Crescentic, proliferative IgA nephropathy: Clinical and histological response to methylprednisolone and intravenous cyclophosphamide

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 2 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.