mycophenolic-acid 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

Diarrhea of unspecified cause frequently occurs after renal transplantation and is usually ascribed to mycophenolic acid toxicity. Norovirus (NoV) and sapovirus (SaV) have been sporadically reported to cause chronic diarrhea in immunocompromised patients.. We undertook a retrospective study (2008-2009) to examine the clinical and epidemiologic significance of NoV and SaV infections in adult renal transplant recipients hospitalized for acute or chronic diarrhea.. Ninety-six renal transplant recipients were hospitalized for diarrhea at our institution during a 16-month period, 87 of whom were included in the study, including 46 patients with chronic diarrhea. Among 41 patients with unexplained diarrhea, 20 patients were screened for NoV/SaV, 16 of whom were positive. Fifteen of them (94%) had chronic diarrhea. When compared with bacterial and parasitic infections, NoV/SaV infections were associated with a greater weight loss at the time of admission, a 8.7-fold longer duration of symptoms and a more frequent need for mycophenolic acid dosage reduction. Eighty-one percent of patients hospitalized for NoV/SaV-associated diarrhea experienced acute renal failure. Five and one patients subsequently had biopsy-diagnosed active graft rejection and oxalate nephropathy, respectively. Ten of the 14 patients who underwent a longitudinal study of NoV/SaV stool's clearance exhibited a prolonged viral shedding period with a median time of 289 days (107-581 days).. Our study indicates that NoV/SaV infection causes posttransplant chronic diarrhea potentially complicated by severe kidney graft impairment.

Topics: Acute Kidney Injury; Adult; Aged; Algorithms; Caliciviridae Infections; Diarrhea; Gastroenteritis; Graft Rejection; Hospitalization; Humans; Kidney Transplantation; Longitudinal Studies; Middle Aged; Mycophenolic Acid; Norovirus; Retrospective Studies; Sapovirus; Virus Shedding; Young Adult

Mycophenolate mofetil (MMF) is an effective and commonly used immunosuppressant but has frequent adverse events. Genetic polymorphisms may contribute to variability in MMF efficacy and related complications. In this study we explore the distribution frequencies of common single nucleotide polymorphisms (SNPs) of IMPDH1, IMPDH2 and ABCC2 and investigate whether these SNPs influence MMF adverse events in 59 pediatric heart recipients.. Genotypes were assessed by TaqMan analysis of: ABCC2 rs717620; IMPDH2 rs11706052; and IMPDH1 rs2288553, rs2288549, rs2278293, rs2278294 and rs2228075. Gastrointestinal (GI) intolerance was defined as diarrhea, vomiting, nausea or abdominal pain requiring dose-holding for >48 hours or MMF discontinuation. Bone marrow toxicity was evaluated using Common Terminology Criteria for Adverse Events Version 3 (CTCAE).. GI intolerance occurred in 21 patients, and 21 had bone marrow toxicity. The ABCC2 rs717620 A variant was significantly associated with GI intolerance leading to drug discontinuation (p < 0.001); the IMPDH1 rs2278294 A variant and rs2228075 A variant were also associated with greater GI intolerance (p = 0.029 and p = 0.002, respectively). The IMPDH2 rs11706052 G variant was associated with more frequent neutropenia requiring dose-holding (p = 0.046).. In this small sample of pediatric heart transplant patients receiving MMF, ABCC2, IMPDH1 and IMPDH2 SNPs were associated with MMF GI intolerance and bone marrow toxicity. Thus, genetic polymorphisms may directly influence MMF adverse events.

Topics: Adolescent; Alleles; Bone Marrow Cells; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastroenteritis; Genetic Predisposition to Disease; Genotype; Heart Transplantation; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Infant; Male; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Mycophenolic Acid; Polymorphism, Single Nucleotide