Tacrolimus Treatment of Patients With Idiopathic Membranous Nephropathy

Tacrolimus Treatment of Patients With Idiopathic

The purpose of this study is:

• To explore the potential role of tacrolimus in the treatment of membranous nephropathy.
• To investigate the safety and tolerability of tacrolimus vs methylprednisolone plus cyclophosphamide.

Idiopathic membranous nephropathy is the most common cause of nephrotic syndrome in adults. Over the past decade, a number of studies have reported therapeutic efficacy for treatment with Cyclosporine-A (CSA) in patients with nephrotic syndrome including patients with membranous nephropathy. This study will evaluate the safety and effectiveness of a new calcineurin immunosuppressive drug, tacrolimus (FK506), in reducing the amount of protein in the urine in patients with membranous nephropathy. Forty patients with biopsy-proven membranous nephropathy will be recruited. Candidates must have completed at least six month of treatment with a stable dose of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). They will be screened with a medical history, physical examination, blood tests, and an examination for infection, cancers, and other conditions that can cause membranous nephropathy. The investigators plan to conduct an open-label study of the efficacy and safety of tacrolimus in the treatment of membranous nephropathy. They will be treated with oral tacrolimus for 6 months, followed by 6 months of maintenance. Proteinuria, renal function will be monitored. Complete remission is defined as 24-hour urinary protein excretion to less than 0.4 mg/day. This study will explore the potential role of tacrolimus in the treatment of membranous nephropathy, which is usually resistant to conventional therapy.

Inclusion Criteria:

• Biopsy-proven idiopathic membranous nephropathy
• Nephrotic syndrome with proteinuria ( > 4 g/day) and serum albumin < 30 g/dl
• Age 18-60 years with informed consent

Exclusion Criteria:

• Patient with abnormal liver function tests
• Prior therapy with sirolimus, CSA, MMF, or azathioprin, cytoxan, chlorambucil, levamisole, methotrexate, or nitrogen mustard in the last 90 days
• Active/serious infection
• Patient with hepatitis B surface antigen or who is hepatitis C antibody positive
• Patient who is diabetic
• Patient is allergic or intolerant to macrolide antibiotics or tacrolimus