title: Serum level of soluble (pro)renin receptor is modulated in chronic kidney disease.
abstract: BACKGROUND
  Prorenin, the precursor of renin, binds to the (pro)renin receptor [(P)RR] and triggers intracellular signaling. The ligand binding sites of (P)RR are disconnected and are present in the soluble form of the receptor in serum. Given that the clinical significance of serum prorenin and soluble (P)RR in chronic kidney disease (CKD) is unclear, we investigated the relationship between serum prorenin, soluble (P)RR, and various clinical parameters in patients with CKD.
  
  
  METHODS
  A total of 374 patients with CKD were enrolled. Serum samples were collected, and the levels of soluble (P)RR and prorenin were measured using ELISA kits. Serum creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA), hemoglobin (Hb), soluble secreted α-Klotho, and the urine protein/Cr ratio were also measured. Similarly, clinical parameters were also evaluated using serum and urine sample collected after 1 year (n = 204).
  
  
  RESULTS
  Soluble (P)RR levels were positively associated with serum Cr (P < 0.0001, r = 0.263), BUN (P < 0.0001, r = 0.267), UA (P < 0.005, r = 0.168) levels, CKD stage (P < 0.0001, r = 0.311) and urine protein/Cr ratio (P < 0.01, r = 0.157), and inversely with estimated glomerular infiltration rate (eGFR) (P < 0.0001, r = -0.275) and Hb (P < 0.005, r = -0.156). Soluble (P)RR levels were inversely associated with α-Klotho levels (P < 0.001, r = -0.174) but did not correlate with prorenin levels. With respect to antihypertensive drugs, soluble (P)RR levels were significantly lower in patients treated with an angiotensin II receptor blocker (ARB) than in those without ARB therapy (P < 0.005). Soluble (P)RR levels were significantly lower in CKD patients with diabetes mellitus or primary hypertension than in those without these conditions (P < 0.05). In contrast, serum levels of prorenin did not correlate with parameters related to renal function. Serum prorenin levels were significantly higher in CKD patients with diabetes mellitus than in nondiabetic patients (P < 0.05), but not in CKD patients with hypertension (P = 0.09). Finally, with respect to the relationship between basal soluble (P)RR levels and the progression rates of renal function, soluble (P)RR levels were positively associated with ΔCr (P < 0.05, r = 0.159) and inversely associated with ΔeGFR (P < 0.05, r = -0.148).
  
  
  CONCLUSIONS
  Serum levels of soluble (P)RR correlated with the stage of CKD. Our findings suggest that soluble (P)RR may be involved in renal injury and influence the progression of CKD.
authors.affiliation: Department of Endocrinology, Metabolism and Nephrology, Kochi University School of Medicine, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
authors.forename: Kazu
authors.initials: K
authors.lastname: Hamada
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Shimamura
authors.forename: Kosuke
authors.initials: K
authors.lastname: Inoue
authors.forename: Koji
authors.initials: K
authors.lastname: Ogata
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishihara
authors.forename: Taro
authors.initials: T
authors.lastname: Horino
authors.forename: Shimpei
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohguro
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yoshimoto
authors.forename: Mika
authors.initials: M
authors.lastname: Ikebe
authors.forename: Kenji
authors.initials: K
authors.lastname: Yuasa
authors.forename: Eri
authors.initials: E
authors.lastname: Hoshino
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Iiyama
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Ichihara
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Terada
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000188:drug therapy; D012083:Renin / Q000097:blood*; D000093342:Prorenin Receptor
chemical_list: D057911:Angiotensin Receptor Antagonists; D011956:Receptors, Cell Surface; D003404:Creatinine; D005966:Glucuronidase; D000090265:Klotho Proteins; D012083:Renin; D000093342:Prorenin Receptor
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