Are RAS inhibitors necessary during intensive immunosuppression for lupus nephritis? Real-world evidence from the STAR cohort

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OBJECTIVE: While guidelines advocate renin-angiotensin system inhibitors (RASi) for renoprotection in lupus nephritis (LN), evidence is largely extrapolated from non-lupus populations. Evidence specifically evaluating RASi efficacy during the intensive induction phase of active LN remains scarce. This study aimed to evaluate the real-world impact of adding RASi to standard induction therapy on renal remission and glucocorticoid tapering in LN. METHODS: This retrospective cohort study used data from the STAR (Treat-SLE-to-Target) registry. Patients receiving ≥3 months of continuous RASi during induction were classified as RASi, while those without RASi exposure during follow-up were classified as non-RASi. Propensity score overlap weighting was applied to balance baseline characteristics. The primary endpoints were rates of complete renal remission (CRR) at 12 months. Secondary endpoints included total renal remission (TRR), the magnitude and rate of proteinuria reduction and glucocorticoid dosage. RESULTS: Among 314 patients, 220 received RASi and 94 did not. The RASi group had higher baseline 24-hour urinary protein and hypertension prevalence. After weighting, characteristics were balanced. Weighted analyses showed no significant difference in CRR at 12 months (58.7% vs 64.7%, p=0.428) or 6 months (43.1% vs 53.4%, p=0.169). Conversely, 6-month TRR was significantly lower in the RASi group (59.0% vs 76.8%, p=0.026). Proteinuria percentage reduction was comparable between groups, and RASi use was not associated with accelerated glucocorticoid tapering or more rapid decline in disease activity. Multivariable analysis identified LN at SLE onset and baseline pyuria as independent predictors of CRR, but not RASi usage. CONCLUSION: Adding RASi to standard induction therapy provided no additive benefit for renal remission or proteinuria reduction within the first 12 months nor did it facilitate glucocorticoid tapering. The haemodynamic antiproteinuric effects of RASi appear overshadowed by potent anti-inflammatory treatment during active LN.

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