Membranous glomerulopathy (MN) is a common immune-mediated glomerular disease and the leading
cause of nephrotic syndrome in Caucasian adults. 1 Because of its frequency, it remains the
second or third cause of end-stage renal disease caused by a primary glomerulonephritis. 2 At
presentation, 70% to 80% of patients have the nephrotic syndrome. 1, 3, 4 Proteinuria greater
than 2.0 grams per day is found in > 80% of patients at presentation, with greater than 10
grams found in as many as 30%. 5 The disease affects patients of all ages, but it is most
often diagnosed in middle age with the peak incidence during the fourth and fifth decades of
life. There is close to a two-to-one predominance of males to females diagnosed with the
disease. Idiopathic MN affects all races. Current therapeutic options include corticosteroids
alone or in combination with alkylating agents, cyclosporin A, and mycophenolate mofetil. The
most widely recognized, and best-validated regimen is combination therapy with
corticosteroids and an alkylating agent, but its use is associated with significant adverse
effects. Recent meta-analysis confirmed that present day treatments are far from ideal 6
Thus, it should not come as a surprise that the outcome of MN has not substantially improved
over the past 30 years, and up to 40% of patients still progress to end-stage renal failure.
7 Like in other glomerular diseases the amount of protein in the urine correlates well with
long term prognosis. Thus, this parameter has been used in previous studies, and will be used
in this study, as the primary indicator of effectiveness of therapy. We proposed to do a
pilot study to test the hypothesis that selective B lymphocyte depletion will result in
disappearance of pathogenic antibodies and induction of remission of the nephrotic syndrome
in patients with idiopathic membranous nephropathy. Our population will be 10 adults. The
study will be conducted between our Nephrology Divisions at Mayo Clinic Rochester,
Jacksonville, and Scottsdale. We will enroll patients with a GFR 25 ml/min as estimated by
creatinine clearance and proteinuria > 4g/24h, while receiving an ACEI or ARB and with BP
controlled of < 130/80 mmHg. Patients will receive Rituximab 1g on Day 1 and 15. Patients
followed for 1 years following completion of treatment. The primary outcome will be change in
urinary protein excretion at 6 months. Secondary outcomes will be changes in serum albumin,
serum lipid?s profile, the number of partial remissions, time to remission, and incidence of
relapses. We will also perform a pharmacokinetic study to evaluate the effect of proteinuria
on the bio-availability and effects of the drug.