Pharmacotherapy for lupus nephritis based on stage

 

Pharmacotherapy for Lupus Nephritis Based on Stage

Classes I and II

Minimal mesangial (class I) lupus nephritis requires no specific therapy.

Mesangial proliferative (class II) lupus nephritis may require treatment if proteinuria is greater than 1000 mg/day. Consider prednisone in low-to-moderate doses (ie, 20-40 mg/day) for 1-3 months, with subsequent taper.

Classes III and IV

Patients with either focal (class III) or diffuse (class IV) lupus nephritis are at high risk of progressing to ESRD and thus require aggressive therapy.

Administer prednisone 1 mg/kg/day for at least 4 weeks, depending on clinical response. Then, taper it gradually to a daily maintenance dose of 5-10 mg/day for approximately 2 years. In acutely ill patients, intravenous (IV) methylprednisolone at a dosage of up to 1000 mg/day for 3 days may be used to initiate corticosteroid therapy.

In patients who do not respond to corticosteroids alone, who have unacceptable toxicity to corticosteroids, who have worsening renal function, who have severe proliferative lesions, or who have evidence of sclerosis on renal biopsy specimens, use immunosuppressive drugs in addition to corticosteroids.

Both cyclophosphamide and azathioprine are effective in proliferative lupus nephritis, although cyclophosphamide is apparently more effective in preventing progression to ESRD. Mycophenolate mofetil has been shown to be at least as effective as IV cyclophosphamide, with less toxicity, in patients with focal or diffuse lupus nephritis who have stable renal function. It may be used alone^[ or sequentially after a 6-month course of IV cyclophosphamide.

Appel et al studied 370 patients with lupus nephritis in a randomized open-label study and found no significant difference in clinical improvement was observed with mycophenolate mofetil compared with IV cyclophosphamide. The study included induction and maintenance therapy, and both study groups received prednisone.

Administer IV cyclophosphamide monthly for 6 months and every 2-3 months thereafter, depending on clinical response. The usual duration of therapy is 2-2.5 years. Reduce the dose if the creatinine clearance is less than 30 mL/min. Adjust the dose depending on the hematologic response. The gonadotropin-releasing hormone analogue leuprolide acetate has been shown to protect against ovarian failure.

Azathioprine can also be used as a second-line agent, with dose adjustments depending on hematologic response.

Mycophenolate mofetil was found to be superior to azathioprine in maintaining control and preventing relapses of lupus nephritis in patients who have responded to induction therapy.

Class V

Patients with membranous lupus nephritis are generally treated with prednisone for 1-3 months, followed by tapering for 1-2 years if a response occurs. If no response occurs, the drug is discontinued. Immunosuppressive drugs are generally not used unless renal function worsens or a proliferative component is present on renal biopsy samples. Some clinical evidence indicates that azathioprine, cyclophosphamide, cyclosporine, and chlorambucil are effective in reducing proteinuria. Mycophenolate mofetil may also be effective.

In a study of membranous lupus nephritis, 38 patients were treated with corticosteroids and azathioprine; after 12 months of treatment, 67% of patients had a complete remission and 22% had a partial remission, with only 11% resistant to treatment.^[ Long-term follow-up of 12 years showed 19 episodes of renal flares. Retreatment with corticosteroids and azathioprine showed similar responses.

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