Urinary fibrogenic cytokines ET-1 and TGF-β1 are associated with urinary angiotensinogen levels in obese children.
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.
Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, Rua das Taipas, nº 135, 4050-600, Porto, Portugal. liane@med.up.pt.|Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal. liane@med.up.pt.|Department of Pediatrics, Faculty of Medicine, University of Porto, Porto, Portugal. liane@med.up.pt.
Liane
L
Correia-Costa
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.|Center for Drug Discovery and Innovative Medicines (MedInUP), University of Porto, Porto, Portugal.|Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Manuela
M
Morato
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.|Center for Drug Discovery and Innovative Medicines (MedInUP), University of Porto, Porto, Portugal.
Teresa
T
Sousa
Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, Rua das Taipas, nº 135, 4050-600, Porto, Portugal.|Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.
Dina
D
Cosme
Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, Rua das Taipas, nº 135, 4050-600, Porto, Portugal.|Department of Clinical Pathology, Centro Hospitalar São João, Porto, Portugal.|Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal.
João Tiago
JT
Guimarães
Department of Pediatrics, Faculty of Medicine, University of Porto, Porto, Portugal.|Division of Pediatric Nutrition, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal.
António
A
Guerra
Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.
Franz
F
Schaefer
Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, Rua das Taipas, nº 135, 4050-600, Porto, Portugal.|Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal.|Department of Pediatrics, Faculty of Medicine, University of Porto, Porto, Portugal.
Alberto Caldas
AC
Afonso
Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, Rua das Taipas, nº 135, 4050-600, Porto, Portugal.|Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine, University of Porto, Porto, Portugal.
Ana
A
Azevedo
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.|Center for Drug Discovery and Innovative Medicines (MedInUP), University of Porto, Porto, Portugal.
António
A
Albino-Teixeira
D000293:Adolescent; D000367:Age Factors; D000808:Angiotensinogen / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D015992:Body Mass Index; D002648:Child; D003430:Cross-Sectional Studies; D019332:Endothelin-1 / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D063766:Pediatric Obesity / Q000175:diagnosis / Q000503:physiopathology / Q000652:urine*; D012084:Renin-Angiotensin System; D053773:Transforming Growth Factor beta1 / Q000652:urine*; D016482:Urinalysis
C534931:AGT protein, human; D015415:Biomarkers; D019332:Endothelin-1; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D000808:Angiotensinogen
Angiotensinogen; Childhood obesity; Endothelin-1; Kidney injury; Transforming growth factor-β1; Urinary biomarkers