Patients with a failed renal transplant

Despite the advances in the care of recipients and in immunosuppression, long-term graft survival has experienced little improvement in the last 10 years. An important number of recipients present progressive loss of graft function and have to be readmitted on dialysis therapy. Before starting dialysis, these patients are re-exposed to the complications of chronic renal failure but there are no specific guidelines for their treatment. The Kidney Disease Quality Initiative Advisory Board clinical practice guidelines given for the non-transplant chronic kidney disease patients have been recommended for ameliorating their clinical situation and the rate of progression of graft failure. The time when dialysis has to be restarted and the type of dialysis procedure, hemodialysis or peritoneal dialysis, are under discusion. But there is no evidence about the superiority of either type of dialysis procedure. Systematic graft nephrectomy has been considered to improve the inflammatory status of the patients with a failed graft which could contribute to a worse control of some complications such as anemia and to the increased rates of cardiovascular mortality. As in the patients with primary end-stage renal disease, retransplantation is the best treatment for a patient with a failed graft. Due to the shortage of organs for transplantation the number of patients who are retransplanted has remained stable. Recurrent diseases such as glomerulonephritis, lyphoproliferative diseases, BK virus nephopathy and previous non-adherence to the treatment do not necessarily preclude retransplantation.     

Results of retransplantation in individuals who received two successive cadaver kidneys.

At the Royal Victoria Hospital in Montreal, 22 patients received two successive cadaver renal transplants. The results were analysed to determine which factors have the best predictive value for success or failure in renal retransplantation. The fate of a second cadaver renal allograft was found to be about the same as the first if the initial transplant has been lost because of rejection and not technical failure. The duration of survival of the initial transplant serves as the best guide to potential outcome of retransplantation after rejection of the initial graft.     

Patient outcomes after kidney allograft loss

Despite considerable advances in immunosuppression and in short-term graft survival, little improvement has been observed in long-term survival rates. About 30% of patients lose their graft in the first 5 years, and this percentage increases up to 50% at 10 years. Graft losses, due to causes other than death with functioning graft, are an important cause of end-stage renal disease. Patients with failed graft account for 4% to 10% of those admitted yearly for dialysis therapy. There is no evidence about the superiority of hemodialysis or peritoneal dialysis in the treatment of these patients. Graft failure seems to be an important risk factor associated with morbidity and mortality, mostly in the first months after restarting dialysis. The causes of these high morbidity and mortality rates are not very well known. However, a poor control of the chronic kidney disease complications, the persistence of a chronic inflammatory state due to the failed graft, and the lack of a protective effect of the functioning graft could play an important role. This inflammatory state could be mediated by the presence of the rejected graft, and nephrectomy has been recommended. A variable number of patients with failed graft are relisted for a new transplant, thus increasing the shortage of organs. Graft survival of repeat transplantation with the new immunosuppressive regimens is very close to that of first-graft survival. Moreover, retransplantation increases patient survival rates in some series when compared with patients on dialysis. Complications during the first transplant such as BK virus nephropathy or lymphoproliferative diseases do not necessarily recur after the repeat transplant.     

Heart Retransplantation

Retransplants comprise only a small minority (3-4%) of heart transplants, however outcome following retransplantation is compromised. Risk factors for a poor outcome following retransplantation include retransplantation early (<6 months) after primary transplant, retransplantation for acute rejection or early allograft failure, and retransplantation in an earlier era. The incidence of rejection and infection is similar following primary transplant and retransplantation. The compromised outcomes and risk factors for a poor outcome are similar in adult and pediatric heart retransplantation. However, due to the short half-life of the transplanted heart, it is an expectation that patients transplanted in childhood may require retransplantation. Based on the data available and the opinion of the working group, indications for heart retransplantation are (i) chronic severe cardiac allograft vasculopathy with symptoms of ischemia or heart failure (should be considered) or asymptomatic moderate or severe left ventricular dysfunction (may be considered) or (ii) chronic graft dysfunction with symptoms of progressive heart failure in the absence of active rejection. Patients with graft failure due to acute rejection with hemodynamic compromise, especially <6 months post-transplant, are inappropriate candidates for retransplantation. In addition, guidelines established for primary transplant candidacy should be strictly followed.     

Retransplantation following isolated lung transplantation.

The results of retransplantation for early allograft failure are discouraging. Fortunately, with recent technical advances and improved postoperative immunosuppression, airway complications have been significantly reduced. It is now unusual to see patients with airway complications following lung transplantation. This group of patients is not likely to represent a large population in need of retransplantation in the future. However, rejection-mediated OB remains a persistent problem seen in all transplant centers. The group of patients who deteriorate despite augmented immunosuppression will put increasing pressure on transplant programs to provide the only known solution for survival: retransplantation. In the Toronto experience, only 1 patient survived early retransplantation. Three of the 5 recipients retransplanted late in their course have survived and 2 are presently alive and well. Yet this is in sharp contrast to the current 80% 1-year survival for initial transplant recipients. As the demand for donor lungs increases with the growing need for first-time procedures, the use of donor lungs for retransplantation becomes a significant problem. The decision whether to allocate a donor lung (and commit significant hospital resources) to a retransplant recipient or to a first-time recipient is difficult. A patient with early graft failure has a dismal prognosis and a decision not to retransplant may be straightforward. However, the decision to retransplant a patient who has developed OB late following their initial transplant is much more difficult. It is still our responsibility to manage this limited resource and provide donor lungs to those who have the optimal chance of survival.     

Nephrectomy for the failed renal allograft in children: predictors and outcomes

Background

There are no guidelines for the removal of a failed renal allograft, and its impact on subsequent dialysis and retransplantation has not yet been described.

Methods

We performed a 10-year review of allograft failure to study the factors that determined an outcome of transplant nephrectomy and choice of subsequent renal replacement therapy in children with or without nephrectomy.

Results

A total of 34 children developed graft failure over the 10-year study period, of whom 18 (53 %) required transplant nephrectomy. The median graft survival was 1.1 (range 0.2–10.6) versus 7.5 (1.5–15.0) years in the nephrectomy and non-nephrectomy groups, respectively (p?=?0.011). Children with graft failure within 1 year of transplantation were four-fold more likely to require transplant nephrectomy than those with graft failure after 1 year (p?=?0.04). Renal biopsy performed at ≤8 weeks prior to graft loss showed Banff grade II acute rejection in 13 of the 18 children who required subsequent nephrectomy versus three of the 13 children who did not need nephrectomy (p?=?0.01). Inflammation (fever, graft tenderness and raised C-reactive protein (CRP) in the 2 weeks preceding graft failure) was seen in 66 % of nephrectomized children, but not in any in the non-nephrectomy group (p?=?0.0003 for CRP between groups). Banff II rejection, an inflammatory response and the time post-transplantation significantly and independently predicted the outcome of nephrectomy (p?=?0.008, R ²?=?67 %). Human leukocyte antigen (HLA) antibody levels after graft failure were higher in the nephrectomy group (p?=?0.0003), but there was no difference between groups in terms of the presence or class of donor-specific antibodies. Of the children with graft failure, 82 % required dialysis (61 % hemodialysis) and 35 % have to date been successfully retransplanted.

Conclusions

Children with Banff II rejection, an inflammatory response and early graft loss are more likely to require transplant nephrectomy. Nephrectomy may be associated with higher circulating HLA antibody levels.     

Considerations in retransplantation of the failed renal allograft recipient

Routine success in kidney transplantation has significantly improved the quality and length of life for the majority of recipients and made this option the treatment of choice for suitable candidates. Improved patient survival combined with a relative static improvement in long-term graft outcomes has led to an increasing number of transplant recipients with failed allografts who face the eventual option of either returning to dialysis or seeking retransplantation. Although retransplantation is presumed to be a favorable option for many, data to support this belief is limited. Given the wide variance in predicted outcomes for retransplantation, on the basis of the underlying kidney disease and other individual patient comorbidities as well as the expected wait time for a second transplant, each case should be evaluated independently. This review discusses available data and individual considerations that should be taken into account when retransplantation is proposed after failure of a primary allograft.     

Factors related to success or failure of second renal transplants.

From January 1, 1968 to December 31, 1973, 50 patients received two or more kidney transplants. Patient and graft survival was highly dependent upon the source of the donor and to a lesser extent the functional duration of the first transplant and the elapsed time between first and second graft. Survival (patient and graft) was best in patients receiving two related grafts and worst in patients receiving two sequential cadaver grafts. Intermediate rates of success followed cadaver transplantation after rejection of a related graft. The highest failure rate was encountered when those patients who sustained an early loss of the first cadaver graft received a subsequent cadaver graft within a few months. We recommended removal of the acutely rejected graft and delay prior to retransplantation of patients who rapidly reject cadaver grafts in the face of maximal doses of immunosuppression. A delay will permit recovery from both the immunosuppression and any underlying subclinical infections, and will permit the recognition of anti-HL-A antibodies which may not be manifest soon after rejection. Retransplantation of the patient who is slowly rejecting the first kidney does not require prior removal of the rejected graft or delay in retransplantation.     

100 second renal allografts from a single transplantation institution.

Between January 1, 1968 and March 1977, 100 of 131 patients who lost their first transplant at the University of Minnesota received a second renal allograft. Overall patient survival in the retransplanted group was 10% less than that in the dialysis group. The best results (graft function and patient survival were seen in young patients, nondiabetics, patients who received two sequential living related groups, and in those whose first graft was lost secondary to chronic rejection. The poorest results were seen in older patients (greater than 40 years), diabetics, and patients with acute rejection during the initial graft. Shared donor antigens do not affect graft outcome. These findings, although not the product of a randomized prospective study, may be useful in advising patients of the relative risks of retransplantation or hemodialysis.     

Indications for liver transplantation in the cyclosporine era

One hundred seventy orthotopic liver transplants were performed under conventional immunosuppression with azathioprine and steroids with 1- and 5-year survivals of 32.9 per cent and 20.0 per cent, respectively. Since the introduction of cyclosporine-prednisone therapy in March 1980, 313 primary orthotopic liver transplants have been performed. Actuarial survivals at 1 and 5 years have improved to 69.7 per cent and 62.8 per cent, respectively. Biliary atresia is now the most common indication for liver replacement. In adults, primary biliary cirrhosis and sclerosing cholangitis have become more common indications for transplantation, and alcoholic cirrhosis and primary liver malignancy as indications have declined. Early enthusiasm for liver transplantation in patients with hepatic cancer has been tempered by the finding that recurrence is both common and rapid. An increasing number of patients with inborn errors of metabolism originating in the liver are receiving transplants, including patients with Wilson's disease, tyrosinemia, alpha-1-antitrypsin deficiency, glycogen storage disease, familial hypercholesterolemia, and hemochromatosis. Survival in this group of patients has been excellent (74.4 per cent at 1 and 5 years). A hemophiliac who received a transplant for postnecrotic cirrhosis has survived and may have been cured of his hemophilia. About 20 per cent of patients require retransplantation for rejection, technical failure, or primary graft failure. Only four of the patients receiving retransplants under conventional immunosuppression survived beyond 6 months, and all died within 14 months of retransplantation. Sixty-eight patients have received retransplants under cyclosporine-prednisone. Thirty-one patients are surviving, all for at least 1 year. Six of the twelve patients requiring a third transplant are alive 2 to 3 years after the primary operation. An aggressive approach to retransplantation in the patient with a failed graft is justified.     

Return to dialysis after renal transplantation. Which would be the best way?

The exact moment to return to dialysis when a graft fails has not clearly been established. Furthermore, there is no agreement with respect to whether the guidelines accepted for patients entering dialysis for the first time are adequate for this subgroup of patients with advanced renal failure, due to the special characteristics of these patients, derived from the immunosuppressive medications they are taking among other accompanying factors. We reviewed a group of renal transplant patients who returned to dialysis and compared them with a group of patients entering dialysis for the first time. Patients with chronic renal failure due to graft failure had a poorer renal function at the time entering dialysis and a more profound anemia. Additionally, complications considered such as the number of hospital admissions during the first year after initiation of dialysis were considerably higher in the group of transplanted patients. We advocate for an earlier referral to the dialysis unit, a more aggressive erythropoietin therapy in the phase of advanced renal failure due to chronic allograft nephropathy, and in selected cases retransplantation before definitive graft loss.     

Retransplantation in 7,290 primary transplant patients: a 10-year multi-institutional study.

BACKGROUND: Cardiac retransplantation is a controversial procedure due to the disparity between donor heart demand and supply. METHODS: Of 7,290 patients undergoing primary cardiac transplantation between January 1990 and December 1999 at 42 institutions contributing to the Cardiac Transplant Research Database (CTRD), 106 patients later underwent a second and 1 patient a third cardiac transplant procedure. RESULTS: The actuarial freedom from retransplantation was 99.2% and 96.8% at 1 and 10 years, respectively. Reasons for retransplantation included early graft failure (n = 34), acute cardiac rejection (n = 15), coronary allograft vasculopathy (CAV, n = 39), non-specific graft failure (n = 7), and miscellaneous (n = 10). The only risk factor associated with retransplantation was younger age, reflecting the policy of preferential retransplantation of younger patients. Survival after retransplantation was inferior to that after primary transplantation (56% and 38% at 1 and 5 years, respectively). Risk factors associated with death after retransplantation included retransplantation for acute rejection (p = 0.0005), retransplantation for early graft failure (p = 0.03), and use of a female donor (p = 0.005). Survival after retransplantation for acute rejection was poorest (32% and 8% at 1 and 5 years, respectively) followed by retransplantation for early graft failure (50% and 39% at 1 and 5 years, respectively). Survival after retransplantation for CAV has steadily improved with successive eras. CONCLUSIONS: The results of retransplantation for acute rejection and early graft failure are poor enough to suggest that this option is not advisable. However, retransplantation for CAV is currently associated with satisfactory survival and should continue to be offered to selected patients.     

No recurrence of posttransplantation Kaposi's sarcoma three years after renal retransplantation

Kaposi's sarcoma (KS) develops in 0.5-5% of organ transplant patients; it usually regresses upon treatment reduction, but this may result in graft loss necessitating return to dialysis and/or retransplantation. Until now posttransplantation KS is considered to recur upon reintroduction of immunosuppressive treatment, a fact that has limited retransplantation of patients with previous KS. We report a patient with posttransplantation KS who received a second renal transplantation after having been off immunosuppressive treatment for 10 years, in whom KS has not recurred more than 3 years after retransplantation. This unique observation suggests that retransplantation of patients with previous posttransplantation KS is possible.     

Depression levels before and after renal transplantation

Depression is a frequent problem among end-stage renal disease patients and is closely associated with their physical well-being. We sought to compare the depression levels and confounding parameters in renal patients. The 88 patients (62 men, 26 women) included: renal transplant recipients (n = 27); renal transplant waiting list patients (n = 30); and chronic allograft rejection patients on dialysis therapy (n = 31). Their mean age was 31.05 +/- 11.78 years. Age, gender, marital status, presence of chronic rejection, duration of functional graft, and hemodialysis were retrieved from patient records. Depression levels were evaluated by the Beck Depression Inventory. The depression stage of the renal transplant recipients was significantly lower than that of hemodialysis patients with chronic allograft rejection (P =.003). The presence of depression was not related to age or gender. Married patients showed a lower percentage of depression (P <.03). There was an inverse correlation between depression and functional graft duration among patients with transplant failure (r = -.370, P =.04). In conclusion, the return to hemodialysis, especially after a short duration of graft function, is associated with depression. The lower depression percentage among married patients may be due to the psychosocial support of the spouses. Therefore, single persons and transplant failure patients who return to dialysis therapy need greater social and psychologic support. Placing greater numbers of patients on transplant waiting lists decreases depression and may provide a higher quality of life with a better outcome during dialysis therapy.     

Evaluating the survival benefit of kidney retransplantation

BACKGROUND: The magnitude of the survival benefit associated with kidney retransplantation has not been well studied. METHODS: Using data from the Canadian Organ Replacement Register (CORR), we studied patients (n=3,067) initiating renal replacement therapy during 1981-1998 who had received a transplant and experienced graft failure (GF). Such patients were followed until death, loss to follow-up or the end of the observation period (December 31, 1998). Using Cox regression, we estimated the post-GF covariate-adjusted hazard ratio (HR) for retransplant versus dialysis, and determined whether the contrast differed across patient subgroups. Through nonproportional hazards models, we also examine patterns in the retransplant/dialysis HR with time following retransplant. RESULTS: Overall, retransplantation is associated with a covariate-adjusted 50% reduction in mortality, relative to remaining on dialysis (HR=0.50; P<0.0001). This benefit is most pronounced in the 18- to 59-year age group. Retransplanted patients were at significantly higher risk of death relative to patients on dialysis only during the first month posttransplant (HR=1.66; P=0.047), and experienced significantly reduced mortality thereafter. CONCLUSIONS: Following primary graft failure, retransplantation is associated with significantly reduced mortality rates among Canadian end-stage renal disease patients. Further study should be undertaken to assess the applicability of our findings to other patient populations.     

Adverse effect of splenectomy on the survival of patients with more than one kidney transplant

Risk factors associated with death were identified in a cohort of patients who received 2 or more kidney transplants. Data on 19 variables were collected by chart review on 774 patients who received allografts between 1973 and 1980 at any one of 3 hospitals in Philadelphia. 124 of the patients received two or more transplants and were followed for a minimum of 1.5 years. Modified life table analyses of single variables indicated that 7 factors--splenectomy, donor source, age, transplant hospital, number of HLA mismatches, donor sex, and survival time of the prior graft--were significantly related to patient survival. Using all 19 variables, the proportional hazards model was fit to the data. The characteristics most related to survival were splenectomy (P less than .001), donor source (P = .0022), and age (P = .0015). The other 4 factors that were significant on univariate analysis were not significant in this multivariate analysis. The relative risk of death was 5.5 for patients who had had a splenectomy compared with those who had not had a splenectomy. Patients who had received more than one transplant were compared with patients who had received only one transplant, and a subset of recipients of primary transplants who returned to dialysis after primary graft failure. Survival of patients who had received one transplant was approximately the same as that of the retransplanted population. When the proportional hazards model was fit to the populations that received one transplant and compared with the model for the retransplanted group, only age and donor source were common to all three models. The effect of splenectomy on survival was significant for the total population of primary transplant recipients but had no effect on the survival of the subset of recipients whose kidney grafts had failed and were returned to hemodialysis. Infection accounted for 45% of the deaths among splenectomized, retransplanted patients. A higher percentage of septic deaths occurred in patients whose grafts were functioning at the time of death when compared with patients who had returned to dialysis after secondary graft failure. Although retransplantation alone is not associated with an increased mortality, retransplantation in splenectomized patients carries a high risk of death.     

Impact of failed allograft nephrectomy on initial function and graft survival after kidney retransplantation

The management of an asymptomatic failed renal graft remains controversial. The aim of our study was to explore the effect of failed allograft nephrectomy on kidney retransplantation by comparing the outcome of recipients who underwent graft nephrectomy prior to retransplantation with those who did not. Retrospective comparison of patients undergoing kidney retransplantation with (group A, n = 121) and without (group B, n = 45) preliminary nephrectomy was performed, including subgroup analysis with reference to patients with multiple (≥2) retransplantations and patients of the European Senior Program (ESP). Nephrectomy leads to increased panel reactive antibody (PRA) levels prior to retransplantation and is associated with significantly increased rates of primary nonfunction (PNF; P = 0.05) and acute rejection (P = 0.04). Overall graft survival after retransplantation was significantly worse in group A compared with group B (P = 0.03). Among the subgroups especially ESP patients showed a shorter graft survival after previous allograft nephrectomy. On the multivariate analysis, pretransplant graft nephrectomy and PRA >70% were independent and significant risk factors associated with graft loss after kidney retransplantation. Nephrectomy of the failed allograft was not beneficial for retransplant outcome in our series. Patients with failed graft nephrectomy tended to have a higher risk of PNF and acute rejection after retransplantation. The possibility that the graft nephrectomy has a negative impact on graft function and survival after retransplantation is worth studying further.     

A technique for kidney retransplantation after simultaneous kidney pancreas transplantation

Isolated failure of the renal graft after simultaneous kidney-pancreas transplantation (SPK) is a rare but potential outcome. Many of these patients are candidates for kidney retransplantation. This paper describes a series of 3 patients who underwent successful kidney retransplantation after SPK. The operation was completed through an extraperitoneal incision without disruption of the pancreas graft or need for a transplant nephrectomy.     

A single-center experience of late retransplantation of the liver

Liver retransplantation is considered to carry a higher risk than primary transplantation. However, there are an increasing number of retransplant candidates, especially owing to late graft failure. The aim of this study was to analyze a single-center experience in late liver retransplantation. The overall rate of primary retransplantation was 11.4% (28 re-OLT out of 245 primary OLT); the 14 (52%) who underwent retransplantation at more than 3 months after the first transplant were analyzed by a medical record review. Causes of primary graft failure leading to retransplantation were chronic hepatic artery thombosis in five cases (36%); recurrent HCV cirrhosis in four cases (29%); chronic rejection in two cases (14%); veno-occlusive disease; hepatic vein thrombosis or idiopathic graft failure in one case each (7%). UNOS status at re-OLT was always 2A, all patients were hospitalized; three were intensive care unit bound. ICU and total hospital stay had been 7 +/- 5 and 28 +/- 16 days, respectively. One- and 2-year patient and graft survivals were 84% and 62% and 67% and 67%, respectively. Death occurred in four patients. Two out of the three recovered in ICU at the time of retransplantation, at a median interval of 15 +/- 9 days after retransplantation. The survival rate after late retransplantation is improving, and this option should be considered to be a efficient way to save lives, especially by defining the optimal timing for retransplantation.     

Retransplantation in patients with graft loss caused by polyoma virus nephropathy

The characteristics and outcome in 10 patients who underwent retransplantation after losing their renal grafts to BK virus-associated nephropathy (BKAN) are described. The patients underwent retransplantation at a mean of 13.3 months after failure of the first graft. Nephroureterectomy of the first graft was performed in seven patients. Maintenance immunosuppression regimens after the first and second grafts were similar, consisting of a combination of a calcineurin inhibitor, mycophenolate mofetil, and prednisone. BKAN recurred in one patient 8 months after retransplantation, but stabilization of graft function was achieved with a decrease in immunosuppression and treatment with low-dose cidofovir. After a mean follow-up of 34.6 months, all patients were found to have good graft function with a mean creatinine of 1.5 mg/dL. From this collective experience from five transplant centers (although the follow-up after retransplantation was not extensive), it can be concluded that patients with graft loss caused by BKAN can safely undergo retransplantation. The risk of recurrence does not seem to be increased in comparison with the first graft.