Biomarker studies
Measurements of urinary biomarkers at 2 years following a lupus nephritis flare are associated with subsequent renal outcomes
Ryan Baker, 1 Laura Patricia Whittall Garcia , 1,2,3,4 Qixuan Li, 2,5 Michael Kim, 1 Dennisse Bonilla, 1,2 Dafna D Gladman , 1,2,3,4 Murray Urowitz , 1,2,3,4 Zahi Touma , 1,2,3,4 Joan Wither 1,3,4,6
To cite: Baker R, Whittall Garcia LP, Li Q, et al . Measurements of urinary biomarkers at 2 years following a lupus nephritis flare are associated with subsequent renal outcomes. Lupus Science & Medicine 2026; 13 :e001724. doi:10.1136/ lupus-2025-001724 ► Additional supplemental material is published online only. To view, please visit the journal online (https://doi.org/10.1136/ lupus-2025-001724).
ABSTRACT Objective To determine if the levels of five urinary biomarkers (UBs), including cluster of differentiation 163 (CD163), monocyte chemoattractant protein-1 (MCP-1), adiponectin, soluble vascular cell adhesion molecule and platelet factor 4 (PF4), measured 24 months after a lupus nephritis (LN) flare are associated with adverse long-term outcomes. Methods We included patients with an LN flare who had a preflare estimated glomerular filtration rate (eGFR) ≥60 mL/min and stored urine 24±3 months after the flare. The following outcomes were then examined: (1) time to a subsequent LN flare and (2) time to 30% sustained decline in eGFR. UBs were measured by ELISA 24±3 months after the LN flare. The results were normalised to urine creatinine and expressed as pg per mmol of urine creatinine. Results 69 patients with LN were included, the median (IQR) follow-up time after their 24-month urinary sample collection was 129 (97.5–150) months. 50 patients achieved a primary efficacy renal response 24 months after the LN flare. This subcohort of patients had significantly lower UB levels. In this subcohort, 27 (54%) experienced a subsequent LN flare with a median time to flare (IQR) of 3.5 (1.67–6.87) years, and 10 (20%) had a 30% decline in eGFR at a median time of 4.38 (3.73–5.33) years after their 24-month urinary sample collection. Elevated levels of MCP-1 (HR 1.40 (1.11–1.76), p=0.004) and CD163 (HR 1.14 (1.00–1.38), p=0.01) predicted a subsequent LN flare. While CD163 (HR 1.16 (1.02–1.32), p=0.02), MCP-1 (HR 1.33 (1.01–1.74), p=0.04), adiponectin (HR 2.67 (1.68–2.46), p<0.001) and PF4 (HR 1.14 (1.04–1.25), p=0.002) predicted a 30% decline in eGFR. Conclusion UBs measured 24±3 months after an LN flare were associated with subsequent flares and a clinically meaningful decline in kidney function.
advancements in the treatment of LN, long- term renal outcomes remain suboptimal, with 30–40% of patients experiencing subsequent LN flares and 15% progressing to end-stage renal disease (ESRD). 1–5 This holds true even for patients with good clinical control, as 20–30% who achieve a primary efficacy renal response (PERR) or complete renal response still develop progressive renal damage. 5 6 Patients with LN who have persistent histo- logical activity on a repeat kidney biopsy (KB) performed once they have achieved clinical remission are at a higher risk of subsequent LN flares. 7 8 Similarly, Parodis et al 9 showed that patients with high activity index scores on per-protocol repeat KBs conducted 24 months after an LN flare were at increased risk of expe- riencing a subsequent LN flare, regardless of ⇒ Urinary biomarkers measured 24 months after an LN flare could serve as useful biomarkers to identi- fy patients at a high risk of adverse long-term renal outcomes, who may have ongoing subclinical in- flammation requiring additional therapy. WHAT IS ALREADY KNOWN ON THIS TOPIC ⇒ Despite advancements in the management of lupus nephritis (LN), long-term renal outcomes remain suboptimal. Approximately 30–40% of patients ex- perience recurrent LN flares, and 15% progress to end-stage renal disease. Studies have shown that patients who exhibit persistent histological activity on a repeat kidney biopsy, despite achieving clinical remission, are at increased risk for future LN flares. WHAT THIS STUDY ADDS ⇒ Elevated levels of several specific urinary biomark- ers measured 24 months after an LN flare were associated with subsequent flares and a clinically meaningful decline in kidney function. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
RB and LPWG contributed equally.
RB and LPWG are joint first authors.
Received 29 June 2025 Accepted 2 February 2026
For numbered affiliations see end of article. permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. Correspondence to Dr Joan Wither; joan.wither@ uhn.ca © Author(s) (or their employer(s)) 2026. Re-use
INTRODUCTION SLE is a chronic multisystem inflammatory disease commonly affecting the kidney, with 50–60% of patients developing lupus nephritis (LN) over the disease course. 1 2 Despite
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Baker R, et al . Lupus Science & Medicine 2026; 13 :e001724. doi:10.1136/lupus-2025-001724
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