Acute kidney injury in the rat causes cardiac remodelling and increases angiotensin-converting enzyme 2 expression

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.

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Novel Evidence of Acute Kidney Injury in COVID-19

Journal of Clinical Medicine ◽

10.3390/jcm9113547 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3547

Author(s):

Ti-I Chueh ◽

Cai-Mei Zheng ◽

Yi-Chou Hou ◽

Kuo-Cheng Lu

Keyword(s):

Acute Kidney Injury ◽

Angiotensin Converting Enzyme ◽

Kidney Injury ◽

Host Cells ◽

Current Evidence ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Renal Tubular

The coronavirus 2019 (COVID-19) pandemic has caused a huge impact on health and economic issues. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes cellular damage by entry mediated by the angiotensin-converting enzyme 2 of the host cells and its conjugation with spike proteins of SARS-CoV-2. Beyond airway infection and acute respiratory distress syndrome, acute kidney injury is common in SARS-CoV-2-associated infection, and acute kidney injury (AKI) is predictive to multiorgan dysfunction in SARS-CoV-2 infection. Beyond the cytokine storm and hemodynamic instability, SARS-CoV-2 might directly induce kidney injury and cause histopathologic characteristics, including acute tubular necrosis, podocytopathy and microangiopathy. The expression of apparatus mediating SARS-CoV-2 entry, including angiotensin-converting enzyme 2, transmembrane protease serine 2 (TMPRSS2) and a disintegrin and metalloprotease 17 (ADAM17), within the renal tubular cells is highly associated with acute kidney injury mediated by SARS-CoV-2. Both entry from the luminal and basolateral sides of the renal tubular cells are the possible routes for COVID-19, and the microthrombi associated with severe sepsis and the dysregulated renin–angiotensin–aldosterone system worsen further renal injury in SARS-CoV-2-associated AKI. In the podocytes of the glomerulus, injured podocyte expressed CD147, which mediated the entry of SARS-CoV-2 and worsen further foot process effacement, which would worsen proteinuria, and the chronic hazard induced by SARS-CoV-2-mediated kidney injury is still unknown. Therefore, the aim of the review is to summarize current evidence on SARS-CoV-2-associated AKI and the possible pathogenesis directly by SARS-CoV-2.

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Renal complications in coronavirus disease 2019: a systematic review

Inflammation and Regeneration ◽

10.1186/s41232-020-00140-9 ◽

2020 ◽

Vol 40 (1) ◽

Author(s):

Taichiro Minami ◽

Yasunori Iwata ◽

Takashi Wada

Keyword(s):

Systematic Review ◽

Acute Kidney Injury ◽

Severe Acute Respiratory Syndrome ◽

Angiotensin Converting Enzyme ◽

Kidney Injury ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

The World ◽

Life Threatening ◽

Life Threatening Complication

AbstractThe world today is facing a pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which mainly causes a respiratory disease known as coronavirus disease 2019 (COVID-19). Therefore, its pathogenesis and complications should be identified and understood. SARS-CoV-2 infects the host using the angiotensin-converting enzyme 2 (ACE2) as its receptor, which is expressed in several organs including the lungs, heart, kidneys, and intestines. Kidney complications are relatively common, and acute kidney injury (AKI) is a life-threatening complication in patients with COVID-19. In this review, the renal histological patterns of COVID-19 are described in detail, and its potential mechanisms associated with AKI are discussed.

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