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Early conversion to a calcineurin inhibitor-free regimen with SRL in combination with mycophenolate mofetil may be a useful strategy to improve renal function. The identification of appropriate candidates and safe management of SRL-related adverse events will be a key to avoid the high rate of dropouts, which currently limit the broad applicability of this protocol.

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Summary Reperfusion pancreatitis and graft thrombosis often induce early graft loss in simultaneous pancreas–kidney (SPK) transplantation. Antithrombin (AT) is a coagulatory inhibitor with pleiotropic activities that reduces experimental ischemia/reperfusion injury. This study retrospectively analyses prophylactic high‐dose AT application in patients with first SPK. In an university transplantation center, 53 consecutive patients with SPK were studied without randomization. In one group, 3000 IU of AT was given intravenously before pancreatic reperfusion (AT, n = 24). Patients receiving standard therapy including postoperative AT supplementation (controls, n = 29) served as controls. Daily blood sampling was performed as a part of the clinical routine during four postoperative days. There were no differences in demographic and laboratory parameters [donor/recipient age, ischemia time, perfusion solution, body weight, mismatches] between both groups. Baseline creatinine values were lower in the control group versus AT group (P < 0.05). Coagulatory parameters and bleeding incidence were not influenced by AT, while incidence of graft thrombosis was reduced (control: 7/29; AT: 4/24; relative reduction of risk: −33%; P < 0.05). Single‐shot AT application during SPK modulated serum lipase activity on postoperative days 2 and 3, and minimized risk for graft thromboses without increasing perioperative bleeding. This new concept should deserve testing in a prospective clinical trial.

To evaluate the beneficial effect of pancreatic grafting on peripheral microcirculation and long-term clinical outcome, we compared data of 28 Type 1 (insulindependent) diabetic patients either given a pancreatic and kidney graft simultaneously or given a solitary kidney graft (n-17). Peripheral microcirculation was estimated by transcutaneous oxygen pressure measurement (including reoxygenation potential after blood flow occlusion) and erythrocyte flow / velocity by a non-contact laser speckle method. All the measured parameters showed significant differences between diabetic and control subjects in the mean follow-up time of 49 (simultaneous pancreas and kidney transplantation) and 43 (solitary kidney transplantation) months. The data from patients after simultaneous pancreas and kidney transplantation revealed an improvement of transcutaneous oxygen pressure measurement (rise from 46 + 2 mm Hg to 63 + 3 mmHg), reoxygenation time (fall from 224 + 12s to 114 + 6s) and laser speckle measurement (rise from 4.2 + 1.7 to 5.6 + 1.8 relative units). The control group with solitary kidney transplantation did not show a positive evaluation. Data from patients after simultaneous pancreas and kidney transplantation revealed an improvement in transcutaneous oxygen pressure measurement, reoxygenation time and laser speckle measurement whereas the control group with solitary kidney transplantation did not show a positive evaluation. Improved microcirculation was more pronounced in patients with better microvascular preconditions. The results confirm that diabetic microangiopathy is positively influenced by pancreatic transplantation.

Design: Successful pancreas transplantation results in insulin independence and normoglycemia. This prospectivestudywasperformedtoinvestigatelong-termmetabolicchangesafterpancreastransplantation. Methods: Thirty-eight type 1 diabetic patients after simultaneous pancreas/kidney transplantation (SPK) with a pancreas graft survival for at least 10 years were studied in a prospective manner. HbA 1c and glucose levels before and duringan oral glucose tolerance test (OGTT) were analyzed from 3 months to 10 years after SPK. In addition, insulin secretion and glucagon response were measured. Results: Fastingglucose increased slightlyand continuously from 3 months to 10 years (from 78G3to91G 2 mg/dl). Even HbA 1c levels showed a mild but significant increase from 3 months to 10 years after SPK. Glucose tolerance deteriorated markedly 10 years after SPK. Insulin secretion during OGTT remained stable for 10 years. Parameters of insulin resistance and sensitivity did not change significantly but glucagon secretion increased significantly during the course after SPK. Late after SPK, glucagon levels were higher in patients with an impaired or diabetic glucose tolerance. Conclusions: Pancreas transplantation is able to restore endogenous insulin secretion for 10 years or more. Especially, late after SPK, a deterioration of glycemic control was detected, even if glucose values were within the normal range. During prospective long-term follow-up, an increase of glucagon secretion but no decrease of insulin secretion was detected.European Journal of Endocrinology 156 603-610

Summary. Long-term normalization of glucose metabolism is necessary to prevent or ameliorate diabetic complications. Although pancreatic grafting is able to restore normal blood glucose and glycated haemoglobin, the degree of normalization of the deranged diabetic metabolism after pancreas transplantation is still questionable. Consequently glucose, insulin, C-peptide, glucagon, and pancreatic polypeptide responses to oral glucose and i.v. arginine were measured in 36 Type 1 (insulin-dependen0 diabetic recipients of pancreas and kidney aUografts and compared to ten healthy control subjects. Despite normal HbA1 (7.2_+0.2%; normal <8%) glucose disposal was norreal only in 44% and impaired in 56% of the graft recipients, Normalization of glucose tolerance was achieved at the expense of hyperinsulinaemia in 52% of the subjects. C-peptide and glucagon were normal, while pancreatic polypeptide was significantly higher in the graft recipients, Intravenous glucose tolerance (n=21) was normal in 67% and borderline in 23%. Biphasic insulin release was seen in patients with normal glucose tolerance. Glucose tolerance did not deteriorate up to 7 years post-transplant. In addition, stress hormone release (cortisol, growth hormone, prolactin, glucagon, catecholamines) to insulininduced hypoglycaemia was examined in 20 graft recipients and compared to eight healthy subjects. Reduced blood glucose decline indicates insulin resistance, but glucose recovery was normal, despite markedly reduced catecholamine and glucagon release. These data demonstrate the effectiveness of pancreatic grafting in normalizing glucose metabolism, although hyperinsulinaemia and deranged counterregulatory hormone response are observed frequently.

Acute and chronic rejection after kidney transplantation has long been exclusively attributed to cellular and vascular mechanisms. Modern immunosuppressive therapy, therefore, addresses the cellular immune system. Rising experiences in kidney transplantation in the last few decades have revealed that some types of rejection are refractory to the conventional immunosuppressive treatment. Humoral rejection. which has previously been reported as a crucial factor in hyperacute rejection, is now suspected to play also an important role in acute and chronic rejection. Acute humoral rejection (AHR) is characterized by immunohistochemical detection of C4d deposits in peritubular capillaries. As shown for other antibody-mediated diseases, such as some autoimmune diseases, plasmapheresis has been suggested to be an efficient therapeutic approach in AHR. We present four patients with C4d-positive AHR in the early phase after kidney transplantation. In three of the four patients, humoral graft rejection was successfully treated by plasmapheresis. Graft function was significantly improved with a stable long-term outcome. One patient lost the graft. Although the number of patients with C4d-positive AHR treated by plasmapheresis is limited, plasma exchange appears to be an efficient and powerful therapeutic approach to control humoral rejection.