The role of cell-free hemoglobin and haptoglobin in acute kidney injury in critically ill adults with ARDS and therapy with VV ECMO
Jan A. Graw,
Philip Hildebrandt,
Alexander Krannich,
Felix Balzer,
Claudia Spies,
Roland C. Francis,
Wolfgang M. Kuebler,
Steffen Weber-Carstens,
Mario Menk,
Oliver Hunsicker
Affiliations
Jan A. Graw
Department of Anesthesiology and Operative Intensive Care Medicine CCM / CVK, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health
Philip Hildebrandt
Department of Anesthesiology and Operative Intensive Care Medicine CCM / CVK, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health
Alexander Krannich
Clinical Trial Office, Charité - Universitätsmedizin Berlin
Felix Balzer
Institute of Medical Informatics, Charité - Universitätsmedizin Berlin
Claudia Spies
Department of Anesthesiology and Operative Intensive Care Medicine CCM / CVK, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health
Roland C. Francis
Department of Anesthesiology and Operative Intensive Care Medicine CCM / CVK, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health
Wolfgang M. Kuebler
Institute of Physiology, Charité - Universitätsmedizin Berlin
Steffen Weber-Carstens
Department of Anesthesiology and Operative Intensive Care Medicine CCM / CVK, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health
Mario Menk
Department of Anesthesiology and Operative Intensive Care Medicine CCM / CVK, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health
Oliver Hunsicker
Department of Anesthesiology and Operative Intensive Care Medicine CCM / CVK, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health
Abstract Background Increased plasma concentrations of circulating cell-free hemoglobin (CFH) are supposed to contribute to the multifactorial etiology of acute kidney injury (AKI) in critically ill patients while the CFH-scavenger haptoglobin might play a protective role. We evaluated the association of CFH and haptoglobin with AKI in patients with an acute respiratory distress syndrome (ARDS) requiring therapy with VV ECMO. Methods Patients with CFH and haptoglobin measurements before initiation of ECMO therapy were identified from a cohort of 1044 ARDS patients and grouped into three CFH concentration groups using a risk stratification. The primary objective was to assess the association of CFH and haptoglobin with KDIGO stage 3 AKI. Further objectives included the identification of a target haptoglobin concentration to protect from CFH-associated AKI. Measurements and main results Two hundred seventy-three patients fulfilled the inclusion criteria. Of those, 154 patients (56.4%) had AKI at ECMO initiation. The incidence of AKI increased stepwise with increasing concentrations of CFH reaching a plateau at 15 mg/dl. Compared to patients with low [< 5 mg/dl] CFH concentrations, patients with moderate [5–14 mg/dl] and high [≥ 15 mg/dl] CFH concentrations had a three- and five-fold increased risk for AKI (adjusted odds ratio [OR] moderate vs. low, 2.69 [95% CI, 1.25–5.95], P = 0.012; and OR high vs. low, 5.47 [2.00–15.9], P = 0.001). Among patients with increased CFH concentrations, haptoglobin plasma levels were lower in patients with AKI compared to patients without AKI. A haptoglobin concentration greater than 2.7 g/l in the moderate and 2.4 g/l in the high CFH group was identified as clinical cutoff value to protect from CFH-associated AKI (sensitivity 89.5% [95% CI, 83–96] and 90.2% [80–97], respectively). Conclusions In critically ill patients with ARDS requiring therapy with VV ECMO, an increased plasma concentration of CFH was identified as independent risk factor for AKI. Among patients with increased CFH concentrations, higher plasma haptoglobin concentrations might protect from CFH-associated AKI and should be subject of future research.
