Marwa Matboli1, Ahmed E M Azazy2, Seham Adel3, Miram M Bekhet4, Sanaa Eissa5. 1. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, P.O. Box 11381, Cairo, Egypt. Electronic address: DrMarwa__Matboly@med.asu.edu.eg. 2. Armed Forces College of Medicine, Cairo, Egypt. 3. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, P.O. Box 11381, Cairo, Egypt. 4. Diabetes and Endocrinology Unit, Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. 5. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, P.O. Box 11381, Cairo, Egypt. Electronic address: Drsanaa_mohamed@med.asu.edu.eg.
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.
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.
Authors: Maria Beatriz Monteiro; Tatiana S Pelaes; Daniele P Santos-Bezerra; Karina Thieme; Antonio M Lerario; Sueli M Oba-Shinjo; Ubiratan F Machado; Marisa Passarelli; Suely K N Marie; Maria Lúcia Corrêa-Giannella Journal: Front Endocrinol (Lausanne) Date: 2020-04-30 Impact factor: 5.555