Studies have shown that up to 26% of patients with systemic lupus erythematoses nephritis
may suffer from membranous lupus nephropathy. The disease is characterized by high levels
of protein in the urine and may eventually lead to kidney failure.
This study will evaluate the effectiveness and toxic effects of immunosuppressive drug
therapy in patients with membranous lupus nephropathy over a 12 month period. The major
goal of this therapy is to decrease protein losses and ultimately prevent kidney failure.
Patients enrolled in the study will undergo a routine history and physical examination. In
addition, several diagnostic tests will be conducted including; chest x-ray ECG, blood and
urine laboratory tests.
Patients will be divided and grouped according to the severity of their disease as shown by
kidney function. Each group will then randomly be subcategorized by different treatment
plans. Each treatment plan will made up of immunosuppressive medications including
prednisone, cyclophosphamide, cyclosporin A, and combinations of these drugs. Patients will
receive the medications as directed by the study.
The study will last 12 months and require patients to be admitted for two to five days
before the study begins and once the study is completed. Patients will be followed as
outpatients throughout the 12 month study.
This is a phase 2 trial to evaluate the effectiveness and toxicity of immunosuppressive drug
therapy in patients with membranous lupus nephropathy over a 12 month study period.
Patients with renal biopsy documented membranous nephropathy will all be treated with
alternate day prednisone and will be randomized to receive: a) no additional therapy
(control group), b) intravenous cyclophosphamide up to 1.0 gm per m(2) body surface area
every other month for 6 total doses, or c) oral cyclosporin A up to 200 mg per m(2) body
surface area daily for a total of 11 months. Patients with glomerular filtration rates
25-66 ml/min will be randomized only to prednisone alone or to prednisone plus
cyclophosphamide. Renal function and disease activity will be monitored throughout the
study; physiologic measures of glomerular function (GFR, permselectivity) will be examined
at study entry and at the conclusion of the study. Comparison will be made of the number of
favorable outcomes of glomerular function as well as drug related toxicities achieved by
each treatment group at the end of the 12th study month.
INCLUSION CRITERIA - All patients admitted to the study must satisfy each of the following
Ability to provide informed consent to all aspects of the study after full information is
SLE as defined by the presence of at least 4 criteria established by the American
Age 12 years or older.
Membranous lupus nephropathy manifested by 2 or more grams per day of proteinuria in the
absence of infection or recognized non-lupus renal disease. A renal biopsy must reveal
typical membranous lupus nephropathy by light microscopy. Immune deposits must be
predominately sub-epithelial and/or intramembranous in location by electron microscopy.
EXCLUSION CRITERIA - Patients with any one of the following conditions will be excluded:
Medication history of:
- cytotoxic drugs or cyclosporin A for more than 2 weeks during the 10 week period
prior to study entry.
- cytotoxic drug therapy or cyclosporin A for more than 10 weeks at anytime in the
- cytotoxic drug therapy or cyclosporin A during the 30 day period prior to study
- requirement of corticosteroids in doses greater than 20 mg/m(2)/day of prednisone (or
equivalent) for control of extrarenal disease at the time of study entry.
Active acute or chronic infection requiring antimicrobial therapy, or serious viral
infection (eg. hepatitis, herpes zoster).
Pregnant females, nursing mothers, or females not practicing birth control.
Patients with a single functioning kidney.
Insulin-treated diabetes mellitus.
GFR less than 25 ml/min/1.73m(2) BSA.
Known toxicity to cyclophosphamide.
Positive tests for HIV infection.
Furthermore, patients with any one of the following conditions (related to the use of
cyclosporin A) will be excluded from randomization within renal function group 2
(Glomerular filtration rate greater than 66 ml/min/1.73m(2)):
- Renal biopsy revealing global sclerosis of greater than 50 percent of glomeruli,
severe tubular atrophy, or severe interstitial fibrosis.
- Persistently abnormal and unexplained liver function abnormalities (defined as
elevated transaminases, bilirubin, or alkaline phosphatase twice the upper limit of
normal for at least 1 month) or evidence of active viral hepatitis.
- Hypertension difficult to control or uncontrollable with conventional
- Documented coronary artery disease.
- Convulsive disorders.