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Abstract: FR-PO346

Increased Urinary Prostaglandin E2 (PGE2) Precedes Overt Albuminuria in Hyperfiltration-Induced Renal Injury in Children with Solitary Functioning Kidney (SFK)

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Srivastava, Tarak, Children's Mercy Hospital, Kansas City, Missouri, United States
  • Alon, Uri S., Children's Mercy Hospital, Kansas City, Missouri, United States
  • Sharma, Ram, Kansas City VA Medical Center, Kansas City, Missouri, United States
  • Staggs, Vincent S., Children's Mercy Hospital, Kansas City, Missouri, United States
  • Savin, Virginia J., Kansas City VA Medical Center, Kansas City, Missouri, United States
  • McCarthy, Ellen T., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Sharma, Mukut, Kansas City VA Medical Center, Kansas City, Missouri, United States
Background

Children born with SFK are at risk for end stage renal disease from hyperfiltration-induced injury. Urinary albumin and epidermal growth factor (EGF) are established biomarkers of glomerular and tubular injury, respectively. A biomarker to detect glomerular changes preceding microalbuminuria will be valuable in defining early effects of hyperfiltration. In a model of hyperfiltration as a continuum of glomerular changes caused by biomechanical forces, namely fluid flow shear stress (FFSS) and tensile stress, we showed that FFSS upregulates PGE2, cyclooxygenase-2 and PGE2 receptor EP2 in cultured podocytes as well as in unilateral nephrectomized mice. We hypothesized increased urinary PGE2 in children with SFK.

Methods

Urine samples from children with SFK and controls were analyzed for PGE2 by LC-MS/MS, albumin on VITROS autoanalyzer and EGF by ELISA. Patient characteristics of age, gender, Z-scores for height, weight, BMI, and BP were obtained. Wilcoxan-Mann-Whitney test was used group for comparisons and Spearman analyses for correlations.

Results

Children with SFK were comparable to controls except for having lower weight and BMI Z-scores. The median and interquartile range in control vs. SFK children were elevated for urine PGE2 [5.7 (4.0, 8.8) n=72 vs. 9.1 (4.4, 16.7) n=57, p=0.009] ng/mgCr and albumin [7.0 (4.0, 10.3) n=41 vs. 7.6 (4.7, 24.0) n=40, p=0.085] µg/mgCr, but not for EGF [18637 (15298, 25622) n=44 vs. 20098 (13238, 30263) n=44, p=0.746] pg/mgCr. Urine albumin was within the normal reference range. A significant increase in urine PGE2 (p=0.024) and albumin (p=0.019) but not EGF (p=0.412) was observed in SFK when sex, age, weight z-score, height z-score, DBP z-score, and SBP z-score were controlled for in regression modeling. Patient characteristics did not correlate with urine PGE2, albumin or EGF. Urinary PGE2 and albumin, PGE2 and EGF, and EGF and albumin were not correlated.

Conclusion

Urinary PGE2 and albumin, but not EGF, were elevated in children with SFK compared to controls, and were independent of each other reflecting distinct pathophysiologic mechanisms. Urinary PGE2 is a potential biomarker for early glomerular injury caused by hyperfiltration associated increase in FFSS prior to overt microalbuminuria.

Funding

  • NIDDK Support