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Sustained Remission of Membranous Glomerulonephritis after Cyclophosphamide and Prednisone

Frank J. Bruns, MD; Sheldon Adler, MD; Donald S. Fraley, MD; and David P. Segel, MD
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A portion of this study was presented at the annual meeting of the American Society of Nephrology in December 1988.

Requests for Reprints: Frank J. Bruns, MD, Montefiore-University Hospital, 3459 Fifth Avenue, Pittsburgh, PA 15213.

Current Author Addresses: Drs. Bruns, Adler, Fraley, and Segel: Montefiore-University Hospital, 3459 Fifth Avenue, Pittsburgh, PA 15213.

© 1991 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1991;114(9):725-730. doi:10.7326/0003-4819-114-9-725
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Objective: To determine the effect of cyclophosphamide and prednisone on progressive renal failure and on nephrotic features in patients with membranous glomerulonephritis.

Design: Prospective, nonrandomized time series.

Setting: Outpatient clinic at a university medical center.

Patients: Eleven consecutive patients with biopsy-proven membranous glomerulonephritis and rising plasma creatinine levels over at least 6 months.

Intervention: Cyclophosphamide and prednisone in ten patients and cyclophosphamide alone in one patient.

Measurements and Main Results: In ten patients treated with both agents, the median plasma creatinine rose 53 µmol/L (0.6 mg/dL) over the months before treatment from 141 to 194 µmoL/L (1.6 to 2.2 mg/dL) (95% CI, 27 to 141 µmol/L; P = 0.002). After combined therapy for 6 months, the median plasma creatinine fell to 133 µmol/L (1.5 mg/dL) for a median decline of 62 µmol/L (0.7 mg/dL) (CI, 44 to 150 µmol/L; P = 0.006). Pretreatment plasma creatinine levels, which ranged from 159 to 371 µmol/L (1.8 to 4.2 mg/dL), decreased in the ten patients by 6 months and remained stable in seven of the eight patients followed 24 to 54 months after therapy was completed. The median urine protein excretion decreased by 9.6 g/d with 12 months of therapy in the ten patients from 11.9 to 2.3 g/d (CI, 6.0 to 15.1 g/d; P < 0.001). The median plasma albumin rose by 14 g/L from 24 to 38 g/L (CI, 11 to 19 g/L; P < 0.001). The median plasma cholesterol fell by 3.26 µmol/L (140 mg/dL) from 10.45 to 6.52 µmol/L (405 to 252 mg/dL) (CI, 1.42 to 7.16 µmol/L; P = 0.01). One patient who had a relapse 30 months after completing therapy responded to re-treatment with renal function and nephrotic variables returning toward normal. The eleventh patient received cyclophosphamide alone and had a course similar to that of the combined therapy group.

Conclusion: Cyclophosphamide plus prednisone can promote prolonged remissions in membranous glomerulonephritis even when renal function is already declining.





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