Treatment of progressive membranous glomerulopathy. A randomized trial comparing cyclophosphamide and corticosteroids with corticosteroids alone. The Glomerular Disease Collaborative Network.
OBJECTIVE
To determine if deterioration in renal function could be ameliorated by adding cyclophosphamide to corticosteroid therapy in patients with progressive membranous glomerulopathy.


METHODS
Randomized, controlled treatment trial. Patients were followed for a mean of 29.2 +/- 17.1 months.


METHODS
Collaborative network of 120 university and private-practice nephrologists.


METHODS
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.


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


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.
Falk
R J
RJ
Hogan
S L
SL
Muller
K E
KE
Jennette
J C
JC
D000328:Adult; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015433:Glomerulonephritis, Membranous / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000209:etiology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D012042:Registries; D013223:Statistics as Topic; D015996:Survival Rate
D005938:Glucocorticoids; D003520:Cyclophosphamide