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

被引：14

作者：

Gipson, Debbie S. ^{[1
]}

Trachtman, Howard ^{[2
]}

Waldo, Anne ^{[1
]}

Gibson, Keisha L. ^{[3
]}

Eddy, Sean ^{[1
]}

Dell, Katherine M. ^{[4
]}

Srivastava, Tarak ^{[5
,6
]}

Lemley, Kevin, V ^{[7
]}

Greenbaum, Larry A. ^{[8
,9
]}

Hingorani, Sangeeta ^{[10
,11
]}

Meyers, Kevin E. ^{[12
]}

Kaskel, Frederick J. ^{[13
,14
]}

Reidy, Kimberly J. ^{[13
,14
]}

Sethna, Christine B. ^{[15
]}

Tran, Cheryl L. ^{[16
]}

Wang, Chia-shi ^{[8
,9
]}

Tuttle, Katherine R. ^{[17
,18
]}

Oh, Gia ^{[19
]}

Neu, Alicia M. ^{[20
]}

Brown, Elizabeth ^{[21
]}

Lin, Jen-Jar ^{[22
]}

Yee, Jennifer Lai ^{[1
]}

Roth, Therese M. ^{[1
]}

Troost, Jonathan P. ^{[1
]}

Gillespie, Brenda W. ^{[1
]}

Sampson, Matthew G. ^{[23
]}

Kretzler, Matthias ^{[1
]}

Ju, Wenjun ^{[1
]}

机构：

[1] Univ Michigan, Dept Pediat, Div Nephrol, Ann Arbor, MI 48109 USA

[2] NYU, Dept Pediat, Langone Hlth, Div Nephrol, New York, NY 10016 USA

[3] Univ N Carolina, Kidney Ctr Chapel Hill, Chapel Hill, NC 27515 USA

[4] Case Western Reserve Univ, Dept Pediat, Cleveland Clin Childrens, Cleveland, OH 44106 USA

[5] Childrens Mercy Hosp, Sect Nephrol, Kansas City, MO 64108 USA

[6] Univ Missouri, Kansas City, MO 64110 USA

[7] Childrens Hosp LA, Div Nephrol, Los Angeles, CA USA

[8] Emory Univ, Dept Pediat, Div Pediat Nephrol, Atlanta, GA 30322 USA

[9] Childrens Healthcare Atlanta, Atlanta, GA USA

[10] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA

[11] Seattle Childrens Hosp, Div Nephrol, Seattle, WA USA

[12] Childrens Hosp Philadelphia, Dept Pediat, Div Nephrol, Philadelphia, PA 19104 USA

[13] Albert Einstein Coll Med, Dept Pediat, Div Nephrol, New York, NY USA

[14] Montefiore Med Ctr, New York, NY USA

[15] Hofstra Univ, Zucker Sch Med, Cohen Childrens Med Ctr New York, Pediat Nephrol, Hempstead, NY 11550 USA

[16] Mayo Clin, Dept Pediat, Rochester, MN USA

[17] Providence Med Res Ctr, Providence St Joseph Hlth, Spokane, WA USA

[18] Univ Washington, Dept Internal Med, Seattle, WA 98195 USA

[19] Stanford Univ, Dept Pediat, Div Nephrol, Sch Med, Stanford, CA 94305 USA

[20] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Pediat Nephrol, Baltimore, MD 21205 USA

[21] UT Southwestern Med Ctr, Dept Pediat, Div Nephrol, Dallas, TX USA

[22] Wake Forest Univ, Baptist Hlth, Div Pediat Nephrol, Brenner Childrens Hosp, Winston Salem, NC 27101 USA

[23] Boston Childrens Hosp, Div Nephrol, Boston, MA USA

来源：

KIDNEY INTERNATIONAL REPORTS | 2020年 / 5卷 / 04期

基金：

美国国家卫生研究院;

关键词：

disease progression; epidermal growth factor; focal segmental glomerulosclerosis; nephrotic syndrome; pediatrics; DEFINITION; REMISSION;

D O I：

10.1016/j.ekir.2019.11.018

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：414 / 425

页数：12

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