Urinary Serpin-A3 is an Early Predictor of Clinical Response to Therapy in Patients with Proliferative Lupus Nephritis

BACKGROUND: Serpin-A3 is a regulator of different inflammatory processes, however its role in the kidney is unknown. We previously reported that urinary Serpin-A3 excretion (uSerpA3) is significantly elevated in patients with active lupus nephritis (LN) and rats with Chronic Kidney Disease (CKD). OBJECTIVE: Determine the association between uSerpA3 temporal course during the 1st -year of treatment and response to therapy in patients with proliferative LN. HYPOTHESIS: uSerpA3 will correlate with kidney inflammation and will predict poor response to therapy. METHODS: This is an observational longitudinal study including sixty Mexican adults with proliferative LN followed during the 1st -year after LN-flare. uSerpA3 at flare and after 3, 6, and 12 months was evaluated semiquantitatively through Western blot; histological evaluation was performed by kidney biopsy. OUTCOME: Response to therapy 1-year after the LN-flare. Relation between uSerpA3 and histopathologic characteristics at flare was evaluated cross-sectionally; the temporal association between uSerpA3 and response to therapy was analyzed with linear mixed models; prognostic performance for clinical response was evaluated with ROC analysis. RESULTS: Among the 60 patients studied, 21 (35%) were class III and 39 (65%) class IV. The class IV LN had higher serum creatinine, lower C3 levels, and higher histological activity and chronicity indexes. The uSerpA3 was higher in class IV than in class III LN (6.98 vs. 2.89 DPI/mg-creatinine, p=0.01). Furthermore, uSerpA3 had a mild correlation with the histological activity index (r=0.29, p=0.02). There was a significant association between the temporal course of uSerpA3 and the response to therapy. Responders showed a significant drop in uSerpA3 at 6th -month compared to LN-flare (p<0.001), while non-responders persisted with elevated uSerpA3. Moreover, uSerpA3 was significantly lower at flare in responders compared to non-responders (2.69 vs 6.98 DPI/mg-creatinine, p<0.05). Furthermore, uSerpA3 was able to identify non-responders since the 3rd -month after LN-flare, (AUC=0.77). CONCLUSIONS: uSerpA3 is an early indicator of kidney inflammation and a potential predictor of long-term response to therapy in patients with proliferative LN. © FASEB.