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 Int
; 110(11 Pt C): E1187-95, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-23157304
ABSTRACT
UNLABELLED What's known on the subject? and What does the study add? Hydrogen sulphide (H(2) S) 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 H(2) S in many models of tissue ischaemia-reperfusion injury (IRI), including hepatic, myocardial, pulmonary, cerebral and renal IRI. It has previously been shown that H(2) S 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 H(2) S against renal IRI have only involved clamping of the renal pedicle to induce warm IRI. This study investigated the protective effects of H(2) S 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 H(2) S 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 H(2) S during preservation is protective against prolonged cold IRI. These findings suggest that H(2) S has potential utility in improving clinical organ preservation techniques and increasing the overall success of organ transplantation. OBJECTIVE:
⢠To characterize the effects of hydrogen sulphide (H(2) S), 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 ANDMETHODS:
⢠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 (H(2) S) 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.RESULTS:
⢠H(2) S-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. ⢠H(2) S-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.CONCLUSION:
⢠Our results provide the first evidence that supplemental H(2) S 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Preservación de Órganos
/
Daño por Reperfusión
/
Trasplante de Riñón
/
Apoptosis
/
Supervivencia de Injerto
/
Sulfuro de Hidrógeno
/
Inflamación
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
BJU Int
Año:
2012
Tipo del documento:
Article
País de afiliación:
Canadá