Inflamação, estresse oxidativo e lesão endotelial: relação com o grau de nefropatia diabética

Abstract

The chronic and subclinical inflammation plays a key role in the pathogenesis and progression of diabetic nephropathy. The aim of the present study was to investigate possible relation between the presence and degree of albuminuria and markers of inflammation, endothelial damage and oxidative stress in patients with type 1 diabetes mellitus (DM1). The sample was composed by 35 healthy individuals, 93 with normo and microalbuminuria (< 300 mg of albumin/g of creatinine) and 32 with macroalbuminuria ( 300 mg of albumin/g of creatinine). Urinary albumin excretion (UAE) was calculated in firstmorning urine samples. Plasma and urinary cytokines (TNF-á, IL-6 and IL-10) and thrombomodulin levels were determined by ELISA. Oxidative status was evaluated using the TBARS and MTT assays. Diabetic patients with macroalbuminuria presented significantly higher TNF-á and IL-10 urinary levels when compared to other groups. Urinary and plasmatic levels of TNF-á was positively correlated to plasma levels of cystatin C, creatinine, urea and albuminuria, whilst was negatively correlated with estimated glomerular filtration rate (eGFR). Urinary IL-10 levels proved positive correlation with fasting glucose, Hb1Ac, thrombomodulin and TBARS, while IL-6 plasma levels were positively correlated with HbA1c and albuminuria. Diabetic patients were characterized by elevated levels of urinary cytokines (TNF-á, IL-6 and IL-10). However, only urinary TNF-á levels were independently associated with the presence of macroalbuminuria, after logistic regression analysis. In conclusion, this finding suggests that measurement of urinary TNFá levels may be helpful to evaluate progression to nephropaty in DM1 patients.