Thierry Berney

Low risk of anti-human leukocyte antigen antibody sensitization after combined kidney and islet transplantation.

Anti-human leukocyte antigen (HLA) antibody could lead to humoral rejection and a decrease in graft survival after kidney transplantation. A recent report has suggested that islet transplantation alone is associated with a high rate of sensitization. The withdrawal of the immunosuppressive therapy because of the progressive nonfunction of the islets could explain the high rate of sensitization. Because the specific risk of immunization of multiple islet infusions remains unknown, we studied the immunization rate in our cohort of multiple islet infusions transplant recipients. De novo anti-HLA antibodies were analyzed in 37 patients after islets alone (n=8), islet-after-kidney (n=13), and simultaneous islet-kidney (n=16) transplantation by solid phase assays over time. The rate of immunization was 10.8% that is comparable with the risk of immunization after kidney transplantation alone. Multiple islet infusions do not represent a specific risk for the development of anti-HLA antibodies after combined kidney-islets transplantation.

Impairment of renal function after islet transplant alone or islet-after-kidney transplantation using a sirolimus/tacrolimus-based immunosuppressive regimen

The immunosuppressive (IS) regimen based on sirolimus/low‐dose tacrolimus is considered a major determinant of success of the Edmonton protocol. This regimen is generally considered safe or even protective for the kidney. Herein, we analyzed the impact of the sirolimus/low‐dose tacrolimus combination on kidney function. The medical charts of islet transplant recipients with at least 6u2003months follow up were reviewed. There were five islet‐after‐kidney and five islet transplantation alone patients. Serum creatinin, albuminuria, metabolic control markers and graft function were analyzed. Impairment of kidney function was observed in six of 10 patients. Neither metabolic markers nor IS drugs levels were significantly associated with the decrease of kidney function. Although a specific etiology was not identified, some subsets of patients presented a higher risk for decline of kidney function. Low creatinin clearance, albuminuria and long‐established kidney graft were associated with poorer outcome.

Discordant rejection in simultaneous pancreas and kidney transplantation: true discordance or analysis artefact ?

The article by Parajuli etxa0al published in this issue of Transplant International is the latest, and perhaps the most convincing in a relatively small body of literature, to suggest that in a situation of simultaneous pancreas-kidney transplantation (SPK), in which both organs are from the same donor, one organ may be undergoing acute rejection independently from the other (1). The organ hierarchy in immunogeneicity and susceptibility to rejection is a long known biological phenomenon, with the liver at one end of the spectrum and the intestine the other. It was originally thought that such a hierarchy between kidney and pancreas was in disfavor of the latter (2). n nThis article is protected by copyright. All rights reserved.

Successful pregnancy and delivery after simultaneous islet-kidney transplantation

Allogeneic islet of Langerhans transplantation is a recognized beta‐cell replacement therapy for patients affected by type 1 diabetes mellitus. Type 1 diabetes mellitus is a condition associated with an increased risk of adverse outcomes for pregnant women and fetuses. We report the case of a 29‐year‐old woman with type 1 diabetes mellitus, who underwent successful allogeneic islet transplantation with simultaneous kidney transplantation. She achieved durable insulin independence after 2 islet infusions. Pregnancy was desired and planned 2 years after the last islet infusion. Multidisciplinary monitoring of pregnancy was carried out and the immunosuppressive regimen was adapted. Euglycemia was maintained throughout pregnancy without the need for exogenous insulin. After an uneventful pregnancy, she delivered on term an otherwise healthy male child with imperforate anus that was immediately surgically corrected. In conclusion, allogeneic islet transplantation is a suitable treatment for women of childbearing age with complicated type 1 diabetes mellitus, allowing physiologic glycemic control during pregnancy with a low risk of graft loss. This target can be achieved only by a tight multidisciplinary follow‐up, including immunosuppressive therapy adaptation and adequate diabetes and obstetrical monitoring.

Downstaging prior to liver transplantation for hepatocellular carcinoma: advisable but at the price of an increased risk of cancer recurrence - a retrospective study

The use of downstaging prior to liver transplantation for hepatocellular carcinoma (HCC) still needs refinement. This study included patients with HCC listed for transplantation according to the Total Tumour Volume (TTV) ≤115 cm3 and alpha fetoprotein (AFP) ≤400 ng/ml criteria, with and without previous downstaging. Overall, 455 patients were listed, and 286 transplanted. Post‐transplant follow‐up was 38.5 ± 1.7 months. Patients downstaged to TTV115/AFP400 (n = 29) demonstrated similar disease‐free survivals (DFS, 74% vs. 80% at 5 years, P = 0.949), but a trend to more recurrences (14% vs. 5.8%, P = 0.10) than those always within TTV115/AFP400 (n = 257). Similarly, patients downstaged to Milan criteria (n = 80) demonstrated similar DFS (76% vs. 86% at 5 years, P = 0.258), but more recurrences (11% vs. 1.7%, P = 0.001) than those always within Milan (n = 177). Among patients downstaged to Milan, those originally beyond TTV115/AFP400 (n = 27) had similar outcomes as those originally beyond Milan, but within TTV115/AFP400 (n = 53). However, the likelihood of being within Milan at transplant was lower for patients with more advanced original HCCs (P < 0.0001). Overall, despite an expected increase in post‐transplant HCC recurrence, similar survivals can be achieved with and without downstaging, using the TTV115/AFP400 transplantation criteria, and including patients with advanced original HCCs. Downstaging should continue to be performed.

Pancreas preservation fluid microbial contamination is associated with poor islet isolation outcomes - a multi-centre cohort study

The microbiological safety of islet preparations is paramount. Preservation medium contamination is frequent, and its impact on islet yield and function remains unclear. Microbiological samples collected during islet isolations from 2006 to 2016 were analyzed and correlated to isolation and allo‐ and autotransplantation outcomes. Microbial contamination of preservation medium was found in 64.4% of processed donor pancreases (291/452). We identified 464 microorganisms including Staphylococcus (253/464, 54.5%), Streptococcus (31/464, 6.7%), and Candida species (25/464, 5.4%). Microbial contamination was associated with longer warm and cold ischemia times and lower numbers of postpurification islet equivalents, purity, transplant rate, and stimulation index (all P < 0.05). Six percent of the preparations accepted for transplantation showed microbial contamination after isolation (12/200); 9 of 12 were Candida species. Six patients were transplanted with a sample with late microbial growth discovered after the infusion. Insulin independence rate was not affected. This risk of transplanting a contaminated islets preparation was reduced by half following the implementation of an additional sampling after 24 h of islet culture. Pancreas preservation fluid microbial contamination is associated with lower transplant rate and poorer in vitro function, but not with changes in graft survival. Culture medium testing 1 day after isolation reduces the risk of incidental transplantation with contaminated islets.

Effects of remote ischemic preconditioning on intraportal islet transplantation in a rat model

Remote ischaemic preconditioning (RIPC), which is the intermittent interruption of blood flow to a site distant from the target organ, is known to improve solid organ resistance to ischaemia‐reperfusion injury. This procedure could be of interest in islet transplantation to mitigate hypoxia‐related loss of islet mass after isolation and transplantation. Islets isolated from control or RIPC donors were analyzed for yield, metabolic activity, gene expression and high mobility group box‐1 (HMGB1) content. Syngeneic marginal mass transplantation was performed in four streptozotocin‐induced diabetic groups: control, RIPC in donor only, RIPC in recipient only, and RIPC in donor and recipient. Islets isolated from RIPC donors had an increased yield of 20% after 24 h of culture compared to control donors (P = 0.007), linked to less cell death (P = 0.08), decreased expression of hypoxia‐related genes (Hif1a P = 0.04; IRP94 P = 0.008), and increased intra‐cellular (P = 0.04) and nuclear HMGB1. The use of RIPC in recipients only did not allow for reversal of diabetes, with increased serum HMGB1 at day 1; the three other groups demonstrated significantly better outcomes. Performing RIPC in the donors increases islet yield and resistance to hypoxia. Validation is needed, but this strategy could help to decrease the number of donors per islet recipient.

Usefulness of a systematic approach at listing for vaccine prevention in solid organ transplant candidates

Solid organ transplant (SOT) candidates may not be immune against potentially vaccine‐preventable diseases because of insufficient immunizations and/or limited vaccine responses. We evaluated the impact on vaccine immunity at transplant of a systematic vaccinology workup at listing that included (1) pneumococcal with and without influenza immunization, (2) serology‐based vaccine recommendations against measles, varicella, hepatitis B virus, hepatitis A virus, and tetanus, and (3) the documentation of vaccines and serology tests in a national electronic immunization registry (www.myvaccines.ch). Among 219 SOT candidates assessed between January 2014 and November 2015, 54 patients were transplanted during the study. Between listing and transplant, catch‐up immunizations increased the patients’ immunity from 70% to 87% (hepatitis A virus, P = .008), from 22% to 41% (hepatitis B virus, P = .008), from 77% to 91% (tetanus, P = .03), and from 78% to 98% (Streptococcus pneumoniae, P = .002). Their immunity at transplant was significantly higher against S. pneumoniae (P = .006) and slightly higher against hepatitis A virus (P = .07), but not against hepatitis B virus, than that of 65 SOT recipients transplanted in 2013. This demonstrates the value of a systematic multimodal serology‐based approach of immunizations of SOT candidates at listing and the need for optimized strategies to increase their hepatitis B virus vaccine responses.

Surgical Repair of a Living-Donor Kidney Graft Artery Kink by a Postanastomotic External Iliac Artery Rotation and Reanastomosis

A 61-year-old man received a living-donor kidney graft for an end-stage renal disease. In the postoperative course, the patient was oliguric and needed dialysis. The postoperative Doppler showed a normal peak systolic velocity and maintained parenchymal perfusion associated with a parvus tardus signal. The patient was operated, and a kinked renal artery was found. To reposition the artery, the distal iliac artery was clamped, sectioned, shortened, and reanastomosed after a 90° axial rotation. This innovative technic allowed restoration of a normal flow in the parenchyma and avoided an additional clamping, cooling, ischemia, and reanastomosis/reperfusion of the graft. Postoperative diuresis immediately raised >100xa0mL/hr and creatinine durably returned to normal values.