title: IgA nephropathy with severe chronic renal failure: a randomized controlled trial of corticosteroids and azathioprine.
abstract: BACKGROUND
  Therapeutic nihilism is common in IgA nephropathy (IgAN) and renal insufficiency.
  
  
  METHODS
  In a randomized controlled trial comparing steroids alone or combined with azathioprine in 253 IgAN patients, we used a separate randomization list for patients with creatinine >2.0 mg/dL. Twenty patients (group 1) were randomized to 3 intravenous pulses of methylprednisolone 1 g at months 1, 3 and 5, and oral prednisone 0.5 mg/kg every other day plus azathioprine 1.5 mg/kg/day for 6 months, followed by oral prednisone 0.2 mg/kg every other day plus azathioprine 50 mg/day for a further 6 months; 26 patients (group 2) received steroids alone. The primary outcome was renal survival (50% increase in plasma creatinine from baseline); secondary outcomes were proteinuria over time and adverse events.
  
  
  RESULTS
  Six-year renal survival was not different between the 2 groups (50% vs. 57%; log-rank p=0.34). Median proteinuria decreased during follow-up in the whole population (from 2.45 g/day [interquartile range (IQR) 1.50-3.78] to 1.09 g/day [IQR 0.56- 2.46]; p<0.001), with no between-group difference. Multivariate predictors associated with renal survival were sex of patient, proteinuria during follow-up, number of antihypertensive drugs, angiotensin-converting enzyme inhibitors and treatment including azathioprine. Six patients in group 1 (30%) and 4 in group 2 (15%) did not complete the therapy, because of side effects (p=0.406).
  
  
  CONCLUSIONS
  Six-year renal survival was similar in the 2 groups. At Cox analysis the addition of azathioprine may be slightly more effective than corticosteroids alone in patients with chronic renal insufficiency, although with an increase of side effects.
authors.affiliation: Department of Nephrology and Dialysis, A. Manzoni Hospital, Lecco, Italy. claudio.pozzi@icp.mi.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Pozzi
authors.forename: Simeone
authors.initials: S
authors.lastname: Andrulli
authors.forename: Antonello
authors.initials: A
authors.lastname: Pani
authors.forename: Patrizia
authors.initials: P
authors.lastname: Scaini
authors.forename: Dario
authors.initials: D
authors.lastname: Roccatello
authors.forename: Giambattista
authors.initials: G
authors.lastname: Fogazzi
authors.forename: Paola
authors.initials: P
authors.lastname: Pecchini
authors.forename: Roberto
authors.initials: R
authors.lastname: Rustichelli
authors.forename: Pietro
authors.initials: P
authors.lastname: Finocchiaro
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Vecchio
authors.forename: Francesco
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D000328:Adult; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000188:drug therapy* / Q000652:urine; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D011241:Prednisone / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011507:Proteinuria / Q000209:etiology; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D012737:Sex Factors; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; D007166:Immunosuppressive Agents; D003404:Creatinine; D001379:Azathioprine; D011241:Prednisone; D008775:Methylprednisolone