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. 2015 Mar 30;10(3):e0122073.
doi: 10.1371/journal.pone.0122073. eCollection 2015.

Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease: a prospective cohort study

Nathalie Neirynck  1 , Griet Glorieux  1 , Eva Schepers  1 , Francis Verbeke  1 , Raymond Vanholder  1
Affiliations

Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease: a prospective cohort study

Nathalie Neirynck et al. PLoS One. .

Abstract

Background: Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function.

Patients and methods: In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates.

Results: During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1.

Conclusion: sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Dot plots showing the association between sTNFR1 and sTNFR2 (panel A), eGFR and sTNFR1 (panel B) and sTNFR2 (panel C).
sTNFR1: soluble tumor necrosis factor receptor 1. sTNFR2: soluble tumor necrosis factor 2. eGFR: estimated glomerular filtration rate. R2: coefficient of determination. The straight line represents the best fitted linear regression line with 95% confidence interval for the mean.
Fig 2
Fig 2. Kaplan Meier survival plots for sTNFR1 > or < than the median (4.0 ng/ml) and sTNFR2 > or < than the median (7.4 ng/ml).
sTNFR1: soluble tumor necrosis factor receptor 1. sTNFR2: soluble tumor necrosis factor 2.
See this image and copyright information in PMC

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This research is funded by FWO (Fonds voor Wetensschappelijk Onderzoek) –Vlaanderen, project number: G016210N (www.fwo.be). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.