Retransplant Group Research Articles

Selective Retransplant After Graft Loss to Nonadherence: Success with a Second Chance

Nonadherence (NA) is a difficult posttransplant problem that can lead to graft loss. A retransplant is controversial because of a fear of recurrent NA. We reviewed our center's data base and identified 114 kidney recipients who lost their graft to overt NA; of this group, 35 (31%) underwent a retransplant after a thorough reevaluation. We compared this NA retransplant group to a control group of second transplant recipients who did not lose their first graft to overt NA (non-NA) (n = 552). After 8 years of follow-up, we found no significant differences between the groups in actuarial graft or patient survival rates, renal function, or the incidence of biopsy-proven chronic rejection. However, 5 of 35 (14%) NA recipients versus 10 of 552 (2%) non-NA recipients lost their retransplant to NA (p = 0.0001). Twenty of 35 (57%) of the NA group exhibited repeat NA behavior after retransplant. We conclude that prior graft loss to NA is associated with increased graft loss to NA after retransplant. However, the majority of NA retransplant recipients did well-with overall long-term outcomes similar to those of the non-NA group. With careful patient selection and aggressive intervention, prior overt NA should not be an absolute contraindication to retransplantation.

Cardiac retransplantation: is it justified in times of critical donor organ shortage? Long-term single-center experience☆

Survival after heart transplantation has improved significantly over the last decades. There are a growing number of patients that require cardiac retransplantation because of chronic allograft dysfunction. With regard to the critical shortage of cardiac allograft donors the decision to offer repeat heart transplantation must be carefully considered. Since 1983 a total of 807 heart transplantations have been performed at our institution. Among them 41 patients received cardiac retransplantation, 18 patients because of acute graft failure and 23 because of chronic graft failure. Data were analyzed for demographics, morbidity and risk factors for mortality. The acute and chronic retransplant group was compared to those patients undergoing primary transplantation. The mean interval between primary transplantation and retransplantation was 1.9 days in the acute and 6.7 years in the chronic retransplant group. Mean follow-up was 6.9 years. Baseline characteristics were similar in the primary and retransplant group. Actuarial survival rates at 1, 3, 5 and 7 years after primary cardiac transplantation compared to retransplantation were 83, 78, 72 and 64% vs 53, 50, 47 and 36%, respectively (p<0.001). Early mortality after acute retransplantation was significantly higher compared to late retransplantation (10/18, 55.6% vs 4/23, 17.4%, p=0.011). Major causes of death were acute and chronic rejection, infection and sepsis. Cardiac retransplantation is associated with lower survival rates compared to primary transplantation. However, results after retransplantation in chronic graft failure are significantly better compared to acute graft failure. Therefore, we consider cardiac retransplantation in chronic graft failure a justified therapeutic option. In contrast, patients with acute graft failure seem to be inappropriate candidates for cardiac retransplantation.

Risk Factors for Changes in Bone Mineral Density and the Effect of Antiosteoporosis Management After Renal Transplantation

Using the pretransplant bone mineral density (BMD) data records of renal recipients, we retrospectively examined risk factors affecting posttransplant changes in BMD and the effect of antiosteoporosis management. For 294 kidney transplant recipients from January 1996 to September 2003, BMD values were expressed as spine and femur T-scores. Gender, age, pretransplant diabetes, blood type compatibility, mode and duration of dialysis, and previous transplantation were considered to be variables affecting BMD changes. T-test or ANOVA was used to compare risk factors. At the time of transplantation, mean spine T-scores were significantly lower among the retransplant group. Mean femur T-scores were significantly lower among the retransplant group, older patients (older than 45 years), and female recipients. Prolonged hemodialysis (>12 months) and retransplant were risk factors for BMD loss during the first year posttransplant. Early application of antiosteoporosis management was effective to ameliorate posttransplant BMD loss. However, antiosteoporosis management after 1 year posttransplant was relatively ineffective. Pretransplant evaluation of BMD and the possibility of significant BMD loss during the first posttransplant year should not be overlooked. Prophylaxis against bone loss and treatment should be started as soon as possible after transplantation for recipients with either normal or abnormal pretransplant BMD.

Kidney Retransplantation in Comparison With First Kidney Transplantation

Introduction The aim of this study was to depict the outcome of second and third kidney allografts in comparison with first kidney allografts. Methods Among 2150 kidney transplantations are 103 second and 5 third transplantations. Demographic characteristics and survivals of retransplanted patients were compared with a randomly selected group of first kidney recipients, consisting of two cases matched with each retransplanted patient for age, gender, and date of transplantation. Results Retransplanted patients consisted of 78 men and 30 women of mean age 32.63 ± 11.92 years. They had received kidneys from 91 living-unrelated and 17 living-related donors. Median followup was 27 months. One-, 2-, 3-, and 5-year graft survivals were 81.4%, 78.9%, 78.9%, and 73.7% among retransplants, versus 92.9%, 91.5%, 89.8%, and 85.3% in the control group, respectively ( P = .0037). Patient survival was 96%, 94.6%, 92.4%, and 87.8% in the retransplant group versus 93.1%, 92.4%, 90.9%, 87.4% in the control group, respectively ( P = .63). Also, graft survivals were slightly lower in female compared to male retransplant patients ( P = .09). No significant difference in survival rates was seen in different age groups. Conclusion It seems that kidney retransplantation can yield desirable outcomes, albeit relatively lower graft survivals.

A Decade Experience of Cardiac Retransplantation in Adult Recipients

Cardiac retransplantation is considered to be the best therapeutic option for a failing cardiac allograft. However, poor outcomes with retransplantation have previously been reported, a factor that raises important ethical, logistic and financial issues given the limited organ donor supply. Seven hundred sixty-six adult patients underwent cardiac transplantation for end-stage heart failure at our institution from 1992 to 2002. Of these, 41 (5.4%) were retransplants. Variables examined included recipient and donor demographics, indications for retransplant, comorbidities, cytomegalovirus (CMV) serology status, left ventricular assist device use before transplant, donor ischemic time, rate of early mortality (within 30 days), and post-transplantation survival rate. Indications for cardiac retransplant were transplant-related coronary artery disease in 37, acute rejection in 3, and other causes in 1. The mean interval between transplantation and retransplantation was 5.9 +/- 3.4 years. Baseline characteristics such as recipient age, gender, CMV serology status, and donor age were similar in the primary transplant and retransplant groups. Early mortality after transplantation was comparable between the 2 groups, but post-transplant survival was significantly lower in retransplant patients compared with primary transplants with 1-, 3-, 5-, and 7-year actuarial survival rates of 72.2%, 66.3%, 47.5%, and 40.7% vs. 85.1%, 79.2%, 72.9%, and 66.8%, respectively (p < 0.001). Cardiac retransplantation offers short-term outcomes similar to primary transplantation but lower long-term survival rates. Non-retransplant surgical options should also be considered in these patients. Careful patient selection and risk-assessment is necessary to govern appropriate allocation of limited donor organs.

Cardiac retransplantation in children

Background Experience with pediatric cardiac retransplantation is limited. Outcomes should be inspected to insure proper use of donor hearts. Methods Of 152 pediatric heart transplantations, we performed 20 retransplants in 17 children (3 had a second retransplant). The retransplant children were older than the primary transplant children (11.1 ± 4.4 years versus 7.1 ± 6.0 years; p = 0.005). Excluding 1 early retransplant, the interval from primary transplant to retransplant was 5.5 ± 3.3 years (range, 1.1 to 11.1). The retransplant patients were clinically more ill than the primary transplant patients (United Network for Organ Sharing status I, 75% versus 63%; mechanical circulatory support or dialysis, 20% versus 3.8%). Results Donor ischemia time (188 versus 165 minutes) and cardiopulmonary bypass time (127 versus 127 minutes) were not significantly different for the retransplant patients. Excluding 1 retransplant patient who required a tracheostomy, days on the ventilator (2.7 versus 2.7), days on inotropic support (3.0 versus 3.2), intensive care unit days (7.2 versus 6.7), and hospital days (15.9 versus 13.8) were similar in the retransplant group. Freedom from rejection at 90 days and 1 year was not different in the retransplant patients. Actuarial patient survival in the patients undergoing first retransplant was similar to the primary transplant patients at 30 days (95% versus 94.7%), 1 year (94.1% versus 80.7%), and 3 years (78.4% versus 73.1%). Two of 3 children receiving a third transplant died within 1 year of redo retransplantation. Conclusions Cardiac retransplantation can be performed in children with results comparable with those for primary transplantation despite increased clinical acuity. These early results suggest that cardiac retransplantation in children is a reasonable therapeutic option. Children with repeat retransplantation do not fare as well.

FATE OF TYPE I DIABETICS WHOSE GRAFTS FAIL AFTER KIDNEY OR SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTS

363 Although the outcome of type I diabetics (T1DM) after kidney transplants has recently improved, it remains inferior to that in non-diabetics. However, the long-term prognosis for T1DM on dialysis is dismal. The purpose of this study is to compare the outcomes of T1DM who loose their graft after kidney-alone (KA) or simultaneous pancreas-kidney (SPK) transplant to those who maintain their graft. The records of 105 T1DM recipients were reviewed(59 KA and 46 SPK, median follow-up 29 months, 1991-96). The clinical status at last follow-up is shown below: Figure Only 32% of patients with a failed kidney graft were retransplanted and one patient is awaiting retransplantation. In the retransplant group, the mean interval to relisting was 101±120 days (median 56 days). The mean interval to retransplant was 304±392 days (median 104 days). The death rate was fourfold higher in patients who lost their grafts, whether they received a retransplant or not, compared to those with a functioning graft (43% and 47% vs 11%, P=0.001). The proportion of patients remaining on dialysis after failure of the graft was not affected by the type of transplant (KA 73% vs SPK 64%, P=NS). Of the 46 SPK recipients, 24 (52%) are alive with a functioning pancreas graft, 2 (4%) died with a functioning pancreas graft and 16 (34%) have lost their pancreas grafts, 8 due to early post-operative thrombosis. Only 2 (12%) were re-transplanted with a pancreas. We were unable to identify any characteristics that would differentiate patients who remained on dialysis from those who were re-transplanted. The two groups were comparable with respect to dialysis status prior to transplant, race, gender, transplant type (KA vs SPK), age, duration of diabetes and coronary artery disease. In conclusion, T1DM who lose their graft have an increased mortality rate even if they are retransplanted. Only 1/3 of T1DM who lose their graft are retransplanted, whether they had a KA or SPK. Given the poor survival of T1DM on dialysis, the option of a retransplant should be pursued aggressively in these patients.

FATE OF TYPE I DIABETICS WHOSE GRAFTS FAIL AFTER KIDNEY OR SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTS

363 Although the outcome of type I diabetics (T1DM) after kidney transplants has recently improved, it remains inferior to that in non-diabetics. However, the long-term prognosis for T1DM on dialysis is dismal. The purpose of this study is to compare the outcomes of T1DM who loose their graft after kidney-alone (KA) or simultaneous pancreas-kidney (SPK) transplant to those who maintain their graft. The records of 105 T1DM recipients were reviewed (59 KA and 46 SPK, median follow-up 29 months, 1991-96). The clinical status at last follow-up is shown below: FigureOnly 32% of patients with a failed kidney graft were retransplanted and one patient is awaiting retransplantation. In the retransplant group, the mean interval to relisting was 101±120 days (median 56 days). The mean interval to retransplant was 304±392 days (median 104 days). The death rate was fourfold higher in patients who lost their grafts, whether they received a retransplant or not, compared to those with a functioning graft(43% and 47% vs 11%, P=0.001). The proportion of patients remaining on dialysis after failure of the graft was not affected by the type of transplant (KA 73% vs SPK 64%, P=NS). Of the 46 SPK recipients, 24(52%) are alive with a functioning pancreas graft, 2 (4%) died with a functioning pancreas graft and 16 (34%) have lost their pancreas grafts, 8 due to early post-operative thrombosis. Only 2 (12%) were re-transplanted with a pancreas. We were unable to identify any characteristics that would differentiate patients who remained on dialysis from those who were re-transplant. The two groups were comparable with respect to dialysis status prior to transplant, race, gender, transplant type (KA vs SPK), age, duration of diabetes and coronary artery disease. In conclusion, T1DM who lose their graft have an increased mortality rate even if they are retransplanted. Only 1/3 of T1DM who lose their graft are retransplanted, whether they had a KA or SPK. Given the poor survival of T1DM on dialysis, the option of a retransplant should be pursued aggressively in these patients.

Orthotopic liver transplantation for acute hepatic failure in children.

Thirty children received 35 liver transplants for fulminant or late-onset liver failure between March 1988 and May 1993. Aetiology included non-A non-B hepatitis in 12, Wilson's disease in 8, drug-induced hepatic failure in 6, hepatitis B in 1, hepatitis A in 1, tyrosinaemia in 1 and congenital haemochromatosis in 1. Three patients were retransplanted, one each for hepatic artery thrombosis, non-A non-B graft reinfection, and chronic rejection. Two of these three patients received a third transplant for chronic rejection and hepatic artery thrombosis. One patient in the retransplant group survived. Overall, graft and patient survival at a mean follow-up of 17 months were 49% and 57%, respectively. Mortality was related to vascular complications in three patients (hepatic venous obstruction, portal vein thrombosis and hepatic artery thrombosis). Two patients died of primary sepsis (cerebral aspergillosis and cytomegalovirus (CMV) pneumonitis in association with graft-versus-host disease). Systemic sepsis and multiorgan failure was documented as a cause of death in four children and sepsis in association with chronic rejection in a further three patients. One child died of respiratory failure 4 weeks after transplantation. Mortality in eight children less than 2 years was 75% and this was significantly greater than for older children (P < 0.003, Mantel Cox). Earlier referral, even in the absence of a definitive diagnosis and particularly in children under 2 years is advisable and may improve survival.

COMBINED COLD STORAGE-PERFUSION PRESERVATION WITH A NEW SYNTHETIC PERFUSATE

Based upon encouraging experimental results, we began employing a synthetic perfusate for cadaver kidney preservation. The new perfusate contains hydroxyethyl starch (HES) as the sole colloid for oncotic support; 107 cadaver kidneys were preserved and transplanted (93 primary, 14 nonprimary) using the HES solution and were compared with our previous experience of 180 cadaver kidneys (161 primary, 19 nonprimary) preserved and transplanted utilizing an albumin-based perfusate. All cadaver kidneys were locally harvested and preserved by machine perfusion. Donor and preservation characteristics in the HES (n = 61) and the albumin (n = 101) groups were comparable, with a mean preservation time of 30.9 hr. Cold storage in combination with hypothermic pulsatile perfusion (HPP) preservation was performed more often in the HES group (68.2% vs. 31.1%, P less than 0.001). Recipient characteristics were also comparable, and all received quadruple immunosuppressive therapy with sequential/Minnesota antilymphoblast globulin/(MALG)/cyclosporine. After primary transplantation, the incidence of immediate function (82.6% vs. 89.2%), preservation-related dialysis (14.9% vs. 8.6%), and primary nonfunction (2.5% vs. 0) were similar between the 2 groups, with trends favoring the latter HES data. One-month serum creatinine (1.8 vs. 1.7 mg/dl) and graft survival (95% vs. 97.8%) also were comparable. Similar trends were present in the retransplant group, including a significantly lower 1-month serum creatinine in the HES group (2.2 vs. 1.5 mg/dl; P less than 0.05). The preservation-related dialysis rate did not differ between primary and nonprimary transplants. Primary nonfunction has not occurred with our new perfusate. Combined cold-storage-HPP preservation with HES perfusate offers advantages over standard retrieval technology and provides excellent immediate allograft function.

Retransplantation for severe accelerated coronary artery disease in heart transplant recipients

Development of accelerated coronary artery disease (CAD) in the cardiac allograft is one of the major causes of late graft failure in heart transplant recipients. At the Stanford University Medical Center 356 heart transplant procedures were performed in 329 patients by the end of January 1985. Eighty-nine of these patients developed evidence of transplant CAD. Twenty retransplant procedures, including 2 third transplants, were performed in 19 of the 89 patients because of transplant CAD. The graft survival rates after the second transplant were 55%, 25% and 10% after 1,2 and 5 years, respectively. Nine of these retransplant patients currently survive, the longest for 5.5 years. To examine potential risk factors for development of severe transplant CAD, these 20 retransplant procedures were compared with 113 transplant recipients who had no evidence of transplant CAD on annual coronary arteriograms. An excess of rejection episodes (3 ± 2 vs 2 ± 1 episodes/patient, p = 0.02), elevated total cholesterol (266 ± 78 vs 225 ± 47 mg/dl, p = 0.002) and higher low-density lipoprotein levels (176 ± 88 vs 137 ± 46 mg/dl, p = 0.009) were noted in the transplant CAD retransplant group. Five of 11 retransplant recipients who survived >1 year again developed transplant CAD. Characteristic morphologic features and rapid progression of CAD in the second graft were similar to those in the primary graft. In conclusion: (1) retransplantation for the patient with advanced transplant CAD can be successful, but the incidence of recurrent CAD in the second graft is high; and (2) total number of rejection episodes and elevated total cholesterol and low-density lipoprotein levels may be risk factors for the development of transplant CAD.

Clinical study of second kidney transplantation.

During the period from November 1972 to February 1975, 39 patients received second renal grafts in our institution. The clinical course of the patients was analyzed and compared with 121 patients who received only one graft during the same period. The graft survival either from living related or cadaveric sources was inferior in the second graft group. However, mortality was not increased by re-transplantation. Major differences were noted in the occurrence of hyperacute or accelerated type rejections. There was a high incidence of this type of rejection in the second graft group, especially in the simultaneous retransplant group.