A review of Covid-19 and acute kidney injury: from pathophysiology to clinical results / Uma revisão da Covid-19 e lesão renal aguda: da fisiopatologia aos resultados clínicos

Abstract Acute kidney injury (AKI) in hospitalized patients with COVID-19 is associated with higher mortality and a worse prognosis. Nevertheless, most patients with COVID-19 have mild symptoms, and about 5% can develop more severe symptoms and involve hypovolemia and multiple organ dysfunction syndrome. In a pathophysiological perspective, severe SARS-CoV-2 infection is characterized by numerous dependent pathways triggered by hypercytokinemia, especially IL-6 and TNF-alpha, leading to systemic inflammation, hypercoagulability, and multiple organ dysfunction. Systemic endotheliitis and direct viral tropism to proximal renal tubular cells and podocytes are important pathophysiological mechanisms leading to kidney injury in patients with more critical infection, with a clinical presentation ranging from proteinuria and/or glomerular hematuria to fulminant AKI requiring renal replacement therapies. Glomerulonephritis, rhabdomyolysis, and nephrotoxic drugs are also associated with kidney damage in patients with COVID-19. Thus, AKI and proteinuria are independent risk factors for mortality in patients with SARS-CoV-2 infection. We provide a comprehensive review of the literature emphasizing the impact of acute kidney involvement in the evolutive prognosis and mortality of patients with COVID-19.

Resumo A lesão renal aguda (LRA) em pacientes hospitalizados com COVID-19 está associada a maior mortalidade e um pior prognóstico. No entanto, a maioria dos pacientes com COVID-19 tem sintomas leves e cerca de 5% podem desenvolver sintomas mais graves e envolver hipovolemia e síndrome de disfunção de múltiplos órgãos. Em uma perspectiva fisiopatológica, a infecção grave por SARS-CoV-2 é caracterizada por numerosas vias dependentes desencadeadas por hipercitocinemia, especialmente IL-6 e TNF-alfa, levando à inflamação sistêmica, hipercoagulabilidade e disfunção de múltiplos órgãos. A endotelite sistêmica e o tropismo viral direto às células tubulares proximais renais e podócitos são mecanismos fisiopatológicos importantes que levam à lesão renal em pacientes com infecção mais crítica, com uma apresentação clínica que varia de proteinúria e/ou hematúria glomerular a LRA fulminante, exigindo terapias renais substitutivas. Glomerulonefrite, rabdomiólise e drogas nefrotóxicas também estão associadas a danos renais em pacientes com COVID-19. Assim, a LRA e a proteinúria são fatores de risco independentes para mortalidade em pacientes com infecção por SARS-CoV-2. Fornecemos uma revisão abrangente da literatura, enfatizando o impacto do envolvimento renal agudo no prognóstico evolutivo e na mortalidade de pacientes com COVID-19.

COVID-19 and chronic kidney disease: a comprehensive review / COVID-19 e doença renal crônica: uma revisão abrangente

Abstract Kidney impairment in hospitalized patients with SARS-CoV-2 infection is associated with increased in-hospital mortality and worse clinical evolution, raising concerns towards patients with chronic kidney disease (CKD). From a pathophysiological perspective, COVID-19 is characterized by an overproduction of inflammatory cytokines (IL-6, TNF-alpha), causing systemic inflammation and hypercoagulability, and multiple organ dysfunction syndrome. Emerging data postulate that CKD under conservative treatment or renal replacement therapy (RRT) is an important risk factor for disease severity and higher in-hospital mortality amongst patients with COVID-19. Regarding RAAS blockers therapy during the pandemic, the initial assumption of a potential increase and deleterious impact in infectivity, disease severity, and mortality was not evidenced in medical literature. Moreover, the challenge of implementing social distancing in patients requiring dialysis during the pandemic prompted national and international societies to publish recommendations regarding the adoption of safety measures to reduce transmission risk and optimize dialysis treatment during the COVID-19 pandemic. Current data convey that kidney transplant recipients are more vulnerable to more severe infection. Thus, we provide a comprehensive review of the clinical outcomes and prognosis of patients with CKD under conservative treatment and dialysis, and kidney transplant recipients and COVID-19 infection.

Resumo O comprometimento renal em pacientes hospitalizados com infecção por SARS-CoV-2 está associado ao aumento da mortalidade hospitalar e pior evolução clínica, levantando preocupações em relação a pacientes com doença renal crônica (DRC). De uma perspectiva fisiopatológica, a COVID-19 é caracterizada por uma superprodução de citocinas inflamatórias (IL-6, TNF-alfa), causando inflamação sistêmica e hipercoagulabilidade, e síndrome de disfunção de múltiplos órgãos. Dados emergentes postulam que a DRC sob tratamento conservador ou terapia renal substitutiva (TRS) é um fator de risco importante para a gravidade da doença e maior mortalidade hospitalar entre pacientes com COVID-19. Em relação à terapia com bloqueadores RAAS durante a pandemia, havia uma suposição inicial de que a classe pudesse causar um aumento potencial na infectividade, e impacto deletério na gravidade da doença e mortalidade, mas que não foi confirmada na literatura médica. Além disso, o desafio de implementar o distanciamento social em pacientes que necessitam de diálise durante a pandemia incentivou sociedades nacionais e internacionais a publicar recomendações sobre a adoção de medidas de segurança para reduzir o risco de transmissão e otimizar o tratamento de diálise durante a pandemia COVID-19. Os dados atuais mostram que os receptores de transplante renal são mais vulneráveis a infecções mais graves. Assim, fizemos uma revisão abrangente dos desfechos clínicos e prognóstico de pacientes com DRC sob tratamento conservador e diálise, e receptores de transplante renal e infecção por COVID-19.

A review of Covid-19 and acute kidney injury: from pathophysiology to clinical results.

Acute kidney injury (AKI) in hospitalized patients with COVID-19 is associated with higher mortality and a worse prognosis. Nevertheless, most patients with COVID-19 have mild symptoms, and about 5% can develop more severe symptoms and involve hypovolemia and multiple organ dysfunction syndrome. In a pathophysiological perspective, severe SARS-CoV-2 infection is characterized by numerous dependent pathways triggered by hypercytokinemia, especially IL-6 and TNF-alpha, leading to systemic inflammation, hypercoagulability, and multiple organ dysfunction. Systemic endotheliitis and direct viral tropism to proximal renal tubular cells and podocytes are important pathophysiological mechanisms leading to kidney injury in patients with more critical infection, with a clinical presentation ranging from proteinuria and/or glomerular hematuria to fulminant AKI requiring renal replacement therapies. Glomerulonephritis, rhabdomyolysis, and nephrotoxic drugs are also associated with kidney damage in patients with COVID-19. Thus, AKI and proteinuria are independent risk factors for mortality in patients with SARS-CoV-2 infection. We provide a comprehensive review of the literature emphasizing the impact of acute kidney involvement in the evolutive prognosis and mortality of patients with COVID-19.

COVID-19 and chronic kidney disease: a comprehensive review.

Kidney impairment in hospitalized patients with SARS-CoV-2 infection is associated with increased in-hospital mortality and worse clinical evolution, raising concerns towards patients with chronic kidney disease (CKD). From a pathophysiological perspective, COVID-19 is characterized by an overproduction of inflammatory cytokines (IL-6, TNF-alpha), causing systemic inflammation and hypercoagulability, and multiple organ dysfunction syndrome. Emerging data postulate that CKD under conservative treatment or renal replacement therapy (RRT) is an important risk factor for disease severity and higher in-hospital mortality amongst patients with COVID-19. Regarding RAAS blockers therapy during the pandemic, the initial assumption of a potential increase and deleterious impact in infectivity, disease severity, and mortality was not evidenced in medical literature. Moreover, the challenge of implementing social distancing in patients requiring dialysis during the pandemic prompted national and international societies to publish recommendations regarding the adoption of safety measures to reduce transmission risk and optimize dialysis treatment during the COVID-19 pandemic. Current data convey that kidney transplant recipients are more vulnerable to more severe infection. Thus, we provide a comprehensive review of the clinical outcomes and prognosis of patients with CKD under conservative treatment and dialysis, and kidney transplant recipients and COVID-19 infection.