Multicenter study for combined therapy of prednisolone and cyclosporin in refractory nephrotic syndrome
- Conditions
- membranouos nephropathy and focal segmental glomerulosclerosis with primary steroid resistant nephrotic syndrome
- Registration Number
- JPRN-C000000369
- Lead Sponsor
- Project team for treatment of refractory nephrotic syndrome
- Brief Summary
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), 2-3mg/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900 ng/mL) in Group 1A were withdrawn from the study because of complications.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 >=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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete: follow-up complete
- Sex
- All
- Target Recruitment
- 300
Not provided
1) The subject presents with renal dysfunction (Ccr less than 50mL/min or serum creatinine more than 2mg/dL). 2) The subject has been treated with other immunosuppressants within one month prior to the study commencement. 3) The subject should be treated with nephrotoxic or hyperkalemic agents during the study period. 4) The subject has a malignant tumor, or had a recurrent malignant tumor previously. 5) The subject has hypertension uncontrolled with antihypertensive drugs. 6) The subject has malabsorption syndrome, cerebral dysfunction or epilepsy. 7) The subject has hyperkalemia or hyperuricemia. 8) The subject has a severe cardiac, hepatic or pancreatic disease. 9) The subject is currently pregnant, is supposed to be pregnant, or is nursing. 10) The subject has an infectious complication and is not available for the treatment with Immunosuppressants. 11) The subject previously had hypersensitivity to CyA-MEPC. 12) The subject is inappropriate for participation in the study as determined by an investigator.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method