Bengt von Zur-Mühlen

Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation

Summary 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.

Screening of mortality in transplant patients using an assay for immune function

BACKGROUND So far, the ImmuKnow Immune Cell Function Assay (Cylex, Inc., Columbia, MD, USA) has been used to assess risks of infection and rejection in transplant patients. We hypothesized that the ImmuKnow assay might be used for mortality screening in transplant patients overall. METHODS In the period of February 2007 to December 2009, at the Uppsala University Hospital, 362 patients who received either kidney, kidney+pancreas, kidney+islet cells, liver or liver+kidney allografts were randomly screened using the ImmuKnow assay. All causes of mortality were compared between two groups: patients with at least one ImmuKnow assay below 175ng/mL and patients with all ImmuKnow assays from 175ng/mL and above. Subsequently, the frequency of rejection within thirty days of the ImmuKnow assay was compared between these two groups. RESULTS The study included 1031 ImmuKnow assays obtained from the 362 patients. A total of 111 patients had at least one ImmuKnow below 175ng/mL and 251 patients had all their ImmuKnow assays from 175ng/mL and above. By January 31st 2010, 16 of 111 patients (14.4%) with at least one ImmuKnow assay below 175ng/mL were deceased, compared to 13 of 251 patients (5.2%) with all ImmuKnow assays from 175ng/mL and above (p=0.0053, Fishers exact test). There was no difference in the frequency of rejection between the two groups (19.8% versus 17.5%, p=0.66). CONCLUSIONS In addition to assessing relative risks of infection and rejection in transplant patients, the ImmuKnow assay may be used to identify patients with increased risk of short-term mortality. Transplant patients being highly overimmunosuppressed as assessed by the ImmuKnow assay do not seem to have a lower risk of short-term rejection.

Diagnosis, management and treatment of glucometabolic disorders emerging after kidney transplantation: a position statement from the Nordic Transplantation Societies.

After 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.

Single-centre long-term follow-up of live kidney donors demonstrates preserved kidney function but the necessity of a structured lifelong follow-up

Abstract Background. The increase of live kidney donation (LKD) demands that we scrutinize its long-term consequences. Socialized medicine in Sweden has allowed us to survey long-term consequences of LKD with a high response rate. Methods. Between 1974 and 2008, 455 LKDs were performed; 28 donors were deceased and 14 had moved abroad at the time of the survey. Of the remaining 413, 96% agreed to participate in a retrospective study with laboratory testing and answering a questionnaire. Results. Mean age at donation was 49 ± 10 years, and the mean time since nephrectomy was 11 ± 7 years (range 1–33). No death was of renal cause. S-creatinine at follow-up was 93 ± 18 μmol/L, 28% had treated hypertension, of whom only 52% had BP <140/90. Eleven per cent had spot microalbuminuria, and 1% were diagnosed with diabetes mellitus. Seventy-one per cent had check-ups at least every second year, but 14% had no check-ups. Eighty per cent would be willing to donate again if it were possible, and only 3% regretted the donation. Conclusion. Renal function is well preserved in the long term after donation, no case of end-stage renal disease was identified, and a large majority of our donors would donate again if it were possible. Although rates of microalbuminuria and hypertension were at expected levels, a significant number of donors demonstrated elevated blood pressure levels and inadequate antihypertensive treatment. A relatively large number of donors did not receive regular check-ups. Both of these issues demonstrate the need for a better-structured lifelong follow-up.

Utilization of Small Pediatric Donors Including Infants for Pancreas and Kidney Transplantation : Exemplification of the Surgical Technique and the Surveillance

Utilization of Small Pediatric Donors Including Infants for Pancreas and Kidney Transplantation : Exemplification of the Surgical Technique and the Surveillance

Cost and clinical outcome of islet transplantation in Norway 2010-2015

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.

Malignancies in transplanted patients: Multidisciplinary evaluation and switch to mTOR inhibitors after kidney transplantation – experiences from a prospective, clinical, observational study

Abstract 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.

Insulin independence after conversion from tacrolimus to cyclosporine in islet transplantation

Insulin independence after conversion from tacrolimus to cyclosporine in islet transplantation

Few Gender Differences in Attitudes and Experiences after Live Kidney Donation, with Minor Changes Over Time

Background We sought to study gender differences and differences over time with respect to demographics, relation to recipient, donor motives, and experiences of live kidney donation. Material/Methods In all, 455 consecutive live kidney donors, representing all of the donors at our center between 1974 and 2008 were considered for this study. There were 28 deceased donors and 14 donors who had moved abroad, leaving 413 donors; 387 (94%) agreed to participate in this study. A questionnaire was sent and the answers was analyzed for gender differences and, where relevant, for changes over time. Results In all sub-periods, female donors made up the majority (55–62%), except for sibling donors (45%) and child-to-parent donors (40%). No significant gender differences were seen in perceived information given before donation. For males, it was more common that the recipient took the initiative to donate. For females, the motivation for donating was more frequently to help the recipient and because others wanted them to donate. For males, it was more common to feel a moral obligation. Post-operatively, females more frequently felt sad and experienced nausea, and more frequently felt that the donation had a positive impact on their lifes. With the introduction of minimally invasive surgical techniques, donors experienced fewer problems from the operation, with no gender difference. Conclusions Females donate more frequently than males, a difference that did not change over time. Only a few gender differences were seen in donor motives and the donation experience; however, these differences may be relevant to address the gender imbalance in kidney donations.

Few Gender Differences in Attitudes and Experiences after Live Kidney Donation, with Minor Changes over Time

Background We sought to study gender differences and differences over time with respect to demographics, relation to recipient, donor motives, and experiences of live kidney donation. Material/Methods In all, 455 consecutive live kidney donors, representing all of the donors at our center between 1974 and 2008 were considered for this study. There were 28 deceased donors and 14 donors who had moved abroad, leaving 413 donors; 387 (94%) agreed to participate in this study. A questionnaire was sent and the answers was analyzed for gender differences and, where relevant, for changes over time. Results In all sub-periods, female donors made up the majority (55–62%), except for sibling donors (45%) and child to-parent donors (40%). No significant gender differences were seen in perceived information given before donation. For males, it was more common that the recipient took the initiative to donate. For females, the motivation for donating was more frequently to help the recipient and because others wanted them to donate. For males, it was more common to feel a moral obligation. Post-operatively, females more frequently felt sad and experienced nausea, and more frequently felt that the donation had a positive impact on their lifes. With the introduction of minimally invasive surgical techniques, donors experienced fewer problems from the operation, with no gender difference. Conclusions Females donate more frequently than males, a difference that did not change over time. Only a few gender differences were seen in donor motives and the donation experience; however, these differences may be relevant to address the gender imbalance in kidney donations. Figure. No caption available. Table. No title available.