Type 2 diabetes (T2D) is a common risk factor for the development of renal fibrosis and chronic kidney disease. Owing to the nature of diabetes, an increased inflammation and an altered turnover of extracellular matrix (ECM) proteins is seen. Despite ample evidence, few studies have focused on an integrated comparison of various biomarkers of the immune response, growth factors and ECM turnover. We evaluated a comprehensive list of biomarkers including interleukin-1, 6, and 8, VCAM-1, ICAM-1, TNFα, E- and P-selectin, FGF23, YKL40, NT-proBNP, type III collagen degradation (C3M) and type VI collagen deposition (PRO-C6) in 190 patients with T2D with microalbuminuria followed for 6.1 years. Investigated endpoints included all-cause mortality (n=26), a composite of cardiovascular events (CVE; n=37), and decline in eGFR of >30% (deGFR, n=41). Using forward selection in Cox proportional hazard analysis we investigated which biomarkers and traditional risk factors (sex, age, systolic blood pressure, LDL-cholesterol, smoking, HbA1c, creatinine and urinary albumin excretion rate) that were retained in the final model for predicting the outcomes. Hazard ratios with 95% confidence intervals are presented per one standard deviation. For all-cause mortality, smoking (3.85 [1.68-8.83], p=0.002), PRO-C6 (1.53 [1.15-2.03], p=0.004), NT-proBNP (1.59 [1.22-2.08], p=0.0006) and ICAM-1 (1.36 [1.06-1.73], p=0.014) were retained in the final model. For CVEs, age (2.00 [1.21-3.30], p=0.007), LDL (1.37 [1.05-1.78], p=0.02), NT-proBNP (1.42 [1.11-1.81], p=0.006) and TNFα (1.35 [1.13-1.60], p=0.0007) were retained. For deGFR, urinary albumin excretion rate (1.31 [1.00-1.71], p=0.049), PRO-C6 (1.41 [1.09-1.83], p=0.009) and NT-proBNP (2.05 [1.54-2.74], p<0.0001) were retained.
In conclusion, our investigations highlight that the best models for predicting outcome may be found by combining biomarkers of cardiac injury, ECM remodeling and the immune response.
D.G.K. Rasmussen: Employee; Self; Nordic Bioscience. T.W. Hansen: None. A. Møller: None. M. Frimodt-Møller: None. B. von Scholten: Employee; Self; Novo Nordisk A/S. P.K. Jacobsen: None. H.D. Parving: None. M.A. Karsdal: Stock/Shareholder; Self; Nordic Bioscience. P. Rossing: Advisory Panel; Self; Sanofi. Consultant; Self; Astellas Pharma Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Eli Lilly and Company. Stock/Shareholder; Self; Novo Nordisk A/S.
Danish Research Foundation