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.