Madelon van Agteren

ABO-incompatible kidney transplant recipients have a higher bleeding risk after antigen-specific immunoadsorption

Pretransplant removal of antiblood group ABO antibodies is the cornerstone of all current ABO‐incompatible (ABOi) transplantation programmes. In our protocol, plasmapheresis (PP) is performed with a plasmafilter followed by immunoadsorption (IA) of anti‐ABO antibodies. The bleeding complications of this technique are not known. We analysed the data of all 65 consecutive ABOi kidney transplantations between March 2006 and October 2013 and compared these with matched 130 ABO‐compatible (ABOc) kidney transplantations. Cases differed from controls in the pre‐operative regimen, which included IA‐PP and rituximab, tacrolimus, mycophenolate mofetil, prednisone and immunoglobulines. Data on platelet count, blood loss and red blood cell (EC) transfusions during 48 h postoperatively were collected. ABOi patients received EC transfusions more frequently than controls (29% vs. 12%, P = 0.005). Intra‐operative blood loss was higher (544 vs. 355 ml, P < 0.005) and they experienced more major bleeding (≥3 EC within 24 h, 15% vs. 2%, P < 0.0005). Platelet count decreased by 28% after the pre‐operative IA. In a multivariate model, only the number of pre‐operative IAs was associated with the number of ECs given (OR per IA 1.9, P < 0.05). ABOi kidney transplant recipients have a high postoperative bleeding risk, correlating with the number of pre‐operative IA sessions performed.

The First Fifty ABO Blood Group Incompatible Kidney Transplantations: The Rotterdam Experience

This study describes the single center experience and long-term results of ABOi kidney transplantation using a pretransplantation protocol involving immunoadsorption combined with rituximab, intravenous immunoglobulins, and triple immune suppression. Fifty patients received an ABOi kidney transplant in the period from 2006 to 2012 with a follow-up of at least one year. Eleven antibody mediated rejections were noted of which 5 were mixed antibody and cellular mediated rejections. Nine cellular mediated rejections were recorded. Two grafts were lost due to rejection in the first year. One-year graft survival of the ABOi grafts was comparable to 100 matched ABO compatible renal grafts, 96% versus 99%. At 5-year follow-up, the graft survival was 90% in the ABOi versus 97% in the control group. Posttransplantation immunoadsorption was not an essential part of the protocol and no association was found between antibody titers and subsequent graft rejection. Steroids could be withdrawn safely 3 months after transplantation. Adverse events specifically related to the ABOi protocol were not observed. The currently used ABOi protocol shows good short and midterm results despite a high rate of antibody mediated rejections in the first years after the start of the program.

Post-Transplantation Immunoadsorption Can Be Withheld in ABO-Incompatible Kidney Transplant Recipients.

After ABO‐incompatible kidney transplantation, postoperative plasma exchange (PE) or immunoadsorption (IA) is performed per protocol or depending on postoperative A/B‐titers to prevent acute rejection. However, the need for postoperative PE or IA is not known. Since 2006, 30 consecutive patients received three standard postoperative IAs. Starting from 2009, the last 46 patients received only preoperative IA. Preoperative desensitization consisted of rituximab, tacrolimus, mycophenolate mofetil, prednisone and intravenous immunoglobulins. Antigen‐specific IA was performed pre‐operatively with the Glycosorb device. Biopsy‐proven acute rejections either antibody‐mediated (AMR) or mixed cellular and antibody‐mediated (MAR) within 3 months were recorded. The postoperative titer in patients with postoperative IA did not exceed 1:16 (IgG 1:4 [<2–16] median and range). The postoperative IgG titer was not significantly different after abandoning postoperative IA, although three patients had titers of 1:32 and one patient even 1:128. Rejections tended to be more frequent in the group with postoperative IA: 6 AMR and 3 MAR were recorded in 30 patients, vs. 4 AMR and 1 MAR in the 46 patients without postoperative IA (30 vs. 11%, P = 0.067). Baseline characteristics differed however: in the group with postoperative IA the vast majority had blood group O (87 vs. 52%, P = 0.003). Also, the IgG titer on the day of transplantation was higher (1:4 [<2–16] vs. 1:2 [<2–32], P = 0.007). All 14 patients with AMR and MAR rejections had postoperative IgG titers ≤1:16. Postoperative removal of A/B‐antibodies can be safely removed from the ABOi transplantation protocol using strict preoperative criteria for antibody lowering.

Alternative Living Kidney Donation Programs Boost Genetically Unrelated Donation

Donor-recipient ABO and/or HLA incompatibility used to lead to donor decline. Development of alternative transplantation programs enabled transplantation of incompatible couples. How did that influence couple characteristics? Between 2000 and 2014, 1232 living donor transplantations have been performed. In conventional and ABO-incompatible transplantation the willing donor becomes an actual donor for the intended recipient. In kidney-exchange and domino-donation the donor donates indirectly to the intended recipient. The relationship between the donor and intended recipient was studied. There were 935 conventional and 297 alternative program transplantations. There were 66 ABO-incompatible, 68 domino-paired, 62 kidney-exchange, and 104 altruistic donor transplantations. Waiting list recipients (n = 101) were excluded as they did not bring a living donor. 1131 couples remained of whom 196 participated in alternative programs. Genetically unrelated donors (486) were primarily partners. Genetically related donors (645) were siblings, parents, children, and others. Compared to genetically related couples, almost three times as many genetically unrelated couples were incompatible and participated in alternative programs (P < 0.001). 62% of couples were genetically related in the conventional donation program versus 32% in alternative programs (P < 0.001). Patient and graft survival were not significantly different between recipient programs. Alternative donation programs increase the number of transplantations by enabling genetically unrelated donors to donate.

Ruptured pseudoaneurysm in a renal allograft after percutaneous biopsy

Karel W.J. Klop, Oguzhan Karatepe, Jan J. Weening, Madelon van Agteren and Frank J.M.F. Dor Erasmus MC University Medical Center, Division of Transplant Surgery, Department of Surgery, Rotterdam, The Netherlands; Erasmus MC University Medical Center, Department of Pathology, Rotterdam, The Netherlands and Erasmus MC University Medical Center, Division of Nephrology, Department of Internal Medicine, Rotterdam, The Netherlands

Chronic-active antibody-mediated rejection with or without donor-specific antibodies has similar histomorphology and clinical outcome - a retrospective study

Chronic‐active antibody‐mediated rejection (c‐aABMR) is defined as histological evidence of chronic endothelial injury (cg), also known as transplant glomerulopathy, and either microvascular inflammation (MVI) or positivity for C4d. Importantly, the presence of donor‐specific antibodies (DSA) is currently still mandatory for the diagnosis of c‐aABMR. This retrospective study of 41 c‐aABMR patients investigates whether cases suspicious for c‐aABMR (DSA negative, n = 24) differ from cases of c‐aABMR (DSA positive, n = 17) with respect to renal histology, allograft function and long‐term graft survival. All included patients had progressive loss of allograft function and were diagnosed by for cause biopsy and scored according to the Banff ’15 criteria. In all DSApos cases, DSA were de novo and the majority was directed against HLA‐II being mostly anti‐HLA‐DQ antibodies. There were no statistically significant differences in clinical characteristics, decline in allograft function and renal allograft survival in cases with or without DSAs. All cases showed chronic histomorphological damage and inflammation, irrespective of the presence of DSA. Renal histology and clinical outcome of patients suspicious for c‐aABMR (DSAneg) do not significantly differ from patients with a diagnosis of c‐aABMR (DSApos). We believe that our study adds to the ongoing debate regarding the need for DSAs to be present for the diagnosis of c‐aABMR.

Pretransplant Tacrolimus Dose Requirements Predict Early Posttransplant Dose Requirements in Blood Group AB0-Incompatible Kidney Transplant Recipients.

Background: The aim of this study was to investigate whether pretransplant tacrolimus (Tac) dose requirements of patients scheduled to undergo living donor kidney transplantation correlate with posttransplantation dose requirements. Methods: The predictive value of Tac dose requirements (defined as the ratio of the Tac predose concentration, C0, divided by the total daily Tac dose, D) pretransplantation on this same parameter posttransplantation was assessed retrospectively in a cohort of 57 AB0-incompatible kidney transplant recipients. These patients started immunosuppressive therapy 14 days before transplant surgery. All patients were using a stable dose of glucocorticoids and were at steady-state Tac exposure before transplantation. Results: Tac dose requirements immediately before transplantation (C0/Dbefore) explained 63% of the Tac dose requirements on day 3 after transplantation: r2 = 0.633 [F (1, 44) = 75.97, P < 0.01]. No other clinical and demographic variables predicted Tac dose requirements early after transplantation. Conclusions: Steady-state Tac dose requirement before transplantation largely predicted posttransplantation Tac dose requirements in AB0-incompatible kidney transplant recipients. The importance of this finding is that the posttransplantation Tac dose can be individualized based on a patients pretransplantation Tac concentration/dose ratio. Pretransplant Tac phenotyping therefore has the potential to improve transplantation outcomes.

Quiz Page January 2011

m o n m e n ( t 46-year-old kidney transplant ecipient presented with hematuia and malaise. He developed idney failure due to reflux nehritis as a complication of spina ifida, and a Bricker deviation as constructed. The first kidney ransplant failed after 18 months ecause of chronic allograft nehropathy, and his immunosupressive regimen of tacrolimus, ycophenolate, and prednisone as tapered off. Although the secnd transplant maintained excelent function for 5 years (plasma reatinine, 1.1 mg/dL [97.24 mol/L]; estimated glomerular ltration rate [eGFR], 74 mL/min/ s

Quiz page January 2011. A kidney transplant patient with rapidly progressive kidney failure and a radiopaque pyelum wall.

m o n m e n ( t 46-year-old kidney transplant ecipient presented with hematuia and malaise. He developed idney failure due to reflux nehritis as a complication of spina ifida, and a Bricker deviation as constructed. The first kidney ransplant failed after 18 months ecause of chronic allograft nehropathy, and his immunosupressive regimen of tacrolimus, ycophenolate, and prednisone as tapered off. Although the secnd transplant maintained excelent function for 5 years (plasma reatinine, 1.1 mg/dL [97.24 mol/L]; estimated glomerular ltration rate [eGFR], 74 mL/min/ s

A Successful Approach to Kidney Transplantation in Patients With Enteric (Secondary) Hyperoxaluria

Background Enteric hyperoxaluria due to malabsorption may cause chronic oxalate nephropathy and lead to end-stage renal disease. Kidney transplantation is challenging given the risk of recurrent calcium-oxalate deposition and nephrolithiasis. Methods We established a protocol to reduce plasma oxalic acid levels peritransplantation based on reduced intake and increased removal of oxalate. The outcomes of 10 kidney transplantation patients using this protocol are reported. Results Five patients received a living donor kidney and had immediate graft function. Five received a deceased donor kidney and had immediate (n = 1) or delayed graft function (n = 4). In patients with delayed graft function, the protocol was prolonged after transplantation. In 3 patients, our protocol was reinstituted because of late complications affecting graft function. One patient with high-output stoma and relatively low oxalate levels had lost her first kidney transplant because of recurrent oxalate depositions but now receives intravenous fluid at home on a routine basis 3 times per week to prevent dehydration. Patients are currently between 3 and 32 months after transplantation and all have a stable estimated glomerular filtration rate (mean, 51 ± 21 mL/min per 1.73 m2). In 4 of 8 patients who underwent for cause biopsies after transplantation oxalate depositions were found. Conclusions This is the first systematic description of kidney transplantation in a cohort of patients with enteric hyperoxaluria. Common complications after kidney transplantation impact long-term transplant function in these patients. With our protocol, kidney transplantation outcomes were favorable in this population with unfavorable transplantation prospects and even previous unsuccessful transplants.