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

Toni Jäntti; Tuukka Tarvasmäki; Veli-Pekka Harjola; Kari Pulkki; Heidi Turkia; Tuija Sabell; Heli Tolppanen; Raija Jurkko; Mari Hongisto; Anu Kataja; Alessandro Sionis; Jose Silva-Cardoso; Marek Banaszewski; Salvatore DiSomma; Alexandre Mebazaa; Mikko Haapio; Johan Lassus; CardShock investigators

doi:10.1186/s13613-021-00814-8

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

Ann Intensive Care. 2021 Feb 5;11(1):25. doi: 10.1186/s13613-021-00814-8.

Authors

Toni Jäntti¹, Tuukka Tarvasmäki², Veli-Pekka Harjola³, Kari Pulkki⁴, Heidi Turkia⁴, Tuija Sabell², Heli Tolppanen², Raija Jurkko², Mari Hongisto³, Anu Kataja⁵, Alessandro Sionis⁶, Jose Silva-Cardoso⁷, Marek Banaszewski⁸, Salvatore DiSomma⁹, Alexandre Mebazaa¹⁰, Mikko Haapio¹¹, Johan Lassus²; CardShock investigators

Collaborators

CardShock investigators:
Veli-Pekka Harjola, Marek Banaszewski, Lars Køber, Johan Lassus, Alexandre Mebazaa, Marco Metra, John Parissis, Jose Silva-Cardoso, Alessandro Sionis, Salvatore Di Somma, Jindrich Spinar, Katerina Koniari, Astrinos Voumvourakis, Apostolos Karavidas, Jordi Sans-Rosello, Montserrat Vila, Albert Duran-Cambra, Michela Bulgari, Valentina Lazzarini, Jiri Parenica, Roman Stipal, Ondrej Ludka, Marie Palsuva, Eva Ganovska, Petr Kubena, Matias G Lindholm, Christian Hassager, Tom Bäcklund, Raija Jurkko, Kristiina Järvinen, Tuomo Nieminen, Kari Pulkki, Leena Soininen, Reijo Sund, Ilkka Tierala, Jukka Tolonen, Marjut Varpula, Tuomas Korva, Anne Pitkälä, Rossella Marino, Alexandra Sousa, Carla Sousa, Mariana Paiva, Inês Rangel, Rui Almeida, Teresa Pinho, Maria Júlia Maciel, Janina Stepinska, Anna Skrobisz, Piotr Góral

Affiliations

¹ Department of Cardiology, Heart and Lung Center, Helsinki University Hospital, University of Helsinki, 00029 HUS, Helsinki, Finland. toni.jantti@fimnet.fi.
² Department of Cardiology, Heart and Lung Center, Helsinki University Hospital, University of Helsinki, 00029 HUS, Helsinki, Finland.
³ Emergency Medicine, Department of Emergency Medicine and Services, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
⁴ HUSLAB Diagnostic Services, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁵ Internal Medicine, Department of Internal Medicine and Rehabilitation, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
⁶ Intensive Cardiac Care Unit, Cardiology Department, Hospital de La Santa Creu I Sant Pau, Biomedical Research Institute IIB-SantPau, Universidad Autónoma de Barcelona, Barcelona, Spain.
⁷ CINTESIS, Department of Cardiology, São João Hospital Center, and Porto Medical School, University of Porto, Porto, Portugal.
⁸ Intensive Cardiac Therapy Clinic, National Institute of Cardiology, Warsaw, Poland.
⁹ Department of Medical Sciences and Translational Medicine, Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy.
¹⁰ INSERM U942, Department of Anesthesia and Critical Care, Hôpital Lariboisière, APHP, University Paris Diderot, Paris, France.
¹¹ Nephrology, Department of Nephrology, Abdominal Center, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

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.

Associated data

ClinicalTrials.gov/NCT01374867

Abstract

Associated data

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