Kidney biopsy-based management of maintenance immunosuppression is safe and may ameliorate flare rate in lupus nephritis

The optimal duration of maintenance immunosuppressive therapy for patients with lupus nephritis who have achieved clinical remission has not been established. Furthermore, clinical and histologic remissions are often discordant. We postulated that continuing therapy for patients with persistent histologic activity on kidney biopsies done during maintenance and discontinuing therapy only for patients without histologic activity would minimize subsequent lupus nephritis flares. To test this, a cohort of 75 prospectively-followed patients with proliferative lupus nephritis was managed using kidney biopsies performed during maintenance therapy. These patients had been on immunosuppression for at least 42 months, had responded, and had maintained their clinical response for at least 12 months before the kidney biopsy was repeated. Maintenance therapy was withdrawn if the biopsy showed an activity index of zero, but was continued if the biopsy showed an activity index of one or more. A lupus nephritis flare developed in seven patients during the average 50 months from the third biopsy and the final clinic visit for a flare rate of 1.5/year; significantly less than reported flare rates. Baseline clinical parameters (serum creatinine, proteinuria) and serologic parameters (complement C3, C4 and anti-dsDNA) did not predict an activity index of zero on the third biopsy or who would have a lupus nephritis flare. No patients developed end-stage kidney disease. Four patients developed de novo chronic kidney disease. There were no serious adverse events related to biopsy. Thus, at an experienced center, biopsy-informed management of maintenance immunosuppression is safe and may improve the lupus nephritis flare rate compared to conventional clinical management.