Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia
(2023) In Clinical and Translational Science 16(12). p.2729-2743- Abstract
Free heme is released from hemoproteins during hemolysis or ischemia reperfusion injury and can be pro-inflammatory. Most studies on nephrotoxicity of hemolysis-derived proteins focus on free hemoglobin (fHb) with heme as a prosthetic group. Measurement of heme in its free, non-protein bound, form is challenging and not commonly used in clinical routine diagnostics. In contrast to fHb, the role of free heme in acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery is unknown. Using an apo-horseradish peroxidase-based assay, we identified free heme during CPB surgery as predictor of AKI in patients undergoing cardiac valve replacement (n = 37). Free heme levels during CPB surgery correlated with depletion of hemopexin (Hx),... (More)
Free heme is released from hemoproteins during hemolysis or ischemia reperfusion injury and can be pro-inflammatory. Most studies on nephrotoxicity of hemolysis-derived proteins focus on free hemoglobin (fHb) with heme as a prosthetic group. Measurement of heme in its free, non-protein bound, form is challenging and not commonly used in clinical routine diagnostics. In contrast to fHb, the role of free heme in acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery is unknown. Using an apo-horseradish peroxidase-based assay, we identified free heme during CPB surgery as predictor of AKI in patients undergoing cardiac valve replacement (n = 37). Free heme levels during CPB surgery correlated with depletion of hemopexin (Hx), a heme scavenger-protein. In mice, the impact of high levels of circulating free heme on the development of AKI following transient renal ischemia and the therapeutic potential of Hx were investigated. C57BL/6 mice were subjected to bilateral renal ischemia/reperfusion injury for 15 min which did not cause AKI. However, additional administration of free heme in this model promoted overt AKI with reduced renal function, increased renal inflammation, and reduced renal perfusion on functional magnetic resonance imaging. Hx treatment attenuated AKI. Free heme administration to sham operated control mice did not cause AKI. In conclusion, free heme is a predictor of AKI in CPB surgery patients and promotes AKI in transient renal ischemia. Depletion of Hx in CPB surgery patients and attenuation of AKI by Hx in the in vivo model encourage further research on Hx therapy in patients with increased free heme levels during CPB surgery.
(Less)
- author
- Greite, Robert
; Schott, Sebastian
; Wang, Li
; Gohlke, Lukas
; Kreimann, Kirill
; Derlin, Katja
; Gutberlet, Marcel
; Schmidbauer, Martina
; Leffler, Andreas
; Tudorache, Igor
; Salman, Jawad
; Ius, Fabio
; Natanov, Ruslan
; Fegbeutel, Christine
; Haverich, Axel
; Lichtinghagen, Ralf
; Hüsing, Anne M.
; von Vietinghoff, Sibylle
; Schmitt, Roland
; Shushakova, Nelli
; Rong, Song
; Haller, Hermann
; Schmidt-Ott, Kai M.
; Gram, Magnus
LU
; Vijayan, Vijith
; Scheffner, Irina
; Gwinner, Wilfried
and Immenschuh, Stephan
(Less) - organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Clinical and Translational Science
- volume
- 16
- issue
- 12
- pages
- 2729 - 2743
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:85175373131
- ISSN
- 1752-8054
- DOI
- 10.1111/cts.13667
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
- id
- 68020c5a-bcba-4545-9cee-bef95f7eb586
- date added to LUP
- 2023-12-13 14:12:20
- date last changed
- 2024-01-09 15:44:42
@article{68020c5a-bcba-4545-9cee-bef95f7eb586,
abstract = {{<p>Free heme is released from hemoproteins during hemolysis or ischemia reperfusion injury and can be pro-inflammatory. Most studies on nephrotoxicity of hemolysis-derived proteins focus on free hemoglobin (fHb) with heme as a prosthetic group. Measurement of heme in its free, non-protein bound, form is challenging and not commonly used in clinical routine diagnostics. In contrast to fHb, the role of free heme in acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery is unknown. Using an apo-horseradish peroxidase-based assay, we identified free heme during CPB surgery as predictor of AKI in patients undergoing cardiac valve replacement (n = 37). Free heme levels during CPB surgery correlated with depletion of hemopexin (Hx), a heme scavenger-protein. In mice, the impact of high levels of circulating free heme on the development of AKI following transient renal ischemia and the therapeutic potential of Hx were investigated. C57BL/6 mice were subjected to bilateral renal ischemia/reperfusion injury for 15 min which did not cause AKI. However, additional administration of free heme in this model promoted overt AKI with reduced renal function, increased renal inflammation, and reduced renal perfusion on functional magnetic resonance imaging. Hx treatment attenuated AKI. Free heme administration to sham operated control mice did not cause AKI. In conclusion, free heme is a predictor of AKI in CPB surgery patients and promotes AKI in transient renal ischemia. Depletion of Hx in CPB surgery patients and attenuation of AKI by Hx in the in vivo model encourage further research on Hx therapy in patients with increased free heme levels during CPB surgery.</p>}},
author = {{Greite, Robert and Schott, Sebastian and Wang, Li and Gohlke, Lukas and Kreimann, Kirill and Derlin, Katja and Gutberlet, Marcel and Schmidbauer, Martina and Leffler, Andreas and Tudorache, Igor and Salman, Jawad and Ius, Fabio and Natanov, Ruslan and Fegbeutel, Christine and Haverich, Axel and Lichtinghagen, Ralf and Hüsing, Anne M. and von Vietinghoff, Sibylle and Schmitt, Roland and Shushakova, Nelli and Rong, Song and Haller, Hermann and Schmidt-Ott, Kai M. and Gram, Magnus and Vijayan, Vijith and Scheffner, Irina and Gwinner, Wilfried and Immenschuh, Stephan}},
issn = {{1752-8054}},
language = {{eng}},
number = {{12}},
pages = {{2729--2743}},
publisher = {{Wiley-Blackwell}},
series = {{Clinical and Translational Science}},
title = {{Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia}},
url = {{http://dx.doi.org/10.1111/cts.13667}},
doi = {{10.1111/cts.13667}},
volume = {{16}},
year = {{2023}},
}