Role of Emerging Urinary Biomarkers in Predicting Progressive Deterioration of Kidney Function in Congenital Anomalies of Kidney and Urinary Tract: Trefoil Family Factor 3, Alpha Soluble Klotho and Urinary Microalbuminuria.

Abstract

Introduction: Chronic kidney disease is an irreversible fate of many CAKUT (Congenital Abnormalities of the Kidneys and Urinary Tract) patients. Biomarkers involved in the disease progression are raised early in the disease process and aid in identifying the individuals at risk of progressive renal function decline.

Aims: To determine and compare the initial levels of urinary biomarkers in patients of CAKUT with asymptomatic controls and to correlate the same with progression of renal disease.

Results: This study includes 66 children with CAKUT and 22 healthy controls. Initial levels of three urinary Biomarkers: Trefoil family factor 3 (TFF3), Alpha soluble Klotho and Albumin-to-creatinine ratio (ACR) was recorded. Kidney function was assessed initially and at the end of 1 y follow up. Progressive deterioration of renal disease was noted in 26 (fall in GFR by >10 ml/min/m²). Median levels of urinary TFF3, alpha soluble Klotho and ACR was higher in patients with CAKUT (263, 18, 56 mcg/gCr) as compared to controls (15, 5, 6 mcg/gCr) and was further higher in patients having a progressive kidney disease (586, 40, 182 mcg/gCr). The cut-off value of the TEF3 to diagnose progressive renal disease was 178 mcg/g Cr with sensitivity and specificity of 95 % and 96 %, respectively. Using a cut-off of 29 mg/g Cr for ACR, sensitivity and specificity were 97 and 96 %, respectively. Urinary soluble Klotho was a relatively poor urinary biomarker with sensitivity and specificity of only 70 and 78 %, respectively, at a cut-off value of 18 mcg/g Cr.

Conclusion: TFF3 and ACR are useful biomarkers which can be included in the biomarker panel to identify patients having a progressive renal disease and are at a risk of developing CKD.