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1.
Int J Mol Sci ; 24(18)2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37762319

RESUMO

The global donor kidney shortage crisis has necessitated the use of suboptimal kidneys from donors-after-cardiac-death (DCD). Using an ex vivo porcine model of DCD kidney transplantation, the present study investigates whether the addition of hydrogen sulfide donor, AP39, to University of Wisconsin (UW) solution improves graft quality. Renal pedicles of male pigs were clamped in situ for 30 min and the ureters and arteries were cannulated to mimic DCD. Next, both donor kidneys were nephrectomized and preserved by static cold storage in UW solution with or without AP39 (200 nM) at 4 °C for 4 h followed by reperfusion with stressed autologous blood for 4 h at 37 °C using ex vivo pulsatile perfusion apparatus. Urine and arterial blood samples were collected hourly during reperfusion. After 4 h of reperfusion, kidneys were collected for histopathological analysis. Compared to the UW-only group, UW+AP39 group showed significantly higher pO2 (p < 0.01) and tissue oxygenation (p < 0.05). Also, there were significant increases in urine production and blood flow rate, and reduced levels of urine protein, serum creatinine, blood urea nitrogen, plasma Na+ and K+, as well as reduced intrarenal resistance in the UW+AP39 group compared to the UW-only group. Histologically, AP39 preserved renal structure by reducing the apoptosis of renal tubular cells and immune cell infiltration. Our finding could lay the foundation for improved graft preservation and reduce the increasingly poor outcomes associated with DCD kidney transplantation.


Assuntos
Sulfeto de Hidrogênio , Transplante de Rim , Humanos , Masculino , Suínos , Animais , Sulfeto de Hidrogênio/farmacologia , Criopreservação , Mitocôndrias
2.
Pharmacol Res ; 173: 105883, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34525329

RESUMO

Carbon monoxide (CO) was historically regarded solely as a poisonous gas that binds to hemoglobin and reduces oxygen-carrying capacity of blood at high concentrations. However, recent findings show that it is endogenously produced in mammalian cells as a by-product of heme degradation by heme oxygenase, and has received a significant attention as a medical gas that influences a myriad of physiological and pathological processes. At low physiological concentrations, CO exhibits several therapeutic properties including antioxidant, anti-inflammatory, anti-apoptotic, anti-fibrotic, anti-thrombotic, anti-proliferative and vasodilatory properties, making it a candidate molecule that could protect organs in various pathological conditions including cold ischemia-reperfusion injury (IRI) in kidney and heart transplantation. Cold IRI is a well-recognized and complicated cascade of interconnected pathological pathways that poses a significant barrier to successful outcomes after kidney and heart transplantation. A substantial body of preclinical evidence demonstrates that CO gas and CO-releasing molecules (CO-RMs) prevent cold IRI in renal and cardiac grafts through several molecular and cellular mechanisms. In this review, we discuss recent advances in research involving the use of CO as a novel pharmacological strategy to attenuate cold IRI in preclinical models of kidney and heart transplantation through its administration to the organ donor prior to organ procurement or delivery into organ preservation solution during cold storage and to the organ recipient during reperfusion and after transplantation. We also discuss the underlying molecular mechanisms of cyto- and organ protection by CO during transplantation, and suggest its clinical use in the near future to improve long-term transplantation outcomes.


Assuntos
Monóxido de Carbono/uso terapêutico , Isquemia Fria , Transplante de Coração , Transplante de Rim , Traumatismo por Reperfusão/prevenção & controle , Animais , Monóxido de Carbono/farmacologia , Humanos , Transplantes
3.
J Urol ; 189(6): 2214-20, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23219548

RESUMO

PURPOSE: Static cold storage is generally used to preserve kidney allografts from deceased donors. Hypothermic machine perfusion may improve the outcome after transplantation but few studies with limited power have addressed this issue. We reviewed evidence of the effectiveness of storing kidneys from deceased donors after cardiac death before transplantation using cold static storage solution or pulsatile hypothermic machine perfusion. MATERIALS AND METHODS: We searched electronic databases in September 2011 for systematic reviews and/or meta-analyses, randomized, controlled trials and studies of other designs that compared delayed graft function and graft survival. Sources included The Cochrane Library, PubMed® and EMBASE®. Studies excluded from review included those that did not discriminate between donation after cardiac death and donation from a neurologically deceased donor. Primary outcomes were delayed graft function and 1-year graft survival. Statistical analysis was done using RevMan (http://ims.cochrane.org/revman). RESULTS: Nine studies qualified for review. Pulsatile perfusion pumped kidneys from donation after cardiac death donors had decreased delayed graft function compared to kidneys placed in cold storage (OR 0.64, 95% CI 0.43-0.95, p = 0.03). There was a trend toward improved 1-year graft survival in the pulsatile perfusion group but statistical significance was not attained (OR 0.74, 95% CI 0.48-1.13, p = 0.17). CONCLUSIONS: Pulsatile machine perfusion of donation after cardiac death kidneys appears to decrease the delayed graft function rate. We noted no benefit in 1-year graft survival. Due to the great heterogeneity among the trials as well as several confounding factors, the overall impact on allograft function and survival requires more study.


Assuntos
Criopreservação/métodos , Morte , Função Retardada do Enxerto/fisiopatologia , Bombas de Infusão/estatística & dados numéricos , Rim , Intervalos de Confiança , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Masculino , Razão de Chances , Preservação de Órgãos/métodos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Doadores de Tecidos
4.
J Urol ; 190(2): 772-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23246477

RESUMO

PURPOSE: Organ cold storage and subsequent transplantation are associated with significant ischemia-reperfusion injury, leading to cell death, graft inflammation and decreased graft function. MATERIALS AND METHODS: CORM-3s reduce oxidative stress and prevent inflammation in kidneys stored at 4C and subsequently transplanted. Graft survival and function are markedly improved compared to kidneys preserved and stored in University of Wisconsin solution alone. We determined whether CORM-3 has direct antiapoptotic effects on in vitro preparations of human HUVECs exposed to anoxic conditions. We also determined whether direct administration of CORM-3 to renal grafts before and/or after cold storage would prevent renal damage during the transplantation process. RESULTS: CORM-3 supplementation led to a significantly increased frequency of live cells (mean ± SD 72.3% ± 1.9%, p <0.01), reduced apoptosis (14.9% ± 6.1%, p <0.01) and decreased mitochondrial transmembrane potential (40.2% ± 7.2%, p <0.05) in HUVECs exposed to 20 hours of cold storage compared to controls (11.6% ± 3.5%, 82.2% ± 2.3% and 78.2% ± 3.2%, respectively). In keeping with this antiapoptotic effect CORM-3 supplementation led to a mean 7.4 ± 2.1-fold up-regulation in Bcl-2 gene expression. CORM-3 supplementation in standard preservation solution was most beneficial at initial ischemic injury and before cold storage exposure. However, additional reflushing before vascular reperfusion showed an additive benefit to graft survival and function after transplantation. This was confirmed by decreased glomerular and tubular necrosis, and apoptosis in double flushed grafts. CONCLUSIONS: CORM-3 supplementation in standard University of Wisconsin solution has a significant impact on decreasing cellular and graft injury, and improving survival through its antiapoptotic effects, which are likely mediated through mitochondrial membrane stabilization.


Assuntos
Transplante de Rim , Preservação de Órgãos/métodos , Compostos Organometálicos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Adenosina/farmacologia , Alopurinol/farmacologia , Animais , Apoptose/efeitos dos fármacos , Glutationa/farmacologia , Sobrevivência de Enxerto , Inflamação/prevenção & controle , Insulina/farmacologia , Masculino , Soluções para Preservação de Órgãos/farmacologia , Estresse Oxidativo , Rafinose/farmacologia , Ratos Endogâmicos Lew
5.
Biochem Pharmacol ; 202: 115156, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35777450

RESUMO

Carbon monoxide is quickly moving past its historic label as a molecule once feared, to a therapeutic drug that modulates inflammation. The development of carbon monoxide releasing molecules and utilization of heme oxygenase-1 inducers have shown carbon monoxide to be a promising therapy in reducing renal ischemia and reperfusion injury and other inflammatory diseases. In this review, we will discuss the developments and application of carbon monoxide releasing molecules in renal ischemia and reperfusion injury, and transplantation. We will review the anti-inflammatory mechanisms of carbon monoxide in respect to mitigating apoptosis, suppressing dendritic cell maturation and signalling, inhibiting toll-like receptor activation, promoting anti-inflammatory responses, and the effects on renal vasculature.


Assuntos
Nefropatias , Traumatismo por Reperfusão , Anti-Inflamatórios/farmacologia , Monóxido de Carbono/farmacologia , Monóxido de Carbono/uso terapêutico , Humanos , Isquemia , Nefropatias/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle
6.
J Invest Surg ; 35(1): 104-110, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33400888

RESUMO

Objective We have previously demonstrated benefits of kidney preservation utilizing an oxygenated subnormothermic ex vivo perfusion platform. Herein, we aim to compare pulsatile versus centrifugal (steady and uniform flow) perfusion with the goal of optimizing renal preservation with these devices. Materials and methods: Pig kidneys were procured following 30 min of warm ischemia by cross-clamping both renal arteries. Paired kidneys were cannulated and underwent either: oxygenated pulsatile or centrifugal perfusion using a hemoglobin oxygen carrier at room temperature with our ex vivo machine perfusion platform for 4 hr. Kidneys were reperfused with whole blood for 4 hr at 37° C. Renal function, pathology and evidence of inflammation were assessed post-perfusion. Results: Both pump systems performed equally well with organs exhibiting similar renal blood flow, and function post-reperfusion. Histologic evidence of renal damage using apoptosis staining and acute tubular necrosis scores was similar between groups. This was corroborated with urinary assessment of renal damage (NGAL 1) and inflammation (IL-6), as levels were similar between groups. Conclusion: In our porcine model with added warm ischemia simulating the effects of reperfusion after transplantation, pulsatile perfusion yielded similar renal protection compared with centrifugal perfusion kidney preservation. Both methods of perfusion can be used in ex vivo kidney perfusion systems.


Assuntos
Transplante de Rim , Rim , Preservação de Órgãos , Animais , Perfusão , Fluxo Pulsátil , Suínos
7.
Kidney Int ; 79(10): 1080-9, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21270767

RESUMO

Carbon monoxide (CO) can provide beneficial antiapoptotic and anti-inflammatory effects in the context of ischemia-reperfusion injury (IRI). Here we tested the ability of pretreating the kidney donor with carbon monoxide-releasing molecules (CORM) to prevent IRI in a transplant model. Isogeneic Brown Norway donor rats were pretreated with CORM-2 18 h before kidney retrieval. The kidneys were then cold-preserved for 26 h and transplanted into Lewis rat recipients that had undergone bilateral nephrectomy. Allografts from Brown Norway to Lewis rats were also performed after 6 h of cold ischemic time with low-dose tacrolimus treatment. All recipients receiving CORM-2-treated isografts survived the transplant process and had near-normal serum creatinine levels, whereas all control animals died of uremia by the third post-operative day. This beneficial effect was also seen in isografted Lewis recipients receiving kidneys perfused with CORM-3, indicating that CORMs have direct effects on the kidney. Pretreatment of human umbilical vein endothelial cells in culture with CORM-2 for 1 h significantly reduced cytokine-induced nicotinamide adenine dinucleotide phosphate-dependent production of superoxide, activation of the inflammation-relevant transcription factor nuclear factor-κB, upregulated expression of E-selectin and intercellular adhesion molecule-1 adhesion proteins, and leukocyte adhesion to the endothelial cells. Thus, CORM-2-derived CO protects renal transplants from IRI by modulating inflammation.


Assuntos
Transplante de Rim , Rim/irrigação sanguínea , Compostos Organometálicos/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Animais , Interferon gama/farmacologia , Transplante de Rim/mortalidade , NADP/fisiologia , NF-kappa B/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
8.
Can J Surg ; 54(6): 387-93, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21939606

RESUMO

BACKGROUND: To perform complete resection of locally advanced and recurrent rectal carcinoma, total pelvic exenteration (TPE) may be attempted. We identified disease-related outcomes and prognostic factors. METHODS: We conducted a single-centre review of patients who underwent TPE for rectal carcinoma over a 10-year period. RESULTS: We included 28 patients in our study. After a median follow-up of 35 months, 53.6% of patients were alive with no evidence of disease. The 3-year actuarial disease-free and overall survival rates were 52.2% and 75.1%, respectively. On univariate analysis, recurrent disease, preoperative body mass index greater than 30 and lymphatic invasion were poor prognostic factors for disease-free survival, and only lymphatic invasion predicted overall survival. Additionally, multivariate analysis identified lymphatic invasion as an independent poor prognostic factor for disease-free survival in this patient population with locally advanced and recurrent rectal carcinoma. CONCLUSION: Despite the significant morbidity, TPE can provide long-term survival in patients with rectal carcinoma. Additionally, lymphatic invasion on final pathology was an independent prognostic factor for disease-free survival.


Assuntos
Adenocarcinoma/cirurgia , Exenteração Pélvica , Neoplasias Retais/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
9.
Can J Surg ; 53(2): 93-102, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20334741

RESUMO

BACKGROUND: The disparity between the number of patients waiting for an organ transplant and availability of donor organs increases each year in Canada. Donation after cardiac death (DCD), following withdrawal of life support in patients with hopeless prognoses, is a means of addressing the shortage with the potential to increase the number of transplantable organs. METHODS: We conducted a retrospective, single-centre chart review of organs donated after cardiac death to the Multi-Organ Transplant Program at the London Health Sciences Centre between July 2006 and December 2007. In total, 34 solid organs (24 kidneys and 10 livers) were procured from 12 DCD donors. RESULTS: The mean age of the donors was 38 (range 18-59) years. The causes of death were craniocerebral trauma (n = 7), cerebrovascular accident (n = 4) and cerebral hypoxia (n = 1). All 10 livers were transplanted at our centre, as were 14 of the 24 kidneys; 10 kidneys were transplanted at other centres. The mean renal cold ischemia time was 6 (range 3-9.5) hours. Twelve of the 14 kidney recipients (86%) experienced delayed graft function, but all kidneys regained function. After 1-year follow-up, kidney function was good, with a mean serum creatinine level of 145 (range 107-220) micromol/L and a mean estimated creatinine clearance of 64 (range 41-96) mL/min. The mean liver cold ischemia time was 5.8 (range 5.5-8) hours. There was 1 case of primary nonfunction requiring retransplantation. The remaining 9 livers functioned well. One patient developed a biliary anastomotic stricture that resolved after endoscopic stenting. All liver recipients were alive after a mean follow-up of 11 (range 3-20) months. Since the inception of this DCD program, the number of donors referred to our centre has increased by 14%. CONCLUSION: Our initial results compare favourably with those from the transplantation of organs procured from donors after brain death. Donation after cardiac death can be an important means of increasing the number of organs available for transplant, and its widespread implementation in Canada should be encouraged.


Assuntos
Morte , Parada Cardíaca , Transplante de Rim , Transplante de Fígado , Doadores de Tecidos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Cuidados para Prolongar a Vida , Masculino , Pessoa de Meia-Idade , Ontário , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Tempo , Obtenção de Tecidos e Órgãos , Resultado do Tratamento , Suspensão de Tratamento , Adulto Jovem
10.
Transplantation ; 104(3): 482-489, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31568396

RESUMO

BACKGROUND: The optimal method of oxygen delivery to donor kidneys during ex vivo machine perfusion has not been established. We have recently reported the beneficial effects of subnormothermic (22°C) blood perfusion in the preservation of porcine donation after circulatory death kidneys. Since using blood as a clinical perfusate has limitations, including matching availability and potential presence of pathogen, we sought to assess hemoglobin-based oxygen carrier (HBOC-201) in oxygen delivery to the kidney for renal protection. METHODS: Pig kidneys (n = 5) were procured after 30 minutes of warm in situ ischemia by cross-clamping the renal arteries. Organs were flushed with histidine tryptophan ketoglutarate solution and subjected to static cold storage or pulsatile perfusion with an RM3 pump at 22°C for 4 hours with HBOC-201 and blood. Thereafter, kidneys were reperfused with normothermic (37°C) oxygenated blood for 4 hours. Blood and urine were subjected to biochemical analysis. Total urine output, urinary protein, albumin/creatinine ratio, flow rate, resistance were measured. Acute tubular necrosis, apoptosis, urinary kidney damage markers, neutrophil gelatinase-associated lipocalin 1, and interleukin 6 were also assessed. RESULTS: HBOC-201 achieved tissues oxygen saturation equivalent to blood. Furthermore, upon reperfusion, HBOC-201 treated kidneys had similar renal blood flow and function compared with blood-treated kidneys. Histologically, HBOC-201 and blood-perfused kidneys had vastly reduced acute tubular necrosis scores and degrees of terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling staining versus kidneys treated with cold storage. Urinary damage markers and IL6 levels were similarly reduced by both blood and HBOC-201. CONCLUSIONS: HBOC-201 is an excellent alternative to blood as an oxygen-carrying molecule in an ex vivo subnormothermic machine perfusion platform in kidneys.


Assuntos
Transplante de Rim/efeitos adversos , Soluções para Preservação de Órgãos/administração & dosagem , Preservação de Órgãos/métodos , Perfusão/métodos , Traumatismo por Reperfusão/prevenção & controle , Animais , Substitutos Sanguíneos/administração & dosagem , Substitutos Sanguíneos/química , Modelos Animais de Doenças , Hemoglobinas/administração & dosagem , Hemoglobinas/química , Humanos , Preservação de Órgãos/instrumentação , Soluções para Preservação de Órgãos/química , Oxigênio/análise , Oxigênio/metabolismo , Perfusão/instrumentação , Traumatismo por Reperfusão/etiologia , Sus scrofa , Isquemia Quente/efeitos adversos
11.
Clin Transplant ; 23(1): 96-100, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19200221

RESUMO

Recurrence of focal segmental glomerular sclerosis (FSGS) in the allograft following renal transplantation can be graft threatening. To assess risk factors associated with FSGS recurrence, we analyzed 22 patients with FSGS who underwent transplantation between 1996 and 2004. Five patients (Group I, 23%) developed FSGS post-transplantation. Of these patients, 60% had undergone bilateral nephrectomy (BN) for progressive disease compared with none of the patients that were free of recurrence (Group II) (p = 0.0006). Other factors linked with recurrent FSGS were time to first dialysis (Group I: 3.1 +/- 1.1 yr vs. Group II: 11.9 +/- 1.9 yr; p = 0.03), pre-transplant proteinuria (Group I: 7.0 +/- 1.8 g/d vs. Group II: 2.5 +/- 0.7 g/d; p = 0.02), young age at transplantation (p = 0.09) and female sex (Group I: 80% vs. Group II: 24%; p = 0.021). Eighty percent of Group I patients received a living related transplant vs. 24% in Group II (p = 0.021). All grafts continue to function at last follow-up with comparable serum creatinines. Overall, post-transplant FSGS recurrence may be associated with BN, severity of pre-transplant FSGS, female gender, and living donation. These patients should be monitored closely for early recurrence and may benefit from early plasmapheresis to restore and facilitate long-term graft function.


Assuntos
Função Retardada do Enxerto/prevenção & controle , Glomerulosclerose Segmentar e Focal/diagnóstico , Rejeição de Enxerto/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Creatinina/sangue , Feminino , Seguimentos , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia , Plasmaferese , Prognóstico , Recidiva , Diálise Renal , Fatores de Risco , Transplante Homólogo
12.
Clin Transplant ; 23(1): 9-15, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18713265

RESUMO

INTRODUCTION: To assess the efficacy of calcineurin inhibitor (CNI)-free immunosuppression vs. calcineurin-based immunosuppression in patients receiving expanded criteria donor (ECD) kidneys. PATIENT AND METHODS: Thirteen recipients of ECD kidneys were enrolled in this pilot study and treated with induction therapy and maintained on sirolimus, mycophenolate mofetil (MMF) and prednisone. A contemporaneous control group was randomly selected comprised of 13 recipients of ECD kidneys who had been maintained on CNI plus MMF and prednisone. RESULTS: For the study group vs. the control group, two-yr graft survival was 92.3% vs. 84.6% (p = NS), two-yr patient survival was 100% vs. 92.3% (p = NS) and the acute rejection rates were 23% vs. 31% (p = NS), respectively. Renal function was significantly better in the study group compared with control up to the six-month mark, after which, it remained numerically but not statistically significant. Complications were more common in the study group, but serious adverse events requiring discontinuation were rare. CONCLUSION: This pilot study demonstrates that CNI-free regimens can be safely implemented in patients receiving ECD kidneys with excellent two-yr patient and graft survival and good renal allograft function. Longer follow-up in larger randomized controlled trials are necessary to establish these findings.


Assuntos
Inibidores de Calcineurina , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Falência Renal Crônica/prevenção & controle , Transplante de Rim , Estudos de Casos e Controles , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Terapia de Imunossupressão , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Projetos Piloto , Prednisona/uso terapêutico , Estudos Prospectivos , Sirolimo/uso terapêutico , Taxa de Sobrevida , Resultado do Tratamento , Listas de Espera
13.
Transl Androl Urol ; 8(2): 118-125, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31080771

RESUMO

With increasing demands for 'less than ideal' kidneys for transplantation, machine perfusion of kidneys has been utilized to improve the preservation of kidneys during storage. Hypothermic machine perfusion (HMP) of renal allografts has been shown to reduce delayed graft function rates in both expanded criteria and donation after cardiac death renal allografts. However, the beneficial impact upon long-term graft function is unclear. There has been emerging evidence that both subnormothermic (room temperature) and normothermic machine perfusion (NMP) of allografts have beneficial effects with regards to early graft function, survival and injury in pre-clinical and early clinical studies. Additionally, machine perfusion allows functional assessment of the organ prior to transplantation. Ultimately, the greatest benefit of machine perfusion may be the ability to treat the organ with agents to protect the graft against ischemia reperfusion injury, while awaiting transplantation.

14.
Kidney Int Rep ; 4(9): 1323-1333, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517151

RESUMO

INTRODUCTION: The current methods of preserving donor kidneys in nonoxygenated cold conditions minimally protect the kidney against ischemia-reperfusion injury (IRI), a major source of complications in clinical transplantation. However, preserving kidneys with oxygenated perfusion is not currently feasible due to the lack of an ideal perfusion mechanism that facilitates perfusion with blood at warm temperature. Here, we have designed an innovative renal pump circuit system that can perfuse blood or acellular oxygen carrier under flexible temperatures, pressures, and oxygenation. We have tested this apparatus to study optimal conditions of storage of our porcine model of donation after cardiac death (DCD) kidneys. METHODS: Porcine kidneys were retrieved after 30 minutes of cross-clamping renal pedicles in situ. Cessation of blood mimics postcardiac death in humans and simulates DCD warm ischemic injury. Procured kidneys were flushed and subjected to static cold storage (SCS) for 4 hours. For warm perfusion, kidneys were cannulated for pulsatile oxygenated perfusion with blood:PlasmaLyte for 4 hours at 15 °C, 22 °C, and 37 °C. To mimic posttransplant scenario, all kidneys were reperfused with blood for an additional 4 hours at 37 °C. RESULTS: Compared with all other groups, 22 °C perfusion resulted in significant reduction of acute tubular necrosis (ATN), apoptosis, kidney damage markers, Toll-like receptor signaling, and cytokine production. It was associated with maximal renal blood flow and urine output. Kidneys stored at 15 °C thrombosed within 2 hours under this condition. Martius Scarlet Blue staining confirmed that 22 °C was the optimal temperature to minimize hemorrhage and blood clots. CONCLUSION: Our novel study shows that oxygenated perfusion at near-room-temperature provides optimal donor kidney storage conditions.

15.
Transplantation ; 102(7): 1066-1074, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29677080

RESUMO

BACKGROUND: Carbon monoxide (CO) inhalation protects organ by reducing inflammation and cell death during transplantation processes in animal model. However, using CO in clinical transplantation is difficult due to its delivery in a controlled manner. A manganese-containing CO releasing molecules (CORM)-401 has recently been synthesized which can efficiently deliver 3 molar equivalents of CO. We report the ability of this anti-inflammatory CORM-401 to reduce ischemia reperfusion injury associated with prolonged cold storage of renal allografts obtained from donation after circulatory death in a porcine model of transplantation. METHODS: To stimulate donation after circulatory death condition, kidneys from large male Landrace pig were retrieved after 1 hour warm ischemia in situ by cross-clamping the renal pedicle. Procured kidneys, after a brief flushing with histidine-tryptophan-ketoglutarate solution were subjected to pulsatile perfusion at 4°C with University of Wisconsin solution for 4 hours and both kidneys were treated with either 200 µM CORM-401 or inactive CORM-401, respectively. Kidneys were then reperfused with normothermic isogeneic porcine blood through oxygenated pulsatile perfusion for 10 hours. Urine was collected, vascular flow was assessed during reperfusion and histopathology was assessed after 10 hours of reperfusion. RESULTS: We have found that CORM-401 administration reduced urinary protein excretion, attenuated kidney damage markers (kidney damage marker-1 and neutrophil gelatinase-associated lipocalin), and reduced ATN and dUTP nick end labeling staining in histopathologic sections. CORM-401 also prevented intrarenal hemorrhage and vascular clotting during reperfusion. Mechanistically, CORM-401 appeared to exert anti-inflammatory actions by suppressing Toll-like receptors 2, 4, and 6. CONCLUSIONS: Carbon monoxide releasing molecules-401 provides renal protection after cold storage of kidneys and provides a novel clinically relevant ex vivo organ preservation strategy.


Assuntos
Monóxido de Carbono/farmacologia , Transplante de Rim/efeitos adversos , Manganês/química , Preservação de Órgãos/métodos , Traumatismo por Reperfusão/prevenção & controle , Adenosina/química , Aloenxertos/patologia , Alopurinol/química , Animais , Monóxido de Carbono/metabolismo , Isquemia Fria/efeitos adversos , Glutationa/química , Insulina/química , Rim/patologia , Masculino , Modelos Animais , Preservação de Órgãos/instrumentação , Soluções para Preservação de Órgãos/química , Rafinose/química , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Sus scrofa
16.
J Endourol ; 21(6): 625-7, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17638559

RESUMO

We describe laparoscopic partial nephrectomy in a patient with autosomal dominant polycystic kidney disease. Reconstruction was accomplished despite the abnormal quality of the renal tissue. In this patient, with borderline renal function, the warm-ischemia time (50 minutes) was longer than the normally accepted time and was poorly tolerated. In order to avoid the damaging effects of warm ischemia, alternatives to hilar clamping should be employed, and open partial nephrectomy should be considered.


Assuntos
Laparoscopia/métodos , Nefrectomia/métodos , Rim Policístico Autossômico Dominante/cirurgia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Cuidados Pós-Operatórios , Tomografia Computadorizada por Raios X
17.
Can J Urol ; 14(3): 3571-6, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17594748

RESUMO

PURPOSE: Laparoscopic pyeloplasty is a technically challenging procedure. Currently, several robotic surgical systems exist to overcome laparoscopic technical challenges confronted during pyeloplasty. We present a clinical comparison between three robotic surgical systems (Aesop, Zeus and da Vinci) in assisting laparoscopic pyeloplasty procedures. METHODS: From January 2002 to August 2005, 32 dismembered laparoscopic pyeloplasties were performed using three robotic surgical systems. The results of the initial six, five and nine laparoscopic robotic pyeloplasty procedures performed using the Aesop, Zeus and da Vinci platforms were compared. Data relating to the subsequent 12 pyeloplasties using the da Vinci system were also analyzed. RESULTS: The da Vinci robot required significantly more time to set up initially than the Aesop platform (12.5 min versus 39 min, p < 0.05) but the time was similar to that for the Zeus robot. Despite the longer setup time, laparoscopic robotic pyeloplasties performed using the da Vinci robot required 168 min and 35 min for operating time and anastomotic time, respectively. This was significantly faster than that for Aesop (262 min and 75 min) and Zeus (225 min and 71 min) robots (p < 0.05). There were no intra-operative complications. There was only one postoperative complication in the Zeus group involving a delayed urine leak. Narcotic requirements were low and duration of hospital stay was short for all patients. CONCLUSIONS: We show that not all advanced robotic platforms are equal. In this study, procedures performed using the da Vinci robotic system resulted in decreased anastomotic and operating times. With emerging surgical technologies, the role of the robot in surgery continues to be defined.


Assuntos
Laparoscopia/métodos , Robótica/instrumentação , Obstrução Ureteral/cirurgia , Cirurgia Vídeoassistida/instrumentação , Adulto , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Resultado do Tratamento
18.
Can Urol Assoc J ; 11(10): 344-349, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29382448

RESUMO

INTRODUCTION: The relative impact of preoperative and perioperative variables on renal function following partial nephrectomy (PN) is controversial. To further investigate, we assess the effects of tumour complexity, warm ischemic time (WIT), and volume of resected renal parenchyma on ipsilateral renal function (IRF) outcomes following minimally invasive PN. METHODS: Of patients who underwent laparoscopic or robotic-assisted PN between 2002 and 2011 at our institution, 99 met our inclusion criteria. The effects of preoperative tumour complexity (using RENAL nephrometry score), perioperative WIT, and pathological tumour volumes on ipsilateral renal function preservation (%IRF) were analyzed. %IRF was defined as the proportion of postoperative to preoperative ipsilateral renal function calculated using MAG3 nuclear renography. RESULTS: Increasing RENAL nephrometry score (RNS) and WIT were independently predictive of inferior %IRF at 6-12-week postoperative followup in univariate and multivariate analyses. Of RNS properties, masses that were endophytic, near the collecting system, or central in location were associated with inferior %IRF, with nearness to collecting system as the strongest predictor; however, RNS was no longer predictive of %IRF in cases requiring more than 30 minutes of WIT. CONCLUSIONS: In renal masses amenable to resection by minimally invasive PN, longer WIT was the most important predictor of inferior %IRF. Although increasing RNS score influenced %IRF, the overall clinical significance of RNS is limited and should not influence operative decision-making in efforts to preserve renal function. Furthermore, small volumes of renal parenchyma can be safely resected without impairment of long-term IRF.

19.
Transplantation ; 81(1): 117-20, 2006 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-16421486

RESUMO

BK virus associated nephropathy (BKVAN) has emerged as an important cause of renal allograft dysfunction and graft loss. Although several treatment strategies have been proposed, the rate of graft loss remains high. We studied the outcome of renal transplant patients with BKVAN treated with IVIG. After 11.4 +/- 3.9 months (mean +/- SEM) from the time of transplantation, 8 renal allograft recipients were diagnosed with BKVAN. In addition to a reduction of immunosuppressive therapy, patients received 2 g/kg IVIG. After a mean follow-up of 15 months, all except one patient are currently off dialysis. In summary, after IVIG therapy, 88% of patients still have functioning grafts, although renal function continues to be impaired. The benefit of concomitant IVIG and reduction of immunosuppressive therapy in BKVAN needs to be further addressed in randomized, multicentered trials.


Assuntos
Vírus BK/fisiologia , Imunoglobulinas Intravenosas/uso terapêutico , Nefropatias/complicações , Nefropatias/tratamento farmacológico , Transplante de Rim , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/tratamento farmacológico , Adulto , Creatina/sangue , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Humanos , Imunoglobulinas Intravenosas/imunologia , Nefropatias/imunologia , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/imunologia , Fatores de Tempo , Transplante Homólogo/imunologia , Infecções Tumorais por Vírus/tratamento farmacológico , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia
20.
JSLS ; 10(4): 535-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17575777

RESUMO

Percutaneous approaches to upper tract urothelial cancers have been performed in patients unsuitable for radical nephroureterectomy. We present the case of an 82-year-old man with significant comorbidities including dependency on a cardiac pacemaker. Without deactivating the pacemaker, we used bipolar cautery to percutaneously resect a large upper tract urothelial tumor in the renal pelvis. Bipolar cautery is a suitable method of percutaneous or transurethral resection in patients who are pacemaker dependent.


Assuntos
Eletrocoagulação , Neoplasias Renais/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Idoso de 80 Anos ou mais , Comorbidade , Diagnóstico Diferencial , Humanos , Neoplasias Renais/diagnóstico , Masculino , Neoplasias da Bexiga Urinária/diagnóstico
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