Abstract: FR-OR084
Urinary Soluble CD163: A Non-Invasive Biomarker of Activity for Lupus Nephritis
Session Information
- Lupus and Then Some
November 08, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
Abstract Time: 05:06 PM - 05:18 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Mejia-Vilet, Juan M., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, Mexico
- Zhang, Xiaolan, Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Cano verduzco, Mayra Lizbeth, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Toriello Guerra, Mexico
- Cruz, Cristinoc, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Toriello Guerra, Mexico
- Shapiro, John P., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Morales-Buenrostro, Luis E., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, Mexico
- Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Background
Distinction between lupus nephritis (LN) patients with active inflammation and those with chronic kidney damage is challenging. Soluble CD163 derives from cleavage of the CD163 M2c-macrophage receptor, can be quantified in urine and may reflect intra-renal inflammation. We tested urine sCD163 as a biomarker of LN activity.
Methods
The cross-sectional diagnostic yield and the longitudinal course of urinary sCD163 (usCD163) was assessed in two large LN cohorts. We recruited 113 (Mexican cohort) and 129 (OSU cohort) active LN (aLN) patients with prospective follow-up. Patients with other diseases, inactive LN (iLN), and healthy donors were included as controls. ROC curves were obtained from the cross-sectional data. Then 86 LN flares from the Mexican and the OSS study cohort were followed with repeated samples and response to therapy (RTT) evaluated at 6- and 12-months. Linear mixed models were fitted to evaluate the association between usCD163 and RTT.
Results
The highest levels of usCD163 were found in aLN in the Mexican (1805ng/mmol, 760-4334) and OSU (1358ng/mmol, 811-2356) cohorts compared to iLN (10ng/mmol, 0-40, p<0.001) and other diseases. UsCD163 was higher in class IV Vs. other classes and correlated with the histologic activity index (r=+0.527, p<0.001). A usCD163>100ng/mmol differentiated aLN from iLN with 95% sensitivity and 93% specificity. UsCD163 increased from 6-months pre-flare to flare and then diminished to <500ng/mmol at 12 months in 88% of RTT, while usCD163 remained >500ng/mmol at 12-mo in 88% of non-responders. Diagnostic yield of usCD163 to discriminate 12-month RTT was better than that of currently-used biomarkers (Table 1). After adjusting for other predictors, the usCD163 slope was associated with RTT.
Conclusion
UsCD163 reflects LN renal inflammation and varies over time with LN activity and treatment. Its levels increase pre-flare and then parallel RTT, being independently associated with response to therapy.
Diagnostic performance of usCD163 and serological biomarkers to discriminate 12-month responders from non-responders
| Sensitivity | Specificity | PPV | NPV | +LR | -LR | |
| usCD163<500 ng/mmol | 0.88 | 0.88 | 0.92 | 0.83 | 7.52 | 7.65 |
| dsDNA-Ab disappearance | 0.60 | 0.65 | 0.72 | 0.51 | 1.69 | 1.60 |
| C3 normalization | 0.60 | 0.65 | 0.72 | 0.51 | 1.69 | 1.60 |
| C4 normalization | 0.46 | 0.50 | 0.61 | 0.36 | 0.92 | 0.93 |
Funding
- Other NIH Support