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Abstract: SA-OR065

Lupus Nephritis Flare after Withdrawal of Immunosuppression Is Predicted by Kidney Biopsy Findings during Maintenance Therapy: A Prospective Observational Cohort Study

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • De Rosa, Marcelo Alejandro, University of Buenos Aires, Buenos Aires, Argentina
  • Toblli, Jorge E., Laboratory of Experimental Medicine Hospital Aleman, Buenos Aires, Argentina
  • De Rosa, Graciela Elena, Hospital de Clinicas, Buenos Aires, Argentina
  • Fuentes, Federico, Hospital de Clínicas, Buenos Aires, Argentina
  • Nagaraja, Haikady N., The Ohio State University, Columbus, Ohio, United States
  • Nash, Ryan R., The Ohio State University, Columbus, Ohio, United States
  • Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Background

The optimal duration of maintenance immunosuppressive therapy in lupus nephritis (LN) is unclear. Withdrawal of immunosuppression is generally based on a patient achieving a sustained clinical remission (CR). However, a significant proportion of patients in CR continue to have persistent histologic activity on kidney biopsy. We postulated that patients with ongoing histologic activity are at risk of LN flare when maintenance therapy is tapered, and designed a prospective observational study to test this hypothesis.

Methods

Patients with Class III/IV±V LN on maintenance therapy who had received at least 3 years of immunosuppression and were in complete CR for at least the last year of treatment were recruited to undergo a kidney biopsy. Maintenance therapy was withdrawan after the kidney biopsy and patients were followed prospectively for 2 years. The primary endpoint of the trial was LN flare.

Results

Out of 44 recruited patients, 36 completed the study. Patients withdrew due to pregnancy, non-renal lupus flare, or by choice. Biopsy showed that 20 patients (55.6%) had achieved complete histologic remission with an NIH activity index (AI) of 0, nine patients (25%) had an AI of 1 or 2, and 7 patients had an AI between 3 and 5. LN flared in 11 patients (30.5%), all but one flare (91%) occurred in patients with persistent histologic activity, and everyone with an AI>2 flared. In multivariable analysis AI and duration of SLE were independent predictors of LN flare, and these variables could discriminate between future flare and no-flare with 100% sensitivity, 88% specificity, an 8.3% misclassification rate, and an area under the ROC curve of 0.98. Among the individual components of the AI, endocapillary proliferation and subendothelial deposits were both significantly associated with the odds of future flare, but endocapillary proliferation was a more robust marker.

Conclusion

Persistent histologic activity in kidney biopsies of LN patients in complete CR on maintenance immunosuppression, especially persistent endocapillary proliferation, is a risk factor for future LN relapse. A kidney biopsy during maintenance immunosuppression may help inform the decision of whether to withdraw or continue maintenance therapy in LN.

Funding

  • Government Support - Non-U.S.