Key result
In obese Zucker rats with established renal injury, perindopril and candesartan reduced systolic blood pressure by 16% (P<0.001) and 10% (P<0.05) respectively, and markedly reduced proteinuria.
Why the study?
Does late inhibition of the renin-angiotensin system with perindopril or candesartan reverse established renal injury in obese Zucker rats?
RCT (n=40)
randomized
Does late inhibition of the renin-angiotensin system with perindopril or candesartan reverse established renal injury in obese Zucker rats?
Effect estimate: 16% reduction (perindopril), 10% reduction (candesartan)
p-value: p=<0.001 (perindopril), <0.05 (candesartan)
In a rat model of established nephropathy, late RAS inhibition with perindopril or candesartan halted glomerulosclerosis and markedly reduced proteinuria, though tubulointerstitial fibrosis and vascular injury remained unchanged.
Supports late RAS inhibition for proteinuria in obese rat models; leaves open reversal of established human renal injury.
BACKGROUND/AIMS: In experimental nephropathies, inhibitors of the renin-angiotensin-system (RAS) halted the progression, or even induced a regression in renal injury. We studied the potential of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the angiotensin receptor blocker candesartan to reverse the established renal injury in the obese Zucker rat (OZR). METHODS: Forty 4-week-old OZRs were uninephrectomized and fed a high-protein diet. After 16 weeks, they were randomized into 4 groups (n = 10 each) with comparable proteinuria: (1) control group sacrificed immediately for baseline data, and groups gavaged daily for 8 weeks with (2) placebo, (3) perindopril (1 mg/kg/day), or (4) candesartan (10 mg/kg/day). RESULTS: Both drugs reduced systolic blood pressure (perindopril -16%, p < 0.001; candesartan -10%, p < 0.05), renal hypertrophy, and proteinuria (perindopril to 32%; candesartan to 37% of pretreatment values). Glomerulosclerosis was halted (perindopril p < 0.001; candesartan p < 0.05), and the numbers of glomerular endothelial and podocyte cells were restored. Mesangiolysis was reversed by perindopril. Metabolic and oxidative parameters were either stabilized (perindopril), or improved (candesartan). CONCLUSION: In the OZR late inhibition of RAS halts the progression of glomerulosclerosis, reverses mesangiolysis and prevents the decline in glomerular endothelial cell and podocyte numbers. Tubulointerstitial fibrosis and vascular injury remain unchanged. Proteinuria shows marked regression.
No takes yet. Share an insight, caveat, or question.
Šebeková et al. (2008) conducted an RCT in established renal injury (n=40). Perindopril and Candesartan vs. placebo was evaluated on systolic blood pressure (16% reduction (perindopril), 10% reduction (candesartan), p=<0.001 (perindopril), <0.05 (candesartan)). In obese Zucker rats with established renal injury, perindopril and candesartan reduced systolic blood pressure by 16% (P<0.001) and 10% (P<0.05) respectively, and markedly reduced proteinuria.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: