UCSF

Background and aims

Tumor necrosis factor receptor type 1 (TNFR1) is associated with kidney disease and mortality risk in various populations. Whether or not kidney function mediates mortality risk is unknown. We evaluated associations of TNFR1 levels with measures of kidney function, cardiovascular events, and mortality in a population of veterans with stable ischemic heart disease.

Methods

TNFR1 was measured from baseline serum samples in the Heart and Soul Study; elevated levels were defined by the highest quartile (Q4, >3.4 ng/ml). We evaluated associations of high TNFR1 with baseline estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) and with longitudinal changes in eGFR (rapid loss), as well as with incident myocardial infarction (MI), heart failure hospitalizations (HF), and mortality over a median follow-up time of 8.9 years. Covariates included demographics and comorbid conditions.

Results

Among 985 participants who had TNFR1 measurements, median TNFR1 was 2.33 ng/ml (IQR 1.8-3.1). Relative to Q1, Q4 had higher risk of eGFR <60 ml/min/1.73 m² (RR 11.71 [95% CI 5.46, 25.11]); ACR ≥ 30 mg/g (2.44 [1.15, 5.19]); and rapid loss in kidney function (2.10 [1.12, 3.92]). Although TNFR1 Q4 was associated with MI, HF, and mortality after demographic adjustment, there were no associations in fully-adjusted models (1.04 [0.44, 2.49]; 1.02 [0.48, 2.15]; 1.42 [0.88, 2.28], respectively).

Conclusions

Levels of TNFR1 are associated longitudinally with kidney function decline but not with MI, HF or mortality risk after adjustment. Kidney disease may mediate the risk of MI, HF, and mortality associated with TNFR1.