Getting to the cause of Chronic Kidney Disease of unknown cause (CKDu): Research protocol and baseline results

There is an epidemic of primarily tubular-interstitial chronic kidney disease (CKD) clustering in agricultural communities in low-and-middle income countries (LMICs). Although it is currently unclear whether there is a common underlying cause, these conditions have been collectively termed CKD of unknown cause (CKDu). CKDu is estimated to have led to the premature deaths of tens to hundreds of thousands of young adults in LMICs over the last two decades. Thus, there is an urgent need to understand the aetiology and pathophysiology of these conditions and to develop preventive interventions. We have now established that CKDu exists in Central America (Nicaragua) and South Asia (India, Sri Lanka), but not in some other tropical countries. It is not clear yet whether the epidemics in Central America and South Asia have common causes or different causes, which is why it is important to conduct research using the same protocols and methods in these different regions. We have therefore established prospective studies in affected communities in Nicaragua, South India, and Sri Lanka to investigate the causes of the epidemics of CKDu, and factors which affect prognosis. The underlying hypothesis is that CKDu is caused by unknown factors to which the populations have become exposed, due to changes in agricultural practice or other environmental changes (e.g. water supply), over recent decades. The objectives of the collaboration are to investigate the environmental causes of renal decline in these high-risk populations, using standardised instruments capturing occupational and environmental exposures. We will address four proposed causes of CKDu: (i) metals and metaloids; (ii) agrochemicals; (iii) infections by organisms that affect the kidney; and (iv) heat/dehydration.