title: Significance of combined cyclosporine-prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial.
abstract: BACKGROUND
  Combined treatment with cyclosporine microemulsion preconcentrate (CyA MEPC) and steroids has been widely used for idiopathic membranous nephropathy (IMN) associated with steroid-resistant nephrotic syndrome (SRNS). Recent studies have shown that once-a-day and preprandial administration of CyA MEPC is more advantageous than the conventional twice-a-day administration in achieving the target blood CyA concentration at 2 h post dose (C2). We designed a randomized trial to compare these administrations.
  
  
  METHODS
  IMN patients with SRNS (age 16-75 years) were divided prospectively and randomly into 2 groups. In group 1 (n = 23), 2-3 mg/kg body weight (BW) CyA MEPC was given orally once a day before breakfast. In group 2 (n = 25), 1.5 mg/kg BW CyA MEPC was given twice a day before meals. CyA + prednisolone was continued for 48 weeks.
  
  
  RESULTS
  Group 1 showed a significantly higher cumulative complete remission (CR) rate (p = 0.0282), but not when incomplete remission 1 (ICR1; urine protein 0.3-1.0 g/day) was added (p = 0.314). Because a C2 of 600 ng/mL was determined as the best cut-off point, groups 1 and 2 were further divided into subgroups A (C2 ≥600 ng/mL) and B (C2 <600 ng/mL). Groups 1A and 2A revealed significantly higher cumulative remission (CR + ICR1) (p = 0.0069) and CR-alone (p = 0.0028) rates. On the other hand, 3 patients with high CyA levels (C2 >900 ng/mL) in Group 1A were withdrawn from the study because of complications.
  
  
  CONCLUSIONS
  CyA + prednisolone treatment is effective for IMN with associated SRNS at a C2 of ≥600 ng/mL. To achieve remission, preprandial once-a-day administration of CyA at 2-3 mg/kg BW may be the most appropriate option. However, we should adjust the dosage of CyA by therapeutic drug monitoring to avoid complications.
authors.affiliation: General Medical Research Center, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan, tsaito@fukuoka-u.ac.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Saito
authors.forename: Masayuki
authors.initials: M
authors.lastname: Iwano
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitarai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Noriaki
authors.initials: N
authors.lastname: Yorioka
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishi
authors.forename: Ashio
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Satoru
authors.initials: S
authors.lastname: Ogahara
authors.forename: Hideki
authors.initials: H
authors.lastname: Shuto
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kataoka
authors.forename: Shiro
authors.initials: S
authors.lastname: Ueda
authors.forename: Akio
authors.initials: A
authors.lastname: Koyama
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
authors.forename: Enyu
authors.initials: E
authors.lastname: Imai
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D011239:Prednisolone / Q000627:therapeutic use; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone