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

Abstract

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.

Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children

“…Based on these published data and on the negative impact that obesity has on the kidney [2], we would expect that overweight/obese children had higher U-AGT than age-matched controls of normal weight. However, as recently reported by our group [36], we observed no significant differences in U-AGT between normal and overweight/obese children. In this study, we further extended this result and clarified that it is observed regardless of the obesity index considered: classes of BMI or tertiles of WHtR or percent body fat mass.…”

“…Also, we Mean ± standard deviation or n (%). BMI z-score classification is according to WHO criteria (normal weight, overweight, and obesity) [32] BMI body mass index, WHtR waist-to-height ratio, MAP mean arterial pressure a According to the population-based Canadian reference curves [30] recently reported [36] that urinary excretion of the fibrogenic cytokines endothelin-1 (ET-1) and transforming growth factor-β1 (TGF-β1) was not increased in obese children in our cohort; indeed, they showed lower levels of urinary ET-1 and TGF-β1 than those of normal weight. Furthermore, U-AGT was associated with urinary excretion of ET-1 and TGF-β1 [23].…”

“…The cross-sectional design of our study might be seen as a limitation. However, as our cohort will be followed until adulthood, we expect to re-evaluate these children in the next evaluation period, when they will be adolescents, and it will BMI body mass index, eGFR estimated glomerular filtration rate by Zappitelli combined formula, P-AGT plasma angiotensinogen, U-albumin urinary albumin-to-creatinine ratio, U-AGT urinary angiotensinogen, U-H 2 O 2 urinary hydrogen peroxide Data concerning AGT ( a ) and H 2 O 2 ( b ) have been recently used by our group as part of studies on the same cohort intended to evaluate the association with urinary fibrogenic cytokines [36] and oxidative stress [37], respectively be possible to perform a longitudinal analysis to complement and expand the hypothesis raised in this study. In addition, longitudinal studies should include a group of children that has experienced weight loss to test whether that would protect them from metabolic changes later in life.…”

“…AGT was quantified by an immunoenzymatic method, using a commercial enzymelinked immunosorbent assay (ELISA) kit (Human Total Angiotensinogen Assay Kit, Immuno-Biological Laboratories Co., Gunma, Japan) and H 2 O 2 evaluated using a microplate fluorometric assay (Amplex Red Hydrogen Peroxide/ Peroxidase Assay Kit, Molecular Probes, Alfagene, Carcavelos, Portugal), according to protocols provided by the manufacturers. Data concerning AGT and H 2 O 2 have been recently used by our group as part of studies on the same cohort to evaluate the association with urinary fibrogenic cytokines [36] and oxidative stress [37], respectively.…”

Angiotensin II: a key mediator in the development of liver fibrosis and cancer

“…In addition, PDGF, TNF-α, interleukin (IL)-6, IL-1β, and IL-13 are also key pro-fibrotic mediators, pharmacological inhibition, and/or gene deletion of these cytokines prevented the progression of hepatic fibrosis (Schwabe et al 2003;Kaviratne et al 2004;Sudo et al 2005). Furthermore, vasoconstrictors (e.g., norepinephrine, angiotensin II (Ang-II)) (Oben and Diehl 2004;Han et al 2017), and endothelin (ET)-1 (Cho et al 2000;Correia-Costa et al 2016) exert potent fibrogenic activities, while vasodilators (e.g., nitric oxide (NO), relaxin) have opposite actions (Iwakiri 2015).…”