title: Urinary renin and angiotensinogen in type 2 diabetes: added value beyond urinary albumin?
abstract: OBJECTIVE
  Urinary levels of renin-angiotensin-aldosterone system (RAAS) components may reflect renal RAAS activity and/or the renal efficacy of RAAS inhibition. Our aim was to determine whether urinary angiotensinogen and renin are circulating RAAS-independent markers during RAAS blockade.
  
  
  METHODS
  Urinary and plasma levels of angiotensinogen, renin, and albumin were measured in 22 patients with type 2 diabetes, hypertension, and albuminuria, during 2-month treatment periods with placebo, aliskiren, irbesartan, or their combination in random order in a crossover study.
  
  
  RESULTS
  Aliskiren and irbesartan both increased plasma renin 3-4-fold, and above 10-fold when combined. Irbesartan decreased plasma angiotensinogen by approximately 25%, and no changes in plasma angiotensinogen were observed during the combination. Urine contained aliskiren at micromolar levels, blocking urinary renin by above 90%. Both blockers reduced urinary angiotensinogen, significant for irbesartan only. Combination blockade reduced urinary angiotensinogen even further. Reductions in urinary angiotensinogen paralleled albuminuria changes, and the urine/plasma concentration ratio of angiotensinogen was identical to that of albumin under all conditions. In contrast, urinary renin did not follow albumin, and remained unaltered after all treatments. Yet, the urine/plasma concentration ratio of renin was more than 100-fold higher than that of angiotensinogen and albumin, and approximately 4-fold reduced by single RAAS blockade, and more than 10-fold by dual RAAS blockade.
  
  
  CONCLUSIONS
  Aliskiren filters into urine and influences urinary renin measurements. The urine/plasma renin ratio, but not urinary renin alone, may reflect the renal efficacy of RAAS blockade. Urinary angiotensinogen is a marker of filtration barrier damage rather than intrarenal RAAS activity.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. frip@steno.dk
authors.forename: Frederik
authors.initials: F
authors.lastname: Persson
authors.forename: Xifeng
authors.initials: X
authors.lastname: Lu
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Garrelds
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000032:analysis*; D000577:Amides / Q000627:therapeutic use; D000808:Angiotensinogen / Q000097:blood / Q000652:urine; D000809:Angiotensins / Q000652:urine*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000652:urine*; D004311:Double-Blind Method; D005260:Female; D005650:Fumarates / Q000627:therapeutic use; D006801:Humans; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood / Q000652:urine*; D012084:Renin-Angiotensin System; D013777:Tetrazoles / Q000627:therapeutic use
chemical_list: D000418:Albumins; D000577:Amides; D000809:Angiotensins; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D005650:Fumarates; D013777:Tetrazoles; D000808:Angiotensinogen; C446481:aliskiren; D012083:Renin; D000077405:Irbesartan