A prospective observational cohort study highlights kidney biopsy findings of lupus nephritis patients in remission who flare following withdrawal of maintenance therapy

Abstract

One of the most difficult management issues in lupus nephritis (LN) is the optimal duration of maintenance immunosuppression after patients are in clinical remission. Most patients receive immunosuppression for years, based mainly on expert opinion. Prospective data are unavailable. Complicating this issue are data that patients in clinical remission can still have histologically active LN; however, the implications of this are unknown. To study this, the Lupus Flares and Histological Renal Activity at the end of Treatment study (ClinicalTrial.gov, NCT02313974) was designed to examine whether residual histologic activity predisposes to LN flares in class III and IV LN. Patients in complete clinical remission for at least 12 months who had received at least 36 months of immunosuppression were eligible. Patients consented to a second kidney biopsy, were tapered off maintenance immunosuppression and were then followed prospectively for LN flares over 24 months. Forty-four patients were enrolled, and 36 completed the study. LN flares occurred in 11 patients, and ten of these had residual histologic activity on the second biopsy. All patients with an NIH activity index over two flared. The activity index and duration of systemic lupus erythematosus at the second biopsy were independent predictors of flare. A predictive equation based on these variables discriminated between flare and no flare with a sensitivity of 100%, specificity of 88%, and a misclassification rate of 8.3%. Thus, a repeat kidney biopsy may be useful in managing maintenance immunosuppression in LN, and patients in histologic remission may be candidates for withdrawal of therapy.

2019 update of the EULAR recommendations for the management of systemic lupus erythematosus

“…These points aim to improve the design of clinical studies in order to answer clinically important questions, for which the current ‘state-of-the-art’ is insufficient. In particular, data regarding the optimal duration and timing of discontinuation of therapy in both renal and extrarenal disease are scarce;157 for the former, recent studies support the value of a repeat kidney biopsy for the management of maintenance therapy, but more data are needed 158 159…”

2019 Update of the Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA–EDTA) recommendations for the management of lupus nephritis

“…Ongoing histological activity was strongly predictive of a subsequent kidney flare when reducing immunosuppression. 103…”

Prediction of prognosis and renal outcome in lupus nephritis

“…Even if the nomenclature and definitions have not been used uniformly in studies of repeat kidney biopsies, several investigations have shown a discordance between clinical and histological outcome after the initial phase of immunosuppressive therapy for LN. More specifically, most studies reporting results from repeat biopsies have shown that residual renal activity may be evident in repeat biopsies from a considerable proportion of patients who have shown complete clinical responses to treatment, the latter mainly based on the proteinuric outcome 45–49. Again, as discussed above, haematuria levels have been demonstrated to yield weak or no correlations with activity components at the level of tissue in both initial and control kidney biopsies 23…”