Idiopathic membranous nephropathy: management strategies

Abstract

Treatment of idiopathic membranous nephropathy is based on a 'symptomatic' therapy that includes ACE inhibitors or angiotensin II receptor antagonists, and on an 'aetiological' therapy aimed at modulating underlying immunological mechanisms. The role of the latter is still debated given the usually indolent course of disease; furthermore, traditional immunosuppressants would not have an impact on patient and renal survival according to a systematic review of literature. However, up to 40% of untreated patients eventually develop end-stage renal disease and remission of nephrotic syndrome protects patients from related life-threatening complications and is the strongest positive prognostic factor for long-term kidney function. Therefore, immunosuppressive therapy seems to be rational in high-risk patients with nephrotic syndrome or deteriorating renal function. This article outlines a possible role for each 'aetiological' therapy on the basis of available evidence in order to provide some practical recommendations. The first-line therapy is based on a 6-month regimen of alternating corticosteroids and an alkylating agent ('Ponticelli' regimen), whereas oral ciclosporin and intramuscular corticotrophin (adrenocorticotrophic hormone) are alternatives that provide comparable results in terms of remission of proteinuria, with a different adverse effect profile. New drugs are emerging as potential treatments, such as mycophenolate mofetil, tacrolimus, intravenous immunoglobulins and rituximab. Specific settings, such as chronic renal failure or elderly age, require a careful balance between benefits and toxicity of immunosuppression. The tailor-made use of this repertoire of drugs can provide a tool to achieve remission of proteinuria and modify the natural course of idiopathic membranous nephropathy.