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.

We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.

Sotrastaurin, a novel immunosuppressant, blocks early T cell activation through protein kinase C inhibition. Efficacy and safety of sotrastaurin with tacrolimus were assessed in a dose-ranging noninferiority study in renal transplant recipients. A total of 298 patients were randomized 1:1:1:1 to receive sotrastaurin 100 (n ¼ 77; discontinued in December 2011) or 200 mg (n ¼ 73) b.i.d. plus standard tacrolimus (sTAC; 5-12 ng/mL), sotrastaurin 300 mg (n ¼ 75) b.i.d. plus reduced tacrolimus (rTAC; 2-5 ng/mL) or enteric-coated mycophenolic acid (MPA) plus sTAC (n ¼ 73); all patients received basiliximab and corticosteroids. Composite efficacy failure (treated biopsyproven acute rejection ! grade IA, graft loss, death or loss to follow up) rates at Month 12 were 18.8%, 12.4%, 10.9% and 14.0% for the sotrastaurin 100, 200 and 300 mg, and MPA groups, respectively. The median estimated glomerular filtration rates were 55.7, 53.3, 64.9 and 59.2 mL/min, respectively. Mean heart rates were faster with higher sotrastaurin doses and discontinuations due to adverse events and gastrointestinal adverse events were more common. Fewer patients in the sotrastaurin groups experienced leukopenia than in the MPA group (1.3-5.5% vs. 16.5%). Sotrastaurin 200 and 300 mg had comparable efficacy to MPA in prevention of rejection with no significant difference in renal function between the groups.

Background Living anonymous donation (LAD) of kidneys was introduced in Sweden in 2004. This study reports on outcomes of Swedish LAD experiences from 2004 to 2016, focusing on donors’ motives, the care they received, psychosocial aspects, and medical status at follow-up. Material/Methods Donor data were collected through a physician interview, medical check-up, review of medical charts, the Hospital Anxiety Depression Scale (HADS), and a routine national questionnaire. Of the 26 LADs during the study period, 1 donor died and 1 declined to participate, leaving a study population of 24. Results Half of the donors were male, which is a higher proportion than for directed living donors. The major motive detected was altruism. Of the 24 LADs, 96% were very satisfied and would donate again if possible, 46% noted increased self-esteem, and a third were happier after the donation. Sixty-two percent received anonymous information about the recipient and 40% would have liked to meet the recipient. HADS scores were normal. Two donors had antidepressant treatment, 1 of whom had received treatment before donation. Half mentioned that the pre-donation assessment took too long. At follow-up, mean eGFR was 62±12 mL/min/1.73 m 2 , of which 16 were in CKD II and 8 were in CKD III. Four donors had developed hypertension, 1 of whom also developed type 2 diabetes. Conclusions Swedish LADs are very satisfied and medical outcomes are acceptable. We propose that the transplant community and the National Board of Health and Welfare take a more active approach to informing the general public about LAD.

Original Clinical Science-General Background. When transplanted human pancreatic islets are exposed to blood during intraportal infusion, an innate immune response is triggered. This instant blood-mediated inflammatory reaction (IBMIR) activates the coagulation and complement cascades and leads to the destruction of 25% of all transplanted islets within minutes, contributing to the need, in most patients, for islets from more than 1 donor. Low molecular dextran sulfate (LMW-DS) has been shown in experimental settings to inhibit IBMIR. Methods. The Clinical Islet Transplantation consortium 01 study was a phase II, multicenter, open label, active control, randomized study. Twenty-four subjects were randomized to peritransplant intraportal and systemic treatment with either LMW-DS or heparin, targeting an activated partial thromboplastin time of 150 ± 10 seconds and 50 ± 5 seconds, respectively. C-peptide response was measured with a mixed meal tolerance test at 75 and 365 days after transplant. Results. Low molecular dextran sulfate was safe and well tolerated with similar observed adverse events (mostly attributed to immunosuppression) as in the heparin arm. There was no difference in the primary endpoint (stimulated C-peptide 75 ± 5 days after the first transplant) between the 2 arms (1.33 ± 1.10 versus 1.56 ± 1.36 ng/mL, P = 0.66). Insulin requirement, metabolic parameters, Clarke and HYPO score, quality of life, and safety were similar between the 2 treatments groups. Conclusions. Even with low dosing, LMW-DS showed similar efficacy in preventing IBMIR to promote islet engraftment when compared to "state-of-the art" treatment with heparin. Furthermore, no substantial differences in the efficacy and safety endpoints were detected, providing important information for future studies with more optimal dosing of LMW-DS for the prevention of IBMIR in islet transplantation.

No abstract

SummaryAfter successful solid organ transplantation, new-onset diabetes (NODAT) is reported to develop in about 15-40% of the patients. The variation in incidence may partly depend on differences in the populations that have been studied and partly depend on the different definitions of NODAT that have been used. The diagnosis was often based on 'the use of insulin postoperatively', 'oral agents used', random glucose monitoring and a fasting glucose value between 7 and 13 mmol/l (126-234 mg/dl). Only few have used a 2-h glucose tolerance test performed before transplantation. There is a huge variation in the literature regarding risk factors for developing NODAT. They can be divided into factors related to glucose metabolism or to patient demographics and the latter into modifiable and nonmodifiable. Screening for risk factors should start early and be re-evaluated while being on the waitlist. Patients on the waiting list for renal transplantation and transplanted patients share many characteristics in having hyperglycaemia, disturbed insulin secretion and increased insulin resistance. We present guidelines for early risk factor assessment and a screening/treatment strategy for disturbed glucose metabolism, both before and after transplantation. The aim was to avoid the increased cardiovascular disease and mortality rates associated with NODAT. Diabetes and transplantation Diabetes emerging after organ transplantation is called new-onset diabetes (NODAT). It is diagnosed according to the World Health Organization (WHO) definition of diabetes as previously described in guidelines for diagnosis and treatment of NODAT published in 2004 [1] and 2005[2]. NODAT has a significant impact on allograft and patient survival, quality of life and health care costs [3][4][5][6]. Furthermore, even moderately elevated fasting or postchallenge glucose concentrations predict future development of diabetes as shown in two studies demonstrating that 15% of renal transplant patients with impaired glucose tolerance (IGT) developed NODAT after 1 year [7] and 27% after 6 years [8]. For these reasons, more focus should be placed on diagnosing and treating NODAT and therefore the transplantation societies in Denmark, Norway and Sweden have endorsed new guidelines as presented in the following. Diagnosis of diabetes and the prediabetic conditionsThe diagnosis of NODAT is made when fasting plasma glucose (FPG) is 7 mmol/l (126 mg/dl) and/or 2-h plasma glucose is 11.1 mmol/l (200 mg/dl) after a 75-g oral tolerance test (OGTT) measured on at least two occasions [WHO and American Diabetes Association (ADA) guidelines] [9,10].Haemoglobin A1c (HbA1c) is today also used for diagnosing diabetes [10], but HbA1c as a diagnostic criterion of

Background Solid organ transplant recipients are at increased risk of developing malignancies. The objective of this prospective, observational, one-armed study was to study the feasibility to add a mammalian target of rapamycin (mTOR) inhibitor to the immunosuppressive regimen in transplanted patients with post-transplant malignancies. During the trial the need to improve identification of post-transplant malignancies and to reassure adequate oncological treatment of these patients became evident. Multidisciplinary team (MDT) evaluation of oncological and immunosuppressive treatments was implemented for all patients with malignancies after renal or combined renal and pancreas transplantation because of the trial. Material and methods At Uppsala University Hospital, Sweden, a MDT consisting of transplant surgeons, nephrologists, oncologists and dermatologists evaluated 120 renal or combined renal and pancreas-transplanted recipients diagnosed with malignancies from September 2006 to July 2012. To identify all malignancies, the population was linked to the Regional Tumor Registry (RTR). We recorded to which extent a switch to mTOR inhibitors was possible and how often the originally planned oncological managements were adjusted. All patients were followed for three years. (ClinicalTrials.gov: NCT02241564). Results In 76 of 120 patients (63%) a switch to mTOR inhibitors was possible. Immunosuppression was interrupted in seven patients (6%), reduced in three patients (2%) and remained unchanged in 34 of 120 patients (28%). Identification of post-transplant malignancies increased significantly after linkage to RTR (p = 0.015). The initially recommended oncological treatment was adjusted in 23 of 44 patients (52%) with solid or hematological malignancies; 36 of these patients (82%) were treated according to national guidelines. Conclusion In two thirds of the patients the immunosuppressive treatment could be changed to an mTOR inhibitor with anti-tumor effects in transplanted patients with post-transplant malignancies. The use of regional tumor registers considerably improved the identification of patients with post-transplant malignancies indicating that post-transplant malignancies might be timely underreported in transplant registers.