Treatment of membranous lupus nephritis with nephrotic syndrome by sequential immunosuppression

The optimal therapy for pure membranous lupus nephritis (MLN) with nephroti c syndrome remains controversial. While the risk of progressive renal deter ioration may be small, persistent heavy proteinuria leads to the complicati ons of oedema, hypoalbuminaemia, hyperlipidaemia, hypercoagulability, and v enous thrombosis. We examined prospectively the efficacy and tolerability of a sequential imm unosuppressive regimen in a cohort of 20 patients with nephrotic syndrome d ue to pure MLN (WHO Class Va and Vb). Initial therapy comprised prednisolon e (0.8 mg/kg/d p.o.) and cyclophosphamide (2-2.5 mg/kg/d p.o.). Prednisolon e dosage was gradually tapered to 10 mg/d at 6 months, when cyclophosphamid e was replaced by azathioprine (2 mg/kg/d p.o.) as maintenance therapy. Wit hin 12 months of therapy 11(55%) patients had complete remission (CR), 7(35 %) patients achieved partial remission (PR) (proteinuria reduced from 6.2 /- 4.0 to 2.0 +/- 1.7 g/24 h, P < 0.01), and 2 patients failed to respond. Improvements in proteinuria and serum albumin level were observed after 3-6 months of treatment. Non-responders had lower baseline serum albumin compa red to complete responders. Renal function remained stable during follow-up for 73.5 +/- 48.9 months. 8 patients had disease relapse at 47 +/- 15 mont hs. Early complications ( less than or equal to 12 months) included herpes tester (40%), minor respiratory or urinary tract infections (25%), mild leu kopenia (15%), and transient amenorrhea (14.3%). 4 of the 20 patients devel oped pulmonary tuberculosis during follow-up, at 35 +/- 24 months after the diagnosis of MLN. 8 patients had hyperlipidaemia. Haemorrhagic cystitis, p ermanent amenorrhea, vascular complications, and mortality were not observe d. We conclude that this sequential immunosuppressive regimen is effective in 90% of patients with MLN and heavy proteinuria. Prudent consideration of th e benefits and potential side-effects is required to determine the optimal management for individual patients.