Urinary Epidermal Growth Factor as a Marker of Disease Progression in Children With Nephrotic Syndrome
Year: 2019
Type: article
Study design: Observational Study
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 m 2 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 m 2 per year per log 2 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.
Source: Kidney International Reports
Authors: Debbie S. Gipson, Howard Trachtman, Anne Waldo, Keisha L. Gibson, Sean Eddy, Katherine M. Dell, Tarak Srivastava, Kevin V. Lemley, Larry A. Greenbaum, Sangeeta Hingorani, Kevin E. Meyers, Frederick J. Kaskel, Kimberly J. Reidy, Christine B. Sethna, Cheryl L. Tran, Chia-shi Wang, Katherine R. Tuttle, Gia Oh, Alicia M. Neu, Elizabeth Brown, Jen-Jar Lin, Jennifer Lai Yee, Therese M. Roth, Jonathan P. Troost, Brenda W. Gillespie, Matthew G. Sampson, Matthias Kretzler, Wenjun Ju
Institutions: University of Michigan, Michigan Medicine, NYU Langone Health, New York University, University of North Carolina at Chapel Hill, Cleveland Clinic, Case Western Reserve University, Children's Mercy Hospital, University of Missouri–Kansas City, Children's Hospital of Los Angeles, Emory University, Children's Healthcare of Atlanta, Seattle Children's Hospital, University of Washington, Children's Hospital of Philadelphia, Albert Einstein College of Medicine, Montefiore Medical Center, Hofstra University, Cohen Children's Medical Center, Mayo Clinic, Stanford Medicine, Stanford University, Johns Hopkins University, Johns Hopkins Medicine, The University of Texas Southwestern Medical Center, Brenner Children's Hospital, Wake Forest University, Boston Children's Hospital
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,625
Funders: Mayo Clinic, Stanford University, Children's Hospital Los Angeles, University of Miami, University of Pennsylvania, University of Michigan, University of Washington, University of Texas Southwestern Medical Center, Children's Mercy Hospital, Temple University, Halpin Foundation, National Institutes of Health, University of North Carolina Wilmington, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
OpenAlex ID: W2992466611