Biopsy-Informed Management Safely, Accurately Predicts Flares in Lupus Nephritis

Compared with conventional clinical management, biopsy-informed management of immunosuppression maintenance therapy in patients with lupus nephritis is safe and may ameliorate lupus nephritis flares, according to research results published in Kidney International.

Using data from a large cohort of patients with lupus nephritis, researchers assessed the feasibility of safely tapering maintenance immunosuppression with the results of kidney biopsies performed at prespecified intervals. Long-term renal outcomes were assessed over the course of several years of follow-up.

Between 2004 and 2014, 76 patients with systemic lupus erythematosus with kidney biopsy-proven proliferative or proliferative plus membranous lupus nephritis received immunosuppressive therapy. Patients were prospectively followed through December 2018. Overall, 65 patients completely responded to therapy, and 11 patients showed improvements, stabilized, and were not expected to undergo further improvement based on the results of a second biopsy. After a median of 42 months of treatment (range, 31-67 months) and a third biopsy, withdrawal of maintenance therapy was considered.

A total of 21 patients demonstrated continued histologic activity (activity index between 1 and 5). Among these patients, maintenance immunosuppression was continued: mycophenolate mofetil in 16 patients, cyclophosphamide added to 1 patient, and rituximab added to 4 patients.

Researchers developed a multiple regression model to determine whether a combination of demographic and clinical variables could noninvasively predict patients’ activity index. Predictors of this model were not significant (P =.53). Age was borderline significant, with increased age linked to lower activity index values (P =.07); however, when used alone, age demonstrated only a weak negative correlation to activity index (r²=0.05).

Investigators also examined the activity and chronicity indices of biopsy 2 as predictors of activity index for biopsy 3 and found that the activity index of biopsy 2 was only weakly correlated with the biopsy 3 activity index (r²=0.09; P =.017); chronicity index showed no association (P =.38).

Researchers followed this cohort for a median of 96 months (range, 53-155 months); all but 2 patients were compliant with repeat biopsy schedules. Overall, only 7 patients developed a lupus nephritis flare during follow-up, with a flare rate of 1.5 lupus nephritis flares per year during the 50 months (range, 12-128 months) between biopsy 3 and the final clinic visit.

A multiple logistic regression model was created using demographic and clinical variables to determine whether lupus nephritis flares could be noninvasively predicted. It was seen that all the predictors together were not significant (P =.23), but individually, proteinuria and anti-double stranded DNA titer were borderline significant (P =.047 and P =.11, respectively).

Study limitations included the lack of generalizability because of the single-center cohort, and the lack of a control group without renal histology for direct comparison.

“[These] data…suggest that clinical data in the absence of histology may not be sufficient to define response to therapy in [lupus nephritis],” the researchers concluded. “This has implications for both clinical care and the assessment of novel therapies being tested in clinical trials.”

Reference

Malvar A, Alberton V, Lococo B, et al. Kidney biopsy-based management of maintenance immunosuppression is safe and may ameliorate flare rate in lupus nephritis [published online August 20, 2019]. Kidney Int. doi:10.1016/j.kint.2019.07.018