Risk factors associated with biochemically detected and hospitalised acute kidney injury in patients prescribed renin angiotensin system inhibitors

Mark, Patrick B.; Papworth, Richard; Ramparsad, Nitish; Tomlinson, Laurie; Sawhney, Simon; Black, Corri; McConnachie, Alex; McCowan, Colin

doi:10.1111/bcp.14141

Cited by 6 publications

(4 citation statements)

References 41 publications

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“…ACE inhibitors reduce the production of angiotensin II, which results in vasodilation and reduced blood pressure. In this case, inhibiting the activities as an angiotensin-converting enzyme would relieve hypertension and hypertension-sensitive conditions, including heart failure, chronic kidney disease, or diabetes mellitus [45]. In mice, the role of the ACE/angiotensin II signaling has been investigated.…”

Section: Two Opposing Health Effects Of Ace On Admentioning

confidence: 99%

Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging

Brown

Malik

et al. 2021

IJMS

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A 2018 report from the American Heart Association shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin–angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, and heart failure, among others. It has been suggested that ACE inhibitors can alleviate the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that genetic variants of the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases, while other variants are associated with reduced risk of AD. In mice, ACE overexpression in the brain reduces symptoms of the AD model systems. Thus, we find two opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin–angiotensin system; (2) amyloid-degrading enzyme that hydrolyzes beta-amyloid, reducing amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to AD to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during midlife, leading to age-related later events.

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Section: Two Opposing Health Effects Of Ace On Admentioning

confidence: 99%

Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging

Brown

Malik

et al. 2021

IJMS

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“…We had previously shown that women tended to have lower doses of ACEIs prescribed relative to men, which may explain the reduced MACE benefit; however, this alone would not explain the greater AKI risk in women 29 . In clinical trials 30 and observational studies, 31 women were more likely to demonstrate an elevation in serum creatinine after initiating RAASIs, whereas the same findings were not replicated in other observational studies 13,32 . It is therefore unclear if women have a greater predisposition to renal injury while using RAASIs.…”

Section: Discussionmentioning

confidence: 96%

Renin‐angiotensin‐aldosterone system inhibitors and major cardiovascular events and acute kidney injury in patients with coronary artery disease

Sud

Chong³

et al. 2021

Pharmacotherapy

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Background Renin‐angiotensin‐aldosterone system inhibitors (RAASIs) are recommended for most patients with coronary artery disease (CAD). However, there is debate across guidelines as to which patients with CAD benefit the most from these agents. This study investigated the association between RAASIs and cardiovascular outcomes and acute kidney injury in a contemporary cohort of patients with CAD. Methods Patients ≥65 years of age with CAD alive on April 1, 2012 in Ontario, Canada were included. Outcomes included major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction (MI), unstable angina, stroke, or coronary revascularization), and acute kidney injury (AKI) hospitalizations at 4 years. Inverse probability of treatment‐weighted Cox proportional hazards regression models was used to compare the rates of each outcome in patients treated with and without RAASIs (angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers). Results There were 165,058 patients with CAD identified (mean age 75 years, 65.5% male, 64.7% prescribed RAASIs). After inverse‐probability weighting, treatment with RAASIs was associated with a lower rate of MACE compared with treatment without RAASIs (17.6% vs 18.2%, hazard ratio [HR]: 0.96, 95% CI: 0.93–0.99, respectively). However, treatment with RAASIs was associated with a higher rate of AKI compared with treatment without RAASIs (1.7% vs 1.5%, HR: 1.14, 95% CI: 1.02–1.29, respectively). The reduction in MACE was greater in patients with prior MI (HR: 0.87, 95% CI: 0.82–0.92) compared with patients without prior MI (HR: 1.00, 95% CI: 0.97–1.04, interaction p < 0.01). The increase in AKI was lower in patients with prior MI (HR: 0.82, 95% CI: 0.66–1.00) compared with patients without prior MI (HR: 1.37, 95% CI: 1.19–1.57, interaction p < 0.01). Conclusions This study supports the continued use of RAASIs in patients with CAD, although the benefit appears smaller in magnitude than observed in prior trials. High‐risk patients, particularly those with prior MI, appear to benefit the most from RAASIs.

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“…ACE inhibitors will reduce the production of angiotensin II, leading to vasodilation and reduced blood pressure. In this case, inhibiting the activities as an angiotensin-converting enzyme would relieve hypertension and hypertension sensitive health conditions, including heart failure, diabetes mellitus, or chronic kidney disease [37]. In mice, it also reduces AD symptoms in the mouse AD model [38].…”

Section: Two Opposing Health Effects Of Ace On Alzheimer's Disease (Ad)mentioning

confidence: 99%

Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging

Le¹,

Brown²,

Malik³

et al. 2021

Preprint

View full text Add to dashboard Cite

A recent report from the American Heart Association in 2018 shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin-angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, heart failure among others. It has been suggested that ACE inhibitors can reduce the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that alterations in the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases. In mice, overexpression of ACE in the brain reduces symptoms of the AD-model systems. Thus, we find opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin-angiotensin system; (2) amyloid-degrading enzyme that can hydrolyze beta-amyloid and reduce amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to Alzheimer’s disease to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during the midlife, leading to age-related later events.

show abstract

Risk factors associated with biochemically detected and hospitalised acute kidney injury in patients prescribed renin angiotensin system inhibitors

Cited by 6 publications

References 41 publications

Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging

Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging

Renin‐angiotensin‐aldosterone system inhibitors and major cardiovascular events and acute kidney injury in patients with coronary artery disease

Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging

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