Predictive Factors for Glucocorticoid-Free Remission in Lupus Nephritis

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Predictive Factors for Glucocorticoid-Free Remission in Lupus Nephritis

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Co-author 1

Ryota Sakai r_sakai@saitama-med.ac.jp Saitama Medical Center, Saitama Medical University Department of Rheumatology and Clinical Immunology Kawagoe Japan *

Co-author 2

Taiji Kosaka taiji-k@saitama-med.ac.jp Saitama Medical Center, Saitama Medical University Department of Rheumatology and Clinical Immunology Kawagoe Japan -

Co-author 3

Takumi Aoki takumafu@saitama-med.ac.jp Saitama Medical Center, Saitama Medical University Department of Rheumatology and Clinical Immunology Kawagoe Japan -

Co-author 4

Yuri Sasaki yuri614@saitama-med.ac.jp Saitama Medical Center, Saitama Medical University Department of Rheumatology and Clinical Immunology Kawagoe Japan -

Co-author 5

Shoichi Yoshinaga s_yoshin@saitama-med.ac.jp Saitama Medical Center, Saitama Medical University Department of Rheumatology and Clinical Immunology Kawagoe Japan -

Co-author 6

Akiko Shibata a_shiba@saitama-med.ac.jp Saitama Medical Center, Saitama Medical University Department of Rheumatology and Clinical Immunology Kawagoe Japan -

Co-author 7

Takahiko Kurasawa t_kura@saitama-med.ac.jp Saitama Medical Center, Saitama Medical University Department of Rheumatology and Clinical Immunology Kawagoe Japan -

Co-author 8

Koichi Amano amanokoi@saitama-med.ac.jp Saitama Medical Center, Saitama Medical University Department of Rheumatology and Clinical Immunology Kawagoe Japan -

Co-author 9

Hironari Hanaoka hhanaoka@saitama-med.ac.jp Saitama Medical Center, Saitama Medical University Department of Rheumatology and Clinical Immunology Kawagoe Japan -

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

Glucocorticoids (GCs) are essential for induction therapy in lupus nephritis (LN), but they also contribute to long-term organ damage, metabolic complications, infections, and a reduced quality of life. The KDIGO 2024 guideline recommends tapering GCs to the lowest possible dose and considering discontinuation after ≥12 months of complete renal remission, reflecting a growing consensus toward GC withdrawal once remission is stable.
However, evidence on GC discontinuation in LN, especially among Asian and Japanese populations, remains scarce. Moreover, while clinical trials have examined rapid tapering, few studies have assessed long-term outcomes or predictors of successful GC withdrawal in real-world settings.
This study investigated the clinical factors associated with achieving and maintaining GC-free remission in Japanese patients with LN treated at a tertiary referral center.

Methods

We retrospectively analyzed patients diagnosed with class III, IV, or V LN at our institution between 2000 and 2024. All patients received induction therapy consisting of immunosuppressants combined with prednisolone (PSL) at a dose of≥0.5 mg/kg/day and were followed for a period of≥12 months. Complete remission (CR) was defined as a urine protein-to-creatinine ratio (UPCR) < 0.5 g/gCr, estimated GFR ≥ 60 mL/min/1.73 m² or within 10% of baseline, and no PSL re-escalation. GC-free remission was defined as sustained CR without relapse for ≥ 2 years after GC discontinuation. Predictive factors for achieving GC-free remission were explored using Cox proportional hazards analysis.

Results

Among 148 patients (median follow-up 105.5 months [54.2–160.8]), 41 (27.8%) achieved GC-free remission (Figure 1). Compared with non-achievers, GC-free achievers more frequently received methylprednisolone intravenous pulses (HR 2.58, 95% CI 1.15–5.78, p = 0.0212) and hydroxychloroquine (HR 4.01, 95% CI 1.37–11.77, p = 0.0114), and were more likely to have tapered PSL to ≤ 7.5 mg/day at 12 months (HR 2.57, 95% CI 1.21–5.46, p = 0.0138).

Conclusion

Methylprednisolone intravenous pulses, concomitant hydroxychloroquine use, and tapering PSL to ≤ 7.5 mg/day within 12 months are associated with achieving GC-free remission in LN. These findings support the clinical feasibility of GC-free management in appropriately selected patients with LN.

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