title: Update on uncertain etiology of chronic kidney disease in Sri Lanka's north-central dry zone.
abstract: This manuscript updates a review previously published in a local journal in 2012, about a new form of chronic kidney disease that has emerged over the past two decades in the north-central dry zone of Sri Lanka, where the underlying causes remain undetermined. Disease burden is higher in this area, particularly North Central Province, and affects a rural and disadvantaged population involved in rice-paddy farming. Over the last decade several studies have been carried out to estimate prevalence and identify determinants of this chronic kidney disease of uncertain etiology.
  
  
  
  Summarize the available evidence on prevalence, clinical profile and risk factors of chronic kidney disease of uncertain etiology in the north-central region of Sri Lanka.
  
  
  
  PubMed search located 16 manuscripts published in peer-reviewed journals. Three peer-reviewed abstracts of presentations at national scientific conferences were also included in the review.
  
  
  
  Disease prevalence was 5.1%-16.9% with more severe disease seen in men than in women. Patients with mild to moderate stages of disease were asymptomatic or had nonspecific symptoms; urinary sediments were bland; 24-hour urine protein excretion was <1 g; and ultrasound demonstrated bilateral small kidneys. Interstitial fibrosis was the main pathological feature on renal biopsy. The possibility of environmental toxins affecting vulnerable population groups in a specific geographic area was considered in evaluating etiological factors. Pesticide residues were detected in affected patients' urine, and mycotoxins detected in foods were below maximum statutory limits. Calcium-bicarbonate-type water with high levels of fluoride was predominant in endemic regions. Significantly high levels of cadmium in urine of cases compared to controls, as well as the disease's dose-related response to these levels, has drawn attention to this element as a possible contributing factor. Familial clustering of patients is suggestive of a polygenic inheritance pattern comparable to that associated with diseases of multifactorial etiology.
  
  
  
  Available data suggest that chronic kidney disease of uncertain etiology is an environmentally acquired disease, but to date no definitive causal factor has been identified. Geographic distribution and research findings suggest a multifactorial etiology.
authors.affiliation: University of Sri Jayewardenepura, Gangodawilla, Nugegoda, Sri Lanka. kamaniw@sltnet.lk.
authors.forename: Kamani
authors.initials: K
authors.lastname: Wanigasuriya
mesh_terms: D000383:Agriculture; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002980:Climate; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D000075322:Heavy Metal Poisoning; D006801:Humans; D008297:Male; D012275:Oryza; D010575:Pesticides / Q000506:poisoning; D011041:Poisoning; D011204:Poverty Areas; D015995:Prevalence; D039781:PubMed; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000209:etiology; D012307:Risk Factors; D017678:Sex Distribution; D013188:Sri Lanka / Q000453:epidemiology; D014118:Toxins, Biological / Q000506:poisoning
chemical_list: D015415:Biomarkers; D010575:Pesticides; D014118:Toxins, Biological