Circulating TNF Receptors 1 and 2 Predict Mortality in Patients with End-stage Renal Disease Undergoing Dialysis

Abstract

Relatively high circulating levels of soluble tumor necrosis factor (TNF) receptors (TNFRs: TNFR1, TNFR2) have been associated with not only progression to end-stage renal disease but also mortality in patients with diabetes. It remains unknown whether elevated TNFR levels in haemodialysis patients are associated with mortality. We studied 319 patients receiving maintenance haemodialysis who were followed for a median of 53 months. Circulating markers of TNF pathway (TNFα and TNFRs) were measured with immunoassay. Strong positive correlations between TNFR1 and TNFR2 were observed (r = 0.81, P < 0.0001). During follow-up, 88 (27.6%) patients died of any cause (40 [45.5%] died of cardiovascular disease). In the Cox multivariate model, either TNFR but not TNFα remained a significant independent predictor of all-cause mortality (TNFR1: hazard ratio [HR] 2.34, 95% confidence interval [CI], 1.50–3.64; TNFR2: HR 2.13, 95% CI 1.38–3.29) after adjustment for age, prior cardiovascular disease, predialysis systolic blood pressure, and large systolic blood pressure decline during dialysis session. For cardiovascular mortality, significance was only observed in TNFR1 (TNFR1: HR 2.15, 95% CI 1.13–4.10). Elevated TNFRs levels were associated with the risk of cardiovascular and/or all-cause mortality independent of all relevant covariates in patients undergoing haemodialysis.

Obesity‐associated glomerular inflammation increases albuminuria without renal histological changes

“…Recent studies clearly show that TNF‐α and its receptors, TNF receptors 1 and 2, are correlated with estimated glomerular filtration rate . Interestingly, these inflammatory markers are significantly increased in CKD patients without diabetes .…”

Circulating TNF receptors 1 and 2 predict progression of diabetic kidney disease: A meta‐analysis

“…In another cohort that contained 522 patients with DKD (eGFR<60 mL/min/1.73 m 2 and/or UACR>30 mg/g), TNFR‐1 proved to be a strong prognostic factor for all‐cause mortality . However, Gohda et al reported that in a cohort that included 319 patients receiving maintenance hemodialysis, circulating TNFR‐1 was not associated with the risk of all‐cause mortality in patients with diabetes . In Gohda's study, the DKD progression was a subgroup analysis of only 50% of subjects who were diabetic patients, so the results should be cautiously interpreted.…”

“…The specific characteristics of the 11 studies are shown in Table . . Overall, the analysis included 6526 participants from 11 cohorts with TNFR‐1 measurements and 5385 participants from 10 prospective studies with TNFR‐2 measurements.…”

“…Some prospective studies suggested that a higher level of circulating TNFR‐1 or TNFR‐2 was associated with an increased risk of DKD progression . However, in a cohort study, neither circulating TNFR‐1 nor TNFR‐2 was significantly related to the risk of all‐cause mortality in patients with diabetes . Circulating TNFR‐2 levels also failed to predict renal progression in another cohort of type 2 diabetes .…”

Obesity-associated glomerular inflammation increases albuminuria without renal histological changes

“…Recent studies clearly show that TNF-a and its receptors, TNF receptors 1 and 2, are correlated with estimated glomerular filtration rate [17]. Interestingly, these inflammatory markers are significantly increased in CKD patients without diabetes [18].…”