biostudies-literatureScurt FGDeutsche ForschungsgemeinschaftEuropean Commission1373-1386https://www.ebi.ac.uk/biostudies/studies/S-EPMC6829192biostudies-literatureUnknown4(10)<h4>Aim</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 (<i>P</i> < 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 (<i>P</i> < 0.001).<h4>Conclusion</h4>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.Kidney international reportsSystemic Inflammation Precedes Microalbuminuria in Diabetes.PMC6829192HEALTH-2011-278249-EU-MASCARAGRK 2408ME-1365/7-2ME-1365/9-1SFB 854Rabelink TJJanuszewicz ABernhardt ARuilope LMRump LCKatayama SRitz EViberti GIto SMenne JChatzikyrkou CHaller HROADMAP Steering CommitteeMimram AScurt FGBrandt SMertens PRIzzo JLfalseSystemic Inflammation Precedes Microalbuminuria in Diabetes.<h4>Aim</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 (<i>P</i> < 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 (<i>P</i> < 0.001).<h4>Conclusion</h4>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.2019-01-01T00:00:00Z2019 Oct2025-04-04T10:33:08.121Z2019-11-15T08:05:22ZS-EPMC68291923170104710.1016/j.ekir.2019.06.005