Renin-angiotensin-aldosterone system dynamics after targeted blood pressure control using angiotensin II or norepinephrine in cardiac surgery: mechanistic randomised controlled trial

Coulson, Tim G; Miles, Lachlan F; Zarbock, A.; Burrell, Louise M; Patel, Sheila K.; Groote, Thilo von; Pilcher, David; Weinberg, Laurence; Landoni, Giovanni; Bellomo, Rinaldo

doi:10.1016/j.bja.2023.06.056

Cited by 7 publications

(5 citation statements)

References 17 publications

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“…11,13,17,26 In line with this assumption, a randomized feasibility study of AT-II as a primary vasopressor started at the time of surgery initiation suggested a possible reduction in the occurrence of AKI after cardiac surgery and effect of AT-II on renin kinetics. 27,28 In an exploratory analysis of renin kinetics in our trial, we also found that the administration of AT-II showed a more pronounced decrease of renin levels than placebo.…”

Section: Discussionsupporting

confidence: 55%

A Pilot Study of Renin-Guided Angiotensin-II Infusion to Reduce Kidney Stress After Cardiac Surgery

Sadjadi,

von Groote,

Weiss

et al. 2024

Anesthesia &Amp; Analgesia

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BACKGROUND: Vasoplegia is common after cardiac surgery, is associated with hyperreninemia, and can lead to acute kidney stress. We aimed to conduct a pilot study to test the hypothesis that, in vasoplegic cardiac surgery patients, angiotensin-II (AT-II) may not increase kidney stress (measured by [TIMP-2]*[IGFBP7]). METHODS: We randomly assigned patients with vasoplegia (cardiac index [CI] > 2.1l/min, postoperative hypotension requiring vasopressors) and Δ-renin (4-hour postoperative–preoperative value) ≥3.7 µU/mL, to AT-II or placebo targeting a mean arterial pressure ≥65 mm Hg for 12 hours. The primary end point was the incidence of kidney stress defined as the difference between baseline and 12 hours [TIMP-2]*[IGFBP7] levels. Secondary end points included serious adverse events (SAEs). RESULTS: We randomized 64 patients. With 1 being excluded, 31 patients received AT-II, and 32 received placebo. No significant difference was observed between AT-II and placebo groups for kidney stress (Δ-[TIMP-2]*[IGFBP7] 0.06 [ng/mL]2/1000 [Q1–Q3, −0.24 to 0.28] vs −0.08 [ng/mL]2/1000 [Q1–Q3, −0.35 to 0.14]; P = .19; Hodges-Lehmann estimation of the location shift of 0.12 [ng/mL]2/1000 [95% confidence interval, CI, −0.1 to 0.36]). AT-II patients received less fluid during treatment than placebo patients (2946 vs 3341 mL, P = .03), and required lower doses of norepinephrine equivalent (0.19 mg vs 4.18mg, P < .001). SAEs were reported in 38.7% of patients in the AT-II group and in 46.9% of patients in the placebo group. CONCLUSIONS: The infusion of AT-II for 12 hours appears feasible and did not lead to an increase in kidney stress in a high-risk cohort of cardiac surgery patients. These findings support the cautious continued investigation of AT-II as a vasopressor in hyperreninemic cardiac surgery patients.

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Section: Discussionsupporting

confidence: 55%

A Pilot Study of Renin-Guided Angiotensin-II Infusion to Reduce Kidney Stress After Cardiac Surgery

Sadjadi,

von Groote,

Weiss

et al. 2024

Anesthesia &Amp; Analgesia

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“…The first randomized trial comparing the intraoperative infusion of Ang II with that of norepinephrine in cardiac surgery patients was performed as a feasibility trial [ 37 ]. Following the confirmatory results regarding adherence without any concerns for adverse events [ 37 ], the authors explored the effect of Ang II on RAS within this randomized trial [ 38 ]. Compared to baseline, the renin level at ICU admission significantly increased in the norepinephrine group (52 [IQR, 115–137] vs. 112 [IQR, 49–410] µU/mL; P < 0.001), but not in the Ang II group (87 [IQR, 40–232] vs. 82 [IQR, 24–172] µU/mL; P = 0.36).…”

Section: Main Textmentioning

confidence: 99%

Renin in critically ill patients

Kotani,

Chappell,

Landoni

et al. 2024

Ann. Intensive Care

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The renin-angiotensin system (RAS) constitutes one of the principal mechanisms to maintain hemodynamic and fluid homeostasis. However, most research until now on RAS primarily focuses on its relationship with hypertension and its role in critically ill hypotensive populations is not well understood. With the approval of angiotensin II (Ang II) in the United States and Europe, following a phase 3 randomized controlled trial showing efficacy in catecholamine-resistant vasodilatory shock, there is growing interest in RAS in critically ill patients. Among the fundamental components of RAS, renin acts as the initial stimulus for the entire system. In the context of hypotension, its release increases in response to low blood pressure sensed by renal baroreceptors and attenuated negative Ang II feedback loop. Thus, elevated renin could reflect disease severity and predict poor outcomes. Studies investigating this hypothesis have validated the prognostic accuracy of renin in various critically ill populations, with several reports indicating its superiority to lactate for mortality prediction. Accordingly, renin reduction has been used to assess the effectiveness of Ang II administration. Furthermore, renin holds potential to identify patients who might benefit from Ang II treatment, potentially paving the way for personalized vasopressor management. Despite these promising data, most available evidence is derived from retrospective analysis and necessitates prospective confirmation. The absence of a rapid, point-of-care and reliable renin assay presents another hurdle to its integration into routine clinical practice. This narrative review aims to describe the current understanding and future directions of renin as a biomarker during resuscitation of critically ill patients.

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“…Postoperative hyperreninemia, linked to higher AKI risk, might be mitigated by AT2's potential to reduce renin and NE needs while preserving aldosterone, unlike NE. 111 – 114 While further research is needed, AT2's potential to lessen AKI, especially in patients with vasoplegia and a history of renin–angiotensin blockade, warrants exploration to improve outcomes.…”

Section: Prevention and Treatment Of Csa-akimentioning

confidence: 99%

Cardiac Surgery–Associated Acute Kidney Injury

Scurt,

Bose,

Mertens

et al. 2024

Kidney360

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Acute kidney injury (AKI) is a common and serious complication of cardiac surgery that has a significant impact on patient morbidity and mortality. The Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI is widely used to classify and identify AKI associated with cardiac surgery (CSA-AKI) based on changes in serum creatinine and/or urine output. There are various pre-, intra-, and postoperative risk factors for the development of CSA-AKI which should be recognized and addressed as early as possible to expedite its diagnosis, reduce its occurrence and prevent or ameliorate its devastating complications. Crucial issues are the inaccuracy of serum creatinine as a surrogate parameter of kidney function in the perioperative setting of cardiothoracic surgery and the necessity to discover more representative markers of the pathophysiology of AKI. However, except for the tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 ratio (TIMP2/IGFBP7), other diagnostic biomarkers with an acceptable sensitivity and specificity are still lacking. This article provides a comprehensive review of various aspects of CSA-AKI, including pathogenesis, risk factors, diagnosis, biomarkers, classification, prevention and treatment management.

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Renin-angiotensin-aldosterone system dynamics after targeted blood pressure control using angiotensin II or norepinephrine in cardiac surgery: mechanistic randomised controlled trial

Cited by 7 publications

References 17 publications

A Pilot Study of Renin-Guided Angiotensin-II Infusion to Reduce Kidney Stress After Cardiac Surgery

A Pilot Study of Renin-Guided Angiotensin-II Infusion to Reduce Kidney Stress After Cardiac Surgery

Renin in critically ill patients

Cardiac Surgery–Associated Acute Kidney Injury

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