tacrolimus and Pancreatic-Diseases

The efficacy and safety of everolimus (EVR) in simultaneous pancreas and kidney transplantation (SPKT) is unclear. We retrospectively evaluated 25 consecutive SPKT recipients at our center from November 2011 to March 2013. All patients received dual induction (Thymoglobulin/basiliximab) and low-dose tacrolimus plus corticosteroids. Nine patients who received EVR were compared with 14 patients who received enteric-coated mycophenolate sodium (EC-MPS); two patients who received sirolimus were excluded from the analysis. With a median follow-up of 14 months, the pancreas graft survival rate was 100% in both groups, and the kidney graft survival rate was 100% and 93% in EVR and EC-MPS patients, respectively. One EC-MPS patient lost her kidney graft from proteinuric kidney disease. Another EC-MPS patient received treatment for clinically diagnosed pancreas and kidney graft rejection. No rejection was observed in EVR patients. Serum creatinine and HbA1c levels were similar between the groups. There was no significant difference of surgical or medical complications. In conclusion, EVR seems to provide comparable short-term outcome to EC-MPS when combined with low-dose tacrolimus/steroids and dual induction therapy. A larger study with a longer follow-up is required to further assess this combination.

Topics: Adult; Dose-Response Relationship, Drug; Everolimus; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Pancreas Transplantation; Pancreatic Diseases; Prognosis; Retrospective Studies; Risk Factors; Sirolimus; Survival Rate; Tacrolimus; Young Adult

Tacrobell(®) (TB) is a generic tacrolimus which showed the comparable efficacy to original product, Prograf(®) (PG) in renal transplantation, but toxicity between two drugs is unclear. The aim of this study was to compare the toxicity between these two formulations. TB and PG (0.5, 1 and 2 mg/kg/day) was administered to rats for 4 weeks. The rat survival rate, kidney, liver and pancreas injury was investigated. The survival rate was similar between TB- and PG-treated rats. TB and PG induced renal dysfunction in a dose-dependent manner. Compared to PG treatment in equal dose, TB treatment reduced urinary creatinine clearance in a less degree and renal interstitial fibrosis was comparable between two regimens. The r-glutamyl transpeptidase was aggravated by tacrolimus treatment, and this was not different between TB and PG treatment. In the intraperitoneal glucose tolerance test, a significant diabetogenic effect was observed in all tacrolimus treated-rats. The glucose tolerance of TB-treated rats was similar to those of PG-treated rats in each dose. The decrement in pancreatic β-cell mass by tacrolimus showed the dose-dependent response and it was comparable between TB and PG treatment. In conclusion, TB is similar to PG in terms of nephrotoxicity, hepatoxicity and diabetogenic effect.

Topics: Animals; Chemical and Drug Induced Liver Injury; Diabetes Mellitus; Drugs, Generic; Fibrosis; Insulin-Secreting Cells; Kidney Diseases; Male; Pancreatic Diseases; Rats; Rats, Sprague-Dawley; Tacrolimus

Topics: Adult; Female; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Pancreatic Diseases; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Tacrolimus; Transplantation, Homologous

Topics: Animals; Animals, Newborn; Autoimmune Diseases; Diabetes Mellitus, Type 1; Graft Survival; Islets of Langerhans; Mice; Mice, Inbred NOD; Pancreas; Pancreas Transplantation; Pancreatic Diseases; Tacrolimus

We investigated the effect of an immunosuppressant FK-506 on histological change of islets, the onset of diabetes, and the change of spleen cell subsets in female non-obese diabetic mice. Mice administered intraperitoneally with FK-506 from 5 to 20 weeks of age showed marked suppression of mononuclear cell infiltration (insulitis) at 10 weeks of age. Among the subsets of the spleen cells, a significant decrease in the population of Thyl.2-positive T cells (pan-T), L3T4-positive T cells (mainly helper/inducer), and Lyt2-positive T cells (mainly suppressor/cytotoxic) was observed in FK-506-treated mice. Furthermore, glucose tolerance of the mice at 15 weeks of age was clearly improved. Cumulative incidence observed up to 40 weeks of age was 86% in control mice and 23% in FK-506-treated mice (p less than 0.01). These data indicate that FK-506 has a preventive effect on insulitis and diabetes by the suppression of cell-mediated autoimmunity in non-obese diabetic mice.

Topics: Animals; Anti-Bacterial Agents; Diabetes Mellitus, Experimental; Female; Immunosuppressive Agents; Mice; Mice, Obese; Pancreas; Pancreatic Diseases; Tacrolimus