Association of albumin-corrected anion gap with mortality in ICU patients with heart failure and acute kidney injury: analysis of the MIMIC-IV database

Abstract

Background: Elevated albumin-corrected anion gap (ACAG) levels have been shown to be associated with increased mortality in various critical illnesses; however, data specifically addressing heart failure (HF) complicated by acute kidney injury (AKI) are lacking.

Method: Data from ICU patients with HF complicated by AKI between 2008 and 2022 were extracted and analyzed from the MIMIC-IV database. The association between baseline ACAG levels and all-cause mortality was assessed using multiple statistical methods, including variance inflation factor analysis, restricted cubic spline (RCS) modeling, Kaplan-Meier analysis, univariate and multivariate Cox regression, subgroup analysis, mediation analysis, and receiver operating characteristic (ROC) curve analysis.

Results: A total of 5425 patients were included in this study. RCS analysis showed a linear relationship between ACAG and mortality (p = 0.075 for nonlinearity). The Kaplan-Meier curve and multivariate Cox regression analysis revealed a positive relationship between ACAG and mortality at both 30 and 365 days post ICU admission. These results were confirmed by subgroup analysis. Mediation analysis showed SAPS II, bicarbonate, BUN, creatinine, hemoglobin, Charlson and ASP III mediated the association between ACAG and all-cause mortality, accounting for 32.34%, - 30.59%, 32.28%, 19.83%, 7.57%, 7.58%, and 25.64% of the mediating effect, respectively (all p values < 0.001). The AUC value for predicting 30-day mortality was 0.643 for ACAG, greater than 0.616 for albumin and 0.604 for AG. For predicting 365-day mortality, the AUC value was 0.641 for ACAG, greater than 0.626 for albumin and 0.597 for AG.

Conclusion: Elevated ACAG is associated with increased mortality in HF patients with AKI, emphasizing the importance of monitoring metabolic parameters in this population. ACAG may be a valuable prognostic marker for HF and AKI. Further research is warranted to determine whether targeted interventions to correct metabolic acidosis could improve outcomes in this vulnerable patient group.

Keywords: Acute kidney injury; Albumin-corrected anion gap; Heart failure; Mortality; Prognosis.

Fig. 1

Patient screening. A total of 19,021 patients were screened and 5425 met the criteria and were included in the study

Fig. 2

RCS analysis. RCS analysis was performed, adjusting for age, gender, heart rate, MBP, respiratory rate, body temperature, SpO2, glucose, diabetes, chronic pulmonary disease, liver disease, platelets, WBC, chloride, sodium, calcium, potassium, PTT, ALT, AST, CKMB, SOFA, lactate, epinephrine, dopamine, and vasopressin. The result showed a linear relationship between ACAG and the risk of all-cause mortality. Shaded areas around the red curve depict 99% confidence intervals

Fig. 3

KM analysis. The KM survival curve showed that the 30-day (panel A) and 365-day (panel B) all-cause survival probabilities were significantly lower in high-ACAG patients than in low-ACAG patients

Fig. 4

Subgroup analysis of ACAG association with mortality at day 30. As shown in this figure, all HRs were greater than 1.00 across all subgroups. CPD chronic pulmonary disease, RD renal disease, MC malignant cancer

Fig. 5

Subgroup analysis of ACAG association with mortality at day 365. As shown in this figure, all HRs were greater than 1.00 across all subgroups. CPD chronic pulmonary disease; RD renal disease; MC malignant cancer

Fig. 6

ROC curve analysis. As shown in this figure, The AUC values for predicting 30-day mortality were 0.693 for SOFA, 0.643 for ACAG, 0.616 for albumin, and 0.604 for AG. For predicting 365-day mortality, the AUC values were 0.674 for SOFA, 0.641 for ACAG, 0.626 for albumin, and 0.597 for AG