title: Comparison of intrarenal renin-angiotensin system activity in diabetic versus non-diabetic patients with overt proteinuria.
abstract: OBJECTIVE
  The intrarenal renin-angiotensin system (RAS) has been reported to be activated in chronic proteinuria patients. This study aimed to compare intrarenal RAS activity between diabetic nephropathy (DN) and non-diabetic nephropathy (NDN) patients with overt proteinuria.
  
  
  METHODS
  A multicenter, cross-sectional study was conducted in 116 patients with overt proteinuria (urinary protein/creatinine ratio [uPCR] > 1 mg/mg Cr). To estimate intrarenal RAS activity we measured urinary excretion of angiotensinogen (uAGT) and renin (uRenin) in patients with DN (n = 38) and NDN (n = 78).
  
  
  RESULTS
  Both natural logarithms of uAGT/urinary creatinine (ln[uAGT/uCr]) and uRenin (ln[uRenin/uCr]) levels were significantly higher in patients with DN compared with those with NDN (ln[uAGT/uCr]: 4.16 ± 1.13 in DN vs. 3.52 ± 1.21 in NDN, P = 0.007; ln[uRenin/uCr]: 5.66 ± 1.60 in DN vs. 4.29 ± 1.48 in NDN, P < 0.001), when estimated glomerular filtration rate (eGFR) and uPCR showed no significant difference between the two groups. In a subgroup analysis, according to amount of proteinuria, both uAGT and uRenin were higher in DN in patients with subnephrotic-range proteinuria (uPCR < 3.5 mg/mg Cr). However, in patients with nephrotic-range proteinuria (uPCR ≥ 3.5 mg/mg Cr), only uRenin was higher in DN compared to NDN. In a multiple regression analysis, diabetes showed independent association with uRenin.
  
  
  CONCLUSIONS
  Consistently elevated uRenin in DN, regardless of the amount of proteinuria, indicates that intrarenal RAS activity may be higher in DN compared to NDN in patients with overt proteinuria.
authors.affiliation: Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Park
authors.forename: Hye Ryoun
authors.initials: HR
authors.lastname: Jang
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Wooseong
authors.initials: W
authors.lastname: Huh
authors.forename: Kyu-Beck
authors.initials: KB
authors.lastname: Lee
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Kwon
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Do
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Yoon-Goo
authors.initials: YG
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000652:urine; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D003928:Diabetic Nephropathies / Q000150:complications / Q000175:diagnosis / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000175:diagnosis / Q000209:etiology / Q000652:urine*; D012083:Renin / Q000652:urine*; D012084:Renin-Angiotensin System; D056910:Republic of Korea; D012189:Retrospective Studies; D015854:Up-Regulation
chemical_list: C534931:AGT protein, human; D015415:Biomarkers; D000808:Angiotensinogen; D003404:Creatinine; D012083:Renin
keywords: angiotensinogen; diabetic nephropathy; proteinuria; renin; renin-angiotensin system