Idiopathic membranous nephropathy (IMN) is a disease in which glomerular basement membrane becomes thickening by light microscopy on renal biopsy and it represents a major cause of primary nephrotic syndrome in adults. A combined alkylating agent and corticosteroid regimen had short- and long-term benefits on adult IMN with nephrotic syndrome. Among alkylating agents, cyclophosphamide was safer than chlorambucil. It should be emphasised that the number of included randomised studies with high-quality design was relatively small and most of the included studies did not have adequate follow-up and enough power to assess the prespecified outcomes. Meanwhile, this regimen was significantly associated with more withdrawals or hospitalisations. Although a six-month course of alternating monthly cycles of corticosteroids and cyclophosphamide was recommended by the KDIGO Clinical Practice Guideline 2012 as the initial therapy for adult IMN with nephrotic syndrome, clinicians should inform their patients of the lack of high-quality evidence for these benefits as well as the well-recognised adverse effects of this therapy. Whether this combined therapy should be indicated in all adult patients at high risk of progression to ESKD or only restricted to those with deteriorating kidney function still remained unclear.
Cyclosporine or tacrolimus was recommended by the KDIGO Clinical Practice Guideline 2012 as the alternative regimen for adult IMN with nephrotic syndrome; however, there was no evidence that calcineurin inhibitors could alter the definite endpoints such as all-cause mortality or risk of ESKD. There was no clear evidence to support the use of either corticosteroid or alkylating agent monotherapy. The numbers of corresponding studies related to tacrolimus, mycophenolate mofetil, adrenocorticotropic hormone, azathioprine, mizoribine, and Tripterygium wilfordii are still too sparse to draw final conclusions.