Epidermal growth factor receptor and podocin predict nephropathy progression in type 2 diabetic patients through interaction with the autophagy influencer ULK-1.

AIMS:Diabetic nephropathy (DN) that progress to end stage renal failure is a serious health problem. Autophagy is involved in DN pathogenesis. Finding renal prognostic biomarkers can help in the future renal status prevision. Therefore, the aim of current study was to evaluate and correlate circulating levels of autophagy regulator protein Unc-51-like kinase 1 (ULK-1) with the widely expressed receptor in mammalian kidney; epidermal growth factor receptor (EGFR); and the key functional podocyte protein podocin (PDCN). METHODS:Serum levels were assessed by ELISA in 72 type 2 diabetic patients classified according to their urinary albumin/creatinine ratio; 19 normoalbuminuric, 37 microalbuminuric and 16 macroalbuminuric patients; age and sex matched with 18 healthy controls. RESULTS:Microalbuminuria and macroalbuminuria patients exhibited decreased ULK-1, EGFR and PDCN levels. Only EGFR showed lower levels in normoalbuminuria compared with controls. ULK-1 and EGFR were significantly higher in normoalbuminuria compared with microalbuminuria and macroalbuminuria patients. ULK-1, EGFR and PDCN were correlated with each other and with some metabolic parameters. CONCLUSIONS:ULK-1 with EGFR can predict early impairment in DN while PDCN can highlight progressive DN risk EGFR and PDCN may interact synergistically with ULK-1 in autophagy dysregulation as a pathogenic mechanism of DN induction and progression.

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