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Abstract: PO1928

Urine Epidermal Growth Factor Levels Are Associated with Kidney Prognosis in Lupus Nephritis

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Mejia, Juan M., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, CDMX, Mexico
  • Shapiro, John P., The Ohio State University Wexner Medical Center Dorothy M Davis Heart and Lung Research Institute, Columbus, Ohio, United States
  • Zhang, Xiaolan, The Ohio State University Wexner Medical Center Dorothy M Davis Heart and Lung Research Institute, Columbus, Ohio, United States
  • Cruz, Cristinoc, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, CDMX, Mexico
  • Zimmerman, Grant R., The Ohio State University Wexner Medical Center Dorothy M Davis Heart and Lung Research Institute, Columbus, Ohio, United States
  • Méndez, Rossa Angelica, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, CDMX, Mexico
  • Parikh, Samir V., The Ohio State University Wexner Medical Center Dorothy M Davis Heart and Lung Research Institute, Columbus, Ohio, United States
  • Nagaraja, Haikady N., Department of Biostatistics, School of Public Health, The Ohio State University, Columbus, Ohio, United States
  • Morales-Buenrostro, Luis E., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, CDMX, Mexico
  • Rovin, Brad H., The Ohio State University Wexner Medical Center Dorothy M Davis Heart and Lung Research Institute, Columbus, Ohio, United States
Background

Epidermal growth factor is a protein specifically synthesized in the kidneys. EGF urine levels have been associated with progressive chronic kidney disease. This study evaluated the role of urine epidermal growth factor (uEGF) as a biomarker of chronic kidney damage in lupus nephritis (LN).

Methods

Through a proteomic approach we identified uEGF as a biomarker of interest in an LN discovery cohort. The expression of uEGF was characterized in two large multiethnic LN cohorts, and the association between uEGF at flare and long-term outcomes assessed in a subset of 120 patients. The expression of uEGF over time was observed in two longitudinal LN cohorts in which serial urine samples were collected.

Results

The proteomic analysis showed lower uEGF in patients with active LN than in normal controls. The peptide sequence was consistent with the proEGF isoform, and this was confirmed by immunoblotting. These findings were verified by ELISA. Patients with active LN had a significantly lower levels of uEGF than patients with active non-renal lupus, patients with inactive lupus, and kidney donors. Urine EGF was inversely correlated with the kidney biopsy chronicity index (r=-0.67, p<0.001). Multivariate survival analysis showed that uEGF at flare was associated with the time to doubling of serum creatinine (HR 0.88, 95% CI 0.77-0.99, p=0.045). In patients who progressed to doubling of serum creatinine (Figure 1A) and end-stage kidney disease (Figure 1B), uEGF was lower at flare and then decreased over the 12 months following flare. A uEGF cutoff <5.3ng/mg identified all patients who progressed to end-stage kidney disease.

Conclusion

Urine EGF levels correlate with histologic kidney damage. Low uEGF levels at flare and decreasing uEGF levels over time are associated with adverse long-term kidney outcomes.

Urine EGF course in patients with stable kidney function compared to patients who progressed to doubling of serum creatinine (A) or end-stage kidney disease (B).

Funding

  • Other NIH Support