Evaluation of low-dose glucocorticoid regimen in association with cyclophosphamide in patients with glomerulonephritis

The treatment of most glomerulonephritides is still based on a combination of an oral corticosteroid and an alkylating agent, with favorable outcomes, but with serious side effects. The objective of this study was to reduce the cumulative corticosteroid dose in patients with high risk of corticosteroid-related adverse events by replacing daily oral corticosteroids with intravenous (iv) methylprednisolone pulses, associated with monthly pulse i.v. cyclophosphamide (according to KDIGO guidelines) in patients with glomerulonephritis.

This was a retrospective cohort study conducted at a single nephrology centre. In the course of a 6-month run-in phase, all the patients received non-immunosuppressive pathogenic treatment. High-risk patients, who still had urinary protein excretion of at least 3.5 g per day at the end of these 6 months, received a combination of corticosteroids and cyclophosphamide. Patients were divided in two groups: group 1 (23 patients)—included patients with high risk of corticosteroid-related adverse events received monthly methylprednisolone 1 g/day, 3 days and i.v. cyclophosphamide for 6 months, and group 2 (84 patients)—received oral corticosteroids (as per KDIGO recommended dose) and i.v. cyclophosphamide. The primary outcome—time to a combined end-point of doubling of serum creatinine, ESRD, need for chronic renal replacement therapy or death; secondary outcomes: complete remission [proteinuria < 0.3 g per 24 h (urinary protein–creatinine rate < 300 mg/g [< 30 mg/mmol]]; partial remission (proteinuria > 0.3 but < 3.5 g per 24 h or a decrease in proteinuria by at least 50% from the initial value) and adverse events.

Our data indicate that low i.v. dose corticosteroids and cyclophosphamide administered monthly in patients with high risk of corticosteroid-related adverse events and primary glomerulonephritis are equally effective, with fewer metabolic disorders and infections.