Association of Serum Concentration of TNFR1 With All-Cause Mortality in Patients With Type 2 Diabetes and Chronic Kidney Disease: Follow-up of the SURDIAGENE Cohort

Abstract

OBJECTIVE: Renal dysfunction is a key risk factor for all-cause mortality in patients with type 2 diabetes (T2D). Circulating tumor necrosis factor receptor 1 (TNFR1) was recently suggested as a strong biomarker for end-stage renal failure in T2D. However, its relevance regarding all-cause death has yet to be conclusively established. We aimed to assess the prognostic value of serum TNFR1 concentration for all-cause death in T2D and diabetic kidney disease (DKD) from the SURDIAGENE (Survie, Diabete de type 2 et Genetique) study. RESEARCH DESIGN AND METHODS: A total of 522 T2D patients with DKD (estimated glomerular filtration rate [eGFR] <60 and/or urinary albumin-to-creatinine ratio [uACR] >30 mg/mmol) were followed for a median duration of 48 months, and 196 deaths occurred. RESULTS: Incidence rate (95% CI) for death increased as quartiles of TNFR1 concentration increased (first quartile: 4.7% patient-years [3.0-6.3%]; second quartile: 7.7% [5.4-10.0%]; third quartile: 9.3% [6.7-11.9%]; fourth quartile: 15.9% [12.2-19.5%]). In multivariate analysis taking age, diabetes duration, HbA1c, uACR, and eGFR into account, compared with the first quartile, patients from the fourth quartile had an adjusted hazard ratio for death of 2.98 (95% CI 1.70-5.23). The integrated discrimination improvement index was statistically significant when adding TNFR1 concentration to the UK Prospective Diabetes Study outcome equation (P = 0.031). CONCLUSIONS: TNFR1 is a strong prognostic factor for all-cause mortality in T2D with renal dysfunction, and its clinical utility is suggested in addition to established risk factors for all-cause mortality.