Compared to proliferative lupus nephritis (PLN), membranous lesions are less inflammatory, have a more benign course, require less aggressive therapy, and have better prognosis.1 The 2012 EULAR/EDTA recommendations for lupus nephritis2 were recently updated (Fanouriakis A, et al 2019 to be submitted).
Goals of therapy Optimisation (preservation or improvement) of renal function with at least 25% reduction in proteinuria at 3 months, 50% at 6 months and a urine protein/creatinine ratio (UPCR) target below 0.5–0.7 mg/g by 12 months (complete renal response).
Initial therapy Glucocorticoids and immunosuppression if UPCR exceeds 1 mg/g despite the optimal use of renin-angiotensin-aldosterone system blockers, or from the beginning when nephrotic-range proteinuria is present. In pure Class V nephritis, mycophenolate mofetil (MMF) (dose 2–3 g/day; or mycophenolic acid [MPA] at equivalent dose) in combination with pulses IV methylprednisolone (total dose 500–2500 mg) followed by oral prednisone (20 mg/day, tapered to ≤5 mg/day by 3 months) can be used as initial treatment based on better efficacy/toxicity ratio. Alternative options include high-dose IV cyclophosphamide (0.5–0.75 g/m2 monthly for 6 months), calcineurin inhibitors (ciclosporin, tacrolimus) or their combination with MMF/MPA, particularly in patients with severe nephrotic syndrome.
Subsequent therapy MMF/MPA (dose: 1–2 g/day) – especially if it was used as initial treatment – or azathioprine (AZA); 2 mg/kg/day – preferred if pregnancy is contemplated – for at least 3 years, in combination with low-dose prednisone (2.5–5 mg/day) when needed. If sustained complete response, gradual drug withdrawal, glucocorticoids first, can then be attempted, with immunosuppressives following after 3–5 years in complete response. Continuation, switching or addition of calcineurin inhibitors can be considered in pure Class V nephritis at the lowest effective dose taking into consideration the possibility for nephrotoxicity.
Refractory disease Treatment may be switched to one of the alternative initial therapies mentioned above or rituximab (1000 mg on days 0 and 14). In a recent randomised controlled trial of rituximab in idiopathic membranous nephropathy, rituximab was equal to cyclosporine in achieving remission at 12 months (60% vs 52%) but superior to cyclosporine in maintaining remission at 24 months (60% vs 20%).3
Adjunct therapy ACE-inhibitors or angiotensin receptor blockers for patients with UPCR >0.5 mg/g or hypertension. Antilipidemics and hydroxychloroquine at a dose not to exceed 5 mg/kg/day. Anticoagulant treatment in cases of nephrotic syndrome with serum albumin <20 g/L, presence of antiphospholipid antibodies or other pro-thrombotic conditions.
Discuss how membranous differs from proliferative disease
Describe how to treat nephropathy membranous
Explain targets of therapy
Describe treatment of refractory disease
Explain adjunct therapy and what it entails
Ward F, Bargman JM. Membranous Lupus Nephritis: The Same, But Different. American journal of kidney diseases : the official journal of the National Kidney Foundation 2016;68(6):954–66.
Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 2012;71(11):1771–82.
Fervenza FC, Appel GB, Barbour SJ, et al. Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. The New England journal of medicine 2019;381(1):36–46.
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