Treatment of Progressive Membranous Glomerulopathy

doi:10.1059/0003-4819-116-6-438

Treatment of Progressive Membranous Glomerulopathy

A Randomized Trial Comparing Cyclophosphamide and Corticosteroids with Corticosteroids Alone

Ronald J. Falk, MD;
Susan L. Hogan;
Keith E. Muller, PhD;
J. Charles Jennette, MD; and
Glomerular Disease Collaborative Network*

Abstract

▪ Objective: To determine if deterioration in renal function could be ameliorated by adding cyclophosphamide to corticosteroid therapy in patients with progressive membranous glomerulopathy.

▪ Design: Randomized, controlled treatment trial. Patients were followed for a mean of 29.2 ± 17.1 months.

▪ Setting: Collaborative network of 120 university and private-practice nephrologists.

▪ Participants: Patients with membranous glomerulopathy whose renal function deteriorated (as evidenced by doubling of the serum creatinine level, a 50% fall in the glomerular filtration rate, or a sustained serum creatinine level of greater than 2.0 mg/dL [reciprocal creatinine value, 0.5], or whose nephrotic range proteinuria persisted in association with morbid complications. Of 156 patients with biopsy-proven membranous glomerulopathy, 36 became eligible for randomization. Twenty-six of these 36 patients were randomly assigned to receive one of the two treatments.

▪ Interventions: Pulse methylprednisolone, oral corticosteroids, and 6 months of intravenous cyclophosphamide or alternate-day corticosteroid therapy alone.

▪ Main Results: At entry, no statistical differences were found between the treatment groups in duration of renal disease, age, gender, serum creatinine level, 24-hour urine protein excretion, or biopsy stage. The groups showed no difference in mean arterial blood pressure during follow-up. Four of the 13 patients receiving corticosteroids alone and 4 of the 13 patients receiving corticosteroids plus intravenous cyclophosphamide progressed to end-stage renal disease during follow-up. Reciprocal creatinine values tested at 6-month intervals showed no statistical differences between treatment groups at any time point. The log of the 24-hour protein excretion values showed no statistical differences between treatment groups after treatment. The power to detect a substantial improvement in renal function, defined as a doubling of the reciprocal of the serum creatinine, at the 0.05 significance level was 0.92.

▪ Conclusions: Combination therapy with intravenous cyclophosphamide and corticosteroids, when compared with corticosteroid therapy alone, does not improve renal function in patients with progressive membranous glomerulopathy.

Article and Author Information

For current author affiliations and addresses, see end of text.
↵* For a listing of the members of the Glomerular Disease Collaborative Network, see the Appendix.
Grant Support: In part by the Jessie Bell DuPont Religious, Charitable and Educational Fund, the Telephone Pioneers of North Carolina (Chapter 35, and the National Institutes of Health General Clinical Research Center (grant RR00046).
Affiliations: From the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Requests for Reprints: Ronald J. Falk, MD, Department of Medicine, Division of Nephrology, CB #7155, 3034 Old Clinic Building, Chapel Hill, NC 27599.
Current Author Addresses: Dr. Falk and Ms. Hogan: Department of Medicine, Division of Nephrology, CB #7155, 3034 Old Clinic Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7155.

Dr. Muller: Department of Biostatistics, CB #7400, 3105 McGavran-Greenberg Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7400.

Dr. Jennette: Department of Pathology, CB #7525, 814 Brinkhous-Bullitt, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525.