Cell-Free Hemoglobin in Acute Kidney Injury after Lung Transplantation and Experimental Renal Ischemia/Reperfusion

Robert Greite, Li Wang, Lukas Gohlke, Sebastian Schott, Kirill Kreimann, Julian Doricic, Andreas Leffler, Igor Tudorache, Jawad Salman, Ruslan Natanov, Fabio Ius, Christine Fegbeutel, Axel Haverich, Ralf Lichtinghagen, Rongjun Chen, Song Rong, Hermann Haller, Vijith Vijayan, Magnus Gram, Irina ScheffnerFaikah Gueler, Wilfried Gwinner, Stephan Immenschuh

Research output: Contribution to journalArticlepeer-review

Abstract

Cell-free hemoglobin (CFH), a pro-oxidant and cytotoxic compound that is released in hemolysis, has been associated with nephrotoxicity. Lung transplantation (LuTx) is a clinical condition with a high incidence of acute kidney injury (AKI). In this study, we investigated the plasma levels of CFH and haptoglobin, a CFH-binding serum protein, in prospectively enrolled LuTx patients (n = 20) with and without AKI. LuTx patients with postoperative AKI had higher CFH plasma levels at the end of surgery compared with no-AKI patients, and CFH correlated with serum creatinine at 48 h. Moreover, CFH levels inversely correlated with haptoglobin levels, which were significantly reduced at the end of surgery in LuTx patients with AKI. Because multiple other factors can contribute to AKI development in the complex clinical setting of LuTx, we next investigated the role of exogenous CFH administration in a mouse model of mild bilateral renal ischemia reperfusion injury (IRI). Exogenous administration of CFH after reperfusion caused overt AKI with creatinine increase, tubular injury, and enhanced markers of renal inflammation compared with vehicle-treated animals. In conclusion, CFH is a possible factor contributing to postoperative AKI after LuTx and promotes AKI in an experimental model of mild transient renal ischemia. Targeting CFH might be a therapeutic option to prevent AKI after LuTx.

Original languageEnglish
Article number13272
JournalInternational Journal of Molecular Sciences
Volume23
Issue number21
DOIs
Publication statusPublished - 2022 Nov

Subject classification (UKÄ)

  • Surgery

Keywords

  • acute kidney injury
  • free hemoglobin
  • hemolysis
  • lung transplantation

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