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Background: Chronic active antibody-mediated rejection (caAMR) in kidney transplants is associated with irreversible tissue damage and a leading cause of graft loss in the long-term. However, the treatment for caAMR remains a challenge to date. Recently, tocilizumab, a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, has shown promise in the treatment of caAMR. However, it has not been systematically investigated so far underscoring the need for randomized controlled studies in this area., Methods: The INTERCEPT study is an investigator-driven randomized controlled open-label multi-center trial in kidney transplant recipients to assess the efficacy of tocilizumab in the treatment of biopsy-proven caAMR. A total of 50 recipients with biopsy-proven caAMR at least 12 months after transplantation will be randomized to receive either tocilizumab (n = 25) added to our standard of care (SOC) maintenance treatment or SOC alone (n = 25) for a period of 24 months. Patients will be followed for an additional 12 months after cessation of study medication. After the inclusion biopsies at baseline, protocol kidney graft biopsies will be performed at 12 and 24 months. The sample size calculation assumed a difference of 5 ml/year in slope of estimated glomerular filtration rate (eGFR) between the two groups for 80% power at an alpha of 0.05. The primary endpoint is the slope of eGFR at 24 months after start of treatment. The secondary endpoints include assessment of the following at 12, 24, and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, and patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection., Discussion: No effective treatment exists for caAMR at present. Based on the hypothesis that inhibition of IL-6 receptor by tocilizumab will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR, therewith slowing the decline in graft function in the long-term., Trial Registration: ClinicalTrials.gov NCT04561986. Registered on September 24, 2020., (© 2024. The Author(s).)

Increased COVID-19-related morbidity and mortality have been reported in solid organ transplant recipients (SOTRs). Most studies are underpowered for rigorous matching. We report infections, hospitalization, ICU care, mortality from COVID-19, and pertinent vaccination data in Swedish SOTRs 2020-2021. We conducted a nationwide cohort study, encompassing all Swedish residents. SOTRs were identified with ICD-10 codes and immunosuppressant prescriptions. Comparison cohorts were weighted based on a propensity score built from potential confounders (age, sex, comorbidities, socioeconomic factors, and geography), which achieved a good balance between SOTRs and non-SOTR groups. We included 10,372,033 individuals, including 9073 SOTRs. Of the SARS-CoV-2 infected, 47.3% of SOTRs and 19% of weighted comparator individuals were hospitalized. ICU care was given to 8% of infected SOTRs and 2% of weighted comparators. The case fatality rate was 7.7% in SOTRs, 6.2% in the weighted comparison cohort, and 1.3% in the unweighted comparison cohort. SOTRs had an increased risk of contracting COVID-19 (HR = 1.15 p < 0.001), being hospitalized (HR = 2.89 p < 0.001), receiving ICU care (HR = 4.59 p < 0.001), and dying (HR = 1.42 p < 0.001). SOTRs had much higher morbidity and mortality than the general population during 2020-2021. Also compared with weighted comparators, SOTRs had an increased risk of contracting COVID-19, being hospitalized, receiving ICU care, and dying. In Sweden, SOTRs were vaccinated earlier than weighted comparators. Lung transplant recipients had the worst outcomes. Excess mortality among SOTRs was concentrated in the second half of 2021.

All chronic and treatment-resistant acute rejections are "difficult-to-treat" and lead to progressive loss of graft function in kidney transplant recipients (KTR), as no effective treatment exists for such rejections to date. We review our experience with a novel strategy to treat such rejections by adding everolimus as a "rescue" to conventional triple maintenance therapy with prednisolone, mycophenolate mofetil and calcineurin inhibitor. We retrospectively analysed data in 28 KTR who received everolimus-based quadruple therapy at our institution for biopsy-proven chronic active T cell-mediated or antibody-mediated rejection (n = 19) or treatment-resistant acute rejections (n = 9) between 2011-2017. The primary outcome was 5-year death-censored graft survival. Main secondary outcomes were response to treatment defined by stable or improved graft function, 5-year patient survival and discontinuation rate of treatment. The Kaplan-Meier estimate for 5-year death-censored graft survival was 79% in all patients, 90% for patients with chronic active T cell-mediated rejections, 78% for chronic active antibody-mediated rejection and 67% for acute rejections. Response to treatment was achieved in 43% and 5-year patient survival was 94%. Treatment was stopped in 12 (43%) patients due to adverse events. Everolimus-based maintenance quadruple therapy, despite high rate of everolimus discontinuation due to adverse events, may be a valid approach in a subset of kidney transplant recipients with such difficult-to-treat rejections, which otherwise would lead to a high rate of graft loss.

Background: Macrophages in renal transplants have been shown to participate in antibody-mediated rejection and are associated with impaired renal function. We calculated the glomerular macrophage index (GMI) in a large transplant biopsy cohort, studied its quantity in different diagnostic groups, to clarify its possible impact on graft survival., Methods: GMI, defined as the mean number of macrophages in 10 glomeruli, was prospectively quantified in 1440 renal transplant biopsies over a 10-year period. The main histopathological diagnoses were grouped into eight disease entities, and GMI was compared to normal transplant biopsies as the reference group. The impact of GMI on graft survival was analyzed., Results: GMI was highest in chronic (mean 9.4) and active (9.7) antibody mediated rejections (ABMR), mixed rejections (7.6), and recurrent or de novo glomerulonephritis (7.5) and differed significantly from normal transplants (1.3) in almost all diagnostic groups. Hazard ratios for graft loss were significantly increased for all biopsies with GMI ≥1.9 compared to GMI < .5 (reference group) in an adjusted Cox regression model and increased with higher GMI levels. Biopsies with GMI ≥ 4.6 had < 60% 10-year graft-survival, compared to > 80% with GMI ≤ 1.8., Conclusion: GMI levels were predictive of graft loss independent of histological diagnoses and may guide clinicians to decide follow-up and therapy., (© 2022 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Solid organ transplant recipients (SOTRs) are on lifelong immunosuppression, which may interfere with adaptive immunity to COVID-19. The data on dynamics and duration of antibody response in SOTRs are limited. This longitudinal study examined the longevity of both anti-spike (S)- and anti-nucleocapsid (N)-specific IgG antibodies after COVID-19 in SOTRs compared to matched immunocompetent persons. SOTRs (n = 65) were matched with controls (n = 65) for COVID-19 disease severity, age, and sex in order of priority. Serum-IgG antibodies against N and S antigens of SARS-CoV-2 were analyzed. At 1 and 9 months after COVID-19, anti-S-IgG detectability decreased from 91% to 82% in SOTRs versus 100% to 95% in controls, whereas the anti-N-IgG decreased from 63% to 29% in SOTRs versus 89% to 46% in controls. A matched paired analysis showed SOTRs having significantly lower levels of anti-N-IgG at all time points (1 month p = .007, 3 months p < .001, 6 months p = .019, and 9 months p = .021) but not anti-S-IgG at any time points. A mixed-model analysis confirmed these findings except for anti-S-IgG at 1 month (p = .005) and identified severity score as the most important predictor of antibody response. SOTRs mount comparable S-specific, but not N-specific, antibody responses to SARS-CoV-2 infection compared to immunocompetent controls., (© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Although it is known that solid organ transplant recipients fare worse after COVID-19 infection, data on the impact of COVID-19 on clinical outcomes and allograft function in lung transplant (LTx) recipients are limited and based mainly on reports with short follow-up. In this nationwide study, all LTx recipients with COVID-19 diagnosed from 1 February 2020 to 30 April 2021 were included. The patients were followed until 1 August 2021 or death. We analysed demographics, clinical features, therapeutic management and outcomes, including lung function. Forty-seven patients were identified: median age was 59 (10-78) years, 53.1% were male, and median follow-up was 194 (23-509) days. COVID-19 was asymptomatic or mild at presentation in 48.9%. Nine patients (19.1%) were vaccinated pre-COVID infection. Two patients (4.3%) died within 28 days of testing positive, and the overall survival rate was 85.1%. The patients with asymptomatic or mild symptoms had a higher median % expected forced expiratory volume during the first second than the patients with worse symptoms (P = 0.004). LTx recipients develop the entire spectrum of COVID-19, and in addition to previously acknowledged risk factors, lower pre-COVID lung function was associated with more severe disease presentation., (© 2021 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1-2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6-7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score., (© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Solid organ transplant (SOT) recipients may be more vulnerable to coronavirus disease 2019 (COVID-19). Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the optimal management strategy for these patients is yet unclear., Methods: We present 53 SOT recipients (31 kidney transplant recipients, 8 liver transplant recipients, 5 heart transplant recipients, 5 lung transplant recipients, 3 liver-kidney transplant recipients, and 1 kidney-after-heart transplant recipient), transplanted at a Swedish high-volume transplant center and each diagnosed with COVID-19 between February 21, 2020 and June 22, 2020. Demographic, clinical, and treatment data were extracted from the electronic patient files., Results: Patients reported fever (61%), cough (43%), diarrhea (31%), and upper respiratory symptoms (29%). The median age was 56 years, and 57% were male. According to severity, 55% had mild, 13% had moderate, 19% had severe, and 13% had critical disease. Thirty-seven patients (70%) were hospitalized, with 8 requiring intensive care. Thirteen of the 37 patients were initially managed as outpatients but later hospitalized. One patient received hydroxychloroquine, and no patients received antivirals. Antimetabolites and calcineurin inhibitors were held or reduced in two-thirds. Twenty-seven of 37 hospitalized patients (73%) received low-molecular-weight heparin. Five (13.5%) hospitalized patients died. Overall survival for the entire cohort was 90.5%. No rejection episodes were noted., Conclusions: Hospitalization, lowering of immunosuppression, and prophylactic anticoagulation were the most common therapeutic interventions for SOT recipients with COVID-19. A significant proportion of patients could be managed on an outpatient basis, while keeping a low threshold for admission. Mild and moderate disease forms seem to have a good outcome., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) ranges from a mild illness to acute respiratory distress syndrome (ARDS), multiorgan dysfunction, and death. Transplant recipients are vulnerable due to comorbidities and immunosuppressants that render them susceptible to infections. The information on COVID-19 in kidney transplant recipients remains limited to small case series., Methods: A systematic literature search was conducted, and 12 case series totalling 204 kidney transplant recipients with COVID-19 were identified. Data were extracted, pooled and analysed., Results: Most patients (74%) were men. The most frequent symptoms were fever (76%), cough (64%) and dyspnoea (43%). At admission, over 70% of the patients had abnormal radiological findings. Leukocyte counts were in the lower normal range. C-reactive protein, ferritin, and D-dimer were consistently increased. Treatments included lowering immunosuppression, hydroxychloroquine, antivirals, tocilizumab and intravenous immunoglobulins. Thirty-one percent of the patients were admitted to intensive care units (ICUs), and 16% required intubation. The overall mortality was 21.2%. Patients who died were significantly older than those who survived (61 ± 12 vs. 51 ± 15, p  < .01). Logistic regression revealed that the odds for death increased by 4.3% for each additional year of age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.005-1.083, p value = .0265)., Conclusions: No substantial conclusions could be drawn on the efficacy of any particular treatment. More rigorous patient stratification is needed when analysing and reporting data to facilitate future meta-analyses.

BK-virus (BKV) associated nephropathy (BKVAN) and BKV associated haemorrhagic cystitis (HC) are complications of BKV infection/reactivation in renal and allogeneic haematopoietic stem cell transplantation (HSCT) patients, respectively. The task of how to manage these diseases was given to the chair by the Swedish Reference Group for Antiviral Therapy (RAV). After individual contributions by members of the working group, consensus discussions were held in a meeting on 23 January 2018 arranged by RAV. Thereafter, the recommendations were published in Swedish on November 2018. The current translation to English has been approved by all co-authors. High BKV serum levels suggest an increased risk for BKVAN and potential graft failure. For detection of BKVAN, careful monitoring of BKV DNA levels in serum or plasma is recommended the first year after renal transplantation and when increased creatinine serum levels of unknown cause are observed. Notably, a renal biopsy is mandatory for diagnosis. To reduce the risk for progression of BKVAN, there is no specific treatment, and tailored individual decrease of immunosuppression is recommended. For BKV-HC, BKV monitoring is not recommended, since BK-viruria frequently occurs in HSCT patients and the predictive value of BKV in plasma/serum has not been determined. However, the risk for BKV-HC is higher for patients undergoing myeloablative conditioning, having an unrelated, HLA-mismatched, or a cord blood donor, and awareness of the increased risk and early intervention may benefit the patients. Also for BKV-HC, no specific therapy is available. Symptomatic treatment, e.g. forced diuresis and analgesics could be of use.

Objectives: To investigate whether measured glomerular filtration rate (mGFR) is a risk factor for death and/or end-stage renal disease (ESRD) after heart transplantation (HTx)., Methods: All adult patients (n = 416) who underwent HTx between 1988 and 2010 were included. mGFR was performed both preoperatively and postoperatively as annual follow-up. Eight patients received a concomitant kidney transplant (KTx), and 15 underwent late KTx due to chronic renal failure after HTx., Results: The mean drop in mGFR compared with the preoperative value was 12% during the first year after HTx. Preoperative mGFR was not predictive of mortality or ESRD. Older or the use of a ventricular assist device (VAD) were preoperative predictors of death. Long-term survival was significantly worse in the patients who experienced a >25% decrease in mGFR during the first year after transplantation. The need for acute postoperative renal replacement therapy (RRT) was associated with impaired survival but did not predict ESRD among survivors. On multivariable analyses, previous heart surgery, preoperative VAD, and a lower mGFR were all predictors of RRT. In the most recent period, death without previous ESRD was lower, and the only preoperative factors associated with ESRD by multivariable analyses were mechanical ventilation and diabetes mellitus., Conclusions: Pretransplantation mGFR was not predictive of mortality or ESRD after HTx, but necessitated simultaneous or late-stage KTx in this selected population of patients. However, patients with a decrease in >25% mGFR during the first year post-transplantation, as well as early postoperative dialysis-dependent acute renal dysfunction, had a poor prognosis. We suggest that patients with severely impaired kidney function, irrespective of pretransplantation renal function, still should be considered for HTx, but also encourage careful interpretation of our results given the selection bias involved in this population., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Islet transplantation is a minimally invasive β-cell replacement strategy. Islet transplantation is a reimbursed treatment in Norway. Here, we summarize the cost and clinical outcome of 31 islet transplantations performed at Oslo University Hospital (OUS) from January 2010 to June 2015. Patients were retrospectively divided into three groups. Thirteen patients received either one or two islet transplantation alone (ITA), while five patients received islet transplantation after previous solid organ transplantation. For the group receiving 2 ITA, Kaplan-Meier estimates show an insulin independence of 20% more than 4 years after their last transplantation. An estimated 70% maintain at least partial graft function, defined as fasting C-peptide >0.1 nmol L -1 , and 47% maintain a HbA1c below 6.5% or 2 percent points lower than before ITA. For all groups combined, we estimate that 44% of the patients have a 50% reduction in insulin requirement 4 years after the initial islet transplantation. The average cost for an islet transplantation procedure was 347 297±60 588 NOK, or 35 424±6182 EUR, of which isolation expenses represent 34%. We hereby add to the common pool of growing experience with islet transplantation and also describe the cost of the treatment at our center., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In organ transplanted patients, impaired renal function is of major prognostic importance and influences therapeutic decisions. Therefore, monitoring of renal function with glomerular filtration rate (GFR) is of importance, both before and after heart transplantation (HTx). The GFR can be measured directly (mGFR) or estimated (eGFR) with equations based on circulating creatinine or cystatin C levels. However, these equations have not been thoroughly validated in the HTx population., Methods: We investigated the correlation, agreement and accuracy between mGFR (using (51)Cr-ethylenediaminetetraacetic acid or iohexol clearance) and three commonly used eGFR equations (Modification of Diet in Renal Disease, Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration) in a retrospective analysis of 416 HTx recipients followed between 1988 and 2012. Comparisons were performed prior to transplantation and at 1, 5 and 10 years of follow-up., Results: The correlations between eGFR and mGFR were only moderate, with r-values ranging from 0.55 preoperatively to 0.82 during follow-up. Most importantly, the level of agreement between eGFR and mGFR was very low for all three estimates, with percentage errors ranging from 93.3 to 157.3%. Also, the percentage of patients with eGFR within 30% of mGFR (P30) rarely reached the National Kidney Foundation recommended minimum level of 75%., Conclusion: We argue that the accuracy and the precision of the most commonly used estimation equations for assessment of kidney function are unacceptably low and we believe that mGFR should be used liberally as the basis for clinical decision-making both before and after HTx when eGFR is subnormal., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

We investigated the antibody persistence in solid organ transplant (SOT) recipients 1 year after immunization with two doses of monovalent AS03-adjuvanted influenza A(H1N1)pdm09 vaccine. We also assessed the boosting effect of the seasonal trivalent inactivated vaccine 2010 (TIV/10) that contained the influenza A(H1N1)pdm09 strain. A total of 49 SOT recipients and 11 healthy controls were included. After a blood sample was obtained to assess the persistent immunity, one dose of TIV/10 was administered and another blood sample was collected 1 month after vaccination. A(H1N1)pdm09 antibodies were measured using a haemagglutination inhibition assay. The percentage of SOT recipients with protective titres decreased between 1 month and 10-14 months after the monovalent influenza A(H1N1)pdm09 vaccination, from 79% (n = 38) to 47% (n = 23) (P = 0.02). The corresponding numbers for the control group were 100% and 63%, respectively (P = 0.008). After the TIV/10 boosting dose, the number of SOT recipients with protective titres increased from 47% (n = 23) to 71% (n = 35) (P = 0.2). All the controls reached a protective titre level. The median titre rise was significantly higher among controls when compared to SOT recipients (P = 0.0036). No rejection or adverse events were seen. The results show an obvious need for vaccine boosting doses in the SOT patients., (© 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background: Histidine-tryptophan-ketoglutarate (HTK) has been established as an alternative to University-of-Wisconsin solution (UWS) for abdominal organ preservation, but data about HTK efficiency to preserve pancreata during prolonged cold ischemia time (CIT) are conflicting. In human islet transplantation, HTK provided similar isolation outcomes after short CIT. The present study aimed to investigate whether islets can be successfully isolated from HTK-preserved pancreata after prolonged CIT compared with UWS., Materials and Methods: Sixty-four human pancreata retrieved from donors meeting criteria for kidney donation were perfused utilizing either HTK or UWS and preserved for more or less than 10 h prior to islet isolation. Along with parameters related to isolation and islet quality assessment, the dry-to-wet weight ratio was evaluated., Results: Donor- and procurement-related factors did not vary between HTK- and UWS-perfused pancreata. The dry-to-wet weight ratio was lower in HTK-preserved pancreata indicated tissue edema (21.0% ± 3.5% versus 24.8% ± 2.0%, P = 0.007). Isolation-related variables differed between experimental groups after prolonged CIT with respect to purified packed tissue volume (9.1 ± 5.0 versus 17.2 ± 8.1 μL/g, P = 0.004) and islet yield (1910 ± 980 versus 3150 ± 1420 IE/g, P = 0.012). Islet purity and survival after culture were similar after HTK or UWS perfusion. The preservation solution did not affect in vitro function and transplantability of isolated islets., Conclusions: Compared with UWS, HTK has similar efficiency to preserve human pancreata for subsequent islet isolation during <10 h CIT but seems to be limited for prolonged cold storage., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The ability to predict clinical function of a specific islet batch released for clinical transplantation using standardized variables remains an elusive goal., Methods: Analysis of 10 donor, 7 islet isolation, 3 quality control, and 6 recipient variables was undertaken in 110 islet-after-kidney transplants and correlated to the pre- to 28-day posttransplant change in C-peptide to glucose and creatinine ratio (ΔCP/GCr)., Results: Univariate analysis yielded islet volume transplanted (Spearman r=0.360, P<0.001) and increment of insulin secretion (r=0.377, P<0.001) as variables positively associated to ΔCP/GCr. A negative association to ΔCP/GCr was cold ischemia time (r=-0.330, P<0.001). A linear, backward-selection multiple regression was used to obtain a model for the transplanted functional islet mass (TFIM). The TFIM model, composed of islet volume transplanted, increment of insulin secretion, cold ischemia time, and exocrine tissue volume transplanted, accounted for 43% of the variance of the clinical outcome in the islet-after-kidney data set., Conclusion: The TFIM provides a straightforward and potent tool to guide the decision to use a specific islet preparation for clinical transplantation.

Limited data are available regarding antibody response and the safety of the monovalent influenza A H1N1/09 vaccine for immunocompromised patients. In this study, the humoral response to this vaccine in solid organ transplant (SOT) recipients and healthy individuals was evaluated. Eighty-two SOT recipients and 28 healthy individuals received two doses of the influenza A H1N1/09 AS03 adjuvanted vaccine containing 3.75 mg of haemagglutinin at a 3- to 4-week interval. Serum samples were drawn at baseline and 3-4 weeks after the first and second vaccine doses. Seroprotective titres were measured with a haemagglutination inhibition. After the first dose seroprotective titres were observed in 69% of the SOT patients and in 96% of the healthy controls (P = 0.006), and increased after the second dose to 80% and 100%, respectively (P = 0.003). All controls and 77% of the SOT recipients achieved a ≥4-fold titre rise after the first immunisation (P = 0.005). The vaccine was well tolerated and no acute rejection was observed. Influenza A H1N1/09 vaccine elicited a protective antibody response in the majority of SOT recipients, but the response was lower when compared with controls. A second dose significantly improved vaccine immunogenicity in SOT recipients. (ClinicalTrials.gov number: NCT01254955)., (© 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.)

The limiting factor in organ transplantation is the availability of organs. Ongoing work to improve donation rates both at the public and the organizational level in donating hospitals is essential. We also think that encouragement of live donation is important, and the possibility of ABO incompatible transplantation has increased the number of LD transplantations. The one-year graft survival rate is excellent and focus has shifted towards achieving long-term results to reduce the attrition rate. There is also an increasing interest in studying and working to reduce comorbidities on a long-term basis and thus, improve survival rates and recipient quality of life.

Background: Pancreas oxygenation during cold storage has been established in islet isolation and transplantation to prevent ischemic tissue damage using perfluorodecalin (PFD) as hyperoxygen carrier. However, studies in humans and pigs provided conflicting results about the efficiency of PFD for pancreas oxygenation. The aim of this study was to compare PFD with a newly developed oxygen carrier composed of perfluorohexyloctane and polydimethylsiloxane 5 (F6H8S5) for long-term storage of human pancreata., Methods: After 24-hr storage in preoxygenated PFD or F6H8S5, pancreata were processed using Liberase HI for pancreas dissociation and a Ficoll gradient for islet purification. Islet quality assessment was performed measuring glucose-stimulated insulin release, viability, islet ATP content, and posttransplant function in diabetic nude mice., Results: Compared with PFD, F6H8S5 significantly increased the intrapancreatic partial oxygen pressure and islet ATP content. This corresponded to an increase of islet yield, recovery after culture, glucose stimulation index, viability, and improved graft function in diabetic nude mice., Conclusions: The present findings indicate clearly that F6H8S5 improves isolation outcome after prolonged ischemia compared with PFD. This observation seems to be related to the significant lipophilicity and almost pancreas-specific density of F6H8S5. Moreover, these characteristics facilitate pancreas shipment without using custom-made transport vessels as required for PFD.

Background: The isolation of islets from the human pancreas critically depends on an efficient enzyme blend. Previous studies have solely focused on the presence of collagenase and neutral protease/thermolysin. Despite improved characterization of these components, the lot-related variability in efficacy still persists suggesting that additional so far disregarded enzymes are required for efficient islet cleavage., Methods: Varying activities of a tryptic-like enzyme were identified within collagenase NB1 lots, which were selected according to a matched ratio between tryptic-like and collagenase activity (TLA-ratio). Rat and human pancreata were processed with current standard procedures., Results: Increasing the TLA-ratio from 1.3% to 10% reduced pancreas dissociation time in rats by 50% without affecting islet yield, viability, or posttransplant function in diabetic nude mice. Enhancing the TLA-ratio from 1.3% to 12.6% for human pancreas processing resulted in a significant reduction of recirculation time and increased incrementally human islet yield without affecting purity, in vitro function or recovery after culture. Optimized pancreas digestion correlated with a higher percentage of islet preparations fulfilling quality criteria for clinical transplantation., Conclusions: We conclude that TLA is an effective component that should be included in moderate amounts in enzyme blends for human islet isolation to optimize the efficiency and minimize the lot-related variability.

Objective: With improvements in long-term results after liver transplantation, chronic kidney disease (CKD) has become a highly relevant problem. The early measurement of the glomerular filtration rate (GFR) can identify those patients who are at risk of developing CKD years after liver transplantation. The aims of this study were to describe the prevalence of CKD 5 years after liver transplantation, to study the correlation between measured GFR early after transplantation and late renal function and to identify patients at risk of developing late CKD after liver transplantation., Material and Methods: A total of 152 patients who were at least 5 years post-liver transplantation were studied. Measured GFR with Chromium EDTA or iohexol clearance was followed-up for 5 years (n 52) and 10 years (n 41)., Results: The overall decrease in measured GFR was 36% after 5 years and 42% after 10 years. Eight patients (5%) required renal replacement therapy. GFR levels pretransplantation showed a poor correlation with later renal function (at 5 years). The GFR measured at 3 months and 1 year post-transplantation correlated well with measured GFR at 5 years post-transplantation. Multivariate analysis showed that measured GFR of less than 30 ml at 3 months post-transplantation was significantly associated with CKD at 5 years post-transplantation., Conclusions: GFR levels below 30 ml/min/1.73 m2 at 3 months post-liver transplantation are associated with the development of later CKD Stage 4-5 long after liver transplantation. The importance of this finding is the possibility of identifying at an early stage those individuals that may benefit from early implementation of calcineurin sparing or a withdrawal regimen with the goal of preserving long-term renal function.

Background: Shipment of pancreata between distant centers is frequently associated with prolonged cold ischemia time (CIT) that leads to poorer outcomes for islet transplantation. Clinical pilot trials have indicated that oxygenation of explanted human pancreata utilizing the two-layer method (TLM) allows the use of marginal donor pancreata for islet transplantation. The present study aimed to clarify whether TLM enhances the ischemic tolerance of human pancreata., Methods: We analyzed retrospectively the outcome of 200 human islet isolations performed after TLM preservation or storage in University of Wisconsin solution (UWS)., Results: Donor characteristics and digestion parameters did not vary significantly between TLM-preserved and UWS-stored pancreata. No differences were observed between experimental groups with regard to islet yield, purity, or dynamic glucose stimulation index after either short or prolonged CIT. However, CIT and stimulation index were negatively correlated in each experimental group. The isolation outcome in donors aged > or =60 years was not increased after TLM preservation when compared to UWS storage. No effect was observed regarding islet posttransplant function in recipients with established kidney grafts., Conclusions: The present study suggests that the ischemic tolerance of human pancreata cannot be extended by TLM preservation. In addition, TLM does not seem to improve the isolation outcome for pancreata from elderly donors.