Urinary immune mediators may reflect renal inflammation in patients with active lupus nephritis

Introduction: Lupus nephritis (LN) affects 40-75% of patients with systemic lupus erythematosus (SLE). Active LN is characterized by renal inflammation, often clinically manifested by the development of proteinuria and hematuria, and it is measured by the renal domain of disease activity score (R-SLEDAI-2K). Elevated urinary levels of immune mediators, such as CCL-2/MCP-1, IL-6, and CXCL-10 have been observed in SLE, but it is not clear if these alterations are associated with disease activity and LN development. Aims: To analyze urinary immune mediators as possible kidney injury biomarkers in patients with active LN. Methods: A cross-sectional study was performed with urine samples from SLE patients (IRB # 60747722.2.0000.5243). SLE and kidney activity were measured using SLEDAI-2K (cut-off point ≥5) and R-SLEDAI indexes (cut-off point ≥4), respectively. The first morning midstream urine was collected, immediately processed (2,000xg 5 min) and stored at -80°C. After thawing, urinary immune mediators were quantified using a multiplex assay. Results: We studied 55 SLE patients (43.3±13.7 years, 92.7% female), with a disease diagnosis time of 10.1±6.8 years and 56.4% with LN. We observed that patients with active LN presented higher urinary levels of interleukin (IL)-6, -8, and CCL-2 (P<0.05). Also, we found that urinary IL-6, IFN-γ, and CCL-5 were significantly correlated with SLEDAI-2K and IL-6 correlated with R-SLEDAI-2K in active LN. Also in this group, the immune mediators IL-13, IFN-γ, CCL-2, and CCL5 were negatively correlated with serum levels of the complement fraction C3. Conclusions: Patients with active SLE and LN present high urinary levels of immune mediators. Also, pro-inflammatory cytokines and chemokines are correlated with the lupus activity index and with complement C3, possibly playing a role in the amplification of renal inflammation.