Management of Membranous Nephropathy in Asia

Abstract

Background: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome (NS) in adults, accounting for about 20.0% of all NS cases. With an increasing prevalence, especially in the elderly, it has received great attention in Asia. Summary: Recently, the prevalence of idiopathic MN (IMN) has significantly increased among the elderly people in Asia and other places in the world. Although the exact mechanism of IMN remains unveiled, the identification of new antigens such as PLA2R and THSD7A has greatly enhanced our understanding of its pathogenesis. However, consensus has not yet been reached for the treatment of IMN in Asia. For example, there are many choices of immunosuppressive agents, including corticosteroid monotherapy, corticosteroids combined with cytotoxic agents [such as alkylating agents, calcineurin inhibitors or mycophenolate mofetil (MMF)] or traditional Chinese medicine (triptolide, Shenqi and other Chinese herbal soups). Patients with IMN in Asia often have a favorable prognosis, and progression to end-stage renal disease is relatively uncommon compared to other populations. Key Messages: The prevalence of MN has significantly increased in the last years. The treatment strategies for IMN have not reached consensus in Asia. Traditional Chinese medicine is generally preferred by the Chinese, and compelling results have been reported recently. Facts from East and West: (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 have been done in Asian membranous patients at high risk of progression. Corticosteroid monotherapy has failed in randomized controlled trial 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, calcineurin inhibitors are the more common first-line treatment. (4) Cyclosporine is predominantly used as monotherapy in North America, although KDIGO (Kidney Disease: Improving Global Outcomes) 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 MMF 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, randomized controlled trial 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.