Systemic Inflammation Precedes Microalbuminuria in Diabetes.

Abstract

AIM:

The aim of the case-control study was to investigate if serum biomarkers indicative of vascular inflammation and endothelial dysfunction can predict the development of microalbuminuria in patients with diabetes mellitus type 2.

METHODS:

Among participants enrolled in the ROADMAP (Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention) and observational follow-up (OFU) studies, a panel of 15 serum biomarkers was quantified from samples obtained at initiation of the study and tested for associations with the development of new-onset microalbuminuria during follow-up. A case-control study was conducted with inclusion of 172 patients with microalbuminuria and 188 matched controls. Nonparametric inferential, nonlinear regression, mediation, and bootstrapping statistical methods were used for the analysis.

RESULTS:

The median follow-up time was 37 months. At baseline, mean concentrations of C-X-C motif chemokine ligand 16 (CXCL-16), transforming growth factor (TGF)-β1 and angiopoietin-2 were higher in patients with subsequent microalbuminuria. In the multivariate analysis, after adjustment for age, sex, body mass index, glycated hemoglobin, duration of diabetes, low-density lipoprotein (LDL), smoking status, blood pressure, baseline urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), time of follow-up and cardiovascular disease, CXCL-16 (odds ratio [OR] 2.60, 95% confidence interval [CI] 1.71-3.96), angiopoietin-2 (OR 1.50, 95% CI 1.14-1.98) and TGF-β1 (OR 1.03, 95% CI 1.01-1.04) remained significant predictors of new-onset microalbuminuria (P < 0.001). Inclusion of these biomarkers in conventional clinical risk models for prediction of microalbuminuria increased the area under the curve (AUC) from 0.638 to 0.760 (P < 0.001).

CONCLUSION:

In patients with type 2 diabetes, elevated plasma levels of CXCL-16, angiopoietin-2, and TGF-β1 are independently predictive of microalbuminuria. Thus, these serum markers improve renal risk models beyond established clinical risk factors.

• Authors: Florian G Scurt, Jan Menne, Sabine Brandt, Anja Bernhardt, Peter R Mertens, Hermann Haller, Christos Chatzikyrkou, ROADMAP Steering Committee
• Journal: Kidney international reports (Kidney Int Rep) Vol. 4 Issue 10 Pg. 1373-1386 (Oct 2019) ISSN: 2468-0249 [Electronic] United States
• PMID: 31701047 (Publication Type: Journal Article)
• Copyright: © 2019 International Society of Nephrology. Published by Elsevier Inc.