Measurements of urinary biomarkers at 2 years following a lupus nephritis flare are associated with subsequent renal outcomes

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.