RESUMO
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-PENK24h > 105.7 pmol/L and P-NGAL24h > 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.
RESUMO
BACKGROUND: Inflammatory responses play an important role in the pathophysiology of cardiogenic shock (CS). The aim of this study was to investigate the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) in CS and to assess their relation to clinical presentation, other biochemical variables, and prognosis. METHODS: Levels of PCT, CRP and IL-6 were analyzed in serial plasma samples (0-120h) from 183 patients in the CardShock study. The study population was dichotomized by PCTmax ≥ and < 0.5 µg/L, and IL-6 and CRPmax above/below median. RESULTS: PCT peaked already at 24 h [median PCTmax 0.71 µg/L (IQR 0.24-3.4)], whereas CRP peaked later between 48 and 72 h [median CRPmax 137 mg/L (59-247)]. PCT levels were significantly higher among non-survivors compared with survivors from 12 h on, as were CRP levels from 24 h on (p < 0.001). PCTmax ≥ 0.5 µg/L (60% of patients) was associated with clinical signs of systemic hypoperfusion, cardiac and renal dysfunction, acidosis, and higher levels of blood lactate, IL-6, growth-differentiation factor 15 (GDF-15), and CRPmax. Similarly, IL-6 > median was associated with clinical signs and biochemical findings of systemic hypoperfusion. PCTmax ≥ 0.5 µg/L and IL-6 > median were associated with increased 90-day mortality (50% vs. 30% and 57% vs. 22%, respectively; p < 0.01 for both), while CRPmax showed no prognostic significance. The association of inflammatory markers with clinical infections was modest. CONCLUSIONS: Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.