GDF-15 Predicts In-Hospital Mortality of Critically Ill Patients with Acute Kidney Injury Requiring Continuous Renal Replacement Therapy: A Multicenter Prospective Study

Abstract

Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine. This study evaluated the association between GDF-15 and in-hospital mortality among patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Among the multicenter prospective CRRT cohort between 2017 and 2019, 66 patients whose blood sample was available were analyzed. Patients were divided into three groups according to the GDF-15 concentrations. The median GDF-15 level was 7865.5 pg/mL (496.9 pg/mL in the healthy control patients). Baseline characteristics were not different among tertile groups except the severity scores and serum lactate level, which were higher in the third tertile. After adjusting for confounding factors, the patients with higher GDF-15 had significantly increased risk of mortality (second tertile: adjusted hazards ratio [aHR], 3.67; 95% confidence interval [CI], 1.05-12.76; p = 0.041; third tertile: aHR, 6.81; 95% CI, 1.98-23.44; p = 0.002). Furthermore, GDF-15 predicted in-hospital mortality (area under the curve, 0.710; 95% CI, 0.585-0.815) better than APACHE II and SOFA scores. Serum GDF-15 concentration was elevated in AKI patients requiring CRRT, higher in more severe patients. GDF-15 is a better independent predictor for in-hospital mortality of critically ill AKI patients than the traditional risk scoring system such as APACHE II and SOFA scores.

Keywords: acute kidney injury; continuous renal replacement therapy; growth differentiation factor-15; in-hospital mortality.

Figure 1

Growth differentiation factor-15 (GDF-15) concentrations in study patients. (A) Distribution of GDF-15. (B) GDF-15 concentration in the tertile healthy individual groups. * p < 0.001 vs. healthy control group. Abbreviation: GDF-15, growth differentiation factor-15.

Figure 2

Association between GDF-15 concentration and in-hospital mortality hazard ratio by restricted cubic spline regression model. The reference value is the median of the first tertile (5187.3 pg/mL). The red line indicates the estimated hazard ratio; the dashed green line indicates the reference line of null hypothesis that the hazard ratio is 1; the dashed black lines indicate the lower and upper 95% confidence limits. Abbreviation: GDF-15, growth differentiation factor-15.

Figure 3

Kaplan–Meier survival curve for in-hospital mortality by GDF-15 tertiles. Abbreviation: GDF-15, growth differentiation factor-15.

Figure 4

Receiver operating characteristic curves of prognostic predictors for in-hospital mortality. (A) Results for single variables. (B) Results for combined variables. The AUC values are as follows: GDF-15 (0.710); APACHE II (0.624); SOFA (0.584); CCI (0.519); eGFR (0.527); GDF-15 + APACHE II (0.735); GDF-15 + SOFA (0.712); APACHE II + SOFA (0.645). Abbreviations: GDF-15, growth differentiation factor-15; APACHE, acute physiology and chronic health evaluation; SOFA, sequential organ failure assessment; CCI, Charlson Comorbidity Index; eGFR, estimated glomerular filtration rate.