ASSOCIATION OF INFLAMMATORY AND GROWTH FACTORS WITH CARDIORENAL SYNDROME IN TYPE 2 DIABETES MELLITUS

Objective: Cardiorenal syndrome is characterized by heart and kidney dysfunction. In diabetes, chronic perturbations lead to endothelial dysfunction, inflammation, oxidative stress and progressive tissue fibrosis which, in turn, lead to heart and renal damage. Aim of this study was to assess the relationship between inflammatory and growth factors and cardiorenal syndrome in type 2 diabetes mellitus (DT2). Design and method: A total of 155 patients with DT2, aged 34 to 75 years, were examined. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of natriuretic peptides (BNP, NTproBNP) and inflammatory biomarkers (FGF-23, TNF-alpha, VEGF-A, hsCRP, IL-6, RANTES, MIG) in baseline plasma samples. Renal function was assessed based on the levels of serum creatinine, GFR, which was calculated according to the CKD-EPI formula, and albuminuria, which was assessed as albumin/creatinine ratio (ACR). An echocardiographic examination was conducted according to the standard protocol with the calculation of dimensional, volume and speed characteristics. Control group included 65 subjects without diabetes. Results: There were significant negative association of VEGF-A, FGF-23, RANTES, TNF-alpha, MIG, IL-6 with creatinine and BNP or NTproBNP (p<0.05). Logistic regression analyses showed that IL-6 was a significant predictor of eGFR decline (AOR 1,334; 1,089–1,636 CI, p=0,005) and that IL-6 and FGF-23 were a significant predictors of BNP and NTproBNP increase (AOR 1,106; 1,015–1,206 CI, p=0,021) and (AOR 1,294; 1,054–1,587 CI, p=0,014), respectively. ROC curve analysis revealed elevated IL-6 to be significantly diagnostic of eGFR decline and IL-6 and FGF-23 for predicting the risk of BNP and NTproBNP increase. An IL-6 value above 2.3 mg/ml diagnosed eGFR decline with an 72% sensitivity and a 60% specificity (AUC-0.75, p<0.0001). The optimum cut-off value in BNP and NTproBNP increase was found to be 2.13 mg/ml for IL-6 and 0.9 pmol/l for FGF-23. Sensitivity, specificity of this IL-6 cut-off (AUC-0.78) were 72% and 60%, respectively and 74% and 71% for FGF-23 (AUC-0.75). Conclusions: Our study identifies FGF-23 and Il-6 as promising targets of novel therapeutic interventions in patients with diabetes type 2 and cardiorenal syndrome.