Evaluation of Urinary Autophagy Transcripts Expression in Diabetic Kidney Disease

Abstract

Background We identified and validated novel urinary autophagy markers in diabetic kidney disease (DKD) based on bioinformatics analysis and clinical validation. Patients & methods We retrieved three novel autophagy genes related to DKD from public microarray databases, namely; microtubule-associated protein light chain (MAP1LC3A), WD Repeat Domain, Phosphoinositide Interacting 2 (WIPI2), and RB1-Inducible Coiled-Coil 1 (RB1CC1). Secondly we assessed the expression of the chosen autophagy transcript in urine sediment of 86 patients with DKD and 74 (age and sex matched) controls by reverse transcription quantitative real-time PCR. Results The urinary expression levels of MAP1LC3A, WIPI, RB1CC1 were significantly lower in DKD than control group (P < 0.001).The receiver-operating characteristic curve (ROC) analyses that each urinary autophagy transcript showed high sensitivity and specificity for distinguishing DKD from control (MAP1LC3A, 81.4% and 81.1%; WIPI, 74.4% and 67.6%, and RB1CC1, 81.4%,70.3%, respectively). Notably, a negative correlation was found between these autophagy markers, serum creatinine and urinary albumin creatinine ratio. The sensitivity and specificity of this urinary autophagy based panel reached 90.6% and 60% in diagnosis of DKD. Conclusion We identified and validated a novel diagnostic urinary autophagy based panel with high sensitivity and moderate specificity representing a vital player in the pathogenesis of DKD.