The treatment of idiopathic membranous nephropathy (IMN) has been a matter of discussion for many years. Given the variable clinical course and potential toxicity of current regimens, the main issue nephrologists face at the moment are who to treat and with what regimen. Conservative management is justified for patients with subnephrotic proteinuria, inasmuch as spontaneous remission occurs more frequently in these patients, and their long-term prognosis is usually excellent.
By contrast, patients with nephrotic syndrome (NS) may show a progression to ESRD and are more frequently affected by any of several extrarenal complications. Thus, initiation of specific therapy is indicated for patients with declining renal function or full-blown NS (1). The guidelines of Kidney Disease: Improving Global Outcome (KDIGO) recommend a 6-month course of alternating monthly cycles of oral and intravenous corticosteroids, and oral alkylating agents. The continuous use of alkylating agents may also be effective but is associated with a greater risk of severe adverse events. Cyclosporine or tacrolimus have been suggested as alternative options in nonresponders or in patients who do not tolerate treatment with steroids and cytotoxic drugs (2).
In the past few years, the discovery that most patients with IMN have circulating antibodies directed against the M-type phospholipase A2 receptor provided important insights into the mechanistic interpretation of IMN (3). Further studies confirmed that this receptor represents the main antigen involved, although other podocyte antigens may also play a role in the pathogenesis of this disease.
In the same period of time, new drugs have been used for IMN, three of which show a potential beneficial effect: mycophenolate mofetil (MMF), adrenocorticotropic hormone (ACTH), and rituximab.
Ponticelli C, Glassock RJ. Glomerular diseases: membranous nephropathy—a modern view. Clin J Am Soc Nephrol 2014; 9:609–616.
Radhakrishnan J, Cattran DC. The KDIGO clinical practice guideline on glomerulonephritis: reading (guide)lines—application to the individual patient. Kidney Int 2012; 82(2):840–856.
Beck LH Jr, et al.. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009; 361:11–21.
Dussol B, et al.. Mycophenolate mofetil monotherapy in membranous nephropathy: a 1-year randomized controlled trial. Am J Kidney Dis 2008; 52:699–705.
Branten AJ, et al.. Mycophenolate mofetil in idiopathic membranous nephropathy: a clinical trial with comparison to a historic control group treated with cyclophosphamide. Am J Kidney Dis 2007; 50:248–256.
Chan TM, et al.. Prospective controlled study on mycophenolate mofetil and prednisolone in the treatment of membranous nephropathy with nephrotic syndrome. Nephrology (Carlton) 2007; 12:576–581.
Senthil Nayagam L, et al.. Mycophenolate mofetil or standard therapy for membranous nephropathy and focal segmental glomerulosclerosis: a pilot study. Nephrol Dial Transplant 2008; 23:1926–1930.
Berg AL, et al.. Beneficial effects of ACTH on the serum lipoprotein profile and glomerular function in patients with membranous nephropathy. Kidney Int 1999; 56:1534–1543.
Ponticelli C, et al.. A randomized pilot trial comparing methylprednisolone plus a cytotoxic agent versus synthetic adrenocorticotropic hormone in idiopathic membranous nephropathy. Am J Kidney Dis 2006; 47:233–240.
Bomback AS, et al.. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther 2011; 5:147–153.
Lindskog Jonsson A, et al.. Effects of melanocortin 1 receptor agonists in experimental nephropathies. PLoS One 2014; 9:e87816.
Fervenza FC, et al.. Rituximab therapy in idiopathic membranous nephropathy: a 2-year study. Clin J Am Soc Nephrol 2010; 5:2188–2198.