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Abstract: FR-PO885

A Urine Biomarker of Renal Prognosis in Lupus Nephritis

Session Information

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
  • Shapiro, John P., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Song, Huijuan, Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Cruz, Cristinoc, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, Mexico
  • Parikh, Samir V., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Cano verduzco, Mayra Lizbeth, 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

Urine epidermal growth factor (uEGF) has been described as a biomarker of progressive kidney failure in adults with glomerular diseases. Through an agnostic proteomic approach, we found decreased urinary pro-epidermal growth factor (EGF) levels in LN patients. Here we verified and evaluated uEGF as a biomarker of chronic kidney damage in lupus nephritis (LN).

Methods

Pro-uEGF was detected by urine proteomics in LN patients from the Ohio SLE Study. Then uEGF was measured by ELISA in two independent cohorts (US [n=29] and Mexican [n=120]) of LN patients. Serial uEGF measurements and renal outcomes were available from 92 patients of the Mexican cohort with long-term (>12 months) follow-up, and their association assessed by linear mixed modeling.

Results

The LC-MS/MS showed decreased pro-EGF peptides in active LN patients compared to normal controls. Western blot analysis corroborated decreased pro-EGF urine levels in LN. Measurement of urinary pro-EGF by ELISA closely correlated with mature uEGF levels. uEGF were decreased in active LN patients compared to LN in remission and healthy kidney donors from both cohorts. uEGF levels correlated with the percentage of glomerular sclerosis (r=-0.539, p<0.001), interstitial fibrosis (r=-0.665, p<0.001), tubular atrophy (r=-0.665, p<0.001) and overall histologic chronicity index (r=-0.669, p<0.001) of the kidney biopsies. uEGF levels at LN flare were independently associated with the combined outcome of doubling of serum creatinine/ progression to ESRD (HR=0.58, 95% CI 0.34-0.98, p=0.043). The slope of uEGF over time correlated with eGFR slope. Patients who developed the combined outcome had significant and progressive decreases in uEGF compared to those who did not (Figure).

Conclusion

uEGF correlates with LN kidney biopsy findings of chronic damage. uEGF at flare and during follow-up is associated with progressive kidney disease.

Funding

  • Government Support - Non-U.S.