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

Abstract

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.

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

“…There is a report of four COVID-19 patients, in whom ACE-Inhs. or ARBs had to be stopped due to acute kidney injury ( Chenna et al, 2020 ). In addition, the use of ACE-Inhs.…”

COVID-19 and APOL-1 High-Risk Genotype-Associated Collapsing Glomerulonephritis

“…SARS-Cov-2 enters ACE2 receptors located in proximal tubules and podocytes in kidneys per postmortem histology [ 7 , 15 ]. In addition to the above mentioned mechanisms, imbalanced RAS activation, hypovolemia, high PEEP, and hemodynamic changes are suggested by Ahmadian et al [ 16 ] Also, IgA nephropathy was seen as a causative agent for AKI in COVID-19 in one case [ 17 ].…”

Lesão renal aguda na COVID-19 e abordagem multiprofissional

“…A LRA na infecção por COVID-19 se deve à combinação de resposta inflamatória sistêmica induzida por citocinas, efeito citotrópico direto induzido por vírus e necrose tubular aguda, devido a falha de múltiplos órgãos e choque. Outros fatores como depleção de volume, toxicidade do medicamento, exposição ao contraste e hipotensão podem resultar em insuficiência renal aguda (IRA) (Chenna et al, 2020).…”

“…A proteína Spike (S) do vírus tem alta afinidade de ligação ao domínio catalítico da ECA2 (Hoffmann et al, 2020), o que pode causar alterações conformacionais na proteína S (Wrapp et al, 2020). As proteases celulares (TMPRSS2) realizam o priming e clivagem da proteína S e, com isso, permitem a fusão das membranas virais e celulares (Hoffmann et al, 2020), mecanismo central na determinação do tropismo tecidual (Chenna et al, 2020). Wrapp et al (2020) demonstraram que, na microscopia crioeletrônica, a proteína S do nCoV tem afinidades 10 a 20 vezes maiores para a ECA2 quando comparada com a do SARS-CoV.…”

“…Isso porque medicamentos comumente usados para o tratamento dessas comorbidades como inibidores da enzima conversora de angiotensina (IECA) e bloqueadores do receptor de angiotensina (BRA), aumentam a expressão do gene ECA2, facilitando a invasão viral, e mitigam a regulação negativa da ECA2. Outros fármacos, como diuréticos e a administração de contraste iodado também contribuem na LRA (Chenna et al, 2020).…”