The Dilemma of Dual Renin-Angiotensin System Blockade in Chronic Kidney Disease: Why Beneficial in Animal Experiments But Not in the Clinic?

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10360728" target="_blank" >RIV/00216208:11130/17:10360728 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00023001:_____/17:00075882 RIV/00216208:11110/17:10360728

Výsledek na webu

<a href="http://www.biomed.cas.cz/physiolres/pdf/66/66_181.pdf" target="_blank" >http://www.biomed.cas.cz/physiolres/pdf/66/66_181.pdf</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

The Dilemma of Dual Renin-Angiotensin System Blockade in Chronic Kidney Disease: Why Beneficial in Animal Experiments But Not in the Clinic?

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

The Dilemma of Dual Renin-Angiotensin System Blockade in Chronic Kidney Disease: Why Beneficial in Animal Experiments But Not in the Clinic?

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30217 - Urology and nephrology

Projekt

<a href="/cs/project/NV15-28671A" target="_blank" >NV15-28671A: Farmakologická blokáda endotelinového systému a solubilní epoxid hydrolázy jako nový přístup k léčbě hypertenzního orgánového poškození.</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Physiological Research

ISSN

0862-8408

e-ISSN

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Svazek periodika

66

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

12

Strana od-do

181-192

Kód UT WoS článku

000404258800002

EID výsledku v databázi Scopus

2-s2.0-85019267575