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2015 ; 1
(2
): 126-37
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Management of Membranous Nephropathy in Western Countries
#MMPMID27536673
Alfaadhel T
; Cattran D
Kidney Dis (Basel)
2015[Sep]; 1
(2
): 126-37
PMID27536673
show ga
BACKGROUND: 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). SUMMARY: 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. KEY MESSAGES: Appropriate
assessment is required to exclude secondary conditions causing membranous
glomerulonephritis. The role of antibodies to phospholipase A2 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. 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 (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.
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