Supplemental hydrogen sulphide protects transplant kidney function and prolongs recipient survival after prolonged cold ischaemia–reperfusion injury by mitigating renal graft apoptosis and inflammation
Article first published online: 16 NOV 2012
© 2012 BJU INTERNATIONAL. NO CLAIM TO ORIGINAL US GOVERNMENT WORKS
Volume 110, Issue 11c, pages E1187–E1195, December 2012
How to Cite
Lobb, I., Mok, A., Lan, Z., Liu, W., Garcia, B. and Sener, A. (2012), Supplemental hydrogen sulphide protects transplant kidney function and prolongs recipient survival after prolonged cold ischaemia–reperfusion injury by mitigating renal graft apoptosis and inflammation. BJU International, 110: E1187–E1195. doi: 10.1111/j.1464-410X.2012.11526.x
- Issue published online: 21 DEC 2012
- Article first published online: 16 NOV 2012
- Accepted for publication 1 June 2012
- hydrogen sulphide;
- ischaemia–reperfusion injury;
- renal transplantation;
- organ preservation;
- graft function;
What's known on the subject? and What does the study add?
Hydrogen sulphide (H2S) has recently been classified as a member of the family of small gaseous molecules called gasotransmitters and has been found to have many important physiological functions. Several recent studies have elucidated the protective effects of H2S in many models of tissue ischaemia–reperfusion injury (IRI), including hepatic, myocardial, pulmonary, cerebral and renal IRI. It has previously been shown that H2S has a number of properties that may contribute to its protection against IRI, including vasodilatory, anti-apoptotic, anti-inflammatory and anti-oxidant effects, although the specific actions appear to vary between tissues.
The few studies investigating the effects of H2S against renal IRI have only involved clamping of the renal pedicle to induce warm IRI. This study investigated the protective effects of H2S in the context of renal transplantation (RTx), which generally involves a more severe period of prolonged cold IRI. A previous study investigated the actions of H2S in RTx, but it was performed ex vivo and did not involve actual transplantation of donor kidneys. To our knowledge, this is the first study using a clinically relevant model of RTx to show that treatment of donor kidneys with H2S during preservation is protective against prolonged cold IRI. These findings suggest that H2S has potential utility in improving clinical organ preservation techniques and increasing the overall success of organ transplantation.
- • To characterize the effects of hydrogen sulphide (H2S), an endogenously produced molecule recently described to have protective effects against warm ischaemic tissue injury, in mitigating transplantation-associated prolonged cold ischaemia–reperfusion injury (IRI) in a clinically applicable in vivo model of renal transplantation (RTx).
MATERIALS AND METHODS
- • After undergoing bilateral native nephrectomy, Lewis rats underwent RTx with kidneys that were flushed with either cold (4 °C) standard University of Wisconsin preservation solution (UW) or cold UW + 150 µM NaHS (H2S) solution and stored for 24 h at 4 °C in the same solution.
- • Recipient rats were monitored for a 14-day time course using metabolic cages to assess various characteristics of renal graft function.
- • Renal grafts were removed at time of death or after the rats were killed for histological, immunohistochemical and quantitative PCR analysis.
- • H2S-treated rats exhibited immediate and significant (P < 0.05) decreases in serum creatinine levels, increased urine output and increased survival compared with UW-treated rats.
- • H2S-treated grafts showed significantly reduced glomerular and tubular necrosis and apoptosis, diminished graft neutrophil and macrophage infiltrates and a trend towards improved inflammatory and anti-apoptotic cytokine profiles.
- • Our results provide the first evidence that supplemental H2S can mitigate renal graft IRI incurred during transplantation and prolonged cold storage, improving early graft function and recipient survival in a clinically applicable model of RTx.