Glucocorticoid reduction in Glomerular Diseases

TL;DR

This paper reviews how reducing glucocorticoid use in glomerular diseases can maintain treatment effectiveness while minimizing side effects.

Contribution

The paper synthesizes evidence on glucocorticoid-sparing strategies across various glomerular diseases, highlighting efficacy and safety of reduced-dose regimens.

Findings

Reduced-dose glucocorticoids in AAV preserve efficacy and lower infection risk.

Combination therapies in MCD and LN allow for steroid sparing and faster remission.

IgAN treatment is shifting away from glucocorticoids with novel immunomodulatory agents.

Abstract

Glucocorticoids (GCs) remain central to the management of many glomerular diseases, providing rapid and potent antiinflammatory effects. However, their well-recognized toxicities have driven growing efforts to reduce cumulative exposure. This review synthesizes evidence from randomized and key noncontrolled studies evaluating GC-sparing strategies across diseases where these agents have historically played a central therapeutic role. In antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), large trials such as the Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis (PEXIVAS) trial and the Effect of Reduced-Dose versus High-Dose Glucocorticoids Added to Rituximab (LoVAS) trial demonstrate that reduced-dose regimens preserve efficacy while lowering infection risk. In lupus nephritis (LN), lower-dose strategies and early use of multipronged regimens incorporating targeted agents such as belimumab, calcineurin inhibitors, or obinutuzumab support faster tapering. In minimal change disease (MCD), combination approaches with calcineurin inhibitors or mycophenolate achieve remission with less steroid exposure. In IgA nephropathy (IgAN), practice is increasingly shifting away from GC use altogether, as novel immunomodulatory agents targeting disease-specific pathways are integrated into care. Although GCs will likely remain essential for induction in select inflammatory glomerulopathies, their role can increasingly be narrowed to early, time-limited use. Future studies should address key uncertainties, particularly the optimal use of i.v. methylprednisolone in rapidly progressive presentations and evaluate the safety and efficacy of even lower-dose regimens.

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