Scandiatransplant Exchange Program (STEP) : Development and Results From an International Kidney Exchange Program

Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.BACKGROUND: Kidney transplant candidates may be incompatible with their intended living donors because of the presence of antibodies against HLA and/or ABO. To increase the possibility of finding an acceptable kidney donor for these patients, the Scandiatransplant Exchange Program (STEP) program within Scandiatransplant was launched in 2019. METHODS: This is a retrospective review of our experiences from the first 4 y of the STEP program, including details about the match runs, performed transplantations, and recipient outcomes within the program. RESULTS: During 2019-2022, 11 match runs and 4 reruns were performed. In total, 114 pairs and 6 anonymous donors participated in these match runs. Fifty-one pairs (45%) participated in 1 match run, 31 pairs (27%) participated in 2 match runs, and 32 pairs (29%) participated in ≥3 match runs. Seventy-two individuals (63%) participated because of HLA incompatibility, 19 (17%) because of ABO incompatibility, and 7 (6%) because of both HLA and ABO incompatibility.Forty percent of the patients enrolled in the program underwent transplantation. In total, 49 transplantations have so far been performed within the program, and 46 (94%) of the recipients had a functioning kidney graft at follow-up in February 2023. CONCLUSIONS: The STEP program offers sensitized patients an enlarged pool of living donors and a chance of a compatible international living donor, resulting in an increased number of total transplantations. Currently, STEP is one of the largest transnational kidney exchange programs and has improved the situation for patients waiting for kidney transplantation in Scandiatransplant.Peer reviewe

Pancreas and Kidney Transplantation in Patients with Type 1 Diabetes and End-Stage Renal Disease: Long-Term Outcomes

Background/objectives: This thesis examines transplant modality and long-term outcomes in type 1 diabetic patients with end-stage renal disease (ESRD), who may be offered a pancreas and kidney transplant simultaneously from the same deceased donor (SPK), or a single kidney transplant from a living donor (LDK) or a deceased donor (DDK) to replace lost kidney function. LDK transplantation has been first priority at our hospital due to better long-term patient and kidney graft survival rates compared with DDK transplantation, and it also reduces the wait list for the latter. Patients with ESRD, particularly those with diabetes, are at high risk of cardiovascular disease (CVD). A successful SPK transplantation restores glycaemic control, and may therefore protect against or halt the development of diabetic complications post-transplant. Previous research has shown conflicting results in terms of superior long-term outcomes with either SPK transplantation or LDK transplantation. The inconsistent results may stem from a combination of factors, including differences in age and comorbidities, immunosuppressive regimens, surgical techniques, as well as small sample sizes or short follow-up. Since we were largely able to overcome these shortcomings, we raised the following four research questions: Compared with kidney transplantation alone (KTA), particularly LDK transplantation, does SPK transplantation (1) improve patient and kidney graft survival rates, (2) improve cardiovascular death rates, (3) prevent progression of coronary artery disease (CAD), and (4) prevent recurrence of diabetic glomerular changes in the kidney graft post-transplant? This thesis advances our understanding of the potential benefits of restoring glycaemic control post-transplant, and enables us to better choose a transplant modality for type 1 diabetic patients with ESRD. Methods: A retrospective observational cohort study was conducted on all kidney transplants performed in Norway between 1983 and 2012 on patients with type 1 diabetes. We collected data from the Norwegian Renal Registry and hospital records. Multivariate Cox regression was used to assess associations between transplant modality and (1) patient and graft survival in 630 patients transplanted with SPK (n=222), LDK (n=171), or DDK (n=237) grafts between 1983 and 2010, and (2) all-cause and CVD- and CAD-related death in 486 patients transplanted with SPK (n=256) or LDK (n=230) grafts from 1983 to the end of 2012. In a subgroup of 42 (25 SPK/17 LDK) recipients receiving grafts between 1983 and 2003 still functioning at median 10.1 years post-transplant, angiographic progression of CAD between baseline and follow-up was studied, and kidney graft biopsies were performed at follow-up to examine for occurrence of diabetic glomerular lesions (e.g., glomerular basement membrane [GBM] thickening and mesangial expansion). Results: The mean follow-up time was 7.1 years in the main cohort of type 1 diabetic kidney transplant recipients transplanted in the period 1983-2010. In multivariate Cox regression, SPK transplantation was associated with superior patient survival compared with both LDK transplantation (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.52, 0.95; p=0.02) and DDK transplantation, which in turn was inferior to LDK transplantation (HR 1.41, 95% CI 1.04, 1.93; p=0.029). SPK superiority over LDK was dependent on donor age. Adjusted kidney graft survival did not differ between SPK and LDK recipients (HR 0.99, 95% CI 0.73, 1.37; p=0.99), while kidney graft survival in DDK recipients was poorer than in LDK recipients (HR 1.45, 95% CI 1.08, 1.96; p=0.014). Pancreas graft survival also improved after year 2000, with a 5-year graft survival rate of 78% versus 61% in previous years (1988-1999). The median follow-up length was 7.9 years in patients transplanted in the period 1983-2012 and studied for CVD-related deaths. The adjusted HR for CVD-related deaths in SPK recipients compared with LDK recipients was 0.63 (95% CI 0.40, 0.99; p=0.047), while the HRs for all-cause and CAD-related mortality were 0.81 (95% CI 0.57, 1.16; p=0.25) and 0.63 (95% CI 0.36, 1.12; p=0.12), respectively. In the subgroup consisting of 25 SPK and 17 LDK patients, median duration of follow-up was 10.1 years. The mean HbA1c levels during follow-up were 5.5±0.4% and 8.3±1.5% in the SPK and LDK group, respectively (p<0.001). The progression of CAD occurred at similar rates (10 of 21 cases in the SPK and 5 of 14 cases in the LDK group; p=0.49). Compared with SPK recipients, LDK recipients had wider GBM (369±109 nm versus 281±57 nm; p=0.008) and increased mesangial volume fraction (median 0.23 [range 0.13-0.59] versus 0.16 [0.10- 0.41]; p=0.007) at follow-up. Absolute estimated glomerular filtration rate (eGFR) change from baseline was -11±21 and -23±15 ml/min/1.73 m² (p=0.060), and eGFR slope was -1.1 (95% CI -1.7, -0.5) and -2.6 (95% CI -3.1, -2.1) ml/min/1.73 m² per year in the SPK and LDK group, respectively (p=0.001). Conclusions: We conclude that in type 1 diabetic patients with ESRD, SPK transplantation was associated with better long-term patient survival compared with both LDK and DDK transplantation, but the difference in survival between SPK and LDK transplantation depended on donor age. Long-term kidney graft survival was inferior in DDK recipients compared with both SPK and LDK recipients, in whom there was no difference in kidney graft survival. There was an association between LDK transplantation and increased risk of cardiovascular death compared with SPK transplantation. Compared with LDK transplantation, SPK transplantation did not slow the progression of CAD, but kidney graft ultrastructure and function were better preserved post-transplant in a subgroup of patients with long-term functioning grafts

Patient selection for islet or solid organ pancreas transplantation: experiences from a multidisciplinary outpatient-clinic approach

Objective β-cell replacement therapy (βCRT), including pancreas transplantation alone (PTA) and islet transplantation (ITX), is a treatment option for selected type 1 diabetes patients. All potential candidates for βCRT in Norway are referred to one national transplant centre for evaluation before any pre-transplant workup is started. This evaluation was performed by a transplant nephrologist alone prior to 2015 and by a multidisciplinary team (MDT) from 2015. We have reviewed the allocation of patients to treatment modality and the 1-year clinical outcome for the patients after transplantation. Research design and methods Medical charts of all patients evaluated for βCRT between 2010 and 2020 in Norway were retrospectively analysed and the outcome of patients receiving βCRT were studied. Results One hundred and forty-four patients were assessed for βCRT eligibility between 2010 and 2020. After MDT evaluation was introduced for βCRT eligibility in 2015, the percentage of referred patients accepted for the transplant waiting list fell from 84% to 40% ( P &lt; 0.005). One year after transplantation, 73% of the PTA and none of the ITX patients were independent of exogenous insulin, 8% of the PTA and 90% of the ITX patients had partial graft function while 19% of the PTA and 10% of the ITX patients suffered from graft loss. Conclusion The acceptance rate for βCRT was significantly reduced during a 10-year observation period and 81% of the PTA and 90% of the ITX patients had partial or normal graft function 1 year post-transplant

Outcomes in pancreas transplantation with exocrine drainage through a duodenoduodenostomy versus duodenojejunostomy

Until recently, pancreas transplantation has mostly been performed with exocrine drainage via duodenojejunostomy (DJ). Since 2012, DJ was substituted with duodenoduodenostomy (DD) in our hospital, allowing endoscopic access for biopsies. This study assessed safety profiles with DD versus DJ procedures and clinical outcomes with the DD technique in pancreas transplantation. DD patients (n = 117; 62 simultaneous pancreas–kidney [SPKDD] and 55 pancreas transplantation alone [PTADD] with median follow-up 2.2 years) were compared with DJ patients (n = 179; 167 SPKDJ and 12 PTADJ) transplanted in the period 1998–2012 (pre-DD era). Postoperative bleeding and pancreas graft vein thrombosis requiring relaparotomy occurred in 17% and 9% of DD patients versus 10% (p = 0.077) and 6% (p = 0.21) in DJ patients, respectively. Pancreas graft rejection rates were still higher in PTADD patients versus SPKDD patients (p = 0.003). Hazard ratio (HR) for graft loss was 2.25 (95% CI 1.00, 5.05; p = 0.049) in PTADD versus SPKDD recipients. In conclusion, compared with the DJ procedure, the DD procedure did not reduce postoperative surgical complications requiring relaparatomy or improve clinical outcomes after pancreas transplantation despite serial pancreatic biopsies for rejection surveillance. It remains to be seen whether better rejection monitoring in DD patients translates into improved long-term pancreas graft survival

Insulin secretion and action after pancreas transplantation. A retrospective single-center study

We explored glucometabolic and renal function after engraftment in all 159 consecutive patients with type 1 diabetes who received pancreas transplantation alone (PTA, n = 80) or simultaneous pancreas and kidney transplantation (SPK, n = 79) in Norway from 2012 until 2017. We report fasting levels of plasma glucose (FPG), C-peptide, eGFR and the homeostasis model assessment of insulin sensitivity (HOMA2(%S)) and beta-cell function (HOMA2(%B)) measured one to three times weekly during the first 8 and at 52 weeks after transplantation. One year after engraftment, in the PTA and SPK groups 52 and 64 were normoglycaemic without exogenous insulin, and two and zero patients were dead. Data at the 52-week visit were missing for 5 and 6 patients in the respective groups. During the first 8 weeks, FPG was lower, C-peptide and HOMA2(%S) were higher and eGFR was lower in the SPK group as compared with the PTA group (all p < .05). 30 out of 157 living patients needed insulin treatment 52 weeks after transplantation, 9/79 in the SPK group and 21/78 in the PTA group (p = .02). In conclusion, patients who underwent SPK showed lower insulin sensitivity, but higher insulin secretory capacity and lower mean blood glucose levels the first 8 weeks after transplantation. Also, a higher proportion of patients in the SPK group were insulin-free after 1 year, compared with the PTA group

Long-term Outcomes After Kidney Transplantation From DBD Donors Aged 70 y and Older

Background. Transplantation of kidneys from elderly donations after brain death (DBD) donors has increased owing to organ shortages. We aimed to assess the impact on long-term kidney transplant outcomes from DBD donors aged 70 y and older compared with kidneys from younger donors. Methods. From 2007 to 2022, 2274 first single kidney transplantations from DBD donors were performed at our center. Data from 1417 kidney transplant recipients receiving a DBD organ were included and categorized into 3 groups according to donor age: 70 y and older (n = 444, median age 74 y), 60–69 y (n = 527, median age 64 y), and a reference group consisting of donors aged 45–54 y (n = 446, median age 50 y). Kaplan-Meier plots and multivariate Cox regression with correction for recipient, donor, and transplant characteristics were used to investigate patient and kidney graft survival outcomes. Results. The median patient follow-up time was 9.3 y (interquartile range, 5.3–13.1). The adjusted hazard ratios for patient death in recipients of kidneys from DBD donors aged 70 y and older compared with 60–69 y and 45–54 y were 1.12 (95% confidence interval [CI], 0.92-1.36; P = 0.26) and 1.62 (95% CI, 1.26-2.07; P < 0.001), respectively. Compared with recipients of donors aged 60–69 y and 45–54 y, the adjusted hazard ratios for kidney graft loss in recipients of donors aged 70 y and older were 1.23 (95% CI, 1.02-1.48; P = 0.029) and 1.94 (95% CI, 1.54-2.45; P < 0.001), respectively. Conclusions. Transplantation of kidneys from DBD donors aged 70 y and older resulted in acceptable long-term outcomes and is encouraging