Difference In Long-term Graft Survival Research Articles

Long-Term Survival After Heart Transplantation at Centers Stratified by Short-Term Performance.

Center differences in short-term survival after heart transplant (HT) are known. We sought to compare long-term graft survival (freedom from death or retransplantation) at currently active United States HT centers stratified by performance for short-term survival. We used the Organ Procurement and Transplant Network database to identify subjects ≥18 years old who received primary HT during 2000 to 2014 at US centers active during 2013 and 2014. Follow-up was available until March 2016. Center case-mix was assessed by computing expected 90-day mortality and short-term performance by 90-day standardized mortality ratio (SMR; observed/expected mortality). Centers were stratified by case-mix as transplanting low-, intermediate-, and high-risk patients and by short-term performance as SMR quintiles. Center-level differences in long-term graft survival were assessed by risk-adjusted, mixed-effects Weibull survival models with center as a random effect. We analyzed 25 467 HT recipients at 96 centers. Those receiving HT at centers with superior (lower) 90-day SMR had longer graft survival (P for trend <0.001). Survival difference among SMR groups remained significant in 90-day conditional survivors (P for trend <0.001). There was significant center-level variation in risk-adjusted graft survival censored at 5 years (P<0.001) and with all follow-up (P<0.001). Adjusting for 90-day SMR was associated with 62% reduction in center variation in 5-year graft survival and 56% reduction in center variation in overall graft survival. HT recipients at centers with superior short-term outcomes have longer graft survival on long-term follow-up. Allocating resources to improve patient care processes and transplant expertise at high-SMR centers may improve short-term and overall survival after HT.

Evaluating the Cost-Effectiveness of Prolonged-Release Tacrolimus Relative to Immediate-Release Tacrolimus in Liver Transplant Patients Based on Data from Routine Clinical Practice.

BackgroundAs of 2014, there were approximately 8300 patients with a functioning liver transplant in the UK Transplant Registry, with 880 liver transplants performed in 2013–2014 alone. Tacrolimus, typically used in combination with steroids and mycophenolate mofetil, currently represents the cornerstone of post-transplant immunosuppression in liver transplant recipients.ObjectivesThe objective of the present study was to evaluate the cost-effectiveness of prolonged-release (PR) tacrolimus (Advagraf®, Astellas Pharma Inc., Tokyo, Japan) versus branded immediate-release (IR) tacrolimus (Prograf®, Astellas Pharma Inc., Tokyo, Japan) in liver transplant recipients in the UK.MethodsA model was developed in Microsoft Excel to estimate costs associated with immunosuppressive medications and retransplantation. Three-year patient and graft survival data were taken from a recent retrospective registry analysis and dose data were taken from prescribing information. Costs in 2014 pounds sterling were taken from the British National Formulary and the National Health Service National Tariff.ResultsOver a 3-year time horizon, the numbers needed to treat with PR tacrolimus relative to IR tacrolimus were 14 to avoid one graft loss and 18 to avoid one death. The model was sensitive to dosing assumptions, with incremental cost estimates varying between a saving of £1642 (standard deviation £885) per patient, assuming the same per-kilogram dosing of PR tacrolimus (Advagraf®) and IR tacrolimus (Prograf®) and an increase of £1350 (£964) using RCT dose data.ConclusionData from a recent analysis of routine clinical practice data in liver transplant recipients on PR tacrolimus and IR tacrolimus showed significant differences in long-term graft survival in favor of PR tacrolimus. Modeling these data in the UK showed that, over a 3-year time horizon, one graft would be saved for every 14 patients treated with PR tacrolimus with minimal impact on costs when compared with branded IR tacrolimus (Prograf®).

Use of Expanded Criteria Donors Gives Significantly Poorer Long-Term Graft Survival

Introduction: The use of expanded criteria donor (ECD) kidneys remains controversial as various groups have reported conflicting outcomes in terms of long-term graft outcomes. It is however well-known that ECD kidneys afford shorter graft survival as compared to kidneys from a standard criteria donor (SCD). In Singapore, patients with end stage renal failure (ESRF) must meet strict medical criteria before they are allowed to be placed on the National Transplant Registry to await a deceased donor kidney, including the absence of clinically overt cardiovascular and cerebrovascular disease. The aim of this study was to determine if there is a difference in long-term graft survival between recipients of SCD and ECD kidneys. Methods: A retrospective review was conducted on all deceased donor renal transplants (DDRT) performed at the Singapore General Hospital from 1st January 2000 to 31 December 2010. Results: During this period, 272 adults underwent a DDRT, with 226 (58.7%) receiving an SCD kidney (Group 1), and 46 (12.0%) receiving an ECD kidney (Group 2). The etiology of ESRF was predominantly chronic glomerulonephritis in both groups (83.1% Group 1 vs 73.9% Group 2, p = 0.75). The mean dialysis duration pretransplant was similar in both groups (45.3+8.7 vs. 46.7+9.0 months in Groups 1 and 2 respectively, p=0.28). While an increased incidence of early acute rejection (a rejection episode within 3 months post-transplant), and delayed graft function (a need for dialysis within a week post-transplant), are risk factors for decreased long-term graft function, the incidence of both events was similar in both groups (10.2% vs. 19.6%, p=0.07, and 42.5% vs. 54.4%, p=0.14, in Groups 1 and 2 respectively). Graft survival at 1 year was similar in both groups (96.0% Group 1 and 91.3% Group 2), but at 5 years there was a clear difference in graft survival (97.1% Group 1 and 68.4% Group 2). The 10-year graft survival was significantly reduced in recipients of ECD kidneys (p< 0.001) (Figure 1). Long term graft survival as described by half-lives was less than 6 years for ECD grafts and more than 10years for SCD grafts.[Figure 1]Conclusion: Patients receiving ECD kidneys, regardless of whether they have experienced an early acute rejection episode or delayed graft function, have a significantly reduced long-term graft survival. This is despite being in similar health as SCD recipients, with the absence of clinically overt cardiovascular and cerebrovascular disease pre-transplant. The use of ECD kidneys should be considered only in selected recipients.

Risk Factors Among Donor Characteristics Which Affect Graft Outcome in Paired Kidney Transplantation

Objective The goal of this study was to identify risk factors among donor characteristics which affect short- and long-term graft outcomes and patient survivals. Materials and Methods This is a retrospective analysis of cases where the kidneys were retrieved from the same donor. We evaluated donor variables including age, sex, cytomegalovirus (CMV) status, infection, blood pressure, electrolyte, urine output, transfusion, cause of death, creatinine level, and cold ischemia time. We also analyzed recipient outcomes and graft function. Results We analyzed 21 donor and 42 recipient records. The majority of donors (85.0%) were <50 years old. The mean donor urine output was 169 mL/h. Delayed graft function was not affected by donor variables. The serum Na and CMV status of the donor were related to the occurrence of an acute rejection episode, but only CMV status showed a significant influence in the multivariate analysis. Among different groups of donor creatinine, better donor function (creatinine <1.0 vs >1.0 mg/dL) was associated with better posttransplantation graft function (creatinine 1.18 vs 2.26 mg/dL). In long-term graft function and survival, donor creatinine showed no significant impact. According to the sequence of transplantation, recipients were divided into group 1 (first kidney transplantation: mean ischemia time, 207 minutes) vs group 2 (second kidney transplantation: mean ischemia time, 441 minutes). Group 1 showed better graft function and survival time. Conclusions Only CMV status of the donor was related to acute rejection episodes after renal transplantation. The donor creatinine data also affected initial posttransplantation creatinine. There was no significant difference in long-term graft survival among various levels of donor kidney function.

LONG-TERM FOLLOW-UP AFTER STEROID RESISTANT ACUTE RENAL ALLOGRAFT REJECTION

P271 Aims: There exist few prospective data on the long-term outcome after steroid resistant renal allograft rejection. We performed this study to investigate long-term outcome of patients with steroid resistant renal allograft rejection and to identify factors predictive for long-term graft survival. Methods: 50 patients (mean age 42 ± 23 years, range from 21 to 65 years) with biopsy proven steroid resistant renal allograft rejection including 20 patients refractory to OKT3 treatment were prospectively evaluated for at least 5 years. All patients had their baseline immunosuppressive treatment switched from cyclosporine to tacrolimus. At the beginning of tacrolimus treatment 27 of these patients were dependent on dialysis. Results: The 3-year and 5-year patient survival rates were 98% and 92%, respectively, while 74% and 68% of renal allografts were functioning after 3 and 5 years. The mean serum creatinine concentrations were 1.84 ± 1.0 mg/dl (3 years) and 1.65 ± 0.7 mg/dl (5 years). There was one patient developing a seminoma that was cured by surgery and chemotherapy; no further malignancies developed during follow-up. The only parameter predictive for long-term graft survival was pre-treatment with OKT3 (3 years: 18/20 with OKT3 vs.19/30 without OKT3, p = 0.035; 5 years 18/20 with OKT3 vs. 16/30 without OKT3, p < 0.01). There was no significant difference in long-term graft survival between patients on dialysis vs. dialysis free patients at the beginning of tacrolimus treatment (3 years: 17/27 patients on dialysis vs. 20/23 free of dialysis; 5 years: 17/27 vs. 17/23, p = n.s.). Other parameters like patient and donor age, CMV-infection, histology score, tacrolimus trough levels, and delayed graft function were not predictive for outcome. Conclusions: Tacrolimus treatment of patients with steroid resistant renal allograft rejection leads to an acceptable long-term graft survival. OKT3 therapy prior to switching baseline immunosuppression to tacrolimus was associated with a favourable outcome.

Acute renal allograft rejection with intimal arteritis: Histologic predictors of response to therapy and graft survival

Acute renal allograft rejection with intimal arteritis is designated by the widely used Banff 97 classification as type 2A or 2B depending on the extent of arteritis, without regard to interstitial inflammation or tubulitis. We examined whether the distinction between type 2A and 2B is relevant to short- and long-term clinical outcomes, and if outcomes in this subset of acute rejection also are affected by tubulitis, interstitial inflammation, and several additional histologic and clinical parameters. Pathology records were searched to identify cases of acute renal allograft rejection with intimal arteritis diagnosed between January 1985 and September 2000. For each case, the patient's chart was reviewed to determine the response of the rejection episode to therapy, type(s) of therapy given, and length of graft survival. All biopsies were reviewed and Banff acute and chronic indices recorded by a pathologist blinded to these data. Biopsies not showing type 2A or 2B rejection were excluded, as were repeat biopsies from the same patient and cases with recurrent glomerular disease, viral infection, donor-specific antibodies, or more than mild chronic change. The initial response to anti-rejection therapy was significantly worse in patients with type 2B acute rejection (N = 29) than in those with type 2A (N = 102) by univariate and multivariate analyses, despite more aggressive treatment of type 2B rejection. In a Cox proportional hazards model the hazard ratio for graft failure for 2B versus 2A was 1.9 (P = 0.05), but this was not significant when adjusted for the initial response to therapy. Cases with minimal or mild tubulitis responded better to therapy than those with moderate or severe tubulitis, although graft survival was not significantly affected by the tubulitis score. The distinction between types 2A and 2B acute rejection in the Banff 97 classification has significant prognostic value with regard to both short- and long-term clinical outcomes, although the difference in long-term graft survival is mainly related to the initial response to therapy. Reports of biopsies showing type 2A or 2B rejection also should specify the degree of tubulitis present, as the latter may significantly influence the initial response to therapy.

Immunosuppressive medications for renal transplantation: A multiple choice question

Immunosuppressive medications for renal transplantation: A multiple choice question

Operative treatment of tertiary hyperparathyroidism: a single-center experience.

To review the experience with the operative treatment of tertiary hyperparathyroidism (TH) from a single renal transplant center. Most patients with chronic renal failure show evidence of secondary hyperparathyroidism by the time maintenance hemodialysis begins. Persistent secondary hyperparathyroidism (i.e., TH) requiring surgical intervention is uncommon in the authors' experience. Charts of patients who underwent parathyroidectomy for TH were reviewed retrospectively. Information obtained included demographics, laboratory data, symptoms, operative procedure (including morbidity and mortality rates), and pathology. Comparisons of demographic data and allograft survival were made between the transplant population as a whole and a matched cohort group of patients. Thirty-eight patients from 4344 renal transplant procedures during a 29-year period required parathyroidectomy for TH. All patients had hypercalcemia; 20 were asymptomatic and 18 had varying symptoms. Mean time from renal transplantation to parathyroidectomy was 997 +/- 184 days, with a mean preoperative calcium level of 12.2 +/- 0.14 mg/dl. Total parathyroidectomy with parathyroid autograft was performed in 26 of 34 primary procedures. There were no deaths. The operative morbidity rate was 6% (wound separation and vocal cord hemiparesis, one each). Pathology was reported in all patients and recently reviewed in 28 patients. Twenty-four had diffuse hyperplasia and nine had nodular hyperplasia; one had an adenoma. Parathyroid glands diagnosed as nodular hyperplasia were significantly larger by total mass than those with diffuse hyperplasia. Comparison of allograft survival between the study group and a matched cohort group of patients revealed no difference in long-term graft survival. Operative intervention is recommended in patients with an asymptomatic increase in serum calcium to >12.0 mg/dl persisting for >1 year after the transplant, acute hypercalcemia (calcium >12.5 mg/dl) in the immediate posttransplant period, and symptomatic hypercalcemia.

In situ preservation of kidneys from non-heart-beating donors--a proposal for a standardized protocol.

The growing success in renal transplantation has resulted in an increase in the need for donor organs. Procurement of kidneys from heart-beating (HB) donors is unlikely ever to meet this demand. Non-heart-beating (NHB) donors offer a yet untapped source of renal grafts. Cadaver kidneys from patients who have sustained cardiac standstill are often considered unsuitable for transplantation due to prolonged warm ischemia time. Using an emergency in situ perfusion technique it is possible to limit warm ischemic damage and to salvage these kidneys for transplantation. The procedure requires prompt action and cooperation of emergency service personnel. This report presents a protocol for the emergency in situ preservation procedure that can be practiced in most hospitals. At the University Hospital of Maastricht, The Netherlands, implementation of this procedure resulted in 20% more kidneys available for transplantation. Although NHB donor kidneys showed a higher rate of delayed function compared with a matched HB donor kidney population, there was no significant difference in long-term graft survival between the two groups.

CAUSES OF GRAFT LOSS BEYOND TWO YEARS IN THE CYCLOSPORINE ERA

While CsA has improved renal-allograft survival rates in the first 2 years compared with Aza, Terasaki's multicenter study (1) failed to show any difference in long-term graft survival in CsA-Pred versus Aza-Pred-treated recipients. The present study examines the long-term graft-survival rates at a single center using CsA immunosuppression and seeks to discern the causes of 58 graft losses among 343 patients with functioning grafts beyond 2 years posttransplantation. The 6-year primary and cadaveric actuarial graft survival at this institution is 59% with a graft half-life of 10 years, which is better than the 40% and 7.7 years, respectively, reported by Terasaki (1) for primary cadaveric recipients on Aza-Pred. It is also better than the 41%, 6-year survival and 5.5-year half-life for primary cadaveric recipients treated with CsA-Pred as reported in the multicenter study. (1) Less experience with the use of CsA may explain the latter comparison. Primary LRD grafts at this institution (2/3 haploidentical) have a 6-year actuarial survival of 77% and a half-life very closely approximating that of HLA-identical LRD grafts under Aza (23.4 years). These results demonstrate that CsA mitigates the effects of HLA incompatibility to reduce graft survival. The most common cause of graft loss beyond 2 years was chronic rejection (36.2%) followed by noncompliance (27.6%). Patient deaths resulted in 13 of the 58 graft losses; most of the deaths were related to cardiovascular diseases. Only 3 patients died from causes that could be attributed to CsA immunosuppression; 2 from sepsis and 1 from viral hepatitis. Acute rejection caused 8.6% of the graft losses on continuous CsA therapy. When immunologic risk factors were analyzed, the entire graft-loss group had a significantly higher proportion of retransplant patients than the graft-survival group (P less than 0.005), suggesting that prior transplantation imposes a higher risk for graft loss not only acutely but long term as well. However, retransplanted patients were significantly less likely to lose their grafts because of noncompliance (P less than 0.005). Male patients were found to be significantly more noncompliant.

Influence of Early Function on Long-Term Pediatric Cadaveric Renal Allograft Survival

The significance of early renal graft function on long-term transplant survival is controversial. From our pediatric renal transplant population we studied 151 children who had an initial cadaveric rehal transplant, were dependent on dialysis before transplantation and were 5 to 19 years old at transplantation. We used dependence upon dialysis as the parameter for early graft function.There was a statistically significant difference in long-term graft survival between patients who were independent of and dependent on dialysis at 1 week and 1 month postoperatively. Our results show that early renal graft function is important for long-term graft survival. All efforts should be directed to obtaining early renal graft function by proper organ procurement, storage, operative technique and aggressive postoperative management. (J. Urol., 143: 326–329, 1990).