Sequential use of cyclophosphamide and azathioprine in the treatment of membranous lupus nephropathy (MLN) with nephrotic syndrome

Abstract

The optimal therapy for MLN remains to be established. We retrospectively reviewed the outcome of patients with nephrotic syndrome and 'pure' MLN, who had been treated with a sequential regimen comprising prednisolone [starting dose 0.8 mg/kg/d p.o.] and cyclophosphamide [2-2.5 mg/kg/d p.o.] for 6 months, followed by low dose prednisolone and azathioprine maintenance. 20 [F:M 1:19, age 39±9 yr] patients were included, with follow-up duration 74±49 months. Proteinuria at presentation was 6.6±4.5 g/d. 8 patients had a history of proliferative LN, 2 of whom had abnormal creatinine prior to the development of MLN. Other symptoms/signs included hypertension in 11(55%) patients, skin ± joint involvement in 17(85%), and reduced WBC ± platelet count in 9(45%). Raised anti-DNA and reduced C3 were noted in 8(40%) and 7(35%) patients respectively. Serological abnormalities improved in all patients after treatment. 10(50%) patients had complete resolution of proteinuria and hypoalbuminemia, 9 had partial improvement [proteinuria decreased from 6.5±5.5 to 1.5±0.6 g/d], and I had persistent nephrotic syndrome. Creatinine clearance remained stable. The clinical response was not related to initial proteinuria, serum albumin, anti-DNA, or C3 levels. Complications included transient amenorrhea in 2 patients, zoster in 9, bacterial infection in 5, and tuberculosis in 5. Hemorrhagic cystitis and permanent amenorrhea were not observed. 8 patients had disease relapse at 47 ± 15 months after the diagnosis of MLN. We conclude that the sequential regimen confers clinical benefit to 95% of patients with nephrotic syndrome due to MLN. Response to therapy cannot be predicted by biochemical or serological parameters at presentation. Despite the absence of serious morbidity and mortality, infection remains a significant complication.