Abstract
Chronic kidney disease of unknown etiology (CKDu) has emerged as a significant public health problem in Sri Lanka. The role of environmental exposure to cadmium and arsenic in the aetiology of CKDu is still unclear. Identification of a panel of novel urinary biomarkers would be invaluable in the study of toxin mediated damage postulated to be the aetiology of CKDu. The aims of this study were to evaluate the profile of novel urinary biomarkers in CKDu patients and identify any association with environmental exposure to heavy metals. Thirty seven randomly selected CKDu patients attending a renal clinic in the North Central Province and two control groups namely a farmer group (n=39) and a non-farmer group (n=40) from a non-endemic area were included in this comparative cross sectional study. Urine samples were analyzed for heavy metals and five urinary biomarkers. CKDu patients had significantly elevated urinary levels of fibrinogen (198.2 ng/mg creatinine p<0.001), clusterin (3479 ng/mg creatinine p<0.001), cystatin-C (5124.8 ng/mg creatinine p<0.001) and β2-microglobulin (9913.4 ng/mg creatinine p<0.001) compared to the control groups. Fibrinogen and β2-microglobulin were the best to discriminate CKDu patients from normal individuals with the receiver operator areas under the curve being 0.867 and 0.853, respectively. Urinary fibrinogen and KIM-1 levels correlated positively with urinary arsenic levels. KIM-1 levels correlated positively with urinary mercury and lead levels but no correlation was seen with urinary cadmium levels. Fibrinogen and β2-microglobulin have the potential of being a screening tool for detection of CKDu and may aid the early diagnosis of toxin mediated tubular injury in CKDu. Their usefulness need to be further validated in a larger epidemiological study of patients with early stages of CKDu.
Highlights
Chronic kidney disease of unknown etiology (CKDu) has emerged as a significant public health problem in Sri Lanka
Thirty seven randomly selected CKDu patients attending a renal clinic in the North Central Province and two control groups namely a farmer group (n=39) and a non-farmer group (n=40) from a non-endemic area were included in this comparative cross sectional study
Kidney injury molecule-1 (KIM-1) levels correlated positively with urinary mercury and lead levels but no correlation was seen with urinary cadmium levels
Summary
Chronic kidney disease of unknown etiology (CKDu) has emerged as a significant public health problem in Sri Lanka. Identification of a panel of novel urinary biomarkers would be invaluable in the study of toxin mediated damage postulated to be the aetiology of CKDu. Chronic kidney disease of unknown aetiology (CKDu), which emerged at the beginning of this century, has reached epidemic proportions in the North Central Dry Zone of Sri Lanka [1,2]. The diagnosis of CKDu is based on exclusion of known aetiological factors of chronic kidney disease and presence of tubulo-interstitial pathology on renal biopsy [3,4]. The estimated prevalence of CKDu in a community based study was reported as 16.9% in women and 12.9% in men, but the severe stages were seen more frequently in men, leading to a higher mortality and morbidity in men [5,6]
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