Simvastatin and l-Arginine Preserve Renal Function after Ischemia/Reperfusion Injury

Inman, Sharon R.; Davis, Nancy; Mazzone, Maria E.; Olson, Kristen; Lukaszek, Victoria A.; Yoder, Kristy N.

doi:10.1097/00000441-200501000-00003

Cited by 26 publications

(17 citation statements)

References 21 publications

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“…Studies have shown both direct and indirect blockade of T cells reduced renal functional and structural injury in murine renal IRI models [51,52,53]. In athymic nu/nu mice (T-cell knockout mouse strain) subjected to IRI, not only protection from initial renal injury but also an adoptive T-cell transfer into these mice restored the renal injury [54]. Inactivation of these cells is a prerequisite to achieve some protection against IRI [54].…”

Section: Role Of Thymoglobulin In Ischemia-reperfusion Injurymentioning

confidence: 99%

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Thymoglobulin and Its Use in Renal Transplantation: A Review

2013

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Thymoglobulin (Thymoglobulin®; Genzyme, Cambridge, Mass., USA) is a polyclonal antibody which has been used in the field of transplantation over the last four decades. With an initial hesitancy, it is widely used now in the prevention and treatment of rejection following renal transplantation. Thymoglobulin's lack of nephrotoxic properties (unlike calcineurin inhibitors) may potentiate it to be a very useful induction therapy during the early days following transplantation, particularly in a donation after circulatory death programme. More recently its role in conjunction with inhibitors of terminal complement activation has been shown to be beneficial in cross-match-positive transplantation. This review article consolidates up-to-date available evidence to address the therapeutic role of thymoglobulin in immunological tolerance, ischemia perfusion, live donor transplantation, delayed graft function, prevention and treatment of rejection, graft survival and post-transplant lymphoproliferative disorder following renal transplantation.

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Section: Role Of Thymoglobulin In Ischemia-reperfusion Injurymentioning

confidence: 99%

“…In athymic nu/nu mice (T-cell knockout mouse strain) subjected to IRI, not only protection from initial renal injury but also an adoptive T-cell transfer into these mice restored the renal injury [54]. Inactivation of these cells is a prerequisite to achieve some protection against IRI [54]. …”

Section: Role Of Thymoglobulin In Ischemia-reperfusion Injurymentioning

confidence: 99%

Thymoglobulin and Its Use in Renal Transplantation: A Review

2013

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“…This was demonstrated in experimental studies with the combination of ischemia and cyclosporine A that has a nephrotoxic and vasoconstricting action side by side with its immunosuppressor effect 10,11 . Another mechanism of action of statins concerns the promotion of angiogenesis, as suggested by Chade et al…”

Section: Discussionmentioning

confidence: 93%

Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats

Tucci¹,

Molina²,

Cassini³

et al. 2012

Acta Cir. Bras.

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PURPOSE:To investigate the effect of lovastatin on renal ischemia followed by reperfusion. METHODS:Thirty one Wistar rats submitted to left renal ischemia for 60 minutes followed by contralateral nephrectomy were divided into two groups: A (n =17, control, no treatment), and B (n=14, lovastatin 15 mg/kg/day p.o. ten days before ischemia). The animals were sacrificed at the end of ischemia, after 24 hours and at seven days after reperfusion. Survival, serum urea and creatinine levels and renal mitochondrial function were evaluated. RESULTS:Mortality was 29.4% in group A and 0.7% in group B. Urea and creatinine levels were increased in both groups, but the values were significantly lower in group B. Mitochondrial function showed decoupling in 83.4% of group A, as opposed to 38.4/% of group B. CONCLUSIONS:The result shows a protective action of renal function by lovastatin administered before ischemia/reperfusion. Since most of the mitochondrial fraction presented membranes with the ability to maintain ATP production in group B, stabilization of the mitochondrial membrane should be considered as part of the protective action of lovastatin on renal function in ischemia/reperfusion. Key words: Lovastatin. Mitochondria. Reperfusion Injury. Ischemia. Rats. RESUMO OBJETIVO:Investigar a ação da lovastatina na isquemia renal seguida de reperfusão. MÉTODOS:Trinta e um ratos Wistar submetidos à isquemia renal esquerda durante 60 minutos, seguida da nefrectomia contralateral, foram distribuídos em dois grupos: A (n=17, controle, sem tratamento) e B (n=14, recebendo 15 mg/Kg/dia de lovastatina via oral), durante os dez dias que antecederam a isquemia. Os animais foram mortos ao final da isquemia, e com 24 horas e sete dias após a reperfusão. Foram avaliadas a sobrevida, os valores séricos de uréia e creatinina e a função mitocondrial renal. RESULTADOS:A mortalidade foi 29,4% no grupo A e 0,7% no grupo B. Os níveis de uréia e creatinina elevaram-se nos dois grupos, mas foram significativamente menores no grupo B. No grupo A a função mitocondrial renal ficou desacoplada em 83,4% dos ensaios, enquanto que no grupo B isto ocorreu em apenas 38,4% dos ensaios. CONCLUSÕES:Os resultados mostram que a administração de lovastatina antes do episódio de isquemia protege a função renal. No grupo B, como a maior parte da fração mitocondrial isolada apresentou função acoplada à produção de ATP, deve-se também considerar a estabilização da membrana mitocondrial como parte da ação protetora da lovastatina na função renal durante isquemia e reperfusão.

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“…8,[38][39][40][41][42][43][44][45][46][47][48][49] In animals, increased NO production by agents such as L-arginine or molsidomine has been shown to ameliorate the CNI nephrotoxicity, whereas depletion of NO by L-NAME, a competitive inhibitor of eNOS, augments the nephrotoxicity. 48 These data indicating the importance of NO in the pathogenesis of CNI nephrotoxicity suggest that the NOS3 SNP found in this study may have a mechanistic role.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Nitric Oxide Synthase Gene Variation Associated With Chronic Kidney Disease After Liver Transplant

Bambha

Kim

Rosen

et al. 2010

Mayo Clinic Proceedings

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OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with risk of developing chronic kidney disease (CKD), a prevalent comorbidity, after liver transplant (LT). PATIENTS AND METHODS:This study consists of a cohort of adult (≥18 years) primary-LT recipients who had normal renal function before LT and who survived 1 year or more after LT at a high-volume US LT program between January 1, 1990, and December 31, 2000. Patients with adequate renal function (estimated glomerular filtration rate, ≥40 mL/min per 1.73 m 2 during follow-up; n=308) and patients with incident CKD (estimated glomerular filtration rate, <40 mL/min per 1.73 m 2 after LT; n=92) were identified. To investigate the association of 6 candidate genes with post-LT CKD, we selected SNPs that have been associated with renal function in the literature. Hazard ratios were estimated using Cox regression, adjusted for potential confounding variables. RESULTS:The variant allele (298Asp) of the Glu298Asp SNP in the endothelial nitric oxide synthase gene (NOS3) was significantly associated with CKD after LT (P=.05; adjusted for multiple comparisons). The 5-year incidence of CKD was 70% among patients homozygous for the NOS3 variant allele (298Asp) compared with 42% among those not homozygous for the NOS3 variant allele. Specifically, homozygosity for the NOS3 variant allele conferred a 2.5-fold increased risk of developing CKD after LT (P=.005, adjusted for confounding variables). CONCLUSION:Homozygosity for the variant allele of NOS3 (298Asp) is associated with CKD after LT and may be useful for identifying recipients at higher risk of post-LT CKD. Proc. 2010;85(9):814-820 BMI = body mass index; CI = confidence interval; CKD = chronic kidney disease; CNI = calcineurin inhibitor; eGFR = estimated glomerular filtration rate; eNOS = endothelial nitric oxide synthase; GFR = glomerular filtration rate; HR = hazard ratio; LT = liver transplant; NO = nitric oxide; PCR = polymerase chain reaction; SNP = single nucleotide polymorphism Mayo Clin

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Simvastatin and l-Arginine Preserve Renal Function after Ischemia/Reperfusion Injury

Cited by 26 publications

References 21 publications

Thymoglobulin and Its Use in Renal Transplantation: A Review

Thymoglobulin and Its Use in Renal Transplantation: A Review

Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats

Endothelial Nitric Oxide Synthase Gene Variation Associated With Chronic Kidney Disease After Liver Transplant

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