Nephrol Dial Transplant (2003) 18: 1321-1329
© 2003 European Renal Association-European Dialysis and Transplant Association
Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide
1 Division of Nephrology and 2 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
Background. IgA nephropathy is an immune-complex glomerulopathy that can result in capillary or extra-capillary proliferation. Previous attempts to correlate specific histological findings including cellular crescents or endocapillary proliferation, with clinical outcomes, have produced conflicting results.
Methods. We conducted a prospective open-labelled trial of 12 patients with crescentic, proliferative IgA nephropathy and clinically progressive disease and treated them with pulse steroids and intravenous cyclophosphamide. Therapy included pulse solumedrol at 15 mg/kg/day for 3 days, followed by monthly intravenous cyclophosphamide at 0.5 g/m2 body surface area for 6 months. Clinically significant proteinuria (>1.0 g/24 h) was present in all patients, while nephrotic-range proteinuria (>3.0 g/24 h) was observed in eight of 12 patients. All patients were hypertensive (BP >140/90 mmHg).
Results. After 6 months of treatment, the mean serum creatinine was reduced from a maximum of 2.65±0.39 to 1.51±0.10 mg/dl (P<0.03), while proteinuria was reduced from 4.04 to 1.35 g/24 h (P<0.01). The mean slope of 1/serum creatinine increased from -0.0398±0.02 to 0.0076±0.01 after 6 months of therapy, but this trend did not reach statistical significance (P<0.08). A repeat kidney biopsy was performed in all treated patients. Endocapillary proliferation, cellular crescents and karyorrhexis were eliminated in all 12 patients after 6 months of therapy, while interstitial fibrosis and tubule dropout remained unchanged. To determine the long-term efficacy of the treatment, treated patients were compared to 12 historical controls matched for severity of IgA on initial biopsy. After 36 months, the rate of end-stage renal disease in the treated group was lower (1/12) than in the historical controls (5/12).
Conclusions. We conclude that steroids and intravenous cyclophosphamide reduce proliferative lesions, reduce proteinuria and stabilize renal function in patients with crescentic IgA nephropathy.
Keywords: crescents; endocapillary proliferation; end-stage renal disease; hypertension; IgA nephropathy; proteinuria
Correspondence and offprint requests to: Dr James A. Tumlin, Emory University School of Medicine, Renal Division, 1364 Clifton Road, NE, Atlanta, GA 30322, USA. Email: jtumlin{at}emory.edu
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