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900 ng/mL) in Group 1A were withdrawn from the study because of complications.

CONCLUSION:

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: Takao Saito, Masayuki Iwano, Koichi Matsumoto, Tetsuya Mitarai, Hitoshi Yokoyama, Noriaki Yorioka, Shinichi Nishi, Ashio Yoshimura, Hiroshi Sato, Satoru Ogahara, Hideki Shuto, Yasufumi Kataoka, Shiro Ueda, Akio Koyama, Shoichi Maruyama, Masaomi Nangaku, Enyu Imai, Seiichi Matsuo, Yasuhiko Tomino, Refractory Nephrotic Syndrome Study Group
• Journal: Clinical and experimental nephrology (Clin Exp Nephrol) Vol. 18 Issue 5 Pg. 784-94 (Oct 2014) ISSN: 1437-7799 [Electronic] Japan
• PMID: 24363128 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Glucocorticoids
• Immunosuppressive Agents
• Cyclosporine
• Prednisolone

Topics

• Adolescent
• Adult
• Aged
• Cyclosporine (administration & dosage, blood)
• Drug Therapy, Combination
• Female
• Glomerulonephritis, Membranous (blood, complications, drug therapy)
• Glucocorticoids (therapeutic use)
• Humans
• Immunosuppressive Agents (administration & dosage, blood)
• Male
• Middle Aged
• Nephrotic Syndrome (blood, complications, drug therapy)
• Prednisolone (therapeutic use)
• Prospective Studies
• Young Adult