Membranous nephropathy is an immune mediated kidney disease associated with an increased risk for progressive renal failure and for the cardiovascular and thromboembolic complications of the nephrotic syndrome. It is one of the most common causes of adult-onset nephrotic syndrome in the world, accounting for approximately 20 percent of cases. In developed counties, most cases of membranous nephropathy are considered to be idiopathic. Systemic lupus erythematosus is another relatively common cause of membranous nephropathy. Idiopathic and lupus membranous nephropathy are frequently treated with immunosuppressive drug regimens (prednisone, cyclophosphamide, chlorambucil or cyclosporine) based on experimental evidence that glomerular capillary wall injury in membranous nephropathy is mediated by immune complex formation and complement activation. Despite indications that cyclosporine and cytotoxic drug therapies may be effective for some patients with idiopathic and lupus membranous nephropathy, there are reservations regarding the balance of efficacy and toxicity of these regimens for the treatment of membranous nephropathy. Sirolimus has been approved by the FDA as an agent to prevent acute rejection in renal allograft recipients. Sirolimus has immunosuppressive, anti-proliferative and anti-fibrotic properties which suggest that it may be an effective treatment for patients with membranous nephropathy. Furthermore, sirolimus is less nephrotoxic than cyclosporine and has not been associated with gonadal toxicity, hemorrhagic cystitis or malignancy that may complicate cytotoxic drug regimens. This is a phase 2 trial to evaluate the safety and effectiveness of a new immunosuppressive drug, sirolimus, in patients with idiopathic and lupus membranous nephropathy. Patients (older than 13 years) are invited to participate if they have persistent nephrotic range proteinuria despite standard treatment with an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker. Patients with persistent nephrotic range proteinuria are at increased risk for renal function deterioration as well as cardiovascular and thromboembolic complications. Renal function, the degree of proteinuria and side effects will be monitored closely throughout the study. Physiologic measures of glomerular function will be examined at study entry and at the conclusion of the trial. Four patients have completed one to seven months of treatment. Other patients have expressed interest and are being evaluated.
| Waldman, Meryl; Austin 3rd, Howard A (2009) Controversies in the treatment of idiopathic membranous nephropathy. Nat Rev Nephrol 5:469-79 |
