Soluble suppression of tumorigenesis-2 is a strong predictor of all-cause, cardiovascular and infection-related mortality risk in haemodialysis patients with diabetes mellitus

Fabian Hammer; Bernd Genser; Benjamin Dieplinger; Margot Egger; Thomas Müller; Christiane Drechsler; Winfried März; Stefan Störk; Christoph Wanner; Vera Krane

doi:10.1093/ckj/sfac142

Soluble suppression of tumorigenesis-2 is a strong predictor of all-cause, cardiovascular and infection-related mortality risk in haemodialysis patients with diabetes mellitus

Clin Kidney J. 2022 May 18;15(10):1915-1923. doi: 10.1093/ckj/sfac142. eCollection 2022 Oct.

Authors

Fabian Hammer^{1

2

3}, Bernd Genser^{4

5}, Benjamin Dieplinger⁶, Margot Egger⁶, Thomas Müller⁷, Christiane Drechsler⁸, Winfried März⁹, Stefan Störk^{2

3}, Christoph Wanner^{3

8}, Vera Krane^{3

8}

Affiliations

¹ Department of Internal Medicine B, Division of Cardiology, University Medicine Greifswald, Greifswald, Germany.
² Department of Internal Medicine I, Division of Cardiology, University Hospital Würzburg, Würzburg, Germany.
³ Comprehensive Heart Failure Centre, University Hospital Würzburg, Würzburg, Germany.
⁴ Center for Preventive Medicine and Digital Health Baden-Württemberg, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁵ BGStats Consulting, Vienna, Austria.
⁶ Department of Laboratory Medicine, Konventhospital Barmherzige Brueder Linz and Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria.
⁷ Department of Laboratory Diagnostics, Hospital of Gmunden, Gmunden, Austria.
⁸ Department of Medicine I, Division of Nephrology, University Hospital Würzburg, Würzburg, Germany.
⁹ Synlab Akademie für ärztliche Fortbildung, Synlab Services GmbH, Mannheim, Germany.

Abstract

Background: Soluble suppression of tumorigenesis-2 (sST2) is a strong prognostic biomarker of cardiovascular (CV) disease. End-stage kidney disease (ESKD) patients are at high risk of CV events and infections. Herein we investigated the utility of sST2 to predict all-cause and cause-specific mortality in haemodialysis (HD) patients with diabetes mellitus.

Methods: sST2 concentrations were measured in plasma samples of 1196 participants of the German Diabetes and Dialysis (4D) study who had type 2 diabetes mellitus and received maintenance HD for ESKD. Hazard ratios (HRs) for prespecified, adjudicated endpoints were determined according to sST2 levels at baseline by multivariate Cox proportional hazards analysis.

Results: Participants (mean age 66 years, 54% male) had a median sST2 concentration of 25 ng/mL and were followed up for 4 years. After adjustment for possible confounders, participants with sST2 concentrations in the highest (>32.6 ng/mL) compared with the lowest (<20.1 ng/mL) quartile exhibited a 2-fold higher all-cause mortality risk {[HR 2.06 95% confidence interval (CI) 1.61-2.61]; P < .001}. High sST concentrations (fourth versus first quartile) were strongly associated with the risk of cardiac death [HR 2.29 (95% CI 1.55-3.39); P < .001]. Analysis of individual components of cardiac causes of death showed an increased risk of sudden death [HR 2.24 (95% CI 1.33-3.77); P < .001], death due to myocardial infarction [HR 2.12 (95% CI 0.9-5.0); P = .087] and heart failure [HR 3.34 (95% CI 1.15-9.75); P = .027] in participants with sST2 levels in the highest compared with the lowest quartile. Likewise, participants with the highest sST2 levels had an increased risk of fatal stroke [HR 1.92 (95% CI 1.17-3.14); P = .009] and fatal infections [HR 2.01 (95% CI 1.2-3.37); P = .008]. In contrast to fatal CV events, sST2 was not associated with the risk of non-fatal myocardial infarction [HR 0.68 (95% CI 0.41-1.12); P = .132] or non-fatal stroke [HR 1.28 (95% CI 0.64-2.53); P = .485].

Conclusions: In HD patients with diabetes mellitus, high concentrations of sST2 were strongly and independently associated with an increased risk of all-cause mortality, CV mortality and death due to infection but not non-fatal CV events.

Keywords: biomarker; cardiovascular; diabetes mellitus; dialysis; sepsis.