Diabetes, Metabolic Syndrome and Obesity (Jun 2022)
Clinical Significance of Glomerular Autophagy in Evaluation of Diabetic Kidney Disease Progression
Abstract
Xian Wang,1 Han-Xu Zeng,1 Ling Jiang,1 Xue-Qi Liu,1 Yue-Bo Huang,1 Yong-Gui Wu1,2 1Department of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 2Center for Scientific Research of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of ChinaCorrespondence: Yong-Gui Wu, Department of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China, Tel +86 551 6292 2111, Email [email protected]: Diabetic kidney disease (DKD) is closely associated with the death or survival of resident kidney cells.Aim: The purpose of this study was to determine the changes in renal cell survival and death in DKD and their diagnostic values in DKD progression.Materials and Methods: This study analyzed a dataset of renal tissues from DKD patients to identify changes in genes associated with renal cell death and survival. Our findings were subsequently validated in human kidney tissues. Differential indicators of DKD patients’ clinicopathological data screened by stepwise regression and glomerular P62 protein expression were included in binary logistic regression analysis to assess the impact of these parameters on DKD progression. A receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic value of P62 protein in DKD progression.Results: Bioinformatics analysis results revealed that glomerular autophagy in DKD was more significantly altered, which was consistent with the semi-quantitative results of P62 in glomeruli. Further studies established that P62 expression was mainly increased in podocytes. Stepwise regression analysis indicated that changes in the expressions of glomerular P62 and apolipoprotein A1 (ApoA1) might be involved in the progression of DKD. However, binary logistic regression analysis results suggested that only P62 was significantly associated with DKD development. ROC curve analysis showed that the area under the curve (AUC) of P62 for the detection of DKD was 0.905.Conclusion: Autophagy inhibition occurred in both glomeruli and tubules, and was most pronounced in glomerular podocytes. The levels of P62 protein in glomeruli, as an autophagy activity indicator, was one of the predictors of entering the stage of macroalbuminuria in DKD.Graphical Abstract: Keywords: diabetic kidney disease, autophagy, glomerulus, podocyte
