Renopancreatic Transplantation: Evaluation of 15 Years in 131 Patients.

BACKGROUND: The most common multiple-organ transplant is the simultaneous pancreas-kidney transplantation (SPK). It is usually offered to patients who have insulin-dependent diabetes mellitus and those with diabetic nephropathy and renal failure that has already been established. In this study we present the results of 15 years of SPK in a transplant hospital center in Paraná, Brazil, and evaluated survival, immunosuppression, and transplant-related problems. METHODS: This study was a retrospective analysis of 131 SPK transplants performed at the Angelina Caron Hospital between January 2001 and December 2015. RESULTS: The mean age of SPK recipients was 34 years, with slight a predominance of males (50.4%). Mean graft ischemia time was 11 hours. Exocrine drainage was predominantly vesical, but this approach was abandoned after 2011. As for immunosuppression, induction was performed with basiliximab or thymoglobulin and maintained with prednisone, mycophenolate mofetil, tacrolimus, and/or sirolimus. Patient survival increased from 68.1% in 2001 to 2005 to 77.6% in 2011 to 2015. Graft survival at the end of the period was 85.7% for kidney and 75.5% for pancreas. The main surgery-derived problems for pancreas and kidney was thrombosis (15% and 6%, respectively). The main clinical problems were rejection of the pancreas (18.3%) and urinary infection of the kidney (33.3%). The main cause of death was intra-abdominal sepsis (11.4%). CONCLUSION: There was an improvement in survival rates over the time frame observed, but it remains necessary to adopt measures to reduce transplant-derived problems, including review of the antibiotic therapy protocol and measures to avoid graft thrombosis.

Use of mycophenolate mofetil as rescue therapy after pediatric liver transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) has been increasingly used after liver transplantation (LT) in adults. We report our preliminary experience with MMF as rescue therapy after pediatric LT. METHODS: A total of 19 children received MMF for 21 indications. Median age at LT was 30 months (range 7-149). The median initial oral dose of MMF was 23 mg/kg/day (range 12-43) orally. Median follow-up after initiation of MMF therapy was 642 days (range 229-1606). RESULTS: 1) EFFICACY: MMF was indicated for rejection or insufficient immunosuppression in 16 cases, with normalization of both liver function tests and liver histology in 10 (62%). MMF was successfully used in one patient with post-LT immmune hepatitis and one patient with corticodependence. In three patients with renal function impairment, MMF allowed reduction of cyclosporine A or tacrolimus blood levels, without subsequent rejection. 2) Tolerance: Six patients (32%) experienced eight side effects, mainly gastrointestinal and hematological, which resolved after cessation of MMF in five cases and dose reduction in three. One case of posttransplant lymphoproliferative disease (PTLD) occurred under MMF therapy (5.2%). Four patients had EBV primary infection, while under MMF therapy, without subsequent PTLD. Three patients had CMV primary infection, and five CMV reactivation, under MMF therapy. Seven remained asymptomatic, and one presented with CMV enteritis. CONCLUSIONS: These preliminary results suggest that MMF is an effective and safe immunosuppressant in pediatric LT recipients. Its use is hampered by frequent gastrointestinal and hematological side-effects. MMF does not seem to increase the risk of PTLD nor CMV disease.

[Viability and differentiation of human hepatocytes immunoprotected by macroencapsulation and transplanted in rats]. / Viabilité et état de différenciation des hépatocytes humains immunoprotégés par macroencapsulation et transplantés chez le rat.

OBJECTIVES: To determine the viability and differentiation of human hepatocytes immunoprotected by encapsulation and transplanted in rats without immunosuppression. METHODS: Freshly isolated human hepatocytes were encapsulated in hollow fibers and transplanted in the peritoneal cavity of immunocompetent rats. The fibers were explanted for analysis at D3, D7 and D14 following transplantation. Morphological features under light and electron microscopy and gene expression were compared to those of non-transplanted encapsulated hepatocytes (D0). Human cytochrome P450 3A and albumin mRNAs were quantified by Northern blot. Cytochrome P450 3A proteins were detected by Western blot and cytochrome P450 3A enzyme activity was assessed by measuring the formation of 6beta-hydroxytestosterone by high performance liquid chromatography. RESULTS: Transplanted hepatocytes were more than 60 % viable and exhibited morphological criteria of hepatocytic differentiation up to D7. Albumin and cytochrome P450 3A transcripts were also detected up to D14. At D3 and D7, albumin mRNA levels were of 30 %, compared to control D0 hepatocytes, while cytochrome P450 3A5 and cytochrome P450 3A4 mRNA levels were 65 % and 0 %, respectively. Cytochrome P450 3A immunoreactivity was detected by Western blot up to D14 and 6beta-hydroxylase activity was 17 % at D3 compared to D0, supporting with disappearance of cytochrome P450 3A4 mRNA. CONCLUSIONS: Human hepatocytes remain viable for a short period, following encapsulation and intraperitoneal transplantation in rat. Other experimental conditions need to be tested to prevent or delay a decrease in hepatocyte specific gene expression.