Antioxidant treatment of therapy-resistant idiopathic membranous nephropathy with probucol: a pilot study.
BACKGROUND
Proteinuria in Heymann's nephritis, an experimental rat model disease corresponding to membranous nephropathy, has been shown to be due to lipid peroxidation. Since the pathophysiology might be similar to idiopathic membranous nephropathy in humans, we performed a prospective multicenter trial to investigate the efficacy of the lipid peroxidation scavenger, probucol.


METHODS
Fifteen patients with biopsy-proven idiopathic membranous nephropathy resistant to conventional immunosuppressive therapy (n = 7) and/or ACEI treatment (n = 12) were recruited. Probucol (1 g/d orally) was administered for three months, followed by a washout period of four weeks, whereon lovastatin (10-20 mg/d orally) was administered for additional three months.


RESULTS
A significant reduction in proteinuria was seen during the probucol treatment (median (range): 6.4 (3.8-9.1) g/d vs. 4.7 (1.3-16) g/d; P < 0.05), with partial remission achieved in four patients. Three of these patients had previously been resistant to immunosuppressive therapy. Median protein excretion increased to pretreatment values during the washout period (6.2 (1.9-15) g/d; P < 0.05) and was not significantly different after the intake of lovastatin (4.9 (1.8-19) g/d; P = NS). None of the patients achieved partial remission during lovastatin therapy (P < 0.05 vs. probucol).


CONCLUSIONS
The present study led us to conclude that proteinuria can be reduced by probucol in some patients with idiopathic membranous nephropathy. A randomized multicenter study to further elucidate the influence of lipid peroxidation scavengers on membranous nephropathy is warranted.
Haas
Martin
M
Division of Nephrology and Dialysis, University of Vienna, Austria. Martin.Haas@akh-wien.ac.at
Mayer
Gert
G
Wirnsberger
Gerhard
G
Holzer
Herwig
H
Ratschek
Manfred
M
Neyer
Ullrich
U
Neuweiler
Josef
J
Kramar
Reinhard
R
Schneider
Brigitte
B
Breiteneder-Geleff
Silvana
S
Regele
Heinrich M
HM
Hörl
Walter H
WH
Kerjaschki
Dontscho
D
D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D006801:Humans; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects*; D008148:Lovastatin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011341:Probucol / Q000627:therapeutic use*; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy*; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D000975:Antioxidants; D008148:Lovastatin; D011341:Probucol