Urinary Epidermal Growth Factor as a Marker of Disease Progression in Children With Nephrotic Syndrome

• Type of Material: Article
• Authors: Debbie S. Gipson, University of Michigan; Howard Trachtman, New York University; Anne Waldo, University of Michigan; Keisha L. Gibson, University of North Carolina; Sean Eddy, University of Michigan; Katherine M. Dell, Case Western Reserve University; Tarak Srivastava, Childrens Mercy Hospital; Kevin Lemley, Childrens Hospital Los Angeles; Larry Greenbaum, Emory University; Sangeeta Hingorani, University of Washington; Kevin E. Meyers, Childrens Hospital of Philadelphia; Frederic J. Kaskel, Albert Einstein College of Medicine; Kimberly J. Reidy, Albert Einstein College of Medicine; Christine B. Sethna, Hofstra University; Cheryl L. Tran, Mayo Clinic; Chia-shi Wang, Emory University; Katherine R. Tuttle, University of Washington; Gia Oh, Stanford University; Alicia M. Neu, Johns Hopkins University; Elizabeth Brown, University of Texas Southwestern Medical Center; Jen-Jar Lin, Wake Forest University; Jennifer Lai Yee, University of Michigan; Therese M. Roth, University of Michigan; Jonathan P. Troost, University of Michigan; Brenda W. Gillespie, University of Michigan; Matthew G. Sampson, Boston Childrens Hospital; Matthias Kretzler, University of Michigan; Wenjun Ju, University of Michigan
• Language: English
• Date: 2020-04-01
• Publisher: Elsevier Science Inc.
• Publication Version: Final Published Version
• Copyright Statement: © 2019 International Society of Nephrology. Published by Elsevier Inc.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ekir.2019.11.018
• Title of Journal or Parent Work: Kidney International Reports
• Volume: 5
• Issue: 4
• Start Page: 414
• End Page: 425
• Grant/Funding Information: None declared
• Keywords: Urology & Nephrology; disease progression; Science & Technology; Remission; pediatrics; epidermal growth factor; Life Sciences & Biomedicine; focal segmental glomerulosclerosis; nephrotic syndrome; Definitions
• Research Categories: Health Sciences, Human Development; Health Sciences, Pathology; Health Sciences, Immunology

Abstract

Introduction: Childhood-onset nephrotic syndrome has a variable clinical course. Improved predictive markers of long-term outcomes in children with nephrotic syndrome are needed. This study tests the association between baseline urinary epidermal growth factor (uEGF) excretion and longitudinal kidney function in children with nephrotic syndrome. Methods: The study evaluated 191 participants younger than 18 years enrolled in the Nephrotic Syndrome Study Network, including 118 with their first clinically indicated kidney biopsy (68 minimal change disease; 50 focal segmental glomerulosclerosis) and 73 with incident nephrotic syndrome without a biopsy. uEGF was measured at baseline for all participants and normalized by the urine creatinine (Cr) concentration. Renal epidermal growth factor (EGF) mRNA was measured in the tubular compartment microdissected from kidney biopsy cores from a subset of patients. Linear mixed models were used to test if baseline uEGF/Cr and EGF mRNA expression were associated with change in estimated glomerular filtration rate (eGFR) over time. Results: Higher uEGF/Cr at baseline was associated with slower eGFR decline during follow-up (median follow-up = 30 months). Halving of uEGF/Cr was associated with a decrease in eGFR slope of 2.0 ml/min per 1.73 m2 per year (P < 0.001) adjusted for age, race, diagnosis, baseline eGFR and proteinuria, and APOL1 genotype. In the biopsied subgroup, uEGF/Cr was correlated with EGF mRNA expression (r = 0.74; P < 0.001), but uEGF/Cr was retained over mRNA expression as the stronger predictor of eGFR slope after multivariable adjustment (decrease in eGFR slope of 1.7 ml/min per 1.73 m2 per year per log2 decrease in uEGF/Cr; P < 0.001). Conclusion: uEGF/Cr may be a useful noninvasive biomarker that can assist in predicting the long-term course of kidney function in children with incident nephrotic syndrome.