Faculty Collaboration Database

Urinary prostaglandin E₂ is a biomarker of early adaptive hyperfiltration in solitary functioning kidney. Prostaglandins Other Lipid Mediat 2020 Feb;146:106403

Date

12/16/2019

Pubmed ID

31838197

Pubmed Central ID

PMC9356765

DOI

10.1016/j.prostaglandins.2019.106403

Scopus ID

2-s2.0-85076524994 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

INTRODUCTION: Hyperfiltration is a major contributor to progression of chronic kidney disease (CKD) in diabetes, obesity and in individuals with solitary functioning kidney (SFK). We have proposed hyperfiltration-induced injury as a continuum of overlapping glomerular changes caused by increased biomechanical forces namely, fluid flow shear stress (FFSS) and tensile stress. We have shown that FFSS is elevated in animals with SFK and, it upregulates prostaglandin E₂ (PGE₂), cyclooxygenase-2 and PGE₂ receptor EP2 in cultured podocytes and in uninephrectomized mice. We conceptualized urinary PGE₂ as a biomarker of early effects of hyperfiltration-induced injury preceding microalbuminuria in individuals with SFK. We studied children with SFK to validate our hypothesis.

METHODS: Urine samples from children with SFK and controls were analyzed for PGE₂, albumin (glomerular injury biomarker) and epidermal growth factor (EGF, tubular injury biomarker). Age, gender, and Z-scores for height, weight, BMI, and blood pressure were obtained.

RESULTS: Children with SFK were comparable to controls except for lower BMI Z-scores. The median values were elevated in SFK compared to control for urine PGE₂ [9.1 (n = 57) vs. 5.7 (n = 72), p = 0.009] ng/mgCr and albumin [7.6 (n = 40) vs. 7.0 (n = 41), p = 0.085] μg/mgCr, but not for EGF [20098 (n = 44) vs. 18637 (n = 44), p = 0.746] pg/mgCr. Significant increase in urinary PGE₂ (p = 0.024) and albumin (p = 0.019) but not EGF (p = 0.412) was observed using additional regression modeling. These three urinary analytes were independent of each other.

CONCLUSION: Increased urinary PGE₂ from elevated SNGFR and consequently increased FFSS during early stage of CKD precedes overt microalbuminuria and is a biomarker for early hyperfiltration-induced injury in individuals with SFK.

Author List

Srivastava T, Ju W, Milne GL, Rezaiekhaligh MH, Staggs VS, Alon US, Sharma R, Zhou J, El-Meanawy A, McCarthy ET, Savin VJ, Sharma M

Author

Ashraf El-Meanawy MD, PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Biomarkers
Child
Child, Preschool
Dinoprostone
Female
Glomerular Filtration Rate
Humans
Infant
Kidney Glomerulus
Male
Renal Insufficiency, Chronic
Young Adult