title: Prolonged tacrolimus for pediatric gastrointestinal disorder: Double-edged sword?
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan.|Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hosoi
authors.affiliation: Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Arai
authors.affiliation: Department of Diagnostic Pathology, National Center for Child Health and Development, Tokyo, Japan.|Department of Clinical Laboratory Medicine, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kamei
authors.affiliation: Department of Diagnostic Pathology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakazawa
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Education for Clinical Research, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Julian
authors.initials: J
authors.lastname: Tang
authors.affiliation: Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan.|Department of Pediatrics, Yokohama City University, Kanagawa, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ito
mesh_terms: D001327:Autoimmune Diseases / Q000150:complications / Q000188:drug therapy*; D001706:Biopsy; D002648:Child; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy; D005260:Female; D005759:Gastroenteritis / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007223:Infant; D007668:Kidney / Q000473:pathology; D060046:Maintenance Chemotherapy / Q000009:adverse effects*; D008297:Male; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000175:diagnosis / Q000473:pathology; D012189:Retrospective Studies; D016559:Tacrolimus / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: children; gastrointestinal disorder; kidney biopsy; nephrotoxicity; tacrolimus