Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia

被引：3

作者：

Greite, Robert ^{[1
,11
]}

Schott, Sebastian ^{[1
]}

Wang, Li ^{[1
]}

Gohlke, Lukas ^{[1
]}

Kreimann, Kirill ^{[1
]}

Derlin, Katja ^{[2
]}

Gutberlet, Marcel ^{[2
]}

Schmidbauer, Martina ^{[2
]}

Leffler, Andreas ^{[3
]}

Tudorache, Igor ^{[4
]}

Salman, Jawad ^{[5
]}

Ius, Fabio ^{[5
]}

Natanov, Ruslan ^{[5
]}

Fegbeutel, Christine ^{[5
]}

Haverich, Axel ^{[5
]}

Lichtinghagen, Ralf ^{[6
]}

Huesing, Anne M. ^{[1
]}

von Vietinghoff, Sibylle ^{[1
,7
]}

Schmitt, Roland ^{[1
]}

Shushakova, Nelli ^{[1
]}

Rong, Song ^{[1
]}

Haller, Hermann ^{[1
]}

Schmidt-Ott, Kai M. ^{[1
]}

Gram, Magnus ^{[8
]}

Vijayan, Vijith ^{[9
,10
]}

Scheffner, Irina ^{[1
]}

Gwinner, Wilfried ^{[1
]}

Immenschuh, Stephan ^{[9
]}

机构：

[1] Hannover Med Sch, Dept Nephrol & Hypertens, Hannover, Germany

[2] Hannover Med Sch, Inst Diagnost & Intervent Radiol, Hannover, Germany

[3] Hannover Med Sch, Dept Anesthesiol & Intens Care Med, Hannover, Germany

[4] Univ Hosp Dusseldorf, Dept Cardiac Surg, Dusseldorf, Germany

[5] Hannover Med Sch, Dept Cardiothorac Transplantat & Vasc Surg, Hannover, Germany

[6] Hannover Med Sch, Dept Clin Chem, Hannover, Germany

[7] Univ Hosp Bonn, Med Clin 1, Nephrol Sect, Bonn, Germany

[8] Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Pediat, Lund, Sweden

[9] Hannover Med Sch, Inst Transfus Med & Transplant Engn, Hannover, Germany

[10] Stanford Univ, Sch Med, Div Crit Care Med, Dept Pediat, Stanford, CA USA

[11] Hannover Med Sch, Nephrol, Carl-Neuberg-Str 1, D-30625 Hannover, Germany

来源：

CTS-CLINICAL AND TRANSLATIONAL SCIENCE | 2023年 / 16卷 / 12期

关键词：

PROTECTS RAT-KIDNEY; PERFUSION IMPAIRMENT; CARDIAC-SURGERY; LABILE HEME; OXYGENASE-1; DEFICIENCY; FAILURE; SYSTEMS; MICE;

D O I：

10.1111/cts.13667

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：2729 / 2743

页数：15

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