Clinical characteristics and long-term outcomes of patients undergoing combined heart-kidney transplantation: a single-center experience.

BACKGROUND: The purpose of the study was to describe clinical characteristics and long-term survival of patients undergoing combined heart-kidney transplant in a single center. METHODS: We conducted a retrospective analysis of 22 consecutive patients who underwent combined heart-kidney transplant at our institution between 1995 and 2013. Long-term outcomes were analyzed by means of the Kaplan-Meier method. RESULTS: Four patients underwent re-do transplant (2 cardiac re-transplants, 1 kidney re-transplant, and 1 combined heart-kidney re-transplant). Most frequent underlying cardiac conditions were coronary artery disease (54%), dilated cardiomyopathy (23%), and chronic rejection of a previous heart graft (18%). Known causes of chronic renal dysfunction were nephroangioesclerosis (23%), drug-related toxicity (14%), and Wegener granulomatosis (5%). Non-specified chronic renal dysfunction was present in 50% patients. In-hospital postoperative mortality rate was 5 of 22 (23%). Causes of early death were directly related to kidney transplant surgery in 4 of 5 (80%) patients. Among the remaining 17 patients who surmounted the postoperative period, long-term survival rates 1 year, 5 years, and 10 years after HKT were 88%, 82%, and 65%, respectively. Over a mean follow-up of 6.7 ± 6.4 years, cumulative incidences of cytomegalovirus infection, coronary allograft vasculopathy, malignancy, and acute cardiac graft rejection were 41%, 6%, 24%, and 41%, respectively. There was no episode of acute renal graft rejection. At the end of follow-up, all survivors (n = 11) were in functional New York Heart Association class I. Mean creatinine serum level was 1.68 mg/dL. CONCLUSIONS: In our experience, combined heart-kidney transplant is a feasible therapeutic option that yielded favorable long-term outcomes, with a low cumulative incidence of cardiac graft dysfunction. These results were obtained at the expense of a significant risk of early postoperative mortality, which was mainly related to complications of kidney transplant surgery.

[Renal xenotransplant. Acute vascular rejection]. / Xenotrasplante renal. El rechazo vascular agudo.

INTRODUCTION AND OBJECTIVES: Organ transplant is nowadays a usual and succesful practice, although with limited application due to the lack of organs. Yearly thousands of patients get access to the waiting list and finally will death while they are waiting for an organ. In the U.S.A., 2005 waiting list for kidneys, heart, liver lung and pancreas was around 94.419. Number of transplants performed was 27.966 and died patients while waiting for an organ, 41.392 (1). Pig xenotransplant is one of the possibilities to ameliorate the lack of organs for transplant. Arrangement of pigs with different genetic modifications generated great expectatives on the use of these organs in clinics. Although preclinical experimental studies with kidneys reached prolonged survivals, these are really insufficient to go on with the clinical appliance. Hyperacute rejection produces destruction of the organ immediately. This problem could be pharmacologically precluded in xeno-transplant. However, acute rejection or vascular rejection usually produces the lost of the implant. New inmunosuppresive schedules delay significantly rejection, but not definitively. Xenotransplant as a therapeutic option introduces important scientific problems, as well as ethical and social. This paper reports a summary of our experience in renal xenotransplant and the management of acute rejection. MATERIAL AND METHODS: Twenty xenotransplants from transgenic pig (hDAF) as donor to babuine as receptor. Average weight of the animals ranged 11.4-75 kgrs and babuines 10-26 kg. Xenograft average weight ranged 39-160 grs. Implant was performed to aorta and cava. Four inmunosupressive schedules were used. RESULTS: Average survival was 7-9 days. Final Histological findings are described. Changes observed were secondary to acute tubular necrosis mixed with changes due to acute rejection. Three grafts were lost due to technical major problems. CONCLUSIONS: Although we have observed some promising results, xenotransplant is a very difficult problem to solve in the long-term. A lot of research is still needed-.

Xenotrasplante renal. El rechazo vascular agudo / Renal xenotransplant. Acute vascular rejection

Introducción y objetivos: El trasplante de órganos es hoy una práctica habitual y de éxito, pero de aplicación limitada, debido a la insuficiencia de órganos. Anualmente miles de pacientes en lista de espera fallecen, esperando un órgano. En EEUU en el 2005 la lista de espera para trasplantes de órganos, riñón, corazón, hígado, pulmón, páncreas era de 94.419. El número de trasplantes realizados fue de 27.966 y el de fallecidos esperando un órgano 41.392. (1) El xenotrasplante de órganos de cerdo es una de las esperanzas para aliviar la falta de órganos para el trasplante. La disponibilidad de cerdos con distintas modificaciones genéticas, creó grandes expectativas sobre una pronta utilización clínica de los mismos, sin embargo, aunque los estudios experimentales preclínicos con el riñón han alcanzado supervivencias prolongadas, estas son insuficientes para dar el paso a la fase clínica. El rechazo hiperagudo (RH) con destrucción del órgano de forma inmediata, habitual en el trasplante de órganos entre especies distintas filogenéticamente (trasplante discordante) puede en la actualidad ser evitado sin embargo, la aparición de un posterior rechazo humoral agudo (RHA) también llamado rechazo vascular agudo (RVA) o xenorechazo agudo retardado, da lugar al fracaso del xenotrasplante. La utilización de distintas pautas de inmunosupresión han conseguido retrasar de forma significativa este rechazo, pero no lo previenen de forma sistemática. El xenotrasplante como opción terapéutica plantea importantes problemas científicos, éticos y sociales. En este artículo exponemos un resumen de nuestra experiencia en xenotrasplante renal y comentamos los problemas del RVA. Material y método: Se han practicado 20 xenotrasplantes renales de cerdo transgénico hDAF (donante) a babuino (receptor). El peso de los cerdos osciló entre 11,400 y 75 kg. y el de los babuinos entre 10 y 26,500 kg. El peso del xenoinjerto, riñón del cerdo, osciló entre 39 y 160 g. Resultados: La supervivencia media de los animales estuvo entre 7-9 días. El estudio histológico final de los injertos mostró cambios secundarios a necrosis tubular aguda mezclados con alteraciones propias de rechazo agudo. Tres injertos se perdieron por problemas técnicos mayores. Conclusiones: Aunque hemos observado resultados prometedores, el xenotrasplante es una cuestión de gran dificultad, especialmente a largo plazo. Se precisa aún en la actualidad de mucha actividad investigadora en este campo

Introduction and objectives: Organ transplant is nowadays a usual and succesful practice, although with limited application due to the lack of organs. Yearly thousands of patients get access to the waiting list and finally will death while they are waiting for an organ. In USA, 2005 waiting list for kidneys, heart, liver lung and pancreas was around 94.419. Number of transplants performed was 27.966 and died patients while waiting for an organ, 41.392 (1). Pig xenotransplant is one of the possibilities to ameliorate the lack of organs for transplant. Arrangement of pigs with different genetic modifications generated great expectatives on the use of these organs in clinics. Although preclinical experimental studies with kidneys reached prolonged survivals, these are really insufficient to go on with the clinical appliance. Hyperacute rejection produces destruction of the organ immediately. This problem could be pharmacologically precluded in xenotransplant. However, acute rejection or vascular rejection usually produces the lost of the implant. New inmunosuppresive schedules delay significantly rejection, but not definitively. Xenotransplant as a therapeutic option introduces important scientific problems, as well as ethical and social. This paper reports a summary of our experience in renal xenotransplant and the management of acute rejection. Material and methods: Twenty xenotransplants from transgenic pig (hDAF) as donor to babuine as receptor. Average weight of the animals ranged 11.4-75 kgrs and babuines 10-26 kg. Xenograft average weight ranged 39-160 grs. Implant was performed to aorta and cava. Four inmunosupressive schedules were used. Results: Average survival was 7-9 days. Final Histological findings are described. Changes observed were secondary to acute tubular necrosis mixed with changes due to acute rejection. Three grafts were lost due to technical major problems. Conclusions: Although we have observed some promising results, xenotransplant is a very difficult problem to solve in the long-term. A lot of research is still needed

Incidence of cardiovascular events in renal transplant recipients and clinical relevance of modifiable variables.

INTRODUCTION: The aims of this study were to quantify the incidence of cardiovascular events and identify the clinical relevance of modifiable variables. MATERIALS AND METHODS: The 1729 patients who underwent renal transplantation from 1981 to 2004 were evaluated in an observational, prospective follow-up study with no exclusions. A cardiovascular event was defined as the presence of ischemic cardiac disease (chest pain-myocardial infarction), cardiac insufficiency, arrhythmia (auricular fibrillation), peripheral vascular disease, or cerebrovascular accident. A survival analysis was performed using the Kaplan-Meier method. A Cox regression analysis was applied. Having identified the predictive variables of cardiovascular events, the population attributable fraction (PAF) and the etiological fraction (EF) were estimated. A risk score was calculated using Cox regression coefficients. RESULTS: The accumulated incidence of cardiovascular events was 22.2%, with an incidence rate of 468.6 x 10,000 follow-up years. From the Cox regression model, the variables with an independent effect close to statistical significance to predict cardiovascular events were as follows: recipient age (RR = 1.05), smoking at the time of the transplantation (RR = 2.1), left ventricle hypertrophy during follow-up (RR = 2.4), prior diabetes mellitus, and obesity (body mass index >or=30). At the time of transplantation, 41.7% were smokers. During follow-up, a clear difference was observed in the incidence rates of cardiovascular events between smokers and nonsmokers. Similar phenomena were observed for left ventricle hypertrophy and obesity. The resulting scores ranged between 0 and 5. The area under the ROC curve of the score for the prediction of cardiovascular events was 0.74. CONCLUSION: The incidence of cardiovascular events was consistent with the literature. A series of modifiable variables of major clinical relevance exist to decrease the frequency of cardiovascular events following renal transplantation.

Evaluation of renal grafts in patients with lupus nephritis as cause of end-stage renal disease.

INTRODUCTION: Kidney transplantation is the best option in end-stage renal disease (ESRD). For many years patients affected with lupus nephritis have had poor graft results. However, this has been changing over recent years with the development of new immunosuppressive drugs and a better comprehension of the natural evolution of the entity. METHODS: We studied 20 patients with lupus nephritis who received 22 kidney grafts: 15 women and five men (n = 11) who were treated with cyclosporine or with tacrolimus (n = 11). Secondary immunosuppression included mycophenolate match (MMF) (n = 13) or azathioprine (n = 9). We analyzed human leukocyte antigen, cold ischemia time, acute tubular necrosis, creatinine, cholesterol, triglycerides, glucose, blood pressure, acute rejection episodes, immunosuppression, infections, disease recurrences, as well as graft and patient survival. RESULTS: After a mean cold ischemia time of 22 +/- 4 hours, nine patients displayed delayed graft function of an average duration 9 +/- 4 days. At 36 +/- 35 months nine grafts were lost: two due to acute rejection; five to chronic allograft nephropathy; and two to venous thrombosis. One patient died of hemorrhagic shock. There were five cytomegalovirus infections. Graft survival was dependent on the type of secondary immunosuppression, incidence of acute rejection episodes and occurrence of delayed graft function. CONCLUSIONS: We found no clinical recurrence of lupus nephritis after transplantation and a low incidence of complications, although there was a trend toward thrombosis. The presence of delayed graft function, episodes of acute rejection, and receiving azathioprine instead of MMF as secondary immunosuppression were associated with poorer graft survival.

Basiliximab (Simulect) in renal transplantation with high risk for delayed graft function.

BACKGROUND: Basiliximab (Simulect) is effective in reducing episodes of acute rejection in renal transplantation. Delayed graft function (DGF) predisposes to acute rejection and shortens graft survival. The aim of this study was to determine the effects of basiliximab in renal transplantation recipients at high risk for DGF. METHODS: We studied 87 patients (mean age, 59 years), 42 of whom received basiliximab, 20 mg before transplantation and 20 mg on day 4. This cohort was compared with 45 patients without basiliximab. All received cyclosporine (51%) or tacrolimus (49%), mycophenolate mofetil, and steroids. DGF was defined as the requirement for dialysis within the first week after transplantation or failure to improve preexisting renal function. High-risk factors for DGF were cold ischemia time, recipient and donor age, non-heart-beating donor, HLA matching, and panel reactive antibody (PRA). RESULTS: The incidence of DGF was 18 (43%) in the basiliximab group versus 28 (62%) in the other patients (P = .07). When allografts from non-heart-beating donors were excluded, this incidence was 14 (38%) in the basiliximab group versus 28 (62%) in the other patients (P = .04). Regression analysis showed basiliximab to be a protective factor: 0.26 (range, 0.09-0.76). Basiliximab was well tolerated, and complications were similar in both groups. CONCLUSIONS: Basiliximab reduced the incidence of DGF in patients who received a high-risk allograft. It was well tolerated, and no adverse events were reported. The use of basiliximab may be considered in patients receiving an allograft who are at high risk for DGF.

[Renal xenotransplantation from hDAF pig to baboon. Experience and review]. / Xenotrasplante renal cerdo hDAF-babuino. Experiencia y revisión.

UNLABELLED: The renal xenotransplant could be the solution on the demand of organs for transplantation. We present here our experience and review the actual status of the xenotransplant. METHODS: We have done 20 xenotransplants from transgenic pig h DAF to baboons, with four protocols of immunosuppression. All the hosts were treated with GAS 914. Group A: Cyclophosphamide, Cyclosporine, Mycophenolate, and Steroids (n = 10). Group B: Cyclophosphamide, Cyclosporine, FTY 720, and Steroids (n = 3). Group C: Basiliximab, Cyclosporine, Mycophenolate, and Steroids (n = 3). Group D: Basiliximab, FTY 720, Everolymus, and Steroids (n = 4). RESULTS: The duration of the xenografts ranged between 1 and 31 days. The function of the xenografts in relation to the type of immunosuppression were not significantly different: A) 7 days, B) 8 days, C) 8 days, and D) 9 days. CONCLUSIONS: 1. The cold ischemic time of the graft, has influence in the initial function of the kidneys but not in the evolution and duration of the graft. 2. The hyperacute rejection has been overcome with the utilization of transgenic pigs. The graft failure was due to acute humoral rejection that was not aborted by the actual inmunosupressors. 3. It is necessary to develop new immunosuppression protocols, through new knowledge of their pharmacology and the physiology of the xenografts, and at the same time it is important to avoid the potential risk of transmission of animal infections.

Influence of the management of asystolic donors on kidney transplantation outcome.

Two methods of donor management were analysed, namely, with and without in situ cooling perfusion of the kidney in an attempt to determine the optimal management and preservation methods for asystolic kidney donors. The group of recipients of in situ cooling perfusion kidneys showed more days of oliguria (P <.05), needed more dialysis sessions (P <.05), and showed no transplant function during the first week after surgery. This group also had a greater probability of acute rejection (P =.071) and a higher rate of nonfunctioning grafts (P =.09). We conclude that in situ cooling perfusion of asystolic kidney donors impairs graft function.

Xenotrasplante renal cerdo hDAF-babuino. Experiencia y revisión / Renal xenotrasplantation of HDAF pig to baboons. Experience and review

INTRODUCCIÓN: El xenotrasplante renal puede representar la solución a la creciente demanda de órganos. Presentamos nuestra experiencia y revisamos el estado actual del xenotrasplante. MATERIAL Y MÉTODO: Hemos realizado 20 xenotrasplantes de riñón de cerdo transgénico hDAF a babuino con cuatro protocolos de inmunosupresión. Todos los receptores recibieron GAS 914.Grupo A: Ciclofosfamida, Ciclosporina, Micofenolato y Corticosteroides (n=10).Grupo B: Ciclofosfamida, Ciclosporina, FTY 720 y Corticosteroides (n=3).Grupo C: Basiliximab, Ciclosporina, FTY 720 y Corticosteroides (n=3).Grupo D: Basiliximab, FTY 720, Everolimus y Corticosteroides (n=4). RESULTADOS: La supervivencia de los xenoinjertos osciló entre 1 y 31 días. La supervivencia en relación con los protocolos de inmunosupresión no fue significativamente diferente: A) 7 días, B) 8días, C) 8 días, D) 9 días. CONCLUSIONES: 1. Los tiempos de isquemia fría influyen en la función inicial de los riñones, no en su evolución final. 2. El rechazo hiperagudo ha sido superado con la utilización de cerdos transgénicos, produciéndose el fracaso por rechazo humoral agudo, no controlado con los protocolos de inmunosupresión actuales. 3. Es preciso investigar y desarrollar otros protocolos de inmunosupresión que nos permitan un mejor conocimiento de la fisiología del xenoinjerto y de su potencial riesgo de transmisión de enfermedades (AU)

SUMMARY: The renal xenotrasplant could be the solution on the demand of organs for transplantation. We present here our experience and review the actual status of the xenotransplant. METHODS: We have done 20 xenotransplants from transgenic pig h DAF to baboons, with four protocols of inmunosupression. All the hosts were treated with GAS 914.Group A: Cyclophosphamide, Cyclosporine, Mycophenolate, and Steroids (n=10).Group B: Cyclophosphamide, Cyclosporine, FTY 720, and Steroids (n=3). Group C: Basiliximab, Cyclosporine, Mycophenolate, and Steroids (n=3). Group D: Basiliximab, FTY 720, Everolymus, and Steroids (n=4). RESULTS: The duration of the xenografts ranged between 1 and 31 days. The function of the xenografts in relation to the type of inmunosupression were not significantly different: A) 7 days, B) 8 days, C) 8 days, and D) 9 days. CONCLUSIONS: 1. The cold ischemic time of the graft, has influence in the initial function of the kidneys but not in the evolution and duration of the graft. 2. The hyperacute rejection has been overcome with the utilization of transgenic pigs. The graft failure was due to acute humoral rejection that was not aborted by the actual inmunosupressors. 3. It is necessary to develop new inmunosupression protocols, through new knowledge of their pharmacology and the physiology of the xenografts, and at the same time it is important to avoid the potential risk of transmission of animal infections (AU)

[Echo-guided biopsy in renal transplant]. / Biopsia ecodirigida en el trasplante renal.

A prospective study of 64 biopsies was undertaken to determine the efficacy of ultrasound-guided biopsy of renal grafts. All the biopsies were performed using real-time ultrasound guidance and a Tru-Cut biopsy needle. Sixty-two (97%) of the biopsies were diagnostic; a total of 85 punctions (mean 1.3) were performed. Forty-seven (73.4%) biopsies contained cortical issue, 15 (23.4%) cortical and medullary, and 2 (3.2%) medullary tissue alone. Mild hematuria was observed in 8 (12%) and there were no major complications. Four of the 8 cases (50%) with hematuria required dialysis, while the remaining 4 (50%) did not (p > 0.05). Concerning the type of tissue obtained and the complications, 5 (62.5%) of the patients whose biopsies contained medullary tissue presented complication (p < 0.05) ascribable to the depth of the punction. The mean number of biopsy punctions with hematuria was 1.5 (p < 0.05). In our view, ultrasound-guided biopsy is a highly effective technique for obtaining valid biopsy specimens of the renal graft, which reduces the risk of complications in this percutaneous procedure.

[Renal transplantectomy]. / Trasplantectomia renal.

During the first ten years (1981-1990) of our organ transplantation program a total of 395 Renal Transplants (RTx) have been carried out in our Unit, 90 of which in 88 patients had to be subsequently transplantectomized. In 32 of them the reason was acute rejection (35%) including 7 renal rhexis, and in 30 chronic rejection (33%) (1 rhexis). There were 22 (24%) (1 rhexis) vascular complications leading to such procedure. The technique was chosen mainly depending on the amount of time elapsed between transplantation and transplantectomy, performing 47 subcapsular and 43 extracapsular manoeuvres. The complications developed were 7 (7.7%), mostly haemorrhagic. Our attitude when faced with non-functioning grafts due to chronic rejection is the complete withdrawal of immunosuppression performing transplantectomy only in the event of arterial hypertension or in the presence of symptoms of acute rejection overimposition.