Occupational kidney disease among young populations in northwest Nicaragua

Chronic kidney disease of undetermined aetiology (CKDu) is mainly responsible for the deaths of young males in agricultural lowland regions of Central America. The aim of this thesis was to advance the understanding of the causes of CKDu by conducting several different epidemiological research studies. The systematic review identified a number of cross-sectional studies and occupational cohort studies with limited follow-up periods, but the findings were inconclusive regarding the causes of CKDu. The cohort study described in this PhD thesis is the first community-based cohort study in the region to evaluate the natural history of disease in apparently healthy people aged 18-30 years. It collected information about a wide range of exposure conditions with a questionnaire, biological samples, and water samples. There was an unparalleled, asymptomatic and very rapid decline in renal function among 10% of males and 3.5% of females who had normal renal function at baseline. Meanwhile, the group displaying established renal dysfunction (mean estimated glomerular filtration rate, eGFR: 58 mL/min/1.73 m2) at baseline showed a slower subsequent decline in kidney function (3.6 mL/min/1.73 m2/year). A rapid decrease in eGFR was associated with outdoor work, agricultural work, and a lack of shade during work breaks. The nested case-control study measured eGFR, and urinary neutrophil gelatinase-associated lipocalin (uNGAL) at baseline. After adjusting for eGFR, uNGAL did not improve prediction a rapid decline in kidney function among individuals who initially presented a normal eGFR. This is the first study to show that in northwest Nicaragua, 10% of the male and 3.5% of the female population aged 18-30 years showed a very strong decline in kidney function. Larger community-based and occupational longitudinal studies with more detailed analyses of exposure data are needed to identify the cause(s) of CKDu.