M. Brunet

Pancreas retransplantation: a second chance for diabetic patients?

BACKGROUND If pancreas transplantation is a validated alternative for type 1 diabetic patients with end-stage renal disease, the management of patients who have lost their primary graft is poorly defined. This study aims at evaluating pancreas retransplantation outcome. METHODS Between 1976 and 2008, 569 pancreas transplantations were performed in Lyon and Geneva, including 37 second transplantations. Second graft survival was compared with primary graft survival of the same patients and the whole population. Predictive factors of second graft survival were sought. Patient survival and impact on kidney graft function and survival were evaluated. RESULTS Second pancreas survival of the 17 patients transplanted from 1995 was close to primary graft survival of the whole population (71% vs. 79% at 1 year and 59% vs. 69% at 5 years; P=0.5075) and significantly better than their first pancreas survival (71% vs. 29% at 1 year and 59% vs. 7% at 5 years; P=0.0008) regardless of the cause of first pancreas loss. The same results were observed with all 37 retransplantations. Survival of second simultaneous pancreas and kidney transplantations was better than survival of second pancreas after kidney. Patient survival was excellent (89% at 5 years). Pancreas retransplantation had no impact on kidney graft function and survival (100% at 5 years). CONCLUSION Pancreas retransplantation is a safe procedure with acceptable graft survival that should be proposed to diabetic patients who have lost their primary graft.Background If pancreas transplantation is a validated alternative for type 1 diabetic patients with end-stage renal disease, the management of patients who have lost their primary graft is poorly defined. This study aims at evaluating pancreas retransplantation outcome. Methods Between 1976 and 2008, 569 pancreas transplantations were performed in Lyon and Geneva, including 37 second transplantations. Second graft survival was compared with primary graft survival of the same patients and the whole population. Predictive factors of second graft survival were sought. Patient survival and impact on kidney graft function and survival were evaluated. Results Second pancreas survival of the 17 patients transplanted from 1995 was close to primary graft survival of the whole population (71% vs. 79% at 1 year and 59% vs. 69% at 5 years; P=0.5075) and significantly better than their first pancreas survival (71% vs. 29% at 1 year and 59% vs. 7% at 5 years; P=0.0008) regardless of the cause of first pancreas loss. The same results were observed with all 37 retransplantations. Survival of second simultaneous pancreas and kidney transplantations was better than survival of second pancreas after kidney. Patient survival was excellent (89% at 5 years). Pancreas retransplantation had no impact on kidney graft function and survival (100% at 5 years). Conclusion Pancreas retransplantation is a safe procedure with acceptable graft survival that should be proposed to diabetic patients who have lost their primary graft.

Profiling Sirolimus-Induced Inflammatory Syndrome: A Prospective Tricentric Observational Study

Background The use of the immunosuppressant sirolimus in kidney transplantation has been made problematic by the frequent occurrence of various side effects, including paradoxical inflammatory manifestations, the pathophysiology of which has remained elusive. Methods 30 kidney transplant recipients that required a switch from calcineurin inhibitor to sirolimus-based immunosuppression, were prospectively followed for 3 months. Inflammatory symptoms were quantified by the patients using visual analogue scales and serum samples were collected before, 15, 30, and 90 days after the switch. Results 66% of patients reported at least 1 inflammatory symptom, cutaneo-mucosal manifestations being the most frequent. Inflammatory symptoms were characterized by their lability and stochastic nature, each patient exhibiting a unique clinical presentation. The biochemical profile was more uniform with a drop of hemoglobin and a concomitant rise of inflammatory acute phase proteins, which peaked in the serum 1 month after the switch. Analyzing the impact of sirolimus introduction on cytokine microenvironment, we observed an increase of IL6 and TNFα without compensation of the negative feedback loops dependent on IL10 and soluble TNF receptors. IL6 and TNFα changes correlated with the intensity of biochemical and clinical inflammatory manifestations in a linear regression model. Conclusions Sirolimus triggers a destabilization of the inflammatory cytokine balance in transplanted patients that promotes a paradoxical inflammatory response with mild stochastic clinical symptoms in the weeks following drug introduction. This pathophysiologic mechanism unifies the various individual inflammatory side effects recurrently reported with sirolimus suggesting that they should be considered as a single syndromic entity.

Retreatment by antithymocyte globulin for second kidney transplantation: efficacy, tolerance and safety.

BACKGROUND It is unknown whether kidney transplant patients who receive rabbit antithymocyte globulin (rATG) become immunized against rabbit antibodies, leading to reduced efficacy, or are at higher risk of cytomegalovirus infection or post-transplant lymphoproliferative disorder (PTLD) on retreatment. The efficacy and tolerance of rATG when used as induction for the second time in patients undergoing retransplantation have not been evaluated. METHODS In a retrospective case-control study, 54 retransplanted patients who received rATG (Thymoglobulin) induction for the second time during 2004-2010 were compared to a matched cohort of 108 patients receiving rATG induction for a first kidney transplantation during the same period. Maintenance treatment was similar in both groups. RESULTS Median follow-up was 45.8 months and 47.3 months in the second and first treatment groups, respectively. No differences were observed between the two groups in terms of leukocyte, lymphocyte or platelet depletion. Dose and duration of rATG treatment were similar in both groups, suggesting a similar tolerance profile. Cytomegalovirus infection (including primoinfection and reactivation) occurred in 4/54 retreated patients versus 22/108 controls (p=0.108). Use of cytomegalovirus prophylaxis was similar between groups. PTLD occurred in one control patient and no retreated patients. CONCLUSION A second course of rATG induction results in similar lymphocyte depletion and is as well tolerated as a first course. The incidence of cytomegalovirus infection and post-transplant lymphoproliferative disease was not increased during retreatment. Further studies are required to evaluate specific T cell subpopulation depletion and compare long-term outcome in patients receiving a second induction with rATG.

PANCREAS RETRANSPLANTATION: PATIENT AND PANCREAS GRAFT SURVIVAL AND IMPACT ON KIDNEY GRAFT.: 662

Introduction. Pancreas transplantation is an acceptable therapeutic alternative in diabetic patients with end stage renal disease. However, pancreas graft loss remains frequent and care of patients who lose their first pancreas graft is poorly defined. This study aimed at evaluating the interest of pancreas retransplantation in terms of patient survival, second pancreas graft survival and impact of the pancreas retransplantation procedure on kidney graft. Methods. We retrospectively reviewed the medical files of the 517 pancreas transplantations performed in Lyon University Hospital between 1976 and 2008. Thirty patients who received two successive pancreas grafts were identified. We analyzed patient, first and second pancreas graft survival. The following predictive factors for second pancreas graft survival were studied in an univariate analysis: cause of first pancreas lost, delay between the two transplantations, type of second transplantation : kidney pancreas or pancreas alone, recipient age and gender, donor age and gender, cold ischemia time, portal or systemic venous drainage, enteric or bladder drainage, number of HLA mismatches, type of immunosuppression, anti-HLA antibodies, cytomegalovirus infection. The impact of pancreas transplantation on kidney graft survival and function (estimated by the MDRD formula) was also evaluated. Results. One and five-year patient survival rates were 100% and 92% respectively. The second pancreas graft survival was significantly better than the first graft survival in these patients (60% vs 27% at one year, and 44% vs 14% at five years, p < 0,05). A trend for better survival of the second pancreas graft was observed when the cause of the first pancreas loss was not surgical (75% vs 44% at five years, p = 0,08.). We did not identify any other factor (demographic, donor-related, surgical or immunological) influencing the second pancreas graft survival. Second pancreas transplantation procedure did not negatively impact kidney graft survival (100% at one and five years) or function (GFR: 58 ± 18 ml/ min/1,73m2 before vs 60 ± 15 ml/min/1,73m2 one year after second pancreas transplantation). Conclusion. Pancreas retransplantation is a safe procedure with acceptable graft survival that should be largely proposed to diabetic patients who have lost a first graft.