Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu) among Agricultural Communities in Sri Lanka

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.

Novel urinary biomarkers and their association with urinary heavy metals in chronic kidney disease of unknown aetiology in Sri Lanka: a pilot study

“…Another study reported that the mean urinary β2-microglobulin was significantly higher among CKDu patients compared to controls [20]. De Silva et al demonstrated that urinary KIM-1 and NGAL are capable of detecting early renal damage in the absence of albuminuria among farming communities in Southern Sri Lanka [21]. Our findings indicate that fibrinogen and β2-microglobulin best distinguishe between diagnosed CKDu patients and persons with normal kidney function.…”

“…A number of promising tests have been developed which can be used for detection of early acute kidney injury in various clinical settings [14][15][16][17][18]. The value of novel biomarkers in CKDu diagnosis has been evaluated recently [19][20][21]. Excretion patterns of some biomarkers may be useful in identifying nephrotoxicantinduced injury in the CKDu population.…”

Endemic Nephropathy Around the World

“…Similarly, urinary kidney injury molecule−1 (KIM-1) may represent an early marker of disease 59 . These tests represent more sensitive screening tools, although their cost prevents widespread use.…”

Massive Proteinuria-Induced Injury of Tubular Epithelial Cells in Nephrotic Syndrome is Not Exacerbated by Furosemide

“…Urinary Kim-1 and NGAL are good predictors of tubule injury [21, 22]. Here, we found that when TECs were exposed to urinary protein, the levels of Kim-1 and NGAL in the supernatants significantly increased.…”