scholarly journals Reduced urinary levels of angiotensin-converting enzyme 2 activity predict acute kidney injury in critically ill patients

2020 ◽  
Vol 22 (4) ◽  
pp. 344-354
Author(s):  
Laurent Bitker ◽  
◽  
Sheila K Patel ◽  
Intissar Bittar ◽  
Glenn M Eastwood ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Acute Kidney Injury ◽  
Angiotensin Converting Enzyme ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Urine Collection ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Urine Creatinine

Objective: Angiotensin-converting enzyme 2 activity reflects non-classical renin–angiotensin system upregulation. We assessed the association of urinary angiotensin-converting enzyme 2 (uACE2) activity with acute kidney injury (AKI). Design, setting and participants: A prospective observational study in which we measured uACE2 activity in 105 critically ill patients at risk of AKI. We report AKI stage 2 or 3 at 12 hours of urine collection (AKI12h) and AKI stage 2 or 3 at any time during intensive care unit stay in patients free from any stage of AKI at inclusion (AKIICU). AKI prediction was assessed using area under the receiver-operating characteristics curve (AUROC) and net reclassification indices (NRIs). Main outcome measure: AKI stage 2 or 3 at 12 hours of urine collection. Results: Within 12 hours of inclusion, 32 of 105 patients (30%) had developed AKI12h. Corrected uACE2 activity was significantly higher in patients without AKI12h compared with those with AKI12h (median [interquartile range], 13 [6–24] v 7 [4–10] pmol/min/mL per mmol/L of urine creatinine; P < 0.01). A 10-unit increase in uACE2 was associated with a 28% decrease in AKI12h risk (odds ratio [95% CI], 0.72 [0.46–0.97]). During intensive care unit admission, 39 of 76 patients (51%) developed AKIICU. uACE2 had an AUROC for the prediction of AKI12h of 0.68 (95% CI, 0.57–0.79), and correctly reclassified 28% of patients (positive NRI) to AKI12h. Patients with uACE2 > 8.7 pmol/min/mL per mmol/L of urine creatinine had a significantly lower risk of AKIICU on log-rank analysis (52% v 84%; P < 0.01). Conclusions: Higher uACE2 activity was associated with a decreased risk of AKI stage 2 or 3. Our findings support future evaluations of the role of the non-classical renin–angiotensin system during AKI.

scholarly journals Acute Kidney Injury in a Case Series of Patients with Confirmed COVID-19 (Coronavirus Disease 2019): Role of Angiotensin-Converting Enzyme 2 and Renin-Angiotensin System Blockade

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Avantika Chenna ◽  
Venu Madhav Konala ◽  
Subhasish Bose ◽  
Sasmit Roy ◽  
Bhaskar Reddy Madhira ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Receptor Blockers

The renin-angiotensin system plays a very critical role in hypertension, diabetes, and kidney and heart diseases. The blockade of the renin-angiotensin system results in the prevention of progression of renal and cardiac damage. There have been controversial hypotheses raised regarding the safety of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in COVID-19 (coronavirus disease 2019). We present the case series of four patients (2 men and 2 women; 1 Caucasian and 3 African Americans; two survived and two died) with confirmed COVID-19, presenting with respiratory symptoms and acute kidney injury, who have been on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Membrane-bound angiotensin-converting enzyme 2 (ACE2) has been implicated as the gateway for viral entry into the human cell in causing the infection. The factors contributing to acute kidney injury are diuretics, iodinated contrast administration, hemodynamic instability apart from ACE inhibitors, and angiotensin receptor blockers. The ACE inhibitors and ARBs were stopped in these patients due to acute kidney injury. We also discussed the role of ACE2 and the renin-angiotensin system (RAS) blockade in patients with COVID-19 infection along with pathogenesis.

scholarly journals Pathological Role of Angiotensin II in Severe COVID-19

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e138-e144 ◽  
Author(s):  
Wolfgang Miesbach
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Treatment Options ◽  
Renin Angiotensin System ◽  
Target Cells ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Novel Coronavirus

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.

scholarly journals ACE2 Shedding and the Role in COVID-19

2022 ◽  
Vol 11 ◽  
Author(s):  
Jieqiong Wang ◽  
Huiying Zhao ◽  
Youzhong An
Keyword(s):  
Amino Acids ◽  
Viral Entry ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Underlying Mechanism ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Transmembrane Glycoprotein

Angiotensin converting enzyme 2 (ACE2), a transmembrane glycoprotein, is an important part of the renin-angiotensin system (RAS). In the COVID-19 epidemic, it was found to be the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). ACE2 maintains homeostasis by inhibiting the Ang II-AT1R axis and activating the Ang I (1-7)-MasR axis, protecting against lung, heart and kidney injury. In addition, ACE2 helps transport amino acids across the membrane. ACE2 sheds from the membrane, producing soluble ACE2 (sACE2). Previous studies have pointed out that sACE2 plays a role in the pathology of the disease, but the underlying mechanism is not yet clear. Recent studies have confirmed that sACE2 can also act as the receptor of SARS-COV-2, mediating viral entry into the cell and then spreading to the infective area. Elevated concentrations of sACE2 are more related to disease. Recombinant human ACE2, an exogenous soluble ACE2, can be used to supplement endogenous ACE2. It may represent a potent COVID-19 treatment in the future. However, the specific administration concentration needs to be further investigated.

scholarly journals Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System

2020 ◽  
Vol 126 (10) ◽  
pp. 1456-1474 ◽  
Author(s):  
Mahmoud Gheblawi ◽  
Kaiming Wang ◽  
Anissa Viveiros ◽  
Quynh Nguyen ◽  
Jiu-Chang Zhong ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin

scholarly journals Coronavirus disease 2019 (COVID-19) and the renin-angiotensin system: A closer look at angiotensin-converting enzyme 2 (ACE2)

2020 ◽  
Vol 57 (5) ◽  
pp. 339-350 ◽  
Author(s):  
Annalise E Zemlin ◽  
Owen J Wiese
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
World Health ◽  
Atypical Pneumonia ◽  
Converting Enzyme ◽  
Wholesale Market ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin

Since the first cases of atypical pneumonia linked to the Huanan Seafood Wholesale Market in Wuhan, China, were described in late December 2019, the global landscape has changed radically. In March 2020, the World Health Organization declared COVID-19 a global pandemic, and at the time of writing this review, just over three million individuals have been infected with more than 200,000 deaths globally. Numerous countries are in ‘lockdown’, social distancing is the new norm, even the most advanced healthcare systems are under pressure, and a global economic recession seems inevitable. A novel coronavirus (SARS-CoV-2) was identified as the aetiological agent. From experience with previous coronavirus epidemics, namely the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in 2004 and 2012 respectively, it was postulated that the angiotensin-converting enzyme-2 (ACE2) receptor is a possible port of cell entry. ACE2 is part of the renin-angiotensin system and is also associated with lung and cardiovascular disorders and inflammation. Recent studies have confirmed that ACE2 is the port of entry for SARS-CoV-2. Male sex, advanced age and a number of associated comorbidities have been identified as risk factors for infection with COVID-19. Many high-risk COVID-19 patients with comorbidities are on ACE inhibitors and angiotensin receptor blockers, and this has sparked debate about whether to continue these treatment regimes. Attention has also shifted to ACE2 being a target for future therapies or vaccines against COVID-19. In this review, we discuss COVID-19 and its complex relationship with ACE2.

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