Enhancing Lupus Nephritis Outcomes: The Potential Impact of Lower Glucocorticoid Doses

Lupus nephritis (LN) is a severe kidney condition caused by systemic lupus erythematosus, a disease affecting more than 200,000 individuals in the United States. While systemic lupus erythematosus is more prevalent among women and individuals of African or Asian descent, LN occurs more commonly in men than women.

Traditional LN treatment involves initiating oral glucocorticoids (GC) at doses up to 1 mg/kg/day of prednisone equivalent, often preceded by intravenous methylprednisolone pulse therapy. While effective due to their anti-inflammatory and immunosuppressive properties, GCs can also lead to adverse effects in patients.

Recent clinical guidelines for LN management recommend starting at a lower oral GC dose after intravenous pulse therapy to mitigate potential serious adverse effects. However, there were no direct comparative studies evaluating the clinical efficacy and safety of low versus high starting oral GC dosage. To address this gap, Buyon et al. conducted a pooled analysis of standard of care (SOC) trial arms from high-quality randomized controlled trials (RCTs), with their findings published in Lupus Science and Medicine in January 2024.

Comparing GC doses

The authors performed a pooled analysis of nine RCTs, comparing the effects of low-dose (<0.5 mg/kg/day) and high-dose (>0.5 mg/kg/day to <1 mg/kg/day) starting oral GC. The analysis included 417 patients from five studies with low-dose GC following intravenous pulse and 521 patients from four studies with high-dose GC.

Patient outcomes were evaluated by complete renal response (CRR) and partial renal response (PRR) at 12 months. CRR was defined as a urine protein-creatinine ratio (UPCR) of less than 0.5 mg/mg, whereas PRR was generally characterized by a UPCR improvement of at least 50 percent.

Key findings

The results demonstrated no statistically significant difference in renal outcomes at 12 months between the two initial oral GC dosing regimens. Specifically:

• CRR rates: 25.2 percent of patients in the low-dose GC group achieved CRR, compared to 27.2 percent in the high-dose GC group.
• CRR or PRR rates: 48.7 percent of patients in the low-dose GC group achieved either CRR or PRR, compared to 43.6 percent in the high-dose GC group.

However, patients who initiated with low-dose oral GC had significantly fewer serious adverse events than those in the high-dose GC group (19.4 percent vs. 31.6 percent). Infection-related serious adverse events were also less frequent in the low-dose GC group (9.8 percent vs. 16.5 percent).

These findings reinforce the guideline-recommended strategy of initiating LN treatment with low-dose oral GC after intravenous pulse therapy. Notably, the authors emphasize that intravenous pulse therapy with methylprednisolone is likely still necessary to maintain treatment efficacy when starting oral glucocorticoids at a low dose. Additionally, the lower incidence of serious adverse events and infection-related complications further supports the transition to the low-dose initial GC approach without compromising renal outcomes.

References

Centers for Disease Control and Prevention. (2024, May 15). People with lupus. https://www.cdc.gov/lupus/data-research/index.html

Mejía-Vilet, J. M., & Ayoub, I. (2021). The Use of Glucocorticoids in Lupus Nephritis: New Pathways for an Old Drug. Frontiers in Medicine, 8, 622225. https://doi.org/10.3389/fmed.2021.622225

National Institute of Diabetes and Digestive and Kidney Diseases. (2017, January). Lupus and kidney disease (lupus nephritis). https://www.niddk.nih.gov/health-information/kidney-disease/lupus-nephritis

Saxena, A., Sorrento, C., Izmirly, P., Sullivan, J., Gamez-Perez, M., Law, J., Belmont, H. M., & Buyon, J. P. (2025). Low versus high initial oral glucocorticoid dose for lupus nephritis: a pooled analysis of randomised controlled clinical trials. Lupus Science & Medicine, 12(1), e001351. https://doi.org/10.1136/lupus-2024-001351