title: Plasma Soluble (Pro)renin Receptor Reflects Renal Damage.
abstract: BACKGROUND
  (Pro)renin receptor [(P)RR], a specific receptor for renin and prorenin, was identified as a member of the renin-angiotensin system (RAS). (P)RR is cleaved by furin, and soluble (P)RR [s(P)RR] is secreted into the extracellular space. Previous reports have indicated that plasma s(P)RR levels show a significant positive relationship with urinary protein levels, which represent renal damage. However, it is not fully known whether plasma s(P)RR reflects renal damage.
  
  
  METHODS
  We recruited 25 patients who were admitted to our hospital to undergo heminephrectomy. Plasma s(P)RR levels were examined from blood samples drawn before nephrectomy. The extent of renal damage was evaluated by the levels of tubulointerstitial fibrosis. Immunohistochemical analysis of intrarenal (P)RR and cell surface markers (cluster of differentiation [CD]3, CD19, and CD68) was performed on samples taken from the removed kidney. Moreover, double staining of (P)RR and cell surface markers was also performed.
  
  
  RESULTS
  There were significant positive relationships between plasma s(P)RR and tubulointerstitial fibrosis in all the patients and those not receiving RAS blocker therapy. Significant positive relationships were found between plasma s(P)RR levels and the extent of tubulointerstitial fibrosis after adjustment for age, sex, body weight, blood pressure, and plasma angiotensin II, in all the patients and those not receiving RAS blockers. Moreover, (P)RR expression was elevated in infiltrated mononuclear cells but not connecting tubules or collecting ducts and vessels. Infiltrated cells positive for (P)RR consisted of CD3 and CD68 but not CD19.
  
  
  CONCLUSIONS
  These data suggest that plasma s(P)RR levels may reflect (P)RR expression levels in infiltrated mononuclear cells, which can be a surrogate marker of renal damage.
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Naro
authors.initials: N
authors.lastname: Ohashi
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Isobe
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Ishigaki
authors.affiliation: Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Iwakura
authors.affiliation: Blood Purification Unit, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ono
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujikura
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsuka
authors.affiliation: Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furuse
authors.affiliation: Blood Purification Unit, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kato
authors.affiliation: Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yasuda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy / Q000009:adverse effects*; D009395:Nephritis, Interstitial / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D011956:Receptors, Cell Surface / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000601:surgery*; D025262:Vacuolar Proton-Translocating ATPases / Q000097:blood*; D055815:Young Adult; D000093342:Prorenin Receptor
chemical_list: D015415:Biomarkers; D011956:Receptors, Cell Surface; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor