Kidney Week

Abstract: FR-PO1091

Urine Epidermal Growth Factor Is a Biomarker of Tubulointerstitial Damage in Lupus Nephritis (LN)

Session Information

• Glomerular Diseases: Clinical, Outcomes, Trials - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

• Shapiro, John P., Ohio State University Wexner Medical Center, Columbus, Ohio, United States

John P. Shapiro,

• Mejia-Vilet, Juan M., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, Mexico

Juan M. Mejia-Vilet,

• Song, Huijuan, Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Huijuan Song,

• Birmingham, Daniel J., Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Daniel J. Birmingham,

• Parikh, Samir V., Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Samir V. Parikh,

• Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Brad H. Rovin,

Group or Team Name

• for the CKD Biomarker Consortium

Background

An agnostic proteomic survey of urine from patients with LN showed significantly decreased levels of pro-epidermal growth factor (EGF) in patients who had developed chronic kidney disease (CKD). Urine (u)EGF has previously been shown to predict progressive CKD in several glomerular diseases. Therefore, we examined the association of uEGF with kidney biopsy findings and kidney function in patients with LN.

Methods

EGF was measured by specific ELISA in urine collected at the time of kidney biopsy in 23 Mexican and 29 Midwestern (45% African American, 45% Caucasian) LN patients, and was characterized by immunoblotting. uEGF was also measured in serial urine samples from patients with 1-5 years of longitudinal follow-up.

Results

Results: uEGF in 29 Midwestern LN patients at kidney biopsy was 11.7±10.1 ng/mg Cr compared to 26.5±13.7 ng/mg Cr in 8 lupus patients with no history of LN (p<0.05). Immunoblotting demonstrated uEGF was mainly high molecular weight (pro-EGF forms). uEGF correlated inversely with serum creatinine (SCr), biopsy chronicity index (CI), tubular atrophy and interstitial fibrosis (Table). There was no correlation with proteinuria, biopsy activity index (AI) or the histologic components of the AI (Table). Patients (n=7) with stable CKD showed low but steady levels of uEGF over 1-4 years of follow-up. Patients with progressive CKD (n=6) showed a decline in uEGF over 1-5 years. uEGF fell in patients with acute kidney injury (AKI, n=7), rebounded in 4 (57%) patients when AKI resolved but remained below baseline in 3 (43%) patients, who either did not recover AKI or recovered but later developed CKD.

Conclusion

uEGF is a biomarker of chronic tubulointerstitial damage in LN. Low and falling uEGF suggests progressive CKD. uEGF also decreases in AKI and may signal future CKD if levels do not improve.

Funding

• NIDDK Support