MP67-19 ALISKIREN PROVIDES INCOMPLETE PROTECTION OF THE KIDNEY IN UNILATERAL URETERIC OBSTRUCTION IN THE RAT

Abstract

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology II1 Apr 2016MP67-19 ALISKIREN PROVIDES INCOMPLETE PROTECTION OF THE KIDNEY IN UNILATERAL URETERIC OBSTRUCTION IN THE RAT Fayez Hammad and Loay Lubbad Fayez HammadFayez Hammad More articles by this author and Loay LubbadLoay Lubbad More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1335AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ureteric obstruction (UO) is a common urological condition caused by several conditions such as urolithiasis and might lead to renal impairment. UO induces alterations in renin angiotensin system (RAS) which plays an important role in obstruction-induced renal dysfunction. Renin catalyzes the first and rate limiting step of RAS. However, until recently, direct renin inhibitors were not used effectively in clinical practice due to toxicity, poor bioavailability and limited efficacy. Aliskiren is the first commercially available FDA-approved oral direct renin inhibitor. Very few studies showed that aliskiren ameliorates some of the UO-induced markers of acute renal injury. However, these protective effects do not necessarily imply an improvement in the UO-induced alterations in some of the clinically more relevant parameters such as the glomerular filtration rate (GFR), renal blood flow (RBF) and tubular functions. Indeed, the effect of aliskiren on these parameters in the post-obstruction period has not been studied yet. Thus, the aim of this study was to investigate the effect of aliskiren on the alterations in renal dysfunction following reversible unilateral UO in the rat. METHODS Male Wistar rats underwent reversible left UO for 72 hours. Group-1 (n=10) received aliskiren (60 mg/kg/day) dissolved in water by oral gavage starting one day before and continued throughout the period of UO until the terminal experiment 5 days post reversal when the renal functions were measured using clearance techniques. Group-2 (n=10) underwent similar protocol but had drinking water only. In addition, gene expression of some markers of kidney injury was measured in the kidney tissue using PCR technique. RESULTS The mean arterial blood pressure and heart rate in both groups were similar. UO affected all hemodynamic and tubular parameters in the affected kidney. So in Group-2, left RBF, was 57% of the right RBF (1.82±0.12 vs. 3.19±0.40, P<0.01). Similarly, left GFR was 55% that of the right GFR (0.81±0.08 vs. 1.44±0.09, P<0.01). On the other hand, the left fractional excretion of sodium (FENa) was higher than the right FENa (0.76±0.17 vs. 0.56±0.09, P<0.05). Aliskiren attenuated the UO-related alterations in hemodynamic parameters; so when the left obstructed kidney in Group-2 and Group-1 were compared, RBF was significantly higher in Group-1 (2.44±0.30 vs. 1.82±0.12, P=0.049). GFR was also higher in Group-1 (1.02±0.10 vs. 0.81±0.08, P=0.07) but did not reach statistical significance. On the other hand, the left renal FENa was similar in both groups (0.53±0.08 vs. 0.76±0.17, P=0.12). Aliskiren also decreased the gene expressions of some of the markers of kidney injury such as Lipocalin-2 (2.7±0.2 vs. 5.5±1.2, P=0.03). CONCLUSIONS Aliskiren attenuated the UO-induced alterations in the hemodynamic renal parameters and some of the markers of kidney injury but not the tubular alterations indicating an incomplete protective effect of this renin inhibitor © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e888 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Fayez Hammad More articles by this author Loay Lubbad More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...