title: Increased urinary Angiotensinogen/Creatinine (AGT/Cr) ratio may be associated with reduced renal function in autosomal dominant polycystic kidney disease patients.
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary kidney diseases that frequently result in renal failure. In this cross-sectional observational cohort study, we evaluated urinary angiotensinogen (AGT) as a potential biomarker to assess renal function in ADPKD.
  
  
  METHODS
  Urinary AGT was measured in 233 ADPKD patients and its association with estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume (htTKV) were evaluated. The localization of AGT and other renin-angiotensin system (RAS)-related molecules were identified using immunohistochemistry in human ADPKD tissues.
  
  
  RESULTS
  Baseline urinary AGT/Cr was negatively correlated with CKD-EPI eGFR (r(2) = 0.162, P < 0.001) and positively correlated with htTKV (r(2) = 0.107, P < 0.001). Both urinary AGT/Cr and plasma renin activity levels were significantly elevated in hypertensive ADPKD patients. Among hypertensive subjects, urinary AGT/Cr was significantly increased in the advanced CKD stages (III-V) compared to early CKD stages (I-II) (28.6 ± 60.3 vs. 93.2 ± 139.3 μg/g, P < 0.001). Immunohistochemical study showed strong expression of AGT along the cyst-lining epithelial cells as well as the nearby compressed tubular epithelial cells.
  
  
  CONCLUSIONS
  Our results suggested that urinary AGT/Cr may be a valuable biomarker for renal damage in ADPKD since intrarenal ischemic insults induced by cyst growth and subsequent intrarenal RAS activation may play a potential role in the development of hypertension and renal dysfunction in ADPKD.
authors.affiliation: Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, South Korea. haynepark798@gmail.com.|Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, South Korea. haynepark798@gmail.com.
authors.forename: Hayne Cho
authors.initials: HC
authors.lastname: Park
authors.affiliation: Transplantation Research Institute, Seoul National University, Seoul, South Korea. irisoa@gmail.com.
authors.forename: Ah-Young
authors.initials: AY
authors.lastname: Kang
authors.affiliation: Transplantation Research Institute, Seoul National University, Seoul, South Korea. flowerfntlvj@gmail.com.
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-Ro Jongno-Gu, Seoul, 110-744, South Korea. keeee@hanmail.net.
authors.forename: Hyunsuk
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-Ro Jongno-Gu, Seoul, 110-744, South Korea. myeun81@hanmail.net.
authors.forename: Miyeun
authors.initials: M
authors.lastname: Han
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-Ro Jongno-Gu, Seoul, 110-744, South Korea. ohchris@hanmail.net.
authors.forename: Kook-Hwan
authors.initials: KH
authors.lastname: Oh
authors.affiliation: Department of Radiology, Seoul National University Hospital, Seoul, South Korea. kimshrad@snu.ac.kr.
authors.forename: Seung Hyup
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Hallym University College of Medicine, Seoul, South Korea. jwn8671@unitel.co.kr.
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Noh
authors.affiliation: Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, South Korea. cheonghi@snu.ac.kr.|Department of Pediatrics, Seoul National University Children's Hospital, Seoul, South Korea. cheonghi@snu.ac.kr.
authors.forename: Hae Il
authors.initials: HI
authors.lastname: Cheong
authors.affiliation: Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, South Korea. nephro.hwang@gmail.com.|Department of Internal Medicine, Eulji University College of Medicine, Seoul, South Korea. nephro.hwang@gmail.com.
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Hwang
authors.affiliation: Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, South Korea. curie@snu.ac.kr.|Transplantation Research Institute, Seoul National University, Seoul, South Korea. curie@snu.ac.kr.|Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-Ro Jongno-Gu, Seoul, 110-744, South Korea. curie@snu.ac.kr.
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000378:metabolism / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine*; D003430:Cross-Sectional Studies; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000652:urine*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism / Q000503:physiopathology / Q000652:urine*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000652:urine*; D012083:Renin / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: C534931:AGT protein, human; D015415:Biomarkers; D000808:Angiotensinogen; D003404:Creatinine; D012083:Renin