title: Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide.
abstract: 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/m(2) 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.
authors.affiliation: Division of Nephrology, Emory University, Atlanta, GA 30322, USA. jtumlin@emory.edu
authors.forename: James A
authors.initials: JA
authors.lastname: Tumlin
authors.forename: Verachai
authors.initials: V
authors.lastname: Lohavichan
authors.forename: Randy
authors.initials: R
authors.lastname: Hennigar
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage* / Q000627:therapeutic use*; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D020551:Pulse Therapy, Drug; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D008776:Methylprednisolone Hemisuccinate; D003520:Cyclophosphamide