SP300CIRCULATING TNF RECEPTOR LEVELS AND RENAL DISEASE PROGRESSION IN PATIENTS WITH TYPE 2 DIABETIC NEPHROPATHY AND BLOCKADE OF THE RENIN ANGIOTENSIN SYSTEM

Abstract

Introduction and Aims: Several studies have demonstrated that the levels of various circulating inflammatory markers, including the TNF system activity are associated with the early diabetic nephropathy progression. There is a paucity of literature examining the TNF system activity in advanced diabetic nephropaty with strong proteinuria. In the present study. The aim of this study was to investigate if there is an association of circulating TNF receptor with disease progression in advanced type 2 diabetic nephropathy (DN) with strong proteinuria. Methods: We measured circulating σ soluble TNF receptor (sTNF‐R1) and solubre TNF receptor 2 (sTNF‐R2) levels at baseline, 4 and 12 months in 103 patients during the years 2006 to 2011 included in a multicenter randomized controlled trial to compare angiotensin‐converting enzyme inhibitor (ACEi) lisinopril and the angiotensin receptor blocker (ARB) irbesartan with the efficacy of each drug in monotherapy to slow progression of established type 2 DN. Inclusion criteria: stage 2 or 3 CKD, and a urinary protein‐to‐creatinine ratio (UPCR) >300 mg/g (morning urine spot) on 2 separate occasions Results: The median follow‐up was 32 months (IQR, 18‐48), during which time 26 patients (25.2%) achieved the renal endpoint (>50% increase in serum creatinine concentration or ESRD) and 7 patients died (6.7%). The sTNF‐R1 levels, but no sTNF‐R2 levels, were correlated with other inflammatory markers (IL‐6 r2= 0.36 p= 0.005; hsCRP r2 =0.4 p=0.0001). In the Mixed Model Analysis the sTNF‐R1 y R2 levels did not change after starting any treatment blockade of the renin angiotensin system. In univariate study, high sTNF‐R1 levels was associated to the primary endpoint (HR, 2.92 95%CI 1.01‐8.47; P= 0.048)). In the multivariate Cox regression analysis this association disappear when the baseline proteinuria is included. Conclusions: In patients with diabetic nephropathy and strong proteinuria the level of sTNF‐R1 were not associated with renal disease progression. The levels of sTNF‐R1 are not modified by the blockade of the renin system.