Urine γ-interferon-inducible protein (IP-10) as a biomarker of histological activity of lupus nephritis

Abstract Introduction Conventional markers are not reliable predictors of histological activity of lupus nephritis (LN). We aimed to examine the utility of urine γ-interferon-inducible protein (IP-10) in predicting LN flares, diagnosis of LN, and forecasting treatment response. Methods SLE patients who fulfilled the ACR 1997 criteria with history of LN were enrolled. Urine IP-10 was measured at least once during routine quarterly visits, at the time of diagnosis of active LN, and monthly during induction therapy for 6 months. Results There were 65 active LN and 46 inactive LN included. The mean urine IP-10 levels among the active and inactive LN were 2.69 (95%CI 2.53-2.86) and 2.18 (95%CI 1.96-2.39) log copies/mcg total RNA respectively (p-value < 0.0001). Clinicopathological discordance was observed in 9 of 55 (16%) biopsied patients (5 with proliferative LN without proteinuric flare and 4 with nephrotic-range proteinuria from glomerulosclerosis). Urine IP-10 predicted histological activity of LN with 91% accuracy, compared to 84% with proteinuric flare. Within two years, half of the clinically inactive LN patients with positive baseline urine IP-10 developed LN flare, whereas no flares were observed in patients with negative baseline urine IP-10. Urine IP-10 levels were not associated with treatment response at 6 months. Conclusion Urine IP-10 may reflect histological activity of LN more accurately than conventional markers, especially in patients with clinicopathologic discrepancy. Clinically inactive LN patients with positive urine IP-10 were at a higher risk of developing LN flare. Key messages - The majority of the studies on novel biomarkers in LN lacked renal biopsy and relied on clinical indicators to determine histological activity. As a result, the validity of these studies may be jeopardized. - According to this study, clinicopathological discordance was found in 16% of LN patients who underwent renal biopsy. Urine IP-10 outperformed urinary protein level in differentiating histologically active LN from inactive LN (accuracy 91% versus 84%). - Within two years, half of the clinically inactive LN patients who had positive urine IP-10 developed LN flares, whereas none of those who had negative urine IP-10 did. - Urine IP-10 may aid in the diagnosis of histologically active LN, particularly in patients with clinicopathologic discrepancy. Urine IP-10 monitoring in clinically inactive LN patients may predict the risk of future LN flares.