Key result
In the transgenic Ren2 rat, direct renin inhibition with aliskiren and AT1R blockade with irbesartan similarly attenuated albuminuria, podocyte injury, and renal oxidative stress (p<0.05).
Why the study?
Does treatment with aliskiren or irbesartan improve renal oxidative stress and glomerular injury in transgenic Ren2 rats?
Does treatment with aliskiren or irbesartan improve renal oxidative stress and glomerular injury in transgenic Ren2 rats?
p-value: p=<0.05
Direct renin inhibition and AT1R blockade provide comparable protection against RAS-mediated oxidant stress and podocyte injury in a hypertensive rat model, despite differences in blood pressure reduction.
Preclinical equivalence in Ren2 rats warrants no practice change; leaves open translation to human hypertensive CKD.
Renin-angiotensin system (RAS) activation contributes to kidney injury through oxidative stress. Renin is the rate-limiting step in angiotensin (ANG II) generation. Recent work suggests renin inhibition improves proteinuria comparable to ANG type 1 receptor (AT1R) blockade (ARB). Thereby, we investigated the relative impact of treatment with a renin inhibitor vs. an ARB on renal oxidative stress and associated glomerular structural and functional changes in the transgenic Ren2 rat, which manifests hypertension, albuminuria, and increased tissue RAS activity. Young Ren2 and age-matched Sprague-Dawley (SD) controls (age 6-9 wk) were treated with a renin inhibitor (aliskiren), an ARB (irbesartan), or vehicle for 21 days. Ren2 rats exhibited increases in systolic pressure (SBP), albuminuria, and renal 3-nitrotyrosine content as well as ultrastructural podocyte foot-process effacement and diminution of the podocyte-specific protein nephrin. Structural and functional alterations were accompanied by increased renal cortical ANG II, AT1R, as well as NADPH oxidase subunit (Nox2) expression compared with SD controls. Abnormalities were attenuated to a similar extent with both aliskiren and irbesartan treatment. Despite the fact the dose of irbesartan used caused a greater reduction in SBP than aliskerin treatment (P < 0.05), the effects on proteinuria, nephrin, and oxidative stress were similar between the two treatments. Our results highlight both the importance of pressor-related reductions on podocyte integrity and albuminuria as well as RAS-mediated oxidant stress largely comparable between ARB and renin inhibition treatment.
No takes yet. Share an insight, caveat, or question.
Whaley‐Connell et al. (2009) studied Hypertension and albuminuria (transgenic Ren2 rat model) (n=25). Aliskiren or Irbesartan vs. Vehicle (sham treatment) was evaluated on Glomerular filtration barrier injury (albuminuria, podocyte integrity, and oxidative stress) (p=<0.05). In the transgenic Ren2 rat, direct renin inhibition with aliskiren and AT1R blockade with irbesartan similarly attenuated albuminuria, podocyte injury, and renal oxidative stress (p<0.05).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: