Urinary Soluble CD163: a Novel Noninvasive Biomarker of Activity for Lupus Nephritis.

Significance Statement Although many biomarkers have been tested in lupus nephritis, none have advanced to clinical practice. Treatment is often guided by the level of proteinuria, which lacks the necessary sensitivity to differentiate disease activity from chronic damage to the kidneys. The authors evaluated urinary CD163 as an activity biomarker of lupus nephritis in two large multiethnic populations, with longitudinal follow-up of biomarker expression and testing against clinical and histologic disease activity. They demonstrated that urinary CD163 correlated with disease severity, lupus nephritis class, and histologic activity. Furthermore, the course of urinary CD163 in response to treatment discriminated among response groups and faithfully reflected the disease?s histologic activity in repeated kidney biopsies. These findings suggest that urinary CD163 shows promise as a biomarker reflecting histologic inflammation in lupus nephritis. Background Clinical distinction between patients with lupus nephritis who have active inflammation or chronic kidney damage is challenging. Studies have shown soluble CD163, which derives from cleavage of the CD163 M2c macrophage receptor and can be quantified in urine, correlates with active lupus nephritis. Methods We measured urine CD163 at lupus nephritis flares in patients from a Mexican cohort and cross-sectional and longitudinal United States cohorts. We also performed serial urine CD163 measurements during the treatment of flares in a subset of patients from the Mexican and longitudinal United States cohorts, and assessed response to therapy at 12 months. In addition, we evaluated urinary CD163 agreement with histologic activity in 19 patients from the Mexican cohort who had repeated kidney biopsies on follow-up. Results Urinary CD163 levels were significantly higher in patients with active lupus nephritis than in patients with active extrarenal SLE, inactive SLE, and other glomerular diseases, and correlated with disease clinical severity, histologic class, and the histologic activity index. Urinary CD163 increased from 6 months preflare to flare, diminishing progressively in complete and partial responders, whereas it remained elevated in nonresponders. Urinary CD163 <370 ng/mmol at 6 months predicted complete renal response at 12 months with >87% sensitivity and >87% specificity. Urinary CD163 <370 ng/mmol or >370 ng/mmol perfectly agreed (?=1.0) with a histologic activity index ?1 or >1 in repeated biopsies, respectively. Evaluation of urinary CD163 in patients with persistent proteinuria at 6 months improved the prediction of who would achieve complete renal response at 12 months. Conclusions Urinary CD163 reflects histologic inflammation in lupus nephritis and is a promising activity biomarker that varies over time with lupus nephritis activity and treatment.