Association of Urinary Matrix Metalloproteinase 7 with Incident Renal Flare in Lupus Nephritis

OBJECTIVES Flares of lupus nephritis (LN) are frequent and associated with impaired renal prognosis. One major management obstacle in LN flare is the lack of effective methods to identify at-risk patients earlier in their disease course. Here, we test the utility of urinary matrix metalloproteinase 7 (uMMP7) for dynamically surveillance of renal disease activity and prediction of renal flares in LN. METHODS A prospective, two-stage cohort study was performed in patients with LN. uMMP7 level at biopsy was evaluated in 154 newly-diagnosed patients of two independent cohorts, and were compared with renal histological activity. Furthermore, after a minimum of 12-month renal remission, uMMP7 was monitored bimonthly for 2 years in 65 LN participants. The association between uMMP7 level and development of LN flare was analyzed. RESULTS uMMP7 levels elevated in patients with LN. A higher uMMP7 level in LN was associated with greater renal histological activity. For identifying LN with greater renal histological activity (histological activity index≥7), uMMP7 outperformed clinical markers and improved their performances, linking uMMP7 level to renal disease activity. Furthermore, among patients who had follow-up uMMP7 measurement after long-term renal remission, an elevated uMMP7 during follow-up was independently associated with an increased risk of LN flare. This elevation in uMMP7 hinted a LN flare prior to current laboratory measures. Inclusion of uMMP7 to clinical measures improved the prognostic value for LN flares. CONCLUSION uMMP7 level in LN correlates with renal histological activity. An elevated uMMP7 after renal remission is associated with incident renal flare.