What is causing a mysterious kidney disease in rural Sri Lanka?
Chronic kidney disease of unknown cause was far more common in endemic Sri Lankan districts than earlier estimates suggested, and patients had higher urinary cadmium that rose with disease stage.
Source
Chronic kidney disease of uncertain aetiology: prevalence and causative factors in a developing country
Study at a glance
- Design
- Cross-sectional — Random household prevalence survey in endemic districts plus comparison of urine, blood, hair and nail toxicant levels in CKDu cases versus endemic and non-endemic controls, alongside environmental sampling (2010-2012)
- N
- 6698 people aged 15-70 invited to the prevalence survey (74% responded); 733 CKDu cases identified; metal analyses on subsets (e.g. urine metals in 495 cases, 250 non-endemic controls; hair/nails in 80 cases vs 48 controls; pesticides in 57 cases vs 39 controls)
- Population
- Adults aged 15-70 without diagnosed diabetes in three endemic districts of Sri Lanka's farming regions, plus controls from a non-endemic district (Hambantota)
- Outcome
- Age-standardised CKDu prevalence; risk factors; concentrations of cadmium, arsenic, lead, selenium and pesticide residues in biological and environmental samples
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What they did
Researchers randomly sampled households in three endemic districts and invited 6698 people aged 15-70 without diabetes to be screened with repeated urine albumin tests, blood pressure and HbA1c, using a strict case definition that excluded other known kidney causes. In subsets of cases and controls (from both the endemic area and a non-endemic district), they measured arsenic, cadmium, lead, selenium and other elements in urine, blood, hair and nails, and pesticide residues in urine. They also tested water, food, soil, fertilizer and tobacco for heavy metals.
What they found
Age-standardised prevalence was 16.9% in women and 12.9% in men, much higher than earlier estimates of 2-3%, though men more often had advanced stages. Urinary cadmium was significantly higher in cases than controls from both areas and showed a dose-response with disease stage, while urinary arsenic and lead did not differ. Drinking water was mostly within safe limits, but some foods such as lotus root, plus fertilizer, had high cadmium, and many cases had low selenium and detectable pesticide residues.
The limits
What it doesn't show
This is cross-sectional, so higher cadmium in patients could partly reflect reduced kidney function or shared exposures rather than cause, and the modest ROC performance (AUC about 0.68) means cadmium poorly separates cases from controls. The case definition relied on albuminuria, was not validated against kidney biopsy, excluded low-GFR cases without albuminuria, and used an eGFR equation not validated in South Asians; stage 1 may inflate prevalence. Toxicant subsets were small and not all compared with the same control groups, and infections and genetics were not examined in depth.
Key terms
- CKDu
- Chronic kidney disease of uncertain aetiology: kidney damage not explained by diabetes, hypertension or other known causes.
- Albumin-creatinine ratio (ACR)
- A urine test measuring albumin leakage adjusted for concentration; persistent values of 30 mg/g or more signal kidney damage.
- eGFR
- Estimated glomerular filtration rate, calculated from blood creatinine, which indicates how well the kidneys filter blood.
- Nephrotoxin
- A substance, such as cadmium or certain pesticides, that damages the kidneys.
- Dose-response relationship
- A pattern in which greater exposure is associated with greater disease severity, which strengthens causal arguments.
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Quiz yourself
What was the age-standardised CKDu prevalence in women in the endemic area?
Common questions
Why does a dose-response with disease stage matter?
If more cadmium goes with more advanced disease, that pattern is harder to explain by chance and supports a causal role, although reverse causation is still possible in a cross-sectional study.
If drinking water was safe, how were people exposed to cadmium?
The authors point to the food chain: certain vegetables such as lotus root, freshwater fish, tobacco and phosphate fertilizer had cadmium above recommended limits.
Why might women have higher prevalence but men more severe disease?
The authors speculate that low iron stores in women could increase metal absorption, while male sex is a known risk factor for progression; the study could not test these explanations.
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