The dilemma of dual renin-angiotensin system blockade in chronic kidney disease: why beneficial in animal experiments but not in the clinic?
Language English Country Czech Republic Media print
Document type Journal Article, Review
PubMed
28471687
DOI
10.33549/physiolres.933607
PII: 933607
Knihovny.cz E-resources
- MeSH
- Acute Kidney Injury chemically induced immunology prevention & control MeSH
- Angiotensin II Type 1 Receptor Blockers administration & dosage MeSH
- Renal Insufficiency, Chronic drug therapy immunology MeSH
- Species Specificity MeSH
- Hyperkalemia chemically induced immunology prevention & control MeSH
- Hypertension chemically induced immunology prevention & control MeSH
- Angiotensin-Converting Enzyme Inhibitors administration & dosage adverse effects MeSH
- Humans MeSH
- Evidence-Based Medicine MeSH
- Disease Models, Animal * MeSH
- Renin-Angiotensin System drug effects immunology MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Angiotensin II Type 1 Receptor Blockers MeSH
- Angiotensin-Converting Enzyme Inhibitors MeSH
Drugs interfering with the renin-angiotensin-aldosterone system (RAAS) improved the prognosis in patients with hypertension, heart failure, diabetes and chronic kidney disease. However, combining different drugs brought no further benefit while increasing the risk of hyperkalemia, hypotension and acute renal failure. This was so with combining angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptors type 1 antagonists (ARB). Dissimilarly, in animal disease models this dual therapy proved clearly superior to single drug treatment and became the optimal standard regime for comparison with other treatments. This review analyzes the causes of the discrepancy of effects of the dual therapy between animal experiments versus clinical studies, and is focused on the outcomes in chronic kidney disease. Discussed is the role of species differences in RAAS, of the variability of the disease features in humans versus relative stability in animals, of the genetic uniformity in the animals but not in humans, and of the biased publication habits of experimental versus clinical studies. We attempt to understand the causes and reconcile the discordant findings and suggest to what extent dual RAAS inhibition should be continued in animal experiments and why its application in the clinics should be limited to strictly selected groups of patients.
References provided by Crossref.org
Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease
