Abstract

Chronic Kidney Disease of uncertain etiology (CKDu) is an emerging epidemic among farming communities in rural Sri Lanka. Victims do not exhibit common causative factors, however, histopathological studies revealed that CKDu is a tubulointerstitial disease. Urine albumin or albumin-creatinine ratio is still being used as a traditional diagnostic tool to identify CKDu, but accuracy and prevalence data generated are questionable. Urinary biomarkers have been used in similar nephropathy and are widely recognised for their sensitivity, specificity and accuracy in determining CKDu and early renal injury. However, these biomarkers have never been used in diagnosing CKDu in Sri Lanka. Male farmers (n = 1734) were recruited from 4 regions in Sri Lanka i.e. Matara and Nuwara Eliya (farming locations with no CKDu prevalence) and two CKDu emerging locations from Hambantota District in Southern Sri Lanka; Angunakolapelessa (EL1) and Bandagiriya (EL2). Albuminuria (ACR ≥ 30mg/g); serum creatinine based estimation of glomerular filtration rate (eGFR); creatinine normalized urinary kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were measured. Fourteen new CKDu cases (18%) from EL1 and nine CKDu cases (9%) from EL2 were recognized for the first time from EL1, EL2 locations, which were previously considered as non-endemic of the disease and associated with persistent albuminuria (ACR ≥ 30mg/g Cr). No CKDu cases were identified in non-endemic study locations in Matara (CM) and Nuwara Eliya (CN). Analysis of urinary biomarkers showed urinary KIM-1 and NGAL were significantly higher in new CKDu cases in EL1 and EL2. However, we also reported significantly higher KIM-1 and NGAL in apparently healthy farmers in EL 1 and EL 2 with comparison to both control groups. These observations may indicate possible early renal damage in absence of persistent albuminuria and potential capabilities of urinary KIM-1 and NGAL in early detection of renal injury among farming communities in Southern Sri Lanka.

Highlights

  • Chronic Kidney Disease of unknown etiology (CKDu) is an endemic disease among dry zone farming communities in Sri Lanka

  • Clinical diagnosis depends on urinary markers and conventional creatinine based markers may underestimate the prevalence of the disease

  • The first objective of this study was to determine the prevalence of Chronic Kidney Disease of uncertain etiology (CKDu) using case definition by Jayathilaka et al, [26] mainly focussing on albuminuria (ACR 30mg/g) and estimation of glomerular filtration rate (eGFR) in disease emerging locations in Hambantota district (EL1 & Emerging location 2 (EL2)) and non-endemic areas Matara and Nuwara Eliya (CM & CN) in Sri Lanka

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Summary

Introduction

Chronic Kidney Disease of unknown etiology (CKDu) is an endemic disease among dry zone farming communities in Sri Lanka. First cases were reported in early 1990s in North Central Province (NCP) predominantly among male farmers [1] It has reached epidemic proportions with ever increasing numbers of patients and deaths, becoming a new and emerging health issue that would eventually inflict adverse consequences on food security, merely for the fact that affected populations constitute the major rice farming communities in Sri Lanka. It is a global epidemic as similar types of kidney diseases are reported from Andhra Pradesh in India [2] and in Central America including Nicaragua [3], El Salvador [4] and Costa Rica [5]. Based on clinical and pathological studies, CKDu cases in Sri Lanka show glomerular and tubulointerstitial injury in kidneys [1, 22, 23] and similar glomerular and tubulointerstitial injury have been reported in Mesoamerican nephropathy [24, 25]

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