Summary
ACE inhibitors effectively reduce systemic vascular resistance in patients with hypertension, heart failure or chronic renal disease. This antihypertensive efficacy probably accounts for an important part of their long term renoprotective effects in patients with diabetic and non-diabetic renal disease.
The renal mechanisms underlying the renal adverse effects of ACE inhibitors — intrarenal efferent vasodilation with a consequent fall in filtration pressure — are held to be involved in their renoprotective effects as well. The fall in filtration pressure presumably contributes to the antiproteinuric effect as well as to long term renoprotection. The former is suggested by the positive correlation between the fall in filtration fraction and the reduction in proteinuria found during ACE inhibition. The latter is suggested by the correlation between the (slight) reduction in glomerular filtration rate at onset of therapy and a more favourable course of renal function in the long term. Such a fall in filtration rate at the onset of ACE inhibitor treatment is reversible after withdrawal, and can be considered the tradeoff for long term renal protection in patients with diabetic and nondiabetic chronic renal disease.
In conditions in which glomerular filtration is critically dependent on angiotensin II-mediated efferent vascular tone (such as a post-stenotic kidney, or patients with heart failure and severe depletion of circulating volume), ACE inhibition can induce acute renal failure, which is reversible after withdrawal of the drug.
Systemic and renal haemodynamic effects of ACE inhibition, both beneficial and adverse, are potentiated by sodium depletion. Consequently, sodium repletion contributes to the restoration of renal function in patients with ACE inhibitor-induced acute renal failure. On the other hand, co-treatment with diuretics and sodium restriction can improve therapeutic efficacy in patients in whom the therapeutic response of blood pressure or proteinuria is insufficient.
Patients at the greatest risk for renal adverse effects (those with heart failure, diabetes mellitus and/or chronic renal failure) also can expect the greatest benefit. Therefore, ACE inhibitors should not be withheld in these patients, but dosages should be carefully titrated, with monitoring of renal function and serum potassium levels.
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Navis, G., Faber, H.J., de Zeeuw, D. et al. ACE Inhibitors and the Kidney. Drug-Safety 15, 200–211 (1996). https://doi.org/10.2165/00002018-199615030-00005
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DOI: https://doi.org/10.2165/00002018-199615030-00005