tacrolimus and Gastroenteritis

Topics: Caliciviridae Infections; Diabetes Mellitus, Type 1; Diagnosis, Differential; Diarrhea; Disease Progression; Drug Tapering; Feces; Fluid Therapy; Gastroenteritis; Glucocorticoids; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Multiplex Polymerase Chain Reaction; Mycophenolic Acid; Pancreas Transplantation; Prednisone; Sapovirus; Tacrolimus

Although tacrolimus (TAC) can induce remission in children with refractory inflammatory bowel disease (IBD) or autoimmune gastroenteropathy (AGE), its use in maintenance therapy remains controversial. The aim of this study was to investigate the potential nephrotoxic nature of prolonged TAC use.. This retrospective study reviewed children with gastrointestinal disorder who underwent kidney biopsy for the evaluation of renal damage during TAC therapy for >1 year. The clinical and histological features of renal damage were evaluated in this single-institution cohort.. Eighteen of 121 children with IBD and two children with AGE followed at a national children hospital in Tokyo, Japan, received TAC between August 2006 and April 2013. Among them, five (Crohn's disease, n = 3; autoimmune gastropathy, n = 1; autoimmune enteropathy, n = 1) received TAC for >1 year, and underwent kidney biopsy. All five had achieved remission on TAC, but had histological evidence of chronic nephrotoxicity. Renal damage in one patient with relatively low TAC trough level remained mild. Estimated glomerular filtration rate (eGFR) at the time of kidney biopsy was lower than at the initiation of TAC in all four available patients. Among them, eGFR improved in one patient after the decrease or discontinuation of TAC.. TAC appeared to be effective in children with refractory gastrointestinal disorder, but long-term use seems to cause irreversible renal damage. Rigorous monitoring of eGFR and kidney biopsy in selected cases should be considered for the proper adjustment of TAC.

Topics: Autoimmune Diseases; Biopsy; Child; Crohn Disease; Female; Gastroenteritis; Humans; Immunosuppressive Agents; Infant; Kidney; Maintenance Chemotherapy; Male; Renal Insufficiency; Retrospective Studies; Tacrolimus; Treatment Outcome

Local rectal application of tacrolimus in distal colitis, pouchitis and perianal Crohn's disease has previously been reported to be both effective and safe. We report a patient treated with per rectum local application of tacrolimus, who developed toxic levels of tacrolimus and acute renal injury during an episode of acute gastroenteritis. This case illustrates that local application of tacrolimus, although usually safe, may be associated with significantly raised tacrolimus levels and acute renal injury during acute gastroenteritis. It is important for physicians to be aware of this association when prescribing local rectal tacrolimus.

Topics: Acute Disease; Acute Kidney Injury; Administration, Rectal; Child; Gastroenteritis; Humans; Male; Pouchitis; Proctitis; Tacrolimus

Topics: Arthritis, Juvenile; Child, Preschool; Epstein-Barr Virus Infections; Female; Gastroenteritis; Humans; Immunosuppressive Agents; Prednisolone; Stomach Ulcer; Tacrolimus

No treatment for NVE is available. Immunocompromised patients with NVE treated with OHIG (12 cases) were retrospectively identified and matched 1:1 by age and gender with immunocompromised patients with NVE not treated with OHIG (12 controls). Chi-squared test, t-test, bivariate conditional linear regression analyses, and Kaplan-Meier curve were performed. A total of 58.3% patients were small bowel transplant (SBT) recipients. Although not statistically significant, cases compared with controls were more likely to have had induction therapy (p = 0.25, OR = 65.3), higher peak tacrolimus levels (p = 0.43, OR = 1.04), SBT (p = 0.30, OR = 65.3), prior NVE (p = 0.42, OR = 2.0), TPN support (p = 0.42 OR = 2.0), and decrease in immunosuppression (p = 0.14, OR = 5.0). Treatment with OHIG favored resolution of diarrhea (p = 0.078, OR = 65.3) and decreased stool output seven days after treatment compared with controls (mean difference 11.95 mL/kg/day, p = 0.09). OHIG did not impact total time to resolution of diarrhea (mean 12.08 vs. 11.91 days; p = 0.63), length of hospital stay (p = 0.31, OR = 1.05), or cost of hospitalization (p = 0.32, OR = 1.0). We show a potential role of OHIG treatment for NVE. Resolution of diarrhea and decreased stool output were observed at seven days; no benefit was found for length of hospital stay or hospital cost.

Topics: Administration, Oral; Adolescent; Biopsy; Caliciviridae Infections; Case-Control Studies; Child; Child, Preschool; Female; Gastroenteritis; Hospitalization; Humans; Immunoglobulins; Immunosuppression Therapy; Infant; Intestines; Length of Stay; Male; Norovirus; Tacrolimus

Topics: Child, Preschool; Female; Gastroenteritis; Humans; Immunosuppressive Agents; Liver Transplantation; Postoperative Complications; Rotavirus Infections; Tacrolimus

The diagnosis and treatment of diarrhea in liver transplant recipients often pose a challenge owing to the variety of infectious and non-infectious causes. However, diagnosis is principally focused on ruling out an infectious etiology. Tacrolimus, an immunosuppressive agent generally used after liver transplantation, is absorbed mainly from the duodenum through the upper jejunum. It can be assumed that metabolism of the drug will be influenced by diarrhea.. Four liver transplant recipients who developed an episode of acute gastroenteritis. Infectious etiology was confirmed; trough tacrolimus levels were measured before, during and after gastroenteritis.. All patients presented a two- to three-fold increase in blood tacrolimus levels after the onset of gastroenteritis.. Until the role played by the intestine in the metabolism of tacrolimus is fully understood, it is prudent to recommend early dose reduction of tacrolimus and careful monitoring of trough levels during diarrheal disorders of any nature in pediatric liver-transplanted patients.

Topics: Acute Disease; Child, Preschool; Diarrhea; Female; Gastroenteritis; Humans; Immunosuppressive Agents; Infant; Intestinal Mucosa; Liver Transplantation; Male; Postoperative Complications; Tacrolimus

Topics: Diarrhea; Drug Monitoring; Gastroenteritis; Humans; Immunosuppressive Agents; Kidney Transplantation; Liver Transplantation; Lung Transplantation; Postoperative Complications; Rotavirus Infections; Tacrolimus; Transplantation

Rotavirus (RV) is the most common cause of diarrheal illness in children. We report three solid-organ-transplanted patients in whom RV infection caused increased trough levels of the immunosuppressive macrolide tacrolimus (TAC) by mechanisms that are still under investigation. The virus was detected for longer in the feces of these patients than in infants not receiving immunosuppressive therapy. In association with short-term monitoring of blood trough levels of TAC, the dosage should be reduced early if symptoms of an acute gastroenteritis are present.

Topics: Adult; Child; Diarrhea; Drug Monitoring; Feces; Female; Gastroenteritis; Humans; Immunosuppressive Agents; Infant; Kidney Transplantation; Liver Transplantation; Lung Transplantation; Male; Postoperative Complications; Rotavirus Infections; Tacrolimus; Transplantation

Tacrolimus is an immunosuppressant used to prevent rejection of transplanted organs. It is metabolized in both the gut and the liver by the cytochrome P450 (CYP) 3A4 enzyme system and is a substrate for the P-glycoprotein (P-gp) drug efflux pump. As CYP3A4 enzymes and P-gp are present at differing concentrations throughout the gastrointestinal tract, the bioavailability of tacrolimus may be influenced by changes in gastrointestinal transit time in addition to changes in hepatic metabolism. We report the case of a pediatric renal transplant patient who experienced a three-fold increase in serum tacrolimus concentrations during an episode of gastroenteritis with chronic diarrhea.

Topics: Biological Availability; Child; Chronic Disease; Diarrhea; Female; Gastroenteritis; Humans; Immunosuppressive Agents; Kidney Transplantation; Tacrolimus

Topics: Adolescent; Autoimmune Diseases; Biopsy; Chronic Disease; Colitis; Diarrhea; Duodenum; Gastroenteritis; Humans; Immunosuppressive Agents; Male; Rectum; Tacrolimus