Tumor necrosis factor receptor 1 is an effective marker for all-cause mortality in type 2 diabetes with kidney disease, according to results of a French study.
Additionally, TNFR1 was found to add clinical utility to the U.K. Prospective Diabetes Study (UKPDS) outcome equation for mortality.
"Our data showed a clear and graded relationship between concentrations of serum TNFR1 and risk of all-cause mortality," Pierre Jean Saulnier, Ph.D., of the University of Poitiers (France) and his colleagues wrote.
In a follow-up analysis of the SURDIAGENE study, designed to identify genetic and environmental causes of micro- and macrovascular complications in type 2 diabetes, investigators followed 522 patients with baseline urinary albumin to creatinine ratios (uACR) greater than 30 mg/mmol, an estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m2, or both. Patients with a history of myocardial infarction and/or stroke were considered to have cardiovascular disease at baseline (Diabetes Care 2014 March 12 [doi:10.2337/dc13-2580]).
The primary endpoint was all-cause mortality. The secondary endpoint was the occurrence of a composite renal outcome in patients who did not have end-stage renal disease at baseline. The median duration of the study was 48 months. In that time, 196 deaths occurred.
The increased rate of death correlated with increased levels of TNFR1 across quartiles: 4.7% patient years in the first quartile, 7.7% in the second, 9.3% in the third, and 15.9% in the fourth.
Of note, when the investigators ran a multivariate analysis using age, diabetes duration, hemoglobin A1c, uACR, and eGFR, they found that the risk of death tripled in patients in the fourth quartile (adjusted hazard ratio, 2.98), compared with patients in the first quartile.
When TNFR1 was combined with the UKDPS equation, which uses age, diabetes duration, sex, ethnicity, current smoking status, systolic blood pressure, HbA1c, body mass index, eGFR, heart rate, atrial fibrillation, albuminuria, and peripheral vascular disease, the predictive value for mortality improved significantly (P = .03).
TNFR1 is a proinflammatory marker that a growing body of literature indicates has prognostic value for cardiovascular disease in patients with diabetes. "Our current findings add to this literature," the researchers wrote, adding that while it was not the focus of their study, the data may contribute to understanding the role of TNFR1 in vasculopathy and diabetes-related events such as amputation.
None of the authors of this study reported any relevant disclosures. Funding was provided by the French Ministry of Health, among others.