anti-inflammatory drugs [NSAID] and Acetaminophen), those who took Mu Tong for more than 30 g were more likely to develop ESRD (OR=3.8, 95%CI=2.3-6.3). If we used the Longitudinal Health Insurance Database 2000 to follow up those taking Mu Tong more than 30 g (up to 2007) to conduct a cohort study (compared to those who did not expose to Mu Tong), the results were similar (OR=2.5, 95%CI=1.8-3.4). In the second part of this project, we have surveyed 1000 Chinese medicine users to explore their underlying characteristics and collected their biomarkers to investigate on potential risk factors of renal function impairment. The preliminary results show that high uric acid (OR=2.93, 95%CI=1.60-5.36) was significantly related to chronic kidney diseases. We also established an interactive web-based platform to display results produced by this project for public use. The contents that are prepared to publish on the web include the summary of literature reviews, the utilization of Chinese medicine service in <st1:country-region w:st="on">Taiwan</st1:country-region> and the outcomes of our analyses.
Although the studies on Chinese medicine have preliminary results, we still go a step further on these researches. For example, Zheng-Gu-Zi-Jin-Dan and Ophiopogon found in animal experiments has obvious renal toxicity, we should conduct clinical trial study which use prospective or retrospective method to confirm renal toxicity in the future. We should continue development researches of Chinese herbal medicine in chronic kidney disease for the anti-inflammatory and antifibrotic effect of Angelica, Tithonia diversifolia, Astragalus and Ginseng, Chi-Sheng-Shen-Chi-Wan and Chih-Po-Ti-Huang-Wan. In addition, the traditional Chinese medicine containing Mu Tong is probably related to the chronic kidney disease and ESRD, especially for those with life-time cumulative exposure dosage more than 30 g. We suggest doing more basic research to delineate the pathophysiological mechanism in the relationship between Mu Tong and ESRD. We also urge health authorities and health providers to pay more attention to cumulative dosage and kidney function for those who undertake Mu Tong for any therapeutic purpose.
Under the effort mentioned above, we had made a clearer picture about epidemic, diagnosis, treatment and other important issue. The followed research will be included in the government regular budget and continue the work of prevention and control of chronic kidney disease. All of these will become part of evidence based policy and help us to face the challenge from aging society.