Introduction 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.Objectives 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.Methods 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.Results 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.Conclusions 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.
IntroductionChronic 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 disease burden is most prominent in the North Central Province and has extended to two adjacent provinces, namely, Uva and North Western provinces. The disease is not due to conventional risk factors such as diabetes, hypertension, chronic glomerulonephritis. 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 population in the North Central Province is around 2.5 million according to the last census conducted in 2012 and farming is the main livelihood of the majority. CKDu mainly affects farming communities with poor socioeconomic background [5]. 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].Based on CKDu's clinical profile and risk factors, it was postulate...