Systemic Inflammation Precedes Microalbuminuria in Diabetes

Abstract

AimThe 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.MethodsAmong 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.ResultsThe 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).ConclusionIn 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.

Differential Renoprotective Actions of Simvastatin and Rosuvastatin in Streptozotocin-Induced Diabetes in Sprague-Dawley Rat

“…Reactive Oxygen Species (ROS) and subsequent cellular damage trigger induction of glucose homeostasis transcriptional factors, the proinflammatory cytokines (such as IL-1β), and growth factors (such as TGF-β1) [4][5][6]. The mechanism by which oxidative stress can induce apoptosis may involve increased peroxidation of membrane lipids, increased oxidative injury to macromolecules, changes in cellular redox potential, or depletion of glutathione [7,8].…”

Super-Resolution Imaging with Ultrasound for Visualization of the Renal Microvasculature in Rats Before and After Renal Ischemia: A Pilot Study

“…This will allow us to investigate whether SR imaging is able to detect alterations in the microvascular architecture at the early stages of their occurrence. If early or subtle microvascular alterations have a prognostic value and could allow timely initiation or change of treatment, e.g., in persons who are developing diabetic nephropathy but do not yet show other clinical signs of disease [ 41 ], or in persons undergoing cancer treatment where early readouts of drug or radiation efficacy are crucial [ 42 ], ultrasound SR imaging could fill an unmet need and evolve into a strong tool in the clinical setting.…”

Urinary MMP-9/UCr association with albumin concentration and albumin-creatinine-ratio in Mexican patients with type 2 diabetes mellitus

“…The EMT is characterized by the loss of epithelial markers such as cytokeratin and E-cadherin, and by nuclear translocation of β -catenin accompanied by expression of mesenchymal markers such as vimentin and α -smooth muscle actin ( Tanabe et al, 2020 ). In patients with T2DM, elevated plasma levels of TGF- β 1, CXCL-16 and angiopoietin-2 have been shown as independent predictors of albuminuria and these molecular markers can improve renal risk models beyond established clinical risk factors ( Scurt et al, 2019 ). Through the direct inhibition of Mmp-9 using a neutralizing antibody in a murine model of unilateral ureteral obstruction, Tan et al (2013) have suggested a potential mechanism underlying the contribution of Mmp-9 to kidney fibrosis: (1) Mmp-9 cleaves osteopontin; (2) osteopontin plays a key role in macrophage recruitment; (3) infiltration of macrophages; (4) tubular cell EMT and (5) kidney fibrosis.…”