Plasma Soluble Tumor Necrosis Factor Receptor Concentrations and Clinical Events After Hospitalization: Findings From the ASSESS-AKI and ARID Studies

Abstract

Rationale & objective: The role of plasma soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 in the prognosis of clinical events after hospitalization with or without acute kidney injury (AKI) is unknown.

Study design: Prospective cohort.

Setting & participants: Hospital survivors from the ASSESS-AKI (Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury) and ARID (AKI Risk in Derby) studies with and without AKI during the index hospitalization who had baseline serum samples for biomarker measurements.

Predictors: We measured sTNFR1 and sTNFR2 from plasma samples obtained 3 months after discharge.

Outcomes: The associations of biomarkers with longitudinal kidney disease incidence and progression, heart failure, and death were evaluated.

Analytical approach: Cox proportional hazard models.

Results: Among 1,474 participants with plasma biomarker measurements, 19% had kidney disease progression, 14% had later heart failure, and 21% died during a median follow-up of 4.4 years. For the kidney outcome, the adjusted HRs (AHRs) per doubling in concentration were 2.9 (95% CI, 2.2-3.9) for sTNFR1 and 1.9 (95% CI, 1.5-2.5) for sTNFR2. AKI during the index hospitalization did not modify the association between biomarkers and kidney events. For heart failure, the AHRs per doubling in concentration were 1.9 (95% CI, 1.4-2.5) for sTNFR1 and 1.5 (95% CI, 1.2-2.0) for sTNFR2. For mortality, the AHRs were 3.3 (95% CI, 2.5-4.3) for sTNFR1 and 2.5 (95% CI, 2.0-3.1) for sTNFR2. The findings in ARID were qualitatively similar in terms of the magnitude of association between biomarkers and outcomes.

Limitations: Different biomarker platforms and AKI definitions; limited generalizability to other ethnic groups.

Conclusions: Plasma sTNFR1 and sTNFR2 measured 3 months after hospital discharge were independently associated with clinical events regardless of AKI status during the index admission. sTNFR1 and sTNFR2 may assist with the risk stratification of patients during follow-up.

Keywords: AKI follow-up; Acute kidney injury (AKI); biomarker; end-stage kidney disease (ESKD); heart failure; hospitalization; kidney disease progression; mortality; prognosis; risk stratification; sTNFR2; soluble tumor necrosis factor receptor 1 (sTNFR1).