J. van de Wetering

Successful expansion of the living donor pool by alternative living donation programs.

Between January 2000 and December 2007, 786 potential recipients and 1059 potential donors attended our pretransplant unit with the request for a living‐donor renal transplant procedure. The recipients brought one potential donor in 77.2% and two or more donors in 22.8% of cases. In the regular living donor program, a compatible donor was found for 467 recipients. Without considering alternative donation, 579 donors would have been refused. Alternative living donation programs led to 114 compatible combinations: kidney‐exchange program (35), ABO‐incompatible donation (25), anonymous donation (37) and domino‐paired anonymous donation (17). Together, the 114 alternative program donations and the 467 regular living donations led to 581 living donor transplantations (24.4% increase). Eventually for 54.9% (581/1059) of our donors, a compatible combination was found. Donor–recipient incompatibility comprised 19.4% (89/458) in the final refused population, which is 8.8% of the potential donor–recipient couples. Without considering alternative donation, 30.1% (174/579) of the refused donors would have been refused on incompatibility and 6.4% (37/579) because they were anonymous. This is 20% of the potential donor population (211/1059). The implementation of alternative living donation programs led to a significant increase in the number of transplantations, while transplantations via the direct donation program steadily increased.

A Randomized Controlled Trial Comparing the Efficacy of Cyp3a5 Genotype-Based With Body-Weight-Based Tacrolimus Dosing After Living Donor Kidney Transplantation.

Patients expressing the cytochrome P450 (CYP) 3A5 gene require a higher tacrolimus dose to achieve therapeutic exposure compared with nonexpressers. This randomized‐controlled study investigated whether adaptation of the tacrolimus starting dose according to CYP3A5 genotype increases the proportion of kidney transplant recipients being within the target tacrolimus predose concentration range (10–15 ng/mL) at first steady‐state. Two hundred forty living‐donor, renal transplant recipients were assigned to either receive a standard, body‐weight‐based or a CYP3A5 genotype‐based tacrolimus starting dose. At day 3, no difference in the proportion of patients having a tacrolimus exposure within the target range was observed between the standard‐dose and genotype‐based groups: 37.4% versus 35.6%, respectively; p = 0.79. The proportion of patients with a subtherapeutic (i.e. <10 ng/mL) or a supratherapeutic (i.e. >15 ng/mL) Tac predose concentration in the two groups was also not significantly different. The incidence of acute rejection was comparable between both groups (p = 0.82). Pharmacogenetic adaptation of the tacrolimus starting dose does not increase the number of patients having therapeutic tacrolimus exposure early after transplantation and does not lead to improved clinical outcome in a low immunological risk population.

Altruistic Donor Triggered Domino-Paired Kidney Donation for Unsuccessful Couples from the Kidney-Exchange Program

Between January 2000 and July 2009, 132 individuals inquired about altruistic kidney donation to strangers. These donors were willing to donate to genetically and emotionally unrelated patients. Some altruistic donors wished to donate to a specific person, but most wished to donate anonymously. In domino‐paired donation, the altruistic donor donates to the recipient of an incompatible couple; the donor of that couple (domino‐donor) donates to another couple or to the waiting list. In contrast to kidney‐exchange donation where bilateral matching of couples is required, recipient and donor matching are unlinked in domino‐paired donation. This facilitates matching for unsuccessful couples from the kidney‐exchange program where blood type O prevails in recipients and is under‐represented in donors. Fifty‐one altruistic donors (39%) donated their kidney and 35 domino‐donors were involved. There were 29 domino procedures, 24 with 1 altruistic donor and 1 domino‐donor, 5 with more domino‐donors. Eighty‐six transplantations were performed. Donor and recipient blood type distribution in the couples limited allocation to blood type non‐O waiting list patients. The success rate of domino‐paired donation is dependent on the composition of the pool of incompatible pairs, but it offers opportunities for difficult to match pairs that were unsuccessful in the kidney‐exchange program.

A Multiplex Bead Array Analysis to Monitor Donor-Specific Cytokine Responses After Withdrawal of Immunosuppression in HLA-Identical living Related Kidney Transplant Patients

Immune reactivity after HLA-identical living related (LR) kidney transplantation can be caused by minor histocompatibility antigen and non-HLA antigen mismatches between donor and recipient. In our center, HLA-identical LR kidney transplant recipients receive azathioprine (AZA) or mycophenolate mofetil (MMF) in combination with corticosteroids for 1 year after transplantation. Thereafter, AZA or MMF was withdrawn, and the patients were treated with steroid monotherapy as maintenance therapy. We questioned whether withdrawal of AZA or MMF affected the donor-specific lymphocyte proliferation and cytokine production. Donor and third-party T-cell reactivities were determined by mixed lymphocyte reactions and by cytokine production using multiplex bead array technique. The donor and third-party proliferative capacities were not affected after withdrawal of AZA or MMF. Thirteen of 17 cytokines were detected by the multiplex bead array technique. No differences were observed after third-party induced cytokine production after withdrawal of AZA or MMF. However, production of donor-specific interferon-gamma and macrophage inflammatory protein-1beta increased after discontinuation of AZA or MMF, but no clinically relevant acute rejection was observed. In conclusion, after HLA-identical LR kidney transplantation, donor-specific cytokine responses can be found when AZA or MMF therapy is discontinued. The clinical relevance of this phenomenon is still not evident.

Influence of Temperature and Stimulus Interval Variations on the Propagation of Contractions in the Pig Ureter

The influences of ureter temperature and time interval between stimulations on the velocity of propagation of contractions in the pig ureter were studied in vitro. The propagation velocity was calculated from electromyogram signals measured at regular distances along the ureter. It was found that a temperature decrease of 3 degrees C causes a velocity decrease of nearly 5 mm/s. The influence of the interstimulus interval is much smaller: a reduction from 300 to 10 s causes a 10% drop in propagation velocity. Both phenomena can be understood from changes in the strength-duration curve describing the excitability of the tissue and clarify the discrepancies between propagation velocity measurements in vitro and in vivo.

The Influence of Comorbidity On Graft and Patient Survival After Kidney Transplantation.: Abstract# 2207

2184 Kidneys From DCD Donors Are Underutilized in Pediatric Patients. E. King, N. Desai, D. Segev. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. Background. In pediatric patients, donation after cardiac death (DCD) organs account for just over 2% of all kidney transplants. It is diffi cult to defi nitively ascertain survival of DCD grafts through single center studies when the frequency of DCD transplantation is so low. A comprehensive study of national data is necessary to better defi ne outcomes and utilization of DCD compared to donation after brain death (DBD) kidneys. Methods. SRTR data (April 1994 to September 2013) of 7,318 pediatric kidneyonly deceased donor transplant recipients (age<18) were analyzed. Death censored graft survival was defi ned as the time from transplantation to graft loss or last date of follow-up with a functional graft. Kaplan Meier survival analysis was used to compare graft loss between DCD and DBD kidneys. Lorenz curves and Gini coeffi cient were used to compare center-level clustering in use of DCD versus DBD kidneys in pediatric recipients across US centers. Results. Graft survival was not statistically signifi cantly different between DCD and DBD organs in pediatric kidney recipients (p=0.88). There was a slight but not statistically signifi cant difference in the occurrence of delayed graft function (2.9% and 0.7%, p=0.06), however the mean creatinine at discharge following transplantation was higher among those receiving DCD kidneys compared to DBD (2.1 mg/dL and 1.5 mg/dL, p < 0.05). Lorenz curves demonstrate that around 25% of centers in the US performed 100% of DCD kidney transplants in pediatric recipients, in a pattern far more center-clustered than DBD transplants. Conclusions. DCD kidneys offer comparable outcomes in pediatric kidney transplantation, but only a small number of pediatric transplant centers currently utilize these organs. Abstract# 2185 Long-Term Data On the Use of Everolimus and Low-Dose Ciclosporin A in Children After Kidney Transplantation (Tx). L. Brunkhorst,1 T. Ahlenstiel,1 F. Lehner,2 L. Pape.1 1Pediatric Nephrology, Hannover Medical School, Hannover, Germany; 2Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany. Background: Actually, only short-term trials using Everolimus in children after Tx have been published. This is the fi rst prospective study to present four-year data using low-dose Ciclosporin A (CsA), Everolimus and steroid elimination. Methods: 35 children (median age: 10.7 ± 5.6 years) received Basiliximab, CsA and Prednisolone after Tx. Everolimus (1.6mg/m2/day) treatment was added two weeks post Tx. In 83% of the patients Prednisolone was withdrawn 8-10 months post Tx. Long-term target trough levels for CsA and Everolimus were 30-50 ng/ ml and 2-4 ng/ml. Clinical outcome and side effects were evaluated prospectively. Results: Patient and graft survival were 100% and median eGFR was 62, 61, 58 and 65 ml/min/1.73m2 1-4 years after Tx. Acute rejection (BANFF ≥ Ia) was diagnosed in indication biopsies in in 2/35 (6%) children in the fi rst year after Tx. In the remaining observation time, acute rejection was only diagnosed in one child in year 2 and 4. De novo Donor specifi c antibodies were found in 4/35 patients in yearly checkups with the histopathological diagnosis of chronic humoral rejection in one patient. In the four years observation time, one child developed EBV associated PTLD that was successfully treated with Rituximab. Two patients developed transient wound healing problems, 17% aphthous stomatitis. No signifi cant albuminuria > 100 mg/ mmol creatinine was recognized. Height SDS was -0.73 / -0.74 two and four years after Tx. Despite an elevation of estradiol in 33% of the girls, all sex hormone levels were within the normal range. Conclusions: After ped. kidney Tx, de novo immunosuppression with low-dose CsA, Everolimus, and a withdrawal of Prednisolone is followed by excellent graft survival and function, good growth and only a small number side effects. DISCLOSURE: Pape, L.: Grant/Research Support, Novartis. 2185 Long-Term Data On the Use of Everolimus and Low-Dose Ciclosporin A in Children After Kidney Transplantation (Tx). L. Brunkhorst,1 T. Ahlenstiel,1 F. Lehner,2 L. Pape.1 1Pediatric Nephrology, Hannover Medical School, Hannover, Germany; 2Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany. Background: Actually, only short-term trials using Everolimus in children after Tx have been published. This is the fi rst prospective study to present four-year data using low-dose Ciclosporin A (CsA), Everolimus and steroid elimination. Methods: 35 children (median age: 10.7 ± 5.6 years) received Basiliximab, CsA and Prednisolone after Tx. Everolimus (1.6mg/m2/day) treatment was added two weeks post Tx. In 83% of the patients Prednisolone was withdrawn 8-10 months post Tx. Long-term target trough levels for CsA and Everolimus were 30-50 ng/ ml and 2-4 ng/ml. Clinical outcome and side effects were evaluated prospectively. Results: Patient and graft survival were 100% and median eGFR was 62, 61, 58 and 65 ml/min/1.73m2 1-4 years after Tx. Acute rejection (BANFF ≥ Ia) was diagnosed in indication biopsies in in 2/35 (6%) children in the fi rst year after Tx. In the remaining observation time, acute rejection was only diagnosed in one child in year 2 and 4. De novo Donor specifi c antibodies were found in 4/35 patients in yearly checkups with the histopathological diagnosis of chronic humoral rejection in one patient. In the four years observation time, one child developed EBV associated PTLD that was successfully treated with Rituximab. Two patients developed transient wound healing problems, 17% aphthous stomatitis. No signifi cant albuminuria > 100 mg/ mmol creatinine was recognized. Height SDS was -0.73 / -0.74 two and four years after Tx. Despite an elevation of estradiol in 33% of the girls, all sex hormone levels were within the normal range. Conclusions: After ped. kidney Tx, de novo immunosuppression with low-dose CsA, Everolimus, and a withdrawal of Prednisolone is followed by excellent graft survival and function, good growth and only a small number side effects. DISCLOSURE: Pape, L.: Grant/Research Support, Novartis. Cardiovascular Complications in Kidney Transplantation II Wednesday, July 30, 2014 4:00 PM 5:30 PM Room 3016/3018 Abstract# 2207 The Infl uence of Comorbidity On Graft and Patient Survival After Kidney Transplantation. M. Laging,1 J. Kal-van Gestel,1 J. van de Wetering,1 J. Ijzermans,2 M. Betjes,1 W. Weimar,1 J. Roodnat.1 1Internal Medicine, Erasmus MC, Rotterdam, Netherlands; 2General Surgery, Erasmus MC, Rotterdam, Netherlands. Background 2207 The Infl uence of Comorbidity On Graft and Patient Survival After Kidney Transplantation. M. Laging,1 J. Kal-van Gestel,1 J. van de Wetering,1 J. Ijzermans,2 M. Betjes,1 W. Weimar,1 J. Roodnat.1 1Internal Medicine, Erasmus MC, Rotterdam, Netherlands; 2General Surgery, Erasmus MC, Rotterdam, Netherlands. Background Nowadays patients with a large variety of comorbidities are referred for transplantation. Acceptance criteria for kidney transplantation are continuously being eased. We questioned to what extent increasing severity and number of comorbidities interfere with graft and patient survival. Methods In our center, 1728 patients were transplanted between January 1, 2000 and December 31, 2012. Four pre-transplant comorbidity categories were defi ned: cardiovascular