Soluble Urokinase Plasminogen Activator Receptor Predicts Cardiovascular Events, Kidney Function Decline, and Mortality in Patients With Type 1 Diabetes.

Abstract

Soluble urokinase plasminogen activator receptor (suPAR) is an important inflammatory biomarker implicated in endothelial and podocyte dysfunction. However, suPAR's predictive qualities for complications in type 1 diabetes have yet to be determined. We investigated the prognostic value of suPAR for the development of cardiovascular events, decline in renal function, and mortality in patients with type 1 diabetes. We included 667 patients with type 1 diabetes with various degrees of albuminuria in a prospective study. End points were cardiovascular events (cardiovascular death, nonfatal acute myocardial infarction, nonfatal stroke, or coronary or peripheral arterial interventions), estimated glomerular filtration rate (eGFR) decline ≥30%, progression from lower to higher albuminuric state, development of end-stage renal disease (ESRD), and mortality. Follow-up was 5.2-6.2 years. Results were adjusted for known risk factors. Hazard ratios (HRs) are presented per doubling of suPAR with 95% CI. Relative integrated discrimination improvement (rIDI) was calculated. Quantification of suPAR was available in all participants; median (interquartile range) was 3.4 ng/mL (2.7-4.5). The adjusted HR (95% CI) for cardiovascular events (<i>n</i> = 94), progression in albuminuria (<i>n</i> = 36), eGFR decline (<i>n</i> = 93), ESRD (<i>n</i> = 23), and mortality (<i>n</i> = 58) were 3.13 (1.96-5.45, <i>P</i> < 0.001), 1.27 (0.51-3.19, <i>P</i> = 0.61), 2.93 (1.68-5.11, <i>P</i> < 0.001), 2.82 (0.73-11.9, <i>P</i> = 0.13), and 4.13 (1.96-8.69, <i>P</i> < 0.001), respectively. rIDI was significant for cardiovascular events (22.6%, <i>P</i> < 0.001), eGFR decline (14.4%, <i>P</i> < 0.001), and mortality (23.9%, <i>P</i> < 0.001). In patients with type 1 diabetes and a broad range of albuminuria, a higher level of suPAR is a significant and independent risk factor for cardiovascular events, decline in eGFR ≥30%, and mortality. In addition, suPAR contributes significantly to discrimination for the end points.