title: Na+/Ca2+ exchange inhibitor, KB-R7943, attenuates contrast-induced acute  kidney injury.
abstract: BACKGROUND
  Intracellular Ca2+ overload is considered to be a key factor in contrast-induced acute kidney injury (CI-AKI). The Na+/Ca2+ exchanger (NCX) system is one of the main pathways of intracellular Ca2+ overload. We investigated the effects of KB-R7943, an inhibitor of the reverse mode of NCX, on CI-AKI in a rat model.
  
  
  METHODS
  Rats were divided into control group, CI-AKI group and pretreatment groups (with KB-R7943 dose of 5 or 10 mg/kg). CI-AKI was induced by diatrizoate administration in rats with cholesterol-supplemented diet for 8 weeks. Renal function and renal hemodynamics were determined 1 day following contrast medium administration. Renal histopathology was observed by light microscope. Renal tubular apoptosis was examined by TUNEL. Renal endothelin-1 (ET-1) was measured by radioimmunoassay. Renal malondialdehyde (MDA) and catalase (CAT) were measured as oxidative markers.
  
  
  RESULTS
  Levels of serum creatinine (Scr), renal ET-1, MDA and CAT, and resistance index (RI) of renal blood vessels increased significantly in CI-AKI rats. The  increases in Scr and RI of renal blood vessels induced by diatrizoate were suppressed significantly and  dose-dependently by pretreatment with KB-R7943. Histopathological and TUNEL results showed that  the contrast medium-induced severe renal tubular  necrosis and apoptosis were significantly and dose-dependently attenuated by KB-R7943. KB-R7943 significantly suppressed the increment of renal ET-1 content and MDA and CAT level induced by contrast medium administration.
  
  
  CONCLUSIONS
  Activation of the reverse mode of NCX, followed by ET-1 overproduction and increased oxidative stress, seems to play an important role in the pathogenesis of CI-AKI. The inhibitor of the reverse mode of NCX, KB-R7943, has renoprotective effects on CI-AKI.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, General Hospital of Tianjin Medical University, Tianjin - PR China.
authors.forename: Dingwei
authors.initials: D
authors.lastname: Yang
authors.forename: Dingping
authors.initials: D
authors.lastname: Yang
authors.forename: Ruhan
authors.initials: R
authors.lastname: Jia
authors.forename: Jin
authors.initials: J
authors.lastname: Tan
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D002374:Catalase / Q000032:analysis; D003287:Contrast Media / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D003973:Diatrizoate; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000032:analysis / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009336:Necrosis / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014655:Vascular Resistance
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D003287:Contrast Media; D019332:Endothelin-1; D019831:Sodium-Calcium Exchanger; D003973:Diatrizoate; D008315:Malondialdehyde; D003404:Creatinine; D002374:Catalase; D013890:Thiourea