Kidney Retransplantation after Graft Failure: Variables Influencing Long-Term Survival.

Background: There is an increasing demand for kidney retransplantation. Most studies report inferior outcomes compared to primary transplantation, consequently feeding an ethical dilemma in the context of chronic organ shortage. Objective: To assess variables influencing long-term graft survival after kidney retransplantation. Material and Methods. All patients transplanted at our center between 2000 and 2016 were analyzed retrospectively. Survival was estimated with the Kaplan-Meier method, and risk factors were identified using multiple Cox regression. Results: We performed 1,376 primary kidney transplantations and 222 retransplantations. The rate of retransplantation was 67.8% after the first graft loss, with a comparable 10-year graft survival compared to primary transplantation (67% vs. 64%, p=0.104) but an inferior graft survival thereafter (log-rank p=0.026). Independent risk factors for graft survival in retransplantation were age ≥ 50 years, time on dialysis ≥1 year, previous graft survival <2 years, ≥1 mild comorbidity in the Charlson-Deyo index, active smoking, and life-threatening complications (Clavien-Dindo grade IV) at first transplantation. Conclusion: Graft survival is comparable for first and second kidney transplantation within the first 10 years. Risk factors for poor outcomes after retransplantation are previous graft survival, dialysis time after graft failure, recipient age, comorbidities, and smoking. Patients with transplant failure should have access to retransplantation as early as possible.

Successful Induction of Specific Immunological Tolerance by Combined Kidney and Hematopoietic Stem Cell Transplantation in HLA-Identical Siblings.

Induction of immunological tolerance has been the holy grail of transplantation immunology for decades. The only successful approach to achieve it in patients has been a combined kidney and hematopoietic stem cell transplantation from an HLA-matched or -mismatched living donor. Here, we report the first three patients in Europe included in a clinical trial aiming at the induction of tolerance by mixed lymphohematopoietic chimerism after kidney transplantation. Two female and one male patient were transplanted with a kidney and peripherally mobilized hematopoietic stem cells from their HLA-identical sibling donor. The protocol followed previous studies at Stanford University: kidney transplantation was performed on day 0 including induction with anti-thymocyte globulin followed by conditioning with 10x 1.2 Gy total lymphoid irradiation and the transfusion of CD34+ cells together with a body weight-adjusted dose of donor T cells on day 11. Immunosuppression consisted of cyclosporine A and steroids for 10 days, cyclosporine A and mycophenolate mofetil for 1 month, and then cyclosporine A monotherapy with tapering over 9-20 months. The 3 patients have been off immunosuppression for 4 years, 19 months and 8 months, respectively. No rejection or graft-versus-host disease occurred. Hematological donor chimerism was stable in the first, but slowly declining in the other two patients. A molecular microscope analysis in patient 2 revealed the genetic profile of a normal kidney. No relevant infections were observed, and the quality of life in all three patients is excellent. During the SARS-CoV-2 pandemic, all three patients were vaccinated with the mRNA vaccine BNT162b2 (Comirnaty®), and they showed excellent humoral and in 2 out 3 patients also cellular SARS-CoV-2-specific immunity. Thus, combined kidney and hematopoietic stem cell transplantation is a feasible and successful approach to induce specific immunological tolerance in the setting of HLA-matched sibling living kidney donation while maintaining immune responsiveness to an mRNA vaccine (ClinicalTrials.gov: NCT00365846).

Sleeve gastrectomy enables simultaneous pancreas and kidney transplantation in severely obese recipients.

BACKGROUND: Obesity adversely affects wait-listing and precludes patients with concomitant end-stage renal disease and type 1 diabetes mellitus from getting a simultaneous pancreas and kidney transplantation (SPK). OBJECTIVE: To analyze safety and efficacy of laparoscopic sleeve gastrectomy (LSG) before SPK in severely obese type I diabetics. METHODS: We assessed weight curve, complications, and graft function of three patients who underwent LSG before SPK. RESULTS: LSG was uneventful in all patients. Body mass index dropped from 38.4 (range 35.7 - 39.9) before LSG to 28.5 (26.8 - 30.9) until SPK, with a mean loss of 25.8% (22.4 - 32.3). Interval between LSG and SPK was 364.3 (173 - 587) days. Pancreas and kidney graft function was excellent, with 100% insulin-free and dialysis-free survival over a mean follow-up of 3.6 (2.9 - 4.5) years. A1C dropped from 7% (6.3 - 8.2) before LSG to 4.9% (4.7 - 5.3) and 4.8% (4.5 - 5.1) 1 and 2 years after SPK, respectively. CONCLUSION: LSG before SPK is safe and effective to enable severely obese type I diabetics to receive a lifesaving transplant. This is the first study analyzing the role of bariatric surgery before simultaneous pancreas and kidney transplantation.

Management of Active Surveillance-Eligible Prostate Cancer during Pretransplantation Workup of Patients with Kidney Failure: A Simulation Study.

BACKGROUND AND OBJECTIVES: The general rule that every active malignancy is an absolute contraindication for kidney transplantation is challenged by kidney failure patients diagnosed with active surveillance-eligible prostate cancer during pretransplantation workup. Interdisciplinary treatment teams therefore often face the challenge of balancing the benefits of early kidney transplantation and the risk of metastatic progression. Hence, we compared the quality-adjusted life expectancy of different management strategies in kidney failure patients diagnosed with active surveillance-eligible prostate cancer during pretransplantation workup. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A discrete event simulation model was developed on the basis of a systematic literature search, clinical guidelines, and expert opinion. After model validation and calibration, we simulated four management strategies in a hypothetical cohort of 100,000 patients: Definitive treatment (surgery or radiation therapy) and listing after a waiting period of 2 years, definitive treatment and immediate listing, active surveillance and listing after a waiting period of 2 years, and active surveillance and immediate listing. Individual patient results (quality-adjusted life years; QALYs) were aggregated into strategy-specific means (± SEs). RESULTS: Active surveillance and immediate listing yielded the highest amount of quality-adjusted life expectancy (6.97 ± 0.01 QALYs) followed by definitive treatment and immediate listing (6.75 ± 0.01 QALYs). These two strategies involving immediate listing not only outperformed those incorporating a waiting period of 2 years (definitive treatment: 6.32 ± 0.01 QALYs; active surveillance: 6.59 ± 0.01 QALYs) but also yielded a higher proportion of successfully performed transplantations (72% and 74% versus 56% and 59%), with less time on hemodialysis on average (4.02 and 3.81 years versus 4.80 and 4.65 years). CONCLUSIONS: Among kidney failure patients diagnosed with active surveillance-eligible prostate cancer during pretransplantation workup, the active surveillance and immediate listing strategy outperformed the alternative management strategies from a quality of life expectancy perspective, followed by definitive treatment and immediate listing.

Metagenomic Virome Sequencing in Living Donor and Recipient Kidney Transplant Pairs Revealed JC Polyomavirus Transmission.

BACKGROUND: Before kidney transplantation, donors and recipients are routinely screened for viral pathogens using specific tests. Little is known about unrecognized viruses of the urinary tract that potentially result in transmission. Using an open metagenomic approach, we aimed to comprehensively assess virus transmission in living-donor kidney transplantation. METHODS: Living kidney donors and their corresponding recipients were enrolled at the time of transplantation. Follow-up study visits for recipients were scheduled 4-6 weeks and 1 year thereafter. At each visit, plasma and urine samples were collected and transplant recipients were evaluated for signs of infection or other transplant-related complications. For metagenomic analysis, samples were enriched for viruses, amplified by anchored random polymerase chain reaction (PCR), and sequenced using high-throughput metagenomic sequencing. Viruses detected by sequencing were confirmed using real-time PCR. RESULTS: We analyzed a total of 30 living kidney donor and recipient pairs, with a follow-up of at least 1 year. In addition to viruses commonly detected during routine post-transplant virus monitoring, metagenomic sequencing detected JC polyomavirus (JCPyV) in the urine of 7 donors and their corresponding recipients. Phylogenetic analysis confirmed infection with the donor strain in 6 cases, suggesting transmission from the transplant donor to the recipient, despite recipient seropositivity for JCPyV at the time of transplantation. CONCLUSIONS: Metagenomic sequencing identified frequent transmission of JCPyV from kidney transplant donors to recipients. Considering the high incidence rate, future studies within larger cohorts are needed to define the relevance of JCPyV infection and the donor's virome for transplant outcomes.