Key result
Candesartan and enalapril provide equal renoprotection against glomerulosclerosis in rats with nephrectomy.
Why the study?
Do candesartan and enalapril provide equal renoprotection and alter renal cytokine gene expression in a rat model of chronic renal disease?
Do candesartan and enalapril provide equal renoprotection and alter renal cytokine gene expression in a rat model of chronic renal disease?
Absolute Event Rate: 42% vs 42%
Candesartan and enalapril are equally effective renoprotective agents in the 5/6 nephrectomy rat model, with renoprotection dependent on control of both systolic blood pressure and proteinuria.
Equivalent renoprotection by candesartan and enalapril in this rat model does not alter practice; leaves open translation to human CKD.
Potential determinants of chronic renal disease (CRD) progression were studied in male Munich-Wistar rats subjected to 5/6 nephrectomy and treated with candesartan (Csn; n = 30) or enalapril (Ena; n = 27) from 5 wk postsurgery. Despite control of systolic blood pressure (SBP; 24 wk: Csn = 143 +/- 9; Ena = 148 +/- 8 mmHg), urinary protein excretion rates (U(pr)V) increased over 24 wk (Csn = 92 +/- 10; Ena = 99 +/- 8mg/day). Glomerulosclerosis scores (GS) at 24 wk were similar for Csn (42 +/- 7%) vs. Ena (42 +/- 4%), values close to those of untreated controls at 12 wk (43 +/- 4%). At 24 wk, SBP and UprV correlated strongly with GS, together accounting for 72% of the variance in GS. Renal cortex mRNA levels (determined by competitive RT-PCR) for transforming growth factor (TGF)-beta1 and monocyte chemoattractant protein (MCP)-1 were elevated in Csn and Ena at 12 wk and remained higher at 24 wk vs. sham. Strong correlations were evident among TGF-beta1, MCP-1, and interleukin-1beta and renal injury at 24 wk. Cns and Ena are thus equally effective renoprotective agents in this model. During renin-angiotensin system inhibition, renoprotection is dependent on control of both SBP and UprV. Incomplete suppression of renal cytokine gene expression may also contribute to CRD progression.
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Taal et al. (2001) studied Chronic renal disease progression (n=57). Candesartan vs. Enalapril was evaluated on Glomerulosclerosis scores (GS) at 24 weeks. Candesartan and enalapril were equally effective renoprotective agents in rats with 5/6 nephrectomy, yielding similar glomerulosclerosis scores at 24 weeks (42% vs 42%).
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