Management of Membranous Nephropathy in Western Countries
Authors: Alfaadhel Talal , Cattran Daniel 
Published: September 2015

<b><i>Background:</i></b> Idiopathic membranous nephropathy (IMN) is a common cause of nephrotic syndrome (NS) in adults in Western countries. In 2012, the KDIGO (Kidney Disease: Improving Global Outcomes) working group published guidelines for the management of glomerulonephritis, thus providing a template for the treatment of this condition. While being aware of the impact of the clinicians' acumen and that patients may choose a different therapeutic option due to the risks of specific drugs and also of the evolving guidelines, this review details our approach to the management of patients with IMN in a Western center (Toronto). <b><i>Summary:</i></b> Based on studies published in Europe and North America, we included recent advances in the diagnosis and management of patients with membranous nephropathy similar to our practice population. We highlight the importance of establishing the idiopathic nature of this condition before initiating immunosuppressive therapy, which should include the screening for secondary causes, especially malignancy in the elderly population. The expected outcomes with and without treatment for patients with different risks of progression will be discussed to help guide clinicians in choosing the appropriate course of treatment. The role of conservative therapy as well as of established immunosuppressive treatment, such as the combination of cyclophosphamide and prednisone, and calcineurin inhibitors (CNIs), as well as of newer agents such as rituximab will be reviewed. <b><i>Key Messages:</i></b> Appropriate assessment is required to exclude secondary conditions causing membranous glomerulonephritis. The role of antibodies to phospholipase A<sub>2</sub> receptor (anti-PLA2R) in establishing the primary disease is growing, though more data are required. The increase in therapeutic options supports treatment individualization, taking into account the availability, benefits and risks, as well as patient preference. <b><i>Facts from East and West:</i></b> (1) The prevalence of IMN is increasing worldwide, particularly in elderly patients, and has been reported in 20.0-36.8% of adult-onset NS cases. The presence of anti-PLA2R antibodies in serum or PLA2R on renal biopsy is the most predictive feature for the diagnosis of IMN and is used in both the East and West; however, appropriate screening to rule out secondary causes should still be performed. (2) Several observational (nonrandomized) Asian studies indicate a good response to corticosteroids alone in IMN patients, although no randomized controlled trials (RCTs) have been done in Asian membranous patients at high risk of progression. Corticosteroid monotherapy has failed in randomized controlled studies in Western countries and is therefore not recommended. (3) Cyclophosphamide is the most commonly prescribed alkylating agent in Europe and China. Also, chlorambucil is still used in some Western countries, particularly in Europe. In North America, CNIs are the more common first-line treatment. (4) Cyclosporine is predominantly used as monotherapy in North America, although KDIGO and Japanese guidelines still recommend a combination with low-dose corticosteroids. Clinical studies both in Asia and Europe showed no or little effects of monotherapy with mycophenolate mofetil compared to standard therapies. (5) There are encouraging data from nonrandomized Western studies for the use of rituximab and a few small studies using adrenocorticotropic hormone. Clinical trials are ongoing in North America to confirm these observations. These drugs are rarely used in Asia. (6) A Chinese study reported that 36% of IMN patients suffered from venous thromboembolism versus 7.3% in a North American study. Prophylactic anticoagulation therapy is usually added to IMN patients with a low risk of bleeding in both Eastern and Western countries. (7) The Chinese traditional medicine herb triptolide, which might have podocyte-protective properties, is used in China to treat IMN. An open-label, multicenter RCT showed that Shenqi, a mixture of 13 herbs, was superior to corticosteroids plus cyclophosphamide therapy to restore epidermal growth factor receptor in IMN patients, although proteinuria improvement was equal in the two groups. Importantly, Shenqi treatment induced no severe adverse events while standard therapy did.