A 55-Year-Old Man with Recurrent Gastrointestinal Bleeding Due to Stricture of the Portal Vein Anastomotic Site 12 Years After Combined Pancreas and Kidney Transplantation.

BACKGROUND Varices of the upper gastrointestinal tract are due to portal hypertension and can result from occlusion of the portal venous system. This report is of a 55-year-old man with recurrent gastrointestinal bleeding due to stricture of the portal vein anastomotic site to inferior vena cava (IVC) 12 years after combined pancreas and kidney transplantation. CASE REPORT A 55-year-old man presented bleeding episodes requiring transfusion of more than 70 units of red blood cells (RBCs), complicated by bacterial and viral infection episodes including cytomegalovirus (CMV) reactivation and hepatitis E and transient impairment of function of the renal allograft. Endoscopy, computed tomography (CT) scan, and angiography revealed jejunal varices due to anastomotic stricture at the portal vein to IVC as the cause of the hemorrhage. Neither conservative therapy nor an anastomosis between the splenic vein of the graft and the internal iliac vein as a bypass could stop the life-threatening bleeding. During the recurrent bleeding, CD4 T lymphocytes were low, indicating immunodeficiency despite paused immunosuppressive therapy. After the hemorrhage resolved and immunosuppression was restarted, CD4 T lymphocyte levels normalized. Finally, to stop the hemorrhage and save the transplanted kidney and the patient's life, graft pancreatectomy was performed. Long-term damage to the renal transplant was not found. CONCLUSIONS This report is of a rare case of portal hypertension as a long-term complication of transplant surgery. Although acute venous thrombosis at the anastomotic site is a recognized postoperative complication of pancreatic transplant surgery, this case highlights the importance of post-transplant follow-up and diagnostic imaging.

Tolerability and steady-state pharmacokinetics of everolimus in maintenance renal transplant patients.

BACKGROUND: Current immunosuppressant regimens need to be improved to prevent acute and chronic graft rejection. The novel macrocyclic immunosuppressant everolimus (Certican, RAD) is currently in clinical development to address this issue. METHODS: The primary objective of this multicentre, randomized, double-blind, placebo-controlled, dose-escalating phase 1 study was to evaluate the safety and tolerability of everolimus at four dose levels (0.75, 2.5, 5 and 10 mg/day) in maintenance renal transplant patients receiving cyclosporin and steroids. The secondary objective was to assess the pharmacokinetic profile of two different formulations (capsule and tablet) of everolimus. RESULTS: Fifty-four subjects were randomized for 4 weeks treatment with everolimus (n = 44) or placebo (n = 10). Dose levels of everolimus between 0.75 and 5 mg daily were well tolerated, permitting dose escalation to the highest everolimus dose of 10 mg daily. At this dose, everolimus was associated with a higher incidence and severity of adverse events, most notably thrombocytopenia. Pharmacodynamic assessment showed a relationship between drug exposure and thrombocytopenia. Notable reversible elevations of cholesterol were also observed at the 10 mg/day dose. Other changes in laboratory evaluations, including triglycerides, were minor, reversible and did not appear to be dose dependent. The bioavailability of the tablet formulation was 2.6-fold higher compared with the capsule, with evidence for dose proportionality over the dose range tested. Within-subject pharmacokinetic variability was low (coefficient of variation: 10-19%); however, between-subject variability ranged from 34 to 60% for AUC and C(max). CONCLUSIONS: These results indicate that up to 5 mg/day everolimus results in a dose-proportional exposure, and is adequately well tolerated in renal transplant recipients receiving cyclosporin and steroids.