title: Nephrotoxicity in children with frequently relapsing nephrotic syndrome receiving long-term cyclosporine treatment.
abstract: BACKGROUND
  Steroid-sparing drugs, such as cyclosporine, are recommended as treatment for children with frequently relapsing nephrotic syndrome (FRNS) and steroid-related toxicities. We recently reported a high rate of relapsing nephrotic syndrome 2 years after discontinuation of cyclosporine treatment, suggesting that long-term treatment is necessary. Cyclosporine-associated nephrotoxicity (CAN) is a potential side effect of long-term cyclosporine treatment.
  
  
  METHODS
  We retrospectively reviewed pediatric patients with FRNS treated with cyclosporine for ≥3 years at a single center between 1999 and 2012. The cyclosporine dose was adjusted to maintain the whole-blood cyclosporine trough level at 80-100 ng/ml for 6 months, at 60-80 ng/ml for 18 months, and then at around 50-60 ng/ml thereafter. Maintenance dose of prednisolone was not prescribed. CAN was graded in terms of arteriolar hyalinosis and the degree of interstitial fibrosis.
  
  
  RESULTS
  Thirty-six children (28 males) were enrolled in the study. The median age at the start of long-term cyclosporine treatment was 9.4 years. The median duration of the longest period of cyclosporine treatment was 4.5 years. Most CAN cases were characterized by arteriolar hyalinosis. The frequency of CAN was positively correlated with the duration of cyclosporine treatment, with an odds ratio (95% confidence interval) for CAN of 3.84 (0.79-18.74) after 2-5 years and 6.60 (1.18-36.94) after >5 years of cyclosporine treatment (vs. 0-2 years).
  
  
  CONCLUSIONS
  Although the frequency of CAN was correlated with the duration of cyclosporine treatment in our pediatric patient population, most cases of CAN involved arteriolar hyalinosis. We conclude that long-term cyclosporine treatment is useful for treating FRNS in children, providing its dose is controlled and kidney biopsies are regularly performed.
authors.affiliation: Department of Pediatric Nephrology, Faculty of Medicine, Toho University, 6-11-1 Omori-Nishi, Ota-Ku, Tokyo, 143-8541, Japan. yuhamasaki@med.toho-u.ac.jp.|Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan. yuhamasaki@med.toho-u.ac.jp.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hamasaki
authors.affiliation: Division of Infectious Diseases Control, Health and Welfare Bureau Health Center of Kawasaki City, Kanagawa, Japan.
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Komaki
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.|Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishikura
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Riku
authors.initials: R
authors.lastname: Hamada
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hataya
authors.affiliation: Department of Pathology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ogata
authors.affiliation: Department of Data Management, Japan Clinical Research Support Unit, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ando
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Honda
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D005355:Fibrosis; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008134:Long-Term Care / Q000379:methods; D060046:Maintenance Chemotherapy / Q000009:adverse effects* / Q000379:methods; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D011239:Prednisolone / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D005938:Glucocorticoids; D016572:Cyclosporine; D011239:Prednisolone
keywords: Cyclosporine; Kidney biopsy; Nephrotic syndrome; Nephrotoxicity; Pediatrics