||Abstract of research project
Democratic Socialist Republic of Sri Lanka (hereinafter called "Sri Lanka") is a developing country located in the Indian Ocean with a population of approximately 20,240,000 people. The main industry is agriculture and there are rich natural resources in this country, but it is economically battered because of the civil war that has lasted since 1987. Its GDP is 39,600 million dollars, or 4,600 dollars per person. Since the 22-year civil war ended in 2009, a full-scale economic development in the future is expected. Sri Lanka has a tropical climate, and the northeast of the island is dry except in the rainy season. The Sri Lankan government has promoted the settlement of farmers in this region since 1970's by constructing irrigation facilities for development of the northeast despite the economic difficulties caused by the civil war. The northeast has an area of 10,472 km2 (16% of total area of the county) and the current population of approximately 1,100,000 people.
It has been found that settlers in this region frequently develop a chronic renal disease in recent years, and the prevalence is increasing year by year (1,2). The increase is so remarkable that the local medical resources have been exhausted and the population of young people engaged in agriculture has been decreased. A screening performed in Medawachchiya, a central area of this region, indicated that the prevalence is as high as 4.8% of the population. Additionally, it is estimated that about 7% of these patients may have severe renal disorder (glomerular filtration < 15 ml/min), and 0.33% of the total population may require dialysis. On the other hand, patients with chronic renal failure are increasing in recent years also in Japan due to the aging and the increase in diabetes, but the number of such patients was estimated to be 257,000 with the prevalence of 0.2% by the patient survey in 2005. Of the patient population, those aged 20-60 years account for 32%, and those with chronic glomerulonephritis or diabetic nephropathy account for two-thirds. The prevalence in the northeast of Sri Lanka is approximately 1.7 times higher than the prevalence of dialysis in Japan. In Sri Lanka, however, the chronic renal failure is observed even in younger people aged 20-60 years, and frequencies of glomerulonephritis and diabetes are extremely low. Therefore, the actual prevalence corrected for age and etiology is estimated to be approximately 5 times higher than that in Japan, suggesting different causes from those in our country. Since the management of this disease requires dialysis, the country is forced to spend a great deal of money for the medical care from the limited budget.
In this region, Bandara et al. (3) conducted an environmental epidemiological survey focused on heavy metals in the environment. Among heavy metals, cadmium showed high concentration in drinking water and rice. Furthermore, an epidemiological research identified the following risk factors: high fluorine level in drinking water, frequent use of aluminum tableware, exposure to pesticides, use of ayurveda drugs, history of snake bite and family history (4).
Sri Lanka does not have good relationships with India, European countries or US which supported Tamil in the civil war, and, among the Western developed countries, Japan is the only country that has an embassy in Sri Lanka. A researcher in University of Peradeniya who had studied in Japan offered our department in Kyoto University to conduct a joint research. Thus we started the research in 2008, in which a case-control epidemiological study was performed and heavy metals contained in environmental water, drinking water, rice and ayurveda drugs were comprehensively measured. The results showed no difference in level of heavy metals such as cadmium between the families with patients and those without patients, demonstrating that the environmental pollution with heavy metal is very unlikely to be a cause (5). In August, 2009, a field survey was conducted in the northeast, in which living environment was investigated, and familial aggregation was confirmed. In addition, urine samples were collected from 106 people including patients at different stages of the chronic renal failure and controls, in order to examine the possibility of early diagnosis using the biomarkers of glomerular disorder and tubular disorder. However, even in the group of stage 2 patients with a mild decrease in glomerular filtration, rates of positive tests for primary markers of chronic renal failure including alpha 1 microglobulin, beta 2 microglobulin and N-acetyl-D-glucosaminidase (NAG) were less than 20% . These results indicated that typical renal tubular disorders such as itai-itai disease and glomerular damage due to chronic glomerulonephritis are unlikely . In addition, pathological diagnosis of the biopsy tissue from 19 patients with the chronic renal failure demonstrated that the disease is chronic ischemic lesion from a pathological viewpoint, and is associated with glomerular ischemic lesion, tubular ischemic lesion and renal interstitial fibrosis . These findings well explain the test results of biomarkers in urine. In conclusion, our preliminary study suggested the renal disease model in which renal ischemia attributable to intrinsic factors may progress to the chronic renal failure contributed by environmental factors rather than the conventional model that suspected exposure to environmental substances with renal toxicity.
The purpose of this study is to identify the causes of the chronic renal disease frequently seen in Sri Lanka, thereby contributing to the development of the programs for early detection and prevention.