Predictive value of plasma proenkephalin and neutrophil gelatinase-associated lipocalin in acute kidney injury and mortality in cardiogenic shock

Abstract

Background: Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock.

Results: P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71-150) pmol/mL and 138 (84-214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1-4.4, p = 0.03] and 2.8 [95% CI 1.2-6.5, p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria < 0.5 mL/kg/h for > 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%, p < 0.001). However, the biomarkers provided best discrimination for mortality when measured at 24 h. Identified cut-offs of P-PENK_24h > 105.7 pmol/L and P-NGAL_24h > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1-10.7, p < 0.001) and 5.2 (95% CI 2.8-9.8, p < 0.001) for 90-day mortality. The association remained significant despite adjustments with AKI and two risk scores for mortality in cardiogenic shock.

Conclusions: High levels of P-PENK and P-NGAL at baseline were independently associated with AKI in cardiogenic shock patients. Furthermore, oliguria before study inclusion was associated with worse outcomes only if combined with high baseline levels of P-PENK or P-NGAL. High levels of both P-PENK and P-NGAL at 24 h were found to be strong and independent predictors of 90-day mortality.

Trial registration: NCT01374867 at www.clinicaltrials.gov , registered 16 Jun 2011-retrospectively registered.

Keywords: AKI; Acute kidney injury; Cardiogenic shock; Mortality; NGAL; PENK; Proenkephalin; Prognosis.

Fig. 1

Biomarker medians at different time points separated by occurrence of AKI within 48 h. a P-PENK. b P-NGAL. c Creatinine. Error bars = 95% confidence interval

Fig. 2

P-PENK and P-NGAL median levels at different time points separated by 90-day mortality. a P-PENK. b P-NGAL. Error bars = 95% confidence interval

Fig. 3

Kaplan–Meier curves for occurrence of acute kidney injury by P-PENK and P-NGAL levels at baseline. a Lines separated by P-PENK > 84.8 pmol/mL at baseline. b Lines separated by P-NGAL > 104 ng/mL at baseline

Fig. 4

Venn diagram of P-PENK, P-NGAL at baseline, acute kidney injury and 90-day mortality. PENK high = P-PENK < 84.8 pmol/mL at baseline. P-NGAL high = P-NGAL > 104 ng/mL at baseline. For illustrative purposes. Areas not proportional, unable to show all overlaps

Fig. 5

Kaplan–Meier survival curves for patients with and without AKI separated by P-PENK and P-NGAL levels. a P-PENK higher or lower than 84.8 pmol/mL at baseline. b P-NGAL higher or lower than 104 ng/mL at baseline. §p = 0.07, *p < 0.05, **p < 0.001. AKI acute kidney injury