title: Does aliskiren protect the kidney following ischemia reperfusion injury?
abstract: The effect of blocking the first and rate-limiting step in renin-angiotensin cascade on the renal function in ischemia reperfusion injury has not been previously investigated. We investigated the effect of aliskiren, the first approved direct oral renin inhibitor, on the alterations in renal functional parameters in this condition. Wistar rats underwent left renal ischemia for 40 min. Group-1 received normal saline whereas Group-2 received aliskiren (30 mg/kg/day) by gavage for 6 days commencing one day before IRI. The hemodynamic and tubular functions and gene expression of neutrophil gelatinase-associated lipocalin (NGAL) and plasminogen activating inhibitor (PAI-1) in the right and left kidneys were measured five days following the IRI. Comparing Group-1 and Group-2, the left renal blood flow was significantly higher in Group-2 (1.28+/-0.36 vs. 0.39+/-0.05, P=0.007). Left kidney glomerular filtration rate was also higher in Group-2 but did not reach statistical significance (0.18+/-0.05 vs. 0.10+/-0.02, P=0.07). The left renal FE(Na) was significantly lower in Group-2 (29.9+/-6.4 vs. 49.7+/-7.8, P=0.03). Aliskiren also caused a significant decrease in the gene expression of both NGAL and PAI-1 in the left ischemic kidney. In conclusions, the administration of aliskiren before and after IRI appears to have ameliorated the IRI effect on the total renal artery blood flow, fractional excretion of sodium and gene expression of both NGAL and PAI-1 indicating a renoprotective effects in IRI.
authors.affiliation: Department of Surgery, College of Medicine and Health Sciences, Al Ain, United Arab Emirates. fayez@mail2doctor.com.
authors.forename: F T
authors.initials: FT
authors.lastname: Hammad
authors.forename: S
authors.initials: S
authors.lastname: Al-Salam
authors.forename: L
authors.initials: L
authors.lastname: Lubbad
mesh_terms: D000577:Amides / Q000008:administration & dosage*; D000818:Animals; D005650:Fumarates / Q000008:administration & dosage*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012076:Renal Agents / Q000008:administration & dosage; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control*; D016896:Treatment Outcome; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D005650:Fumarates; D012076:Renal Agents; D000092502:Renin Inhibitors; C446481:aliskiren