Evidence of tubular damage in the very early stage of chronic kidney disease of uncertain etiology in the North Central Province of Sri Lanka: A cross-sectional study

Background: In the North Central Province of Sri Lanka, chronic kidney disease of uncertain etiology (CKDue) has increased markedly over the past 15–20 years.
Methods: From around 4,700 patients who were followed up, 106 affected patients who visited two local clinics in the endemic area for CKDue on August 10, 2009 and 10 pedigrees of 10 of these cases with familial clustering of CKDue participated in this study. Urine samples, collected from affected patients (n = 106), unaffected relative controls (n = 81), and Japanese controls (n = 50), were analyzed for two tubular markers: a1-microglobulin andN-acetyl-b-D -glucosaminidase. Urine samples frompatients with CKDue stages 1–4 (n = 101) and all thesamples from unaffected relatives and Japanese controls were analyzed for urinary cadmium concentration.
Results: Urinary excretion of a1-microglobulin was ele-vated even in the earliest stage of CKDue compared withits levels in unaffected relative controls. Urinary excretionof N-acetyl-b- D-glucosaminidase was elevated only instage 5. In contrast, urinary cadmium excretion was similarin CKDue patients and in the unaffected relative controls,and levels in both these groups were significantly lowerthan the level in the Japanese controls. All levels werebelow the threshold level for renal toxicity, indicating theabsence of any evidence of cadmium toxicity.
Conclusions: The present study indicates that renal tubu-lar damage occurs in the very early stage of CKDueand demonstrates the existence of familial clustering suggesting that CKDue is likely to be the outcome ofexposure to an unknown nephrotoxin in susceptible sub-jects in the endemic region.