Renal failure in myocardial infarction with cardiogenic shock - comparison of established and novel biomarkers - a biomarker substudy of the IABP-SHOCK II-trial

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Background: Impairment of renal function is an important prognostic factor in acute coronary syndromes. In cardiogenic shock loss of renal function is one important sign of inadequate end-organ perfusion. The role of the novel biomarkers Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule 1 (KIM1) and Cystatin C for renal injury in comparison to established serum creatinine has never been investigated before. Methods: In the randomized Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II)-trial 600 patients with Cardiogenic Shock (CS) complicating acute myocardial infarction undergoing early revascularization were assigned to therapy with IABP or no IABP. In 190 patients blood samples were collected directly during primary primary coronary intervention, on day one, and day two after randomization. Blood was centrifuged immediately after sample drawing and serum frozen at -87° C. NGAL, KIM1 and Cystatin C were measured with standard ELISA-Kits, Creatinine was assessed with routine laboratory measurement. All-cause mortality at 30 days was used for outcome assessment. Results: Survivors had lower levels of creatinine (109 [IQR 90; 141] vs. 138 [IQR 102; 186] μmol/L; p<0.001) and NGAL (915 [IQR 568; 1415] vs. 1091 [IQR 769; 2229] ng/mL; p=0.01) than non-survivors at baseline, whereas there was no significant difference for KIM1 (134 [IQR 119; 164] vs. 123 [IQR 108; 178] pg/mL; p=0.82) and Cystatin C (3084 [IQR 2510; 3596] vs. 3366 [IQR 2626; 3778] ng/mL; p=0.16). In repeated measures analysis of variance over all three measurements creatinine (p=0.04) and NGAL (p=0.04) showed significant differences in contrast to KIM1 (p=0.21) and Cystatin C (p=0.42). Receiver operator characteristics (ROC) showed highest values for the area under the curve (AUC) in prediction of 30 day mortality for creatinine at all three time points (AUC baseline 0.65; day one 0.75; day two 0.78), NGAL showed the second best performance (AUC baseline 0.62; day one 0.60; day two 0.66). In c-statistics creatinine showed significant higher AUC over NGAL on day one and day two (p=0.003; p=0.03; respectively) and significant higher AUC at all time points in comparison to KIM1 and Cystatin C. Conclusion: Renal failure has significant impact on outcome in cardiogenic shock. Of novel markers of renal injury NGAL showed the best performance in prediction of 30 day mortality, but was inferior to established serum creatinine measurements.