Summary

Chronic Kidney Disease (CKD) is an irreversible deterioration in renal function. The incidence of CKD is increasing the world over mainly due to increasing rates of diabetes and hypertension, and an aging population. While this is also true for Sri Lanka, the incidence of CKD is disproportionately high in certain regions of the dry zone which occurs in the absence of the well-known aetiological factors – Chronic Kidney Diseases with undetermined aetiology (CKDu). CKDu is more common among males in farming communities in the age group 40-60 years. Early disease is asymptomatic, but there is rapid progression to end stage renal disease resulting in high morbidity and mortality. CKDu is a tubulointerstitial disease with interstitial fibrosis and tubular atrophy. Environmental factors, together with occupational and social factors, are likely to play an important role in its pathogenesis.

A team from the University of Peradeniya has carried out a comprehensive investigation of CKDu in Sri Lanka over a five-year period.

The clinical investigation led to redefining diagnostic criteria and the case definition of CKDu, and identified the superiority of Serum Cystatin C and Creatinine over testing for urinary protein When screening for CKDu. In addition, a four-marker panel has been established to detect and differentiate CKDu from other CKD at an early stage. The investigation also found that bone mineral disease and cardiovascular complications were uncommon while anaemia was common in CKDu when compared with CKD. Rapid disease progression was especially seen in young male patients.

The environmental component of the study investigated possible causative factors associated with water, soil, tank sediment, food, air, etc. for possible aetiological factors. The results showed that there was no association between CKDu and toxic trace elements, such as, Cd, As, Pb and U; the concentrations of all these elements were found to be low, and in most cases several-fold lower than the recommended safe levels in areas where CKDu was prevalent. The levels of some of these trace elements were higher in the samples tested from other geographic regions in Sri Lanka where CKDu is non-endemic. Detailed water analyses in the dry zone CKDu-endemic regions showed the synergetic influence of permanent water hardness with high levels of Mg (rather than Ca) and high fluoride content on the development of CKDu. 

Investigation on a CKDu animal model found that Fluoride caused the renal cell damage in a dose and time dependent manner with decreased cell viability and mitochondrial activity. Fluoride exposure also caused impaired hepatic function. The animal model also showed that dehydration can have a significant, albeit indirect, effect on CKDu progression.

Initial renal damage that can occur in any person who drinks water with high fluoride content and hardness may be reversible if detected early, and by improving water quality. Providing safe drinking water (with reduced hardness and fluoride content) seems, therefore, to be the most important measure to reduce CKDu in the dry zone of Sri Lanka.