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

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 ### Competing Interest Statement Grant funding for research but no other competing interest ### Funding Statement This work was supported by the Thailand Research Fund (grant number MRG6180158); the National Science and Technology Development Agency and the Health Systems Research Institute (grant number FDA-CO-2562-9090-TH). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: the Research Ethics Review Committee for Research Involving Human Subjects of Chulalongkorn University gave ethical approval for this work IRB No. 178/61 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors