Jørn Petter Lindahl

Early versus late acute antibody-mediated rejection in renal transplant recipients.

Background Over the last decade, the diagnostic precision for acute antibody-mediated rejection (aABMR) in kidney transplant recipients has improved significantly. The phenotypes of early and late aABMR may differ. We assessed the characteristics and outcomes of early versus late aABMR. Methods Between January 1, 2005 and December 31, 2010, aABMR was diagnosed in 67 grafts in 65 kidney recipients, with a median follow-up of 3.6 years (range, 61 days–7.3 years). Recipients were stratified by early aABMR (<3 months after transplantation; n=40) and late aABMR (>3 months after transplantation; n=27). The main outcome was kidney allograft loss. Outcome of aABMR was compared with recipients with acute early (n=276) or late (n=100) non-ABMR during the same period. Results Recipients with late aABMR had significantly reduced graft survival compared with recipients with early aABMR (P<0.001, log-rank test; 40% vs. 75% at 4 years; hazard ratio, 3.72; 95% confidence interval, 1.65–8.42). Graft survival in late aABMR was also inferior to late non-ABMR acute rejections (P=0.008). At transplantation, more patients were presensitized to human leukocyte antigens (22 [55%] vs. 4 [15%] in the early vs. late aABMR group). The late aABMR group was characterized by younger recipient age (37.9±12.9 vs. 50.9±11.6 years; P<0.001), increased occurrence of de novo donor-specific antibodies (52% vs. 13%; P=0.001), and nonadherence/suboptimal immunosuppression (56% vs. 0%; P<0.001). Conclusion Compared with early aABMR, late aABMR had inferior graft survival and was characterized by young age, frequent nonadherence, or suboptimal immunosuppression and de novo donor-specific antibodies.

Pancreas Transplantation With Enteroanastomosis to Native Duodenum Poses Technical Challenges—But Offers Improved Endoscopic Access for Scheduled Biopsies and Therapeutic Interventions

To facilitate endoscopic access for rejection surveillance and stenting of the pancreas, we have abandoned the duodenojejunostomy (DJ) in favor of duodenoduodenostomy (DD) in pancreas transplantation (PTx). From September 2012 to September 2013 we performed 40 PTx with DD; 20 solitary‐PTx (S‐PTx) and 20 simultaneous pancreas and kidney transplantation (SPK). We compared the outcomes with results from 40 PTx‐DJ (10 S‐PTx and 30 SPK) from the preceding era. The DD‐enteroanastomoses were performed successfully. Endoscopic pancreas biopsies (endoscopic ultrasound examination [EUS]) yielded representative material in half of the cases. One exocrine fistula was treated by endoscopic stenting. PTxs‐DD were associated with a higher rate of thrombosis compared to PTx‐DJ (23% vs. 5%) and reoperations (48% vs. 30%), as well as inferior graft survival (80% vs. 88%). Time on waiting list, HLA A + B mismatches and reoperations were associated with graft loss. Only recipient age remained an independent predictor of patient death in multivariate analysis. PTx‐DD showed a higher rate of thrombosis and inferior results, but facilitated a protocol biopsy program by EUS that was feasible and safe. Given that technical difficulties can be solved, the improved endoscopic access might confer long‐term benefits, yet this remains to be proven.

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.

Long-term outcomes after organ transplantation in diabetic end-stage renal disease.

Patients with type 1 diabetic end-stage renal disease (ESRD) may be offered single kidney transplantation from a live donor (LDK) or a deceased donor (DDK) to replace the lost kidney function. In the latter setting the patient may also receive a simultaneous pancreas together with a kidney from the same donor (SPK). Also in some cases a pancreas after kidney may be offered to those who have previously received a kidney alone (PAK). The obvious benefit of a successful SPK transplantation is that the patients not only recover from uremia but also obtain normal blood glucose control without use of insulin or other hypoglycemic agents. Accordingly, this combined procedure has become an established treatment for type 1 diabetic patients with ESRD. Adequate long-term blood glucose control may theoretically lead to reduced progression or even reversal of microvascular complications. Another potential beneficial effect may be improvement of patient and kidney graft survival. Development of diabetic complications usually takes a decade to develop and accordingly any potential benefits of a pancreas transplant will not easily be disclosed during the first decade after transplantation. The purpose of the review is to assess the present literature of outcomes after kidney transplantation in patients with diabetic ESRD, with our without a concomitant pancreas transplantation. The points of interest given in this review are microvascular complications, graft outcomes, cardiovascular outcomes and mortality.

Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation

AIMS Patients with type 1 diabetes and end-stage renal disease with simultaneous pancreas and kidney (SPK) or kidney transplants alone (KA) were recruited 9-12 years post transplantation. We investigated differences between these groups with regard to inflammatory parameters and long-term structural changes in kidneys. METHODS Blood samples were analyzed by ELISA and multiplex for chemokines, cytokines, growth factors, cell adhesion molecules and matrix metalloproteinases. Kidney graft biopsies were analyzed by electron microscopy for glomerular basement membrane thickness. Heparan- and chondroitin sulfate disaccharide structures were determined by size exclusion chromatography mass-spectrometry. RESULTS The SPK and the KA group had average glycated hemoglobin A1c (HbA1c) of 5.8% (40 mmol/mol) and 8.6% (70 mmol/mol) respectively. SPK recipients also had 16.2% lower body mass index (BMI) and 46.4% lower triglyceride levels compared with KA recipients, compatible with an improved metabolic profile in the SPK group. Plasminogen activator inhibitor (PAI-1), C-reactive protein (CRP) and vascular endothelial growth factor (VEGF) were lower in the SPK group. In kidney graft biopsies of the KA-patients an 81.2% increase in average glomerular basement membrane thickness was observed, accompanied by alterations in heparan sulfate proteoglycan structure. In addition to a decrease in 6-O-sulfated disaccharides, an increase in non-N-sulfated disaccharides with a corresponding slight decrease in N-sulfation was found in kidney biopsies from hyperglycemic patients. CONCLUSIONS Patients with end stage renal disease subjected to KA transplantation showed impaired inflammatory profile, increased thickness of basement membranes and distinct changes in heparan sulfate structures compared with SPK recipients.

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.

Cardiac Assessment of Patients With Type 1 Diabetes Median 10 Years After Successful Simultaneous Pancreas and Kidney Transplantation Compared With Living Donor Kidney Transplantation.

Background In recipients with type 1 diabetes, we aimed to determine whether long-term normoglycemia achieved by successful simultaneous pancreas and kidney (SPK) transplantation could beneficially affect progression of coronary artery disease (CAD) when compared with transplantation of a kidney-alone from a living donor (LDK). Methods In 42 kidney transplant recipients with functioning grafts who had received either SPK (n = 25) or LDK (n = 17), we studied angiographic progression of CAD between baseline (pretransplant) and follow-up at 7 years or older. In addition, computed tomography scans for measures of coronary artery calcification and echocardiographic assessment of left ventricular systolic function were addressed at follow-up. Results During a median follow-up time of 10.1 years (interquartile range [IQR], 9.1-11.5) 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). Median coronary artery calcification scores were high in both groups (1767 [IQR, 321-4035] for SPK and 1045 [IQR, 807-2643] for LDK patients; P = 0.59). Left ventricular systolic function did not differ between the 2 groups. The SPK and LDK recipients were similar in age (41.2 ± 6.9 years vs 40.5 ± 10.3 years; P = 0.80) and diabetes duration at engraftment but with significant different mean HbA1c levels of 5.5 ± 0.4% for SPK and 8.3 ± 1.5% for LDK patients (P < 0.001) during follow-up. Conclusions In patients with both type 1 diabetes and end-stage renal disease, SPK recipients had similar progression of CAD long-term compared with LDK recipients. Calcification of coronary arteries is a prominent feature in both groups long-term posttransplant.