Urinary fibrogenic cytokines ET-1 and TGF-β1 are associated with urinary angiotensinogen levels in obese children

Pediatr Nephrol. 2016 Mar;31(3):455-64. doi: 10.1007/s00467-015-3232-1. Epub 2015 Oct 19.


Background: Fibrogenic cytokines are recognized as putative drivers of disease activity and histopathological deterioration in various kidney diseases. We compared urinary transforming growth factor β1 (U-TGF-β1) and endothelin 1 (U-ET-1) levels across body mass index classes and assessed their association with the level of urinary angiotensinogen (U-AGT), a biomarker of intrarenal renin-angiotensin-aldosterone system (RAAS).

Methods: The was a cross-sectional evaluation of 302 children aged 8-9 years. Ambulatory blood pressure (BP), insulin resistance (HOMA-IR), aldosterone level and renal function were evaluated. U-ET-1, U-TGF-β1 and U-AGT levels were determined by immunoenzymatic methods.

Results: Obese children presented with the lowest levels of U-ET-1 and U-TGF-β1, but the difference was only significant for U-ET-1. In obese children, the median levels of both U-ET-1 and U-TGF-β1 tended to increase across tertiles (T1-T3) of U-AGT (U-ET-1: T1, 19.9 (14.2-26.3); T2, 32.5 (23.3-141.6); T3, 24.8 (18.7-51.5) ng/g creatinine, p = 0.007; U-TGF-β1: T1, 2.2 (1.8-4.0); T2, 4.3 (2.7-11.7); T3, 4.9 (3.8-10.1) ng/g creatinine, p = 0.004]. In multivariate models, in the obese group, U-ET-1 was associated with HOMA-IR and aldosterone and U-AGT levels, and U-TGF-β1 was associated with U-AGT levels and 24 h-systolic BP.

Conclusions: Whereas the initial hypothesis of higher levels of urinary fibrogenic cytokines in obese children was not confirmed in our study, both TGF-β1 and U-ET-1 levels were associated with U-AGT level, which likely reflects an early interplay between tissue remodeling and RAAS in obesity-related kidney injury.

Keywords: Angiotensinogen; Childhood obesity; Endothelin-1; Kidney injury; Transforming growth factor-β1; Urinary biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Angiotensinogen / urine*
  • Biomarkers / urine
  • Body Mass Index
  • Child
  • Cross-Sectional Studies
  • Endothelin-1 / urine*
  • Female
  • Humans
  • Male
  • Pediatric Obesity / diagnosis
  • Pediatric Obesity / physiopathology
  • Pediatric Obesity / urine*
  • Renin-Angiotensin System
  • Transforming Growth Factor beta1 / urine*
  • Urinalysis


  • AGT protein, human
  • Biomarkers
  • Endothelin-1
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Angiotensinogen