Immune-Related Urine Biomarkers for the Diagnosis of Lupus Nephritis

Abstract

The kidney is one of the main organs affected by the autoimmune disease systemic lupus erythematosus. Lupus nephritis (LN) concerns 30-60% of adult SLE patients and it is significantly associated with an increase in the morbidity and mortality. The definitive diagnosis of LN can only be achieved by histological analysis of renal biopsies, but the invasiveness of this technique is an obstacle for early diagnosis of renal involvement and a proper follow-up of LN patients under treatment. The use of urine for the discovery of non-invasive biomarkers for renal disease in SLE patients is an attractive alternative to repeated renal biopsies, as several studies have described surrogate urinary cells or analytes reflecting the inflammatory state of the kidney, and/or the severity of the disease. Herein, we review the main findings in the field of urine immune-related biomarkers for LN patients, and discuss their prognostic and diagnostic value. This manuscript is focused on the complement system, antibodies and autoantibodies, chemokines, cytokines, and leukocytes, as they are the main effectors of LN pathogenesis.

Keywords: Lupus nephritis; immune effector; non-invasive diagnosis; urine biomarkers.

Figure 1

Physiopathology of LN and urine biomarkers. Renal damage in LN is mediated by the infiltration of effector leukocytes, autoantibody binding to nuclear and non-nuclear autoantigens, and generation of IC. These IC are deposed in the glomeruli, affecting the kidney function and leading to an inflammatory cascade. Consequently, filtering of the blood is hindered, and many immune-related cells and molecules involved in the inflammatory response may be excreted into urine. Assessment of these molecules in urine may help to predict the development of LN, renal flares, as well as response to treatment. GBM: Glomerular basement membrane; IC: immune complex; DC: dendritic cell; FLC free light chains.