#1583 Urinary exosome miRNAs as biomarkers associated with proteinuria and eGFR in lupus nephritis

Abstract Background and Aims Lupus nephritis (LN) is a life-threatening disorder characterized by a relapsing-remitting disease course necessitating immunosuppression to control disease activity. Urinary exosome microRNAs (miRNAs) were previously tested as biomarkers for fibrosis and inflammatory pathways in different kidney diseases, including LN. Method Small RNA sequencing was conducted on urinary exosome miRNAs in 93 patients with ISN/RPS class III/IV ± V LN from a trial with the anti-CD40 mAB BI655064*. Univariable and multivariable regression models were used to identify associations between miRNAs and spot urine protein/urine creatinine ratio (UP/UC, log-transformed), and eGFR, at time of randomization into the study. Results MiRNAs with high correlation (P < 0.01) in the univariable analysis are listed in Table 1 for UP/UC and in Table 2 for eGFR. A multivariable model selection procedure, taking also into account the correlation between individual miRNAs, revealed an association between miR-143-3p, miR-510-5p, miR-429, miR-509-5p, miR-10b-5p, miR-9-3p, miR-509-3p, miR-411-5p, miR-574-5p, and miR-3182 and UP/UC (model R2 = 0.613). Likewise, miR-17-5p, miR-101-3p, miR-146b-5p, miR-3173-3p, miR-545-3p, miR-6790-3p were associated with eGFR (model R2 = 0.453). Distinct miRNAs are known to play key functions during the disease progression of renal diseases (Tables 1 and 2). Conclusion Urinary exosome miRNAs might serve as mechanistic supportive biomarkers associated with proteinuria and eGFR in LN and might have the potential to be used as biomarkers to monitor treatment effects in clinical trials. *Arthritis Rheumatol. 2023 Nov;75(11):1983-1993.