Non-antigen-specific Immunoadsorption Is a Risk Factor for Severe Postoperative Infections in ABO-Incompatible Kidney Transplant Recipients.

ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABO-compatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb® ABO columns to reusable non-antigen-specific Immunosorba® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004-2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3-8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx.

Rescue Allocation Modes in Eurotransplant Kidney Transplantation: Recipient Oriented Extended Allocation Versus Competitive Rescue Allocation-A Retrospective Multicenter Outcome Analysis.

BACKGROUND: Whenever the kidney standard allocation (SA) algorithms according to the Eurotransplant (ET) Kidney Allocation System or the Eurotransplant Senior Program fail, rescue allocation (RA) is initiated. There are 2 procedurally different modes of RA: recipient oriented extended allocation (REAL) and competitive rescue allocation (CRA). The objective of this study was to evaluate the association of patient survival and graft failure with RA mode and whether or not it varied across the different ET countries. METHODS: The ET database was retrospectively analyzed for donor and recipient clinical and demographic characteristics in association with graft outcomes of deceased donor renal transplantation (DDRT) across all ET countries and centers from 2014 to 2021 using Cox proportional hazards methods. RESULTS: Seventeen thousand six hundred seventy-nine renal transplantations were included (SA 15 658 [89%], REAL 860 [4.9%], and CRA 1161 [6.6%]). In CRA, donors were older, cold ischemia times were longer, and HLA matches were worse in comparison with REAL and especially SA. Multivariable analyses showed comparable graft and recipient survival between SA and REAL; however, CRA was associated with shorter graft survival. Germany performed 76% of all DDRTs after REAL and CRA and the latter mode reduced waiting times by up to 2.9 y. CONCLUSIONS: REAL and CRA are used differently in the ET countries according to national donor rates. Both RA schemes optimize graft utilization, lead to acceptable outcomes, and help to stabilize national DDRT programs, especially in Germany.

Interventional Management of Vascular Complications after Renal Transplantation. / Interventionelle Therapieoptionen vaskulärer Komplikationen nach Nierentransplantation.

BACKGROUND: Kidney transplantations are increasing due to demographic changes and are the treatment of choice for end-stage renal disease. Non-vascular and vascular complications may occur in the early phase after transplantation and at later stages. Overall postoperative complications after renal transplantations occur in approximately 12 % to 25 % of renal transplant patients. In these cases, minimally invasive therapeutic interventions are essential to ensure long-term graft function. This review article focuses on the most critical vascular complications after renal transplantation and highlights current recommendations for interventional treatment. METHOD: A literature search was performed in PubMed using the search terms "kidney transplantation", "complications", and "interventional treatment". Furthermore, the 2022 annual report of the German Foundation for Organ Donation and the EAU guidelines for kidney transplantation (European Association of Urology) were considered. RESULTS AND CONCLUSION: Image-guided interventional techniques are favorable compared with surgical revision and should be used primarily for the treatment of vascular complications. The most common vascular complications after renal transplantation are arterial stenoses (3 %-12.5 %), followed by arterial and venous thromboses (0.1 %-8.2 %) and dissection (0.1 %). Less frequently, arteriovenous fistulas or pseudoaneurysms occur. In these cases, minimally invasive interventions show a low complication rate and good technical and clinical results. Diagnosis, treatment, and follow-up should be performed in an interdisciplinary approach at highly specialized centers to ensure the preservation of graft function. Surgical revision should be considered only after exhausting minimally invasive therapeutic strategies. KEY POINTS: · Vascular complications after renal transplantation occur in 3 % to 15 % of patients.. · Image-guided interventional procedures should be performed primarily to treat vascular complications of renal transplantation.. · Minimally invasive interventions have a low complication rate with good technical and clinical outcomes.. CITATION FORMAT: · Verloh N, Doppler M, Hagar MT et al. Interventional Management of Vascular Complications after Renal Transplantation. Fortschr Röntgenstr 2023; 195: 495 - 504.

Evaluation of Deceased Donor Kidney Transplantation in the Eurotransplant Senior Program in Comparison to Standard Allocation.

BACKGROUND The organ shortage and long waiting times have dramatically increased the age of potential kidney transplant recipients. The Eurotransplant Senior Program (ESP) was initiated to allocate kidneys from deceased donors aged ≥65 years to recipients with a comparable age independent of pre-transplant human leucocyte antigen (HLA) matching; however, parameters affecting the long-term benefits of this strategy remain poorly defined. MATERIAL AND METHODS We retrospectively evaluated outcome and risk factors for mortality in kidney recipients aged ≥65 years that were transplanted according to the ESP protocol relative to patients aged >50 years transplanted according to the Eurotransplant kidney allocation system (ETKAS) criteria at the University Freiburg Medical Center, Germany, between 2008 and 2018. RESULTS Graft survival, graft function, the maintenance immunosuppressive therapy, and the incidence of rejections and infections did not differ between groups. Infectious diseases were the main cause of death in both groups; however, infection-associated mortality was more than double in the ESP group, and 5-year patient survival was 61.4% in the ESP group compared to 83.2% in the ETKAS group. Multivariate analysis identified age, the number of HLA mismatches, and the CMV serostatus with a seropositive donor and negative recipient as the main risk factors for mortality. CONCLUSIONS A comparable immunosuppressive regimen used in ESP and ETKAS patients was associated with similar rejection rates and infectious disease complications, and infections were the most common cause of death in both groups. CMV-negative patients receiving an organ from a CMV-positive donor and patients with a high number of HLA mismatches require close follow-up to reduce mortality.

IFNL4 rs368234815 polymorphism does not predict risk of BK virus associated nephropathy after living-donor kidney transplant: A case-control study.

BACKGROUND: BK polyoma virus (BKPyV) associated nephropathy (BKPyVAN) is a major cause of kidney graft loss in renal transplant patients. Interferons (IFNs) are an important innate immune response against viral infections and genetic polymorphisms of the IFN-pathways can affect susceptibility and mortality during viral infection. Here, we investigated whether the dinucleotide polymorphism rs368234815 (ΔG/TT) in the IFNL4 gene contributed to BKPyV reactivation or BKPyVAN after living-donor kidney transplantation. METHODS: This retrospective case-control study determines the prevalence of IFNL4 variants in a Caucasian population of living-donor kidney transplant recipients and donors and explores its association with BKPyV infection and BKPyVAN development. We included 28 recipients with BKPyV reactivation, 10 of which developed BKPyVAN and 30 BKPyV negative controls. Targeted sequencing of the IFNL4 gene from both recipients and their respective donors was performed. RESULTS: We found IFNL4 rs368234815 ΔG allele frequencies of 41.7% in BKPyV negative and 39.3% in BKPyV positive recipients (P = .85), and 41.7% and 40.4% (P>.99) in their respective donors. IFNL4 rs368234815 ΔG allele frequencies in BKPyVAN developing recipients and their respective donors were 50% and 43.7% (P = .60 and P>.99). CONCLUSIONS: Our results indicate that the IFNL4 rs368234815 ΔG allele is not associated with BKPyV reactivation, nor the manifestation of BKPyVAN.

Experiences and Short-Term Outcomes of Kidney Transplantation During the Coronavirus Disease 2019 Pandemic From a Medium-Volume Transplantation and Superregional Coronavirus Disease 2019 Treatment Center.

INTRODUCTION: The coronavirus, which first appeared in 2019, developed into a pandemic during 2020. It remains unclear to what extent the pandemic endangers the safety of kidney transplantation programs. In this study, we evaluated the short-term outcomes of our patients receiving a kidney transplant during the first phase and compared them with patients who received a kidney transplant immediately before the coronavirus pandemic. MATERIALS AND METHODS: Our retrospective study includes 34 kidney transplant recipients between October 1, 2019, and April 30, 2020. Nineteen patients from the phase immediately prior to the first coronavirus wave (pre-corona group), and 15 patients from the phase of the first coronavirus wave (corona group) were studied. We retrospectively evaluated demographic data, postoperative short-term outcomes and complications, immunosuppression regime, coronavirus infection status, and behavior during the first phase of the pandemic. RESULTS: There were no differences between the 2 groups regarding short-term outcomes and postoperative complications or in immunosuppressive medication. After the introduction of intensified hygienic conditions and routine swabs prior to transplantation, no nosocomial SARS-CoV-2 infections occurred. In the outpatient setting, none of the patients developed a SARS-CoV-2 infection. The majority of patients performed voluntary quarantine. CONCLUSIONS: The short-term outcomes after kidney transplantation during the first phase of the coronavirus pandemic were comparable to pre-pandemic patients, and no SARS-CoV-2-associated death or transplant failure occurred in our small cohort. We considered patient compliance with hygiene and self-isolation measures very high. Nevertheless, in further phases of the pandemic, the continuation of the living kidney donation program must be critically evaluated.

Long-term Follow-up of ABO-Incompatible Kidney Transplantation in Freiburg, Germany: A Single-Center Outcome Report.

BACKGROUND: ABO-incompatible kidney transplantation (ABOi-KT) is an established way to enlarge the donor pool around the world. Comparability of long-term success and complications to ABO-compatible kidney transplantation (ABOc-KT) are still under debate. METHODS: We evaluated all patients with a living donor kidney transplantation performed between April 1, 2004, and March 31, 2019. RESULTS: A total of 137 ABOi-KT and 346 ABOc-KT were analyzed. We excluded 4 ABOi-KT recipients and 178 ABOc-KT recipients with cyclosporine A-based immunosuppression or without basiliximab induction. Three patients of the ABOi-KT cohort and 6 patients of the ABOc-KT cohort were lost to follow-up and therefore excluded. The patient characteristics were comparable except for the higher age of transplant recipients in the ABOc-KT cohort and longer follow-up of the ABOi-KT cohort. The mean estimated 15-year recipient survival was 89% in the ABOi-KT cohort and 91% in the ABOc-KT cohort (P = .39). Mean estimated graft survival was 71% in the ABOi-KT cohort and 87% in the ABOc-KT cohort (P = .68). The estimated glomerular filtration rate (Modification of Diet in Renal Disease) measured in the last follow-up was 51 mL/min/1.73 m2 in the ABOi-KT cohort and 50 mL/min/1.73 m2 in the ABOc-KT cohort (P = .36). The incidence for antibody-mediated rejection, T cell-mediated rejections, and infectious complications requiring hospitalization was not different between the cohorts. In the ABOi-KT cohort, we found significantly more lymphoceles and consequent surgical revision procedures. CONCLUSIONS: At our center, ABOi-KT has as good long-term results as ABOc-KT in terms of patient survival, graft survival, and complications, with the exception of increased lymphocele formation.

Simultaneous ipsilateral nephrectomy during kidney transplantation in autosomal dominant polycystic kidney disease: a matched pair analysis of 193 consecutive cases.

BACKGROUND: In end-stage renal transplant recipients with autosomal-dominant polycystic kidney disease (ADPKD), the imperative, optimal timing, and technique of native nephrectomy remains under discussion. The Freiburg Transplant Center routinely performs a simultaneous ipsilateral nephrectomy. METHODS: From April 1998 to May 2017, we retrospectively analyzed 193 consecutive ADPKD recipients, receiving per protocol simultaneous ipsilateral nephrectomy and compared morbidity, mortality, and outcome with 193 non-ADPKD recipients of a matched pair control. RESULTS: The incidence of surgical complications was similar with respect to severe medical, surgical, urological, vascular, and wound-related complications as well as reoperation rates and 30-day mortality. Intraoperative blood transfusions were required more often in the ADPKD (22.8%) compared with the control group (6.7%; p < 0.0001). Early postoperative urinary tract infections occurred more frequent (ADPKD 40.4%/control 29.0%; p = 0.0246). Time of surgery was prolonged by 30 min (ADPKD 169 min; 95%CI 159.8-175.6 min/control 139 min; 95%CI 131.4-145.0 min; p < 0.0001). One-year patient (ADPKD 96.4%/control 95.8%; p = 0.6537) and death-censored graft survival (ADPKD 94.8%/control 93.7%; p = 0.5479) were comparable between both groups. CONCLUSIONS: With respect to morbidity and mortality, per protocol, simultaneous native nephrectomy is a safe procedure. Especially in asymptomatic ADPKD KTx recipients, the number of total operations can be reduced and residual diuresis preserved up until transplantation. In living donation, even preemptive transplantation is possible.

Expanding pancreas donor pool by evaluation of unallocated organs after brain death: Study protocol clinical trial (SPIRIT Compliant).

BACKGROUND: Pancreas graft quality directly affects morbidity and mortality rates after pancreas transplantation (PTx). The criteria for pancreas graft allocation are restricted, which has decreased the number of available organs. Suitable pancreatic allografts are selected based on donor demographics, medical history, and the transplant surgeon's assessment of organ quality during procurement. Quality is assessed based on macroscopic appearance, which is biased by individual experience and personal skills. Therefore, we aim to assess the histopathological quality of unallocated pancreas organs to determine how many unallocated organs are potentially of suitable quality for PTx. METHODS AND ANALYSIS: This is a multicenter cross-sectional explorative study. The demographic data and medical history of donor and cause of rejection of the allocation of graft will be recorded. Organs of included donors will be explanted and macroscopic features such as weight, color, size, and stiffness will be recorded by 2 independent transplant surgeons. A tissue sample of the organ will be fixed for further microscopic assessments. Histopathologic assessments will be performed as soon as a biopsy can be obtained. We will evaluate up to 100 pancreata in this study. RESULT: This study will evaluate the histopathological quality of unallocated pancreas organs from brain-dead donors to determine how many of these unallocated organs were potentially suitable for transplantation based on a histopathologic evaluation of organ quality. CONCLUSION: The comprehensive findings of this study could help to increase the pancreas graft pool, overcome organ shortage, reduce the waiting time, and also increase the number of PTx in the future. Registration number: ClinicalTrials.gov: NCT04127266.

Evidence of Interleukin-2-Receptor-Antibody Induction in Low-Risk Living Donor Kidney Transplantation: A Single-Center Pilot Study.

BACKGROUND: The recommended standard immunosuppressive therapy for renal transplant recipients comprises an initial induction therapy mainly with an interleukin-2-receptor antibody (IL2-RA) and a triple maintenance therapy. With tacrolimus and mycophenolate acid it is unknown whether IL2-RA application affects the short- and long-term results. This question is addressed in the present analysis. METHODS: From July 2007 to June 2019 a total of 127 living donor kidney transplant recipients meeting the center-specific definition of immunologic low risk situation (first transplantation, HLA-mismatch ≤3, panel reactive antibody ≤10%) were identified. In 83 recipients with a first-degree relationship to the donor we omitted the IL2-RA induction (IL2-RA-). The remaining 44 recipients, mostly not first-degree relatives, served as controls (IL2-RA+). Biopsy-proven acute rejection and long-term patient and graft survival rates were compared. RESULTS: Biopsy-proven acute rejection rates after 3 months were similar in both groups with 4.8% (IL2-RA-) vs 13.7% (IL2-RA+; P = .0937), including borderline rejection rates of 18.0% (IL2-RA-) vs 18.3% (IL2-RA+; P = 1.000), respectively. Ten-year long-term survival rates were comparable between the IL2-RA- and the IL2-RA+ group with 95.6% vs 93.5% (patient survival; P = .5465) and 92.1% vs 90.6% (death-censored graft survival; P = .8893). CONCLUSION: For low-risk living donor kidney transplant recipients with first-degree relationship to the donor, it is safe to omit induction therapy with IL2-RA.

Single cohort study: ABO-incompatible kidney transplant recipients have a higher risk of lymphocele formation.

PURPOSE: Since 2004, ABO-incompatible kidney transplantation (ABOi KTx) became an established procedure to expand the living donor pool in Germany. Currently, ABOi KTx comprises > 20% of all living donor KTx. Up to September 2015, > 100 ABOi KTx were performed in Freiburg. Regarding lymphocele formation, only scarce data exist. METHODS: Between April 2004 and September 2015, 106 consecutive ABOi and 277 consecutive ABO-compatible kidney transplantations (ABOc KTx) were performed. Two ABOi and 117 ABOc recipients were excluded due to differences in immunosuppression. One hundred-four ABOi and 160 ABOc KTx patients were analyzed concerning lymphocele formation. RESULTS: The incidence of lymphoceles in ABOi KTx was 25.2% and 10.6% in ABOc KTx (p = 0.003). A major risk factor appeared the frequency of ≥ 8 preoperative immunoadsorption and/or plasmapheresis sessions (OR 5.61, 95% CI 2.31-13.61, p < 0.001). Particularly, these ABOi KTx recipients had a distinctly higher risk of developing lymphocele (40.0% vs. 19.2%, p = 0.044). IA/PE sessions on day of transplantation (no lymphocele 20.0% vs. lymphocele 28.6%, p = 0.362) or postoperative IA/PE sessions (no lymphocele 25.7% vs. lymphocele 24.1%, p = 1.0) showed no influence on formation of lymphoceles. CONCLUSION: In ABOi KTx, the incidence of lymphocele formation is significantly increased compared to ABOc KTx and leads to more frequent surgical reinterventions without having an impact on graft survival.

Modifiable Risk Factors for Delayed Graft Function After Deceased Donor Kidney Transplantation.

PURPOSE: Delayed graft function is a major complication after kidney transplantation affecting patients' long-term outcome. The aim of this study was to identify modifiable risk factors for delayed graft function after deceased donor kidney transplantation. METHODS: This is a single-center retrospective cohort study of a university transplantation center. Univariate and multivariate step-wise logistic regression analysis of patient-specific and procedural risk factors were conducted. RESULTS: We analyzed 380 deceased donor kidney transplantation patients between October 30, 2008 and December 30, 2017. The incidence of delayed graft function was 15% (58/380). Among the patient-specific risk factors recipient diabetes (2.8 [1.4-5.9] odds ratio [OR] [95% confidence interval [CI]]), American Society of Anesthesiologist score of 4 (2.7 [1.2-6.5] OR [95% CI]), cold ischemic time >13 hours (2.8 [1.5-5.3] OR [95% CI]) and donor age >55 years (1.9 [1.01-3.6] OR [95% CI]) revealed significance. The significant intraoperative, procedural risk factors included the use of colloids (3.9 [1.4-11.3] OR [95% CI]), albumin (3.0 [1.2-7.5] OR [95% CI]), crystalloids >3000 mL (3.1 [1.2-7.5] OR [95% CI]) and mean arterial pressure <80 mm Hg at the time of reperfusion (2.4 [1.2-4.8] OR [95% CI]). CONCLUSION: Patients undergoing deceased donor kidney transplantation with a mean arterial pressure >80 mm Hg at the time of transplant reperfusion without requiring excessive fluid therapy in terms of colloids, albumin or crystalloids >3000 mL are less likely to develop delayed graft function.

Results of a randomized controlled trial analyzing telemedically supported case management in the first year after living donor kidney transplantation - a budget impact analysis from the healthcare perspective.

ᅟ: We analyze one-year costs and savings of a telemedically supported case management program after kidney transplantation from the perspective of the German Healthcare System. Recipients of living donor kidney transplantation (N = 46) were randomly allocated to either (1) standard aftercare or (2) standard aftercare plus additional telemedically supported case management. A range of cost figures of each patient's medical service utilization were calculated at month 3, 6 and 12 and analyzed using two-part regression models. In comparison to standard aftercare, patients receiving telemedically supported case management are associated with substantial lower costs related to unscheduled hospitalizations (mean difference: €3,417.46 per patient for the entire one-year period, p = 0.003). Taking all cost figures into account, patients receiving standard aftercare are associated, on average, with one-year medical service utilization costs of €10,449.28, while patients receiving telemedically supported case management are associated with €5,504.21 of costs (mean difference: € 4,945.07 per patient, p < 0.001). With estimated expenditures of €3,001.5 for telemedically supported case management of a single patient, we determined a mean difference of €1,943.57, but this result is not statistically significant (p = 0.128). Sensitivity analyses show that the program becomes cost-neutral at around ten participating patients, and was beneficial starting at 15 patients. Routine implementation of telemedically supported case management in German medium and high-volume transplant centers would result in annual cost savings of €791,033 for the German healthcare system. Patients with telemedically supported case management showed a lower utilization of medical services as well as better medical outcomes. Therefore, such programs should be implemented in medium and high-volume transplant centers. TRIAL REGISTRATION: DRKS00007634 ( http://www.drks.de/DRKS00007634 ).

One hundred ABO-incompatible kidney transplantations between 2004 and 2014: a single-centre experience.

BACKGROUND: ABO-incompatible kidney transplantation (ABOi KTx) expands the living donor transplantation options. However, long-term outcome data, especially in comparison with ABO-compatible kidney transplantation (ABOc KTx), remain limited. Since the first ABOi KTx in Germany on 1 April 2004 at our centre, we have followed 100 ABOi KTx over up to 10 years. METHODS: One hundred ABOi KTx and 248 ABOc KTx from 1 April 2004 until 28 October 2014 were analysed in this observational, single-centre study. Three ABOi KTx and 141 ABOc KTx were excluded because of cyclosporine A-based immunosuppression, and 1 ABOc KTx was lost to follow-up. RESULTS: Median estimated 10-year patient and graft survival in ABOi KTx was 99 and 94%, respectively, and surpassed ABOc-KTx patient and graft survival of 80 and 88%, respectively. The incidence rate of antibody-mediated rejections was 10 and 8%, and that of T-cell-mediated rejections was 17 and 20% in ABOi KTx and ABOc KTx, respectively. Infectious and malignant complications in ABOi KTx were not more common than in ABOc KTx. However, postoperative lymphoceles occurred more frequently in ABOi KTx. Subgroup analysis of ABOi-KTx patients revealed that patients with high-titre isohaemagglutinins before transplantation had equal long-term results compared with low-titre isohaemagglutinin patients. CONCLUSION: Taken together, long-term outcome of ABOi KTx is not inferior to ABOc KTx. Incidences of rejection episodes, infectious complications and malignancies are not increased, despite the more vigorous immunosuppression in ABOi KTx. Our data provide further evidence that ABOi KTx with living donation is a safe, successful and reasonable option to reduce the organ shortage.

An update on ABO-incompatible kidney transplantation.

ABO-incompatible kidney transplantation is nowadays a well-established procedure to expand living donor transplantation to blood group incompatible donor/recipient constellations. In the last two decades, transplantation protocols evolved to more specific isohaemagglutinin elimination techniques and established competent antirejection protection protocols without the need of splenectomy. ABOi kidney transplantation associated accommodation despite isohaemagglutinin reappearance, C4d positivity of peritubular capillaries as well as the increased incidence of bleeding complications is currently under intense investigation. However, most recent data show excellent graft survival rates equivalent to ABO-compatible kidney transplantation outcome.