Treatment of pure membranous lupus nephropathy with prednisone and azathioprine: an open-label trial.
ABSTRACT The aim of this study was to report the outcome of pure membranous lupus nephropathy treated with prednisone and azathioprine (AZA).
Consecutive patients with pure membranous lupus glomerulonephritis (World Health Organization [WHO] Va and Vb) from 4 regional hospitals were recruited for an open-label treatment trial consisting of prednisone and AZA. Remission status was evaluated at 12 months. Maintenance treatment with low-dose prednisone and AZA was continued indefinitely for those who achieved remission. Factors predictive of initial renal remission and subsequent relapse were studied by statistical analyses.
Thirty-eight patients (31 women and 7 men) were studied. The mean age was 35.0 +/- 9.2 years, and the duration of systemic lupus erythematosus was 48.5 +/- 59 months. Seventeen (45%) patients had WHO class Va lupus nephritis, whereas 21 (55%) had class Vb disease. Two patients withdrew from the protocol because of idiosyncratic reactions to AZA. At 12 months, 24 (67%) patients achieved complete remission (CR), 8 (22%) achieved partial remission (PR), and 4 (11%) were treatment resistant. Patients who achieved CR or PR were maintained on low-dose prednisone and AZA. Over a mean follow-up period of 90.4 +/- 59 months, 6 (19%) patients had relapse of nephritis (proteinuric flare in 4 and nephritic flare in 2). The cumulative risk of renal relapse was 12% at 36 months and 16% at 60 months. No particular clinical variables were found to predict renal remission or relapses. Over a mean follow-up of 90 months, 13% of patients had decline of creatinine clearance by 20%, but none had doubling of serum creatinine. Renal outcome was not significantly worse in patients presenting with nephrotic syndrome. Treatment generally was well tolerated.
A combination of prednisone and AZA is reasonably effective for the initial treatment of pure membranous lupus nephritis. Severe adverse effects are uncommon. The additional efficacy of AZA in comparison with prednisone alone has to be confirmed with randomized, controlled trials.
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ABSTRACT: Eighteen patients with lupus membranous nephritis were retrospective identified by reviewing the renal biopsy records of an active renal pathology service. Seven had minimally proliferative membranous nephropathy (World Health Organization (WHO) classes Va and b). Eleven had membranous nephropathy with superimposed changes of focal or diffuse proliferative glomerulonephritis (WHO Vc and d). After mean follow-up periods of 73 +/- 6 and 74 +/- 15 mo, respectively, one patient of seven from WHO Va and b and seven of 11 from WHO Vc and d reached end stage renal disease. The latter patients were distinguishable from the former only by the degree of superimposed proliferation on renal biopsy and not by blood pressure, antinuclear antibody, anti-double stranded DNA, or complement levels. These data stand in contrast to the widely held belief that lupus membranous nephropathy is relatively benign. The belatedness of this observation is partially due to imprecision in nosology for patients with lupus who have renal biopsies with "overlap" characteristics.Modern Pathology 04/1990; 3(2):186-91. · 5.25 Impact Factor
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ABSTRACT: Lymphocytes are believed to play a role in the induction and perpetuation of membranous nephropathy. Fludarabine is a purine nucleoside analog with selective activity against both dividing and resting lymphocytes. We evaluated the tolerance, toxicity, pharmacokinetics, immunologic, and clinical effects of fludarabine in patients with membranous nephropathy in an single arm pilot study. Eight patients with idiopathic (n = 7) or lupus (n = 1) membranous nephropathy who had failed high-dose prednisone (n = 8) and/or alkylating agents (n = 2), or cyclosporine (n = 1) were treated with 6-monthly cycles of fludarabine (cycles 1-2, 20 mg/m2/day x 2 days, cycles 3-6, 20 mg/m2/day x 3 days). Mean proteinuria was 9 g/day with a mean duration of disease of 25 months (range 12-48). Proteinuria, GFR and effective renal plasma flow were compared before and after completing the treatment. Seven patients completed the protocol. CD3, CD4, CD8 and B cell counts decreased by 53%, 46%, 61% and 84%, respectively, at the end of treatment and remained at lower than pretreatment levels 6 months after completing the trial. Despite lymphopenia, serum immunoglobulin levels remained unchanged. Both naive (CD45RA+) and memory CD4+ T cells (CD45RO+) were reduced (naive > memory). Proteinuria decreased by > or = 50% in 5 out of 7 patients (p = 0.11). Filtration fraction improved in all patients with decreased filtration fraction at baseline. The only side-effect observed was one episode of acute bacterial sinusitis that responded promptly to antibiotic therapy. We conclude that low-dose fludarabine treatment in patients with membranous nephropathy is well tolerated and results in significant lymphopenia involving B more than T cells. In this pilot study improvement in proteinuria and filtration rate were observed. Additional studies are required to determine the optimal dose and clinical efficacy of fludarabine.Clinical nephrology 08/1999; 52(2):67-75. · 1.29 Impact Factor
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ABSTRACT: The prognostic significance of glomerular inflammation in patients with lupus membranous glomerulonephritis (MGN) was evaluated by classifying 100 renal biopsies from lupus patients according to World Health Organization (WHO) criteria and correlating the histology with clinical data. There were 22 cases of MGN: in 3 the lesion was pure MGN (Va); in the remainder, diffuse MGN was modified by superimposed mesangial proliferation in 6 (Vb), segmental glomerulonephritis (GN) or sclerosis in 10 (Vc), and diffuse GN in 3 (Vd). Patients in the four categories had similar clinical presentations. When the 4 patients with active proliferative glomerulonephritis (PGN) were grouped and compared to those without PGN, they had more active serologies. Quantitation of glomerular electrondense deposits in MGN showed variation in the percentage of basal lamina covered by subepithelial deposits, segmental subepithelial deposits in 4 cases, focal segmental subendothelial deposits in most cases and massive subendothelial deposits in 5 biopsies. 4 of the latter patients had active PGN, suggesting that only extensive subendothelial deposits are pathogenetically significant. The predicted 5-year survival for all MGN patients was 90%, and the only 2 deaths were not related to renal failure. Thus, it appears valid to include mixed lesions in the membranous category, but it is our impression that the immediate course and prognosis of SLE and associated PGN depends upon the extent and reversibility of the inflammatory lesions.American Journal of Nephrology 02/1984; 4(5):301-11. · 2.62 Impact Factor