title: The relationship between urinary renin-angiotensin system markers, renal function, and blood pressure in adolescents with type 1 diabetes.
abstract: The relationship between the renal renin-angiotensin aldosterone system (RAAS) and cardiorenal pathophysiology is unclear. Our aims were to assess1) levels of urinary RAAS components and2) the association between RAAS components and HbA1c, the urine albumin/creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and blood pressure (BP) in otherwise healthy adolescents with type 1 diabetes mellitus (TID) vs. healthy controls (HC). Urinary angiotensinogen and angtionsin-converting enzyme (ACE) 2 levels, activity of ACE and ACE2, BP, HbA1c, ACR, and eGFR were measured in 65 HC and 194 T1D from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT). Urinary levels of all RAAS components were higher in T1D vs. HC (P< 0.0001). Higher HbA1c was associated with higher urinary angiotensinogen, ACE2, and higher activity of ACE and ACE2 (P< 0.0001,P= 0.0003,P= 0.003, andP= 0.007 respectively) in T1D. Higher ACR (within the normal range) was associated with higher urinary angiotensinogen (P< 0.0001) and ACE activity (P= 0.007), but not with urinary ACE2 activity or ACE2 levels. These observations were absent in HC. Urinary RAAS components were not associated with BP or eGFR in T1D or HC. Otherwise healthy adolescents with T1D exhibit higher levels of urinary RAAS components compared with HC. While levels of all urinary RAAS components correlate with HbA1c in T1D, only urinary angiotensinogen and ACE activity correlate with ACR, suggesting that these factors reflect an intermediary pathogenic link between hyperglycemia and albuminuria within the normal range.
authors.affiliation: Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Burns
authors.affiliation: Department of Pharmacology, University of Toronto, Toronto, Canada.|Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lytvyn
authors.affiliation: Department of Paediatrics, Division of Endocrinology, The Hospital for Sick Children, University of Toronto, Toronto, Canada, JDRF-Canadian Clinical Trial Network (JDRF-CCTN) SickKids Multicenter Clinical Trial Center.
authors.forename: Farid H
authors.initials: FH
authors.lastname: Mahmud
authors.affiliation: Department of Paediatrics, Division of Endocrinology, The Hospital for Sick Children, University of Toronto, Toronto, Canada, JDRF-Canadian Clinical Trial Network (JDRF-CCTN) SickKids Multicenter Clinical Trial Center.
authors.forename: Denis
authors.initials: D
authors.lastname: Daneman
authors.affiliation: Department of Paediatrics, Division of Endocrinology, The Hospital for Sick Children, University of Toronto, Toronto, Canada, JDRF-Canadian Clinical Trial Network (JDRF-CCTN) SickKids Multicenter Clinical Trial Center.
authors.forename: Livia
authors.initials: L
authors.lastname: Deda
authors.affiliation: Department of Pediatrics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
authors.affiliation: University College Hospital, Heart Hospital and Great Ormond Street Hospital, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Deanfield
authors.affiliation: WellChild Laboratory, Evelina Children's Hospital, St Thomas' Hospital, London, United Kingdom.
authors.forename: R Neil
authors.initials: RN
authors.lastname: Dalton
authors.affiliation: Department of Paediatrics, Division of Endocrinology, The Hospital for Sick Children, University of Toronto, Toronto, Canada, JDRF-Canadian Clinical Trial Network (JDRF-CCTN) SickKids Multicenter Clinical Trial Center.
authors.forename: Yesmino
authors.initials: Y
authors.lastname: Elia
authors.affiliation: Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Har
authors.affiliation: Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Julie A D
authors.initials: JA
authors.lastname: Van
authors.affiliation: Department of Paediatrics, Division of Cardiology, The Hospital for Sick Children, University of Toronto, Toronto, Canada; and.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bradley
authors.affiliation: Department of Paediatrics, Division of Cardiology, The Hospital for Sick Children, University of Toronto, Toronto, Canada; and.
authors.forename: Cameron
authors.initials: C
authors.lastname: Slorach
authors.affiliation: Department of Paediatrics, Division of Cardiology, The Hospital for Sick Children, University of Toronto, Toronto, Canada; and.
authors.forename: Wei
authors.initials: W
authors.lastname: Hui
authors.affiliation: Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zimpelmann
authors.affiliation: Department of Paediatrics, Division of Cardiology, The Hospital for Sick Children, University of Toronto, Toronto, Canada; and.
authors.forename: Luc
authors.initials: L
authors.lastname: Mertens
authors.affiliation: Department of Family and Community Medicine, University of Toronto, Toronto, Canada.
authors.forename: Rahim
authors.initials: R
authors.lastname: Moineddin
authors.affiliation: Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Heather N
authors.initials: HN
authors.lastname: Reich
authors.affiliation: Department of Paediatrics, Division of Endocrinology, The Hospital for Sick Children, University of Toronto, Toronto, Canada, JDRF-Canadian Clinical Trial Network (JDRF-CCTN) SickKids Multicenter Clinical Trial Center.
authors.forename: Etienne
authors.initials: E
authors.lastname: Sochett
authors.affiliation: Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: James W
authors.initials: JW
authors.lastname: Scholey
authors.affiliation: Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada; david.cherney@uhn.ca.
authors.forename: David Z I
authors.initials: DZ
authors.lastname: Cherney
mesh_terms: D000293:Adolescent; D000419:Albuminuria / Q000378:metabolism; D000808:Angiotensinogen / Q000652:urine; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology*; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000652:urine; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D015415:Biomarkers; D000808:Angiotensinogen; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A
keywords: ACE; ACE2; hyperglycemia, albumin-to-creatinine ratio; type 1 diabetes