NLRP3 expression and urinary HSP72 in relation to biomarkers of inflammation and oxidative stress in diabetic nephropathy patients.

ABSTRACT

Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease. Nod-like receptors nucleotide-binding domain and leucine-rich repeat pyrin-3 domain (NLRP3) inflammasome displays a considerable role in the chronic inflammatory state observed in diabetic patients. Urinary heat shock protein 72 (uHSP72) is a sensitive and specific biomarker for the early detection of acute kidney injury. The aim of this study was to evaluate NLRP3 relative gene expression, its correlation with inflammatory and oxidative stress markers, and to assess the value of uHSP72 in the early detection of DN in type 2 diabetic patients with different degrees of DN. Forty-five type 2 diabetic patients 15 normoalbuminuric, 15 microalbuminuric, 15 macroalbuminuric, in addition to 15 healthy controls were enrolled in this study. Clinical examination and routine laboratory investigations were performed. NLRP3 mRNA expression was assessed by real time polymerase chain reaction. Serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), interleukin 1ß (IL-1ß), and uHSP72 levels were estimated by enzyme-linked immunosorbent assay. Serum chitotriosidase (CHIT1) activity was examined. NLRP3 mRNA relative expression, serum levels of 8-OHdG, IL-1ß, and uHSP72, in addition to CHIT 1 activity were significantly increased in the macroalbuminuric patient group as compared to control and the other two diabetic groups. Also, a significant positive correlation was documented between the previously mentioned parameters and urinary albumin/creatinine ratio, serum creatinine, and HbA1c. Multiple linear regression analysis using urinary albumin/creatinine ratio as dependent variable confirmed that uHSP72 and NLRP3 mRNA relative expression were the independent predictors of DN (ß were 0.432 and 0.448 respectively, P < 0.001). Receiver operating characteristic analyses revealed that both NLRP3 mRNA relative expression and uHSP72 levels were useful biomarkers discriminating DN patients from patients with type 2 diabetes mellitus (AUC were 0.957 and 0.983, respectively). uHSP72 may be considered as a novel potential diagnostic biomarker for the early detection of DN. Moreover, these data support the pivotal role of NLRP3 in the development and progression of DN. © 2017 IUBMB Life, 69(8)623-630, 2017.