Retinol Binding Protein (RBP4) as a urinary marker of severity in Chronic Kidney Disease of uncertain Sri Lanka

Abstract

Introduction : Chronic Kidney Disease (CKD) is an increasing cause of morbidity and mortality worldwide. Chronic Kidney Disease of Unknown etiology (CKD-u), a tubular interstitial nephropathy, is an emerging epidemic among farmers in North-Central region of Sri Lanka. Serum creatinine remains unchallenged, as the marker of renal function and most appropriate test for screening. One major disadvantage of creatinine is that it remains within normal range even with 50% loss of renal function. Due to limitations of serum creatinine and other available biomarkers of CKD ,there is a huge demand for novel validated markers in screening and clinical care. Retinol binding protein 4 (RBP4) is a low molecular weight protein, which is mainly synthesized in the liver belonging to the lipocalin super family. Its main function is to transport retinol (vitamin A). The role of urinary RBP4 as a biomarker of CKD in proximal tubular diseases, glomerulopathies and in transplantation is well established. Beyond the typical proximal tubulopathies, it has been shown that urinary RBP4 is associated with the risk of CKD progression in some other conditions. The aim of this study was to determine the level of urinary RBP4 as a marker of disease severity in CKD-u patients in Girandurukotte and Wilgamuwa area in Sri Lanka. Method : Thirty nine biopsy proven CKD-u patients from Girandurukotte and Wilgamuwa renal clinics were studied. Blood and random urine samples were collected from participants and centrifuged for 15 minutes at 4000 rpm. Centrifuged urine samples were frozen at -80ºC until assay. RBP4 level was measured in urine by MILLIPLEX MAG CERTKD panel 05 in a Luminex MAGPIX platform. All procedures were performed in accordance with the manufacturer’s instructions. Separated serum was used to measure serum creatinine and estimated glomerular filtration rate (eGFR) was calculated. The disease was categorized into five clinical stages, according to the Kidney Disease Outcomes Quality Initiative (KDOQI) criteria based on the eGFR. Data was analyzed using R programming language. Results : The median urinary RBP4 levels gradually increased with the advancing clinical stage of CKD. There was a negative correlation between the eGFR and the and the urinary RBP4 level (-0.5362). Conclusion : Our results suggest that urinary RBP4 could be a marker of disease severity in CKD-u patients in Sri Lanka. However, a larger control study would be needed to validate these findings.