Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial.
BACKGROUND
IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. Up to 40% progress to end-stage renal disease (ESRD) over 10-20 years. Currently, treatment is limited. We studied the use of mycophenolate mofetil (MMF) vs placebo in a group of North American IgAN patients at high risk for progressive disease.


METHODS
Included were 32 patients aged 18-75 years from multiple centres who had their biopsies read at Columbia and who had at least 1 g of proteinuria per day plus at least two of the following risk factors: (i) male sex; (ii) hypertension >150/90 mmHg or requiring antihypertensive medications; (iii) creatinine clearance, measured by 24 h urine collection, <80 and >20 ml/min at time of enrolment; and (iv) presence of glomerulosclerosis or tubulointerstitial atrophy and fibrosis on renal biopsy. Patients were randomized to either 1 year of MMF, titrated up to a dose of 1000 mg bid, or placebo. Total follow-up was 2 years. All patients received angiotensin inhibition medication. The primary outcome was a 50% increase in baseline serum creatinine (SCr). Secondary outcomes were an increase of 0.5 mg/dl SCr, ESRD and a 50% reduction in proteinuria.


RESULTS
The mean baseline SCr was 2.4 mg/dl. No statistically significant differences were observed for any outcome. Five of 17 who received MMF vs two of 15 patients in the placebo group reached a 50% increase in SCr (P = 0.4). In both groups, all patients who reached the primary outcome also reached ESRD. Ten who received MMF vs seven who received placebo had a 0.5 mg/dl increase in SCr (P = 0.7) Only three MMF and two placebo patients had a 50% reduction in 24 h proteinuria. No serious adverse events occurred in either group.


CONCLUSIONS
No benefit was seen in patients who received MMF in this high risk group, probably reflecting the relatively advanced stage of disease of our population. We conclude that MMF is probably not effective in patients with IgAN who already have moderate renal insufficiency.
Frisch
Gershon
G
New York Presbyterian Hospital, Columbia University, New York, NY, USA. gershon.frisch@mail.mcgill.ca
Lin
Julie
J
Rosenstock
Jordan
J
Markowitz
Glen
G
D'Agati
Vivette
V
Radhakrishnan
Jai
J
Preddie
Dean
D
Crew
John
J
Valeri
Anthony
A
Appel
Gerald
G
D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012307:Risk Factors
D007166:Immunosuppressive Agents; D003404:Creatinine; D009173:Mycophenolic Acid