Inflammatory Indices and Mortality in Acute Heart Failure Complicated by Acute Kidney Injury: A Cross-Database Replication and Missing-Data Analyses
Archives of Academic Emergency Medicine,
Vol. 14 No. 1 (2026),
1 October 2025
,
Page e63
https://doi.org/10.22037/aaem.v14i1.3110
Abstract
Introduction: Acute heart failure (AHF) complicated by acute kidney injury (AKI) carries high short-term mortality. This study compared five inflammatory blood-count indices, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI) and prognostic nutritional index (PNI), across two intensive care unit (ICU) databases with explicit missing-data analyses. Methods: In the Medical Information Mart for Intensive Care IV (MIMIC-IV; derivation), adults with AHF and AKI were analyzed for 28-day in-hospital mortality using Cox regression with a 48-hour landmark; the eICU Collaborative Research Database (eICU-CRD; replication) used in-hospital mortality and logistic regression. Each index (per standard deviation [SD], log-transformed) was adjusted for clinical covariates, with false-discovery-rate (FDR) correction across the five indices. Complete-case analysis and multiple imputation (m=100) were examined as complementary primary analyses. Sensitivity analyses addressed the time origin (including a 48-hour landmark in eICU-CRD), the outcome definition, SIRI extreme values and the missing-data mechanism. Results: MIMIC-IV included 5,764 ICU stays from 5,141 patients (28-day in-hospital mortality 15.0%; 1,478 with a differential count) and eICU-CRD 2,517 (in-hospital mortality 16.3%). Component missingness was 45–75%. After FDR correction and multiple imputation, SIRI was associated with mortality in both databases (MIMIC-IV hazard ratio [HR] 1.18, FDR-adjusted q=0.011; eICU-CRD odds ratio [OR] 1.51, q<0.001); NLR (HR 1.15, q=0.045; OR 1.39, q<0.001) and SII (both q≤0.032) also replicated, whereas PLR was significant only in MIMIC-IV and PNI was inconsistent. Associations were robust to the landmark choice (eICU-CRD 48-hour landmark HR: SIRI 1.50, NLR 1.39, SII 1.33; all q≤0.001), to counting post-discharge deaths and to SIRI extreme values; incremental discrimination was small (change in concordance index (C-index) or area under the curve ≤0.03). Conclusion: Across two independent ICU databases, SIRI showed the most consistent association with short-term mortality, and NLR and SII also replicated. Effect sizes were modest and incremental discrimination was limited; these inexpensive, routinely available indices may provide adjunctive prognostic information but should not be regarded as standalone prediction tools.
- Heart Failure
- Acute Kidney Injury
- Cardio-Renal Syndrome
- Inflammation
- Mortality
How to Cite
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