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

Greite, Robert ; Wang, Li ; Gohlke, Lukas ; Schott, Sebastian ; Kreimann, Kirill ; Doricic, Julian ; Leffler, Andreas ; Tudorache, Igor ; Salman, Jawad and Natanov, Ruslan , et al. (2022) In International Journal of Molecular Sciences 23(21).
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
acute kidney injury, free hemoglobin, hemolysis, lung transplantation
in
International Journal of Molecular Sciences
volume
23
issue
21
article number
13272
publisher
MDPI AG
external identifiers
  • scopus:85141784541
  • pmid:36362059
ISSN
1661-6596
DOI
10.3390/ijms232113272
language
English
LU publication?
yes
id
d867e3b6-4b1d-4501-86da-126dcb0ec004
date added to LUP
2022-11-30 08:57:00
date last changed
2024-06-11 19:42:51
@article{d867e3b6-4b1d-4501-86da-126dcb0ec004,
  abstract     = {{<p>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.</p>}},
  author       = {{Greite, Robert and Wang, Li and Gohlke, Lukas and Schott, Sebastian and Kreimann, Kirill and Doricic, Julian and Leffler, Andreas and Tudorache, Igor and Salman, Jawad and Natanov, Ruslan and Ius, Fabio and Fegbeutel, Christine and Haverich, Axel and Lichtinghagen, Ralf and Chen, Rongjun and Rong, Song and Haller, Hermann and Vijayan, Vijith and Gram, Magnus and Scheffner, Irina and Gueler, Faikah and Gwinner, Wilfried and Immenschuh, Stephan}},
  issn         = {{1661-6596}},
  keywords     = {{acute kidney injury; free hemoglobin; hemolysis; lung transplantation}},
  language     = {{eng}},
  number       = {{21}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Cell-Free Hemoglobin in Acute Kidney Injury after Lung Transplantation and Experimental Renal Ischemia/Reperfusion}},
  url          = {{http://dx.doi.org/10.3390/ijms232113272}},
  doi          = {{10.3390/ijms232113272}},
  volume       = {{23}},
  year         = {{2022}},
}