Chronic kidney disease of uncertain aetiology: prevalence and causative factors in a developing country

Abstract

Background: This study describes chronic kidney disease of uncertain aetiology (CKDu), which cannot be attributed to diabetes, hypertension or other known aetiologies, that has emerged in the North Central region of Sri Lanka.

Methods: A cross-sectional study was conducted, to determine the prevalence of and risk factors for CKDu. Arsenic, cadmium, lead, selenium, pesticides and other elements were analysed in biological samples from individuals with CKDu and compared with age- and sex-matched controls in the endemic and non-endemic areas. Food, water, soil and agrochemicals from both areas were analysed for heavy metals.

Results: The age-standardised prevalence of CKDu was 12.9% (95% confidence interval [CI] = 11.5% to 14.4%) in males and 16.9% (95% CI = 15.5% to 18.3%) in females. Severe stages of CKDu were more frequent in males (stage 3: males versus females = 23.2% versus 7.4%; stage 4: males versus females = 22.0% versus 7.3%; P < 0.001). The risk was increased in individuals aged >39 years and those who farmed (chena cultivation) (OR [odds ratio] = 1.926, 95% CI = 1.561 to 2.376 and OR = 1.195, 95% CI = 1.007 to 1.418 respectively, P < 0.05). The risk was reduced in individuals who were male or who engaged in paddy cultivation (OR = 0.745, 95% CI = 0.562 to 0.988 and OR = 0.732, 95% CI = 0.542 to 0.988 respectively, P < 0.05). The mean concentration of cadmium in urine was significantly higher in those with CKDu (1.039 μg/g) compared with controls in the endemic and non-endemic areas (0.646 μg/g, P < 0.001 and 0.345 μg/g, P < 0.05) respectively. Urine cadmium sensitivity and specificity were 70% and 68.3% respectively (area under the receiver operating characteristic curve = 0.682, 95% CI = 0.61 to 0.75, cut-off value ≥0.397 μg/g). A significant dose-effect relationship was seen between urine cadmium concentration and CKDu stage (P < 0.05). Urine cadmium and arsenic concentrations in individuals with CKDu were at levels known to cause kidney damage. Food items from the endemic area contained cadmium and lead above reference levels. Serum selenium was <90 μg/l in 63% of those with CKDu and pesticides residues were above reference levels in 31.6% of those with CKDu.

Conclusions: These results indicate chronic exposure of people in the endemic area to low levels of cadmium through the food chain and also to pesticides. Significantly higher urinary excretion of cadmium in individuals with CKDu, and the dose-effect relationship between urine cadmium concentration and CKDu stages suggest that cadmium exposure is a risk factor for the pathogensis of CKDu. Deficiency of selenium and genetic susceptibility seen in individuals with CKDu suggest that they may be predisposing factors for the development of CKDu.

Figure 1

Map of Sri Lanka, showing the location of Anuradhapura, Polonnaruwa and Badulla districts, in the endemic area, and Hambantota district, in the non-endemic area.

Figure 2

Flow chart of the study conducted in three districts (Anuradhapura, Polonnaruwa and Badulla) in the endemic area. ACR = albumin–creatinine ratio.

Figure 3

ROC curves generated with urine arsenic, cadmium and lead and serum selenium concentrations.

Figure 4

Concentration of arsenic, cadmium, lead and uranium in water^a in the endemic area (n = 222) and non-endemic area (n = 12). End canal = endemic area canal; End drink = endemic area drinking water; End reser = endemic area reservoir; End spring = endemic area spring; nonend drink = non-endemic area drinking water. Horizontal lines within the boxes represent the median values. The ends of the solid lines extending on either side of the boxes represent the minimum and the maximum. The dark dots are outliers; defined as being more than 1.5 interquartile ranges away from the box. The interquartile range is the distance between the upper part of the box and the lower part of the box. ^a Reference limits: arsenic <10 μg /l, cadmium <3 μg/l, lead <10 μg/l, uranium <2 μg/l [21].

Figure 5

Content of arsenic, cadmium and lead in food, tobacco leaves, pasture and weeds from the endemic area. Horizontal lines within the boxes represent the median values. The ends of the solid lines extending on either side of the boxes represent the minimum and the maximum. The dark dots are outliers ; defined as being more than 1.5 interquartile ranges away from the box. The interquartile range is the distance between the upper part of the box and the lower part of the box. (The cadmium and lead content in certain food items exceeded the maximum stipulated reference value^a). ^a The maximum levels of cadmium permitted by the Codex Alimentarius for vegetables is 0.2 mg/kg [22,23] and by the Commission of the European Communities is 0.05 mg/kg [24]. The maximum concentration of cadmium stipulated for certain types of fish by the Commission of the European Communities is 0.05 mg/kg [24]. The maximum concentration of lead stipulated for vegetables by the Commission of the European communities is 0.10 mg/kg [24].