Urinary CXCL-10/IP-10 and MCP-1 as markers to assess activity of lupus nephritis

Abstract

IP-10 and MCP-1 are pro-inflammatory chemokines which are involved in the immunopathogenesis of lupus nephritis and may thus be useful biomarkers. SLE patients fulfilling ACR 1997 criteria were included. SLEDAI was calculated and blood and urine samples collected. Active lupus was defined as SLEDAI ≥4. Active patients were divided into active renal (proteinuria ≥ 500 mg/day or active sediment in urine) and active non-renal lupus. Patients with active renal lupus were followed until the nephritis became inactive, when a second sample was collected. Serum and urinary levels of MCP-1 and IP-10 (pg/ml) were measured by ELISA. Urinary values were normalized for urinary spot creatinine (in mg/dL. Thus the values were expressed as pg/mg creatinine × 100 creatinine). A total of 136 patients with SLE including 78 active (46 active renal and 32 active non-renal) were included. Median age was 25 (10-55) years and SLE duration was 23 (six to 48) months. Both serum (data not shown) and urinary levels of MCP-1 (35.2 (12.7-71.7), 9.4 (4.4-17), p < 0.001) and IP-10 (9.5 (4.4-17.9), 3.9 (1.9-9.3), p < 0.001) were higher in active compared to inactive SLE. However, in active renal compared to active non-renal SLE, there was no difference in serum levels; only urinary levels of MCP-1 (46.2 (19.9-125), 12.7 (5.8-43.9), p < 0.001) and IP-10 (12.5 (5.6-22.7), 5.2 (2.3-12.2), p < 0.05) were higher. On longitudinal follow-up of active renal patients (n = 24), there was a decrease in urinary levels of MCP-1 and IP-10 (p = 0.005). On ROC analysis, urinary MCP-1 outperformed C4 and urinary IP-10, but was similar to dsDNA and C3 in differentiating active renal from non-renal SLE. Urinary and serum IP-10 and MCP-1 are potentially useful markers of lupus activity; however, only the urinary levels are indicative of renal activity. However, on ROC analysis, they are not better than conventional markers.