The effect of aliskiren on the renal dysfunction following unilateral ureteral obstruction in the rat

Fayez T. Hammad, Loay Lubbad

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Purpose: To investigate the effect of blocking renin-angiotensin system by direct renin inhibition using aliskiren on the renal dysfunction following reversible unilateral ureteral obstruction (UO). Methods: Wistar rats underwent reversible left UO for 72 hours. Group-Alsk (n=12) received aliskiren (30 mg/kg/day) dissolved in water starting one day before creating UO and continued until the terminal experiment five days post reversal when renal functions were measured using clearance techniques. Group-Vx (n=12) underwent similar protocol but had water only. Gene expression analysis of some markers of kidney injury was measured using PCR technique. Results: In Group-Vx, renal blood flow (RBF) and glomerular filtration rate (GFR) in the left kidney were significantly lower than the right kidney (1.82±0.12 vs. 3.19±0.40, P=0.001 and 0.81±0.08 vs. 1.44±0.09, P=0.004, respective­ly). However, left fractional excretion of sodium (FENa) was higher than the right FENa (0.80±0.15 vs. 0.55±0.04, P=0.05). Comparing the left obstructed kidney in Group-Alsk vs. Group-Vx, RBF and GFR were higher in Group-Alsk (2.44±0.30 vs. 1.82±0.12, P=0.049 and 1.02±0.11 vs. 0.81±0.08, P=0.07, respectively). The left renal FENa was lower in Group-Alsk but did not reach statistical significance (0.54±0.07 vs. 0.80±0.15, P=0.07). Aliskiren also de­creased the gene expressions of NGAL, KIM-1 and p53. Conclusion: Direct renin inhibition by aliskiren appears to have protective effect on the renal dysfunction and on the markers of renal injury following UO indicating a potential clinical benefit of this agent. Further, this data and the previous studies indicate that blocking renin-angiotensin system at any level has a protective effect in obstructive nephropathy.

Original languageEnglish
Pages (from-to)70-77
Number of pages8
JournalInternational Journal of Physiology, Pathophysiology and Pharmacology
Volume8
Issue number2
Publication statusPublished - 2016

Keywords

  • Aliskiren
  • Renal function
  • Ureteral obstruction

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Physiology
  • Physiology (medical)

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