COVID-19-related acute kidney injury; incidence, risk factors and outcomes in a large UK cohort

Jewell, Paul; Bramham, Kate; Galloway, James; Post, Frank A.; Norton, Sam; Teo, James; Fisher, Richard; Saha, Rohit; Hutchings, Sam; Hopkins, Phil; Smith, Patrick O.; Joslin, Jennifer; Jayawardene, Satish; McDermott, Michael; Mudhaffer, Ali; Holloway, Amelia; Kibble, Henry; Akter, Mosammat; Zuckerman, Benjamin; Palmer, Kieran; Murphy, Ciara; Iatropoulou, Domniki; Sharpe, Claire C.; Lioudaki, Eirini

doi:10.1186/s12882-021-02557-x

Cited by 46 publications

(48 citation statements)

References 38 publications

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“…We found that patients with a history of pre-existing CKD were not only at increased risk for developing AKI but also had increased need for RRT overall, and in the second wave, but not in the first wave. These findings were echoed in previous studies as well [ 6 , 20 , 21 , 33 ]. We also found that older patients were less likely to undergo RRT during the first wave but not during the second wave.…”

Section: Discussionsupporting

confidence: 83%

Comparison of Two Waves of COVID-19 in Critically Ill Patients: A Retrospective Observational Study

Jana

Yap

Janga

et al. 2022

International Journal of Nephrology

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Background. The SARS-CoV-2 virus caused the global COVID-19 pandemic, with waxing and waning course. This study was conducted to compare outcomes in the first two waves, in mechanically ventilated patients. Methods. This retrospective observational study included all mechanically ventilated COVID-19 patients above 18 years of age, between March 2020 and January 2021. Patients were grouped into first wave from March 2020 to July 2020, and second wave from August 2020 to January 2021. Outcome measures were mortality, the development of acute kidney injury (AKI), and need for renal replacement therapy (RRT). Univariate and multivariate cox regression analysis were used to delineate risk factors for the outcome measures. Results. A total of 426 patients, 285 in the first wave and 185 in the second wave, were included. The incidence of AKI was significantly lower in the second wave (72% vs. 63%; p = 0.04 ). There was no significant difference in mortality (70% vs. 63%; p = 0.16 ) and need for RRT (36% vs. 30%; p = 0.1 ). Risk factors for mortality were increasing age and AKI in both waves, and chronic kidney disease (CKD) (adj. HR 1.7; 95% CI 1.02–2.68; p = 0.04 ) in the second wave. Risk factors for AKI were CKD in both the waves, while it was diabetes (adj. HR 1.4; 95% CI 1.02–1.95; p = 0.04 ) and increasing age in the first wave. Remdesivir (adj. HR 0.5; 95% CI 0.3–0.7; p < 0.01 ) decreased the risk of AKI, and convalescent plasma (adj. HR 0.5; 95% CI 0.3–0.9; p = 0.02 ) decreased the risk of mortality in the first wave, however, such benefit was not observed in the second wave. Conclusions. Our study shows a decrease in the incidence of AKI in critically ill patients, however, the reason for this decrease is still unknown. Studies comparing the waves of the pandemic would not only help in understanding disease evolution but also to develop tailored management strategies.

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Section: Discussionsupporting

confidence: 83%

Comparison of Two Waves of COVID-19 in Critically Ill Patients: A Retrospective Observational Study

Jana

Yap

Janga

et al. 2022

International Journal of Nephrology

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“…The lung is considered the primary site of damage in COVID-19 disease, but there are numerous reports that damage also occurs in other organs ( 5 ). In particular, acute tubular injury has been described in the kidney after severe COVID-19 and increase of proteinuria was associated with poor prognosis and increased mortality ( 6 , 7 ). Here, we therefore investigated local complement over-activation as a common pathomechanism in COVID-19-mediated injury in lung and kidney.…”

Section: Discussionmentioning

confidence: 99%

“…Particularly, the kidney is involved in many patients with a considerable proportion of hospitalized patients experiencing primarily acute kidney injury (AKI). In addition, the occurrence of AKI in severe COVID-19 is associated with a higher mortality (6,7). Some studies suggest direct viral infection of glomerular and tubular cells through the ACE2-receptor possibly causing acute proximal tubular injury and detachment of podocytes (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Complement Activation via the Lectin and Alternative Pathway in Patients With Severe COVID-19

et al. 2022

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Complement plays an important role in the direct defense to pathogens, but can also activate immune cells and the release of pro-inflammatory cytokines. However, in critically ill patients with COVID-19 the immune system is inadequately activated leading to severe acute respiratory syndrome (SARS) and acute kidney injury, which is associated with higher mortality. Therefore, we characterized local complement deposition as a sign of activation in both lungs and kidneys from patients with severe COVID-19. Using immunohistochemistry we investigated deposition of complement factors C1q, MASP-2, factor D (CFD), C3c, C3d and C5b-9 as well as myeloperoxidase (MPO) positive neutrophils and SARS-CoV-2 virus particles in lungs and kidneys from 38 patients who died from COVID-19. In addition, tissue damage was analyzed using semi-quantitative scores followed by correlation with complement deposition. Autopsy material from non-COVID patients who died from cardiovascular causes, cerebral hemorrhage and pulmonary embolism served as control (n=8). Lung injury in samples from COVID-19 patients was significantly more pronounced compared to controls with formation of hyaline membranes, thrombi and edema. In addition, in the kidney tubular injury was higher in these patients and correlated with lung injury (r=0.361*). In autopsy samples SARS-CoV-2 spike protein was detected in 22% of the lungs of COVID-19 patients but was lacking in kidneys. Complement activation was significantly stronger in lung samples from patients with COVID-19 via the lectin and alternative pathway as indicated by deposition of MASP-2, CFD, C3d and C5b9. Deposits in the lung were predominantly detected along the alveolar septa, the hyaline membranes and in the alveolar lumina. In the kidney, complement was significantly more deposited in patients with COVID-19 in peritubular capillaries and tubular basement membranes. Renal COVID-19-induced complement activation occurred via the lectin pathway, while activation of the alternative pathway was similar in both groups. Furthermore, MPO-positive neutrophils were found in significantly higher numbers in lungs and kidneys of COVID-19 patients and correlated with local MASP-2 deposition. In conclusion, in patients who died from SARS-CoV-2 infection complement was activated in both lungs and kidneys indicating that complement might be involved in systemic worsening of the inflammatory response. Complement inhibition might thus be a promising treatment option to prevent deregulated activation and subsequent collateral tissue injury in COVID-19.

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“…AKI is common in COVID-19 patients and is associated with a poor prognosis. Some studies have enlightened the role of acute tubular injury and direct renal tropism in the pathophysiology of COVID-19 AKI [ 39 , 40 , 41 , 42 ]. The latter can also explain why AKI is predominant in the Omicron group.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Variants in Critically Ill Patients: A Comparison of the Delta and Omicron Variant Profiles

Corriero

Ribezzi

Mele

et al. 2022

Infectious Disease Reports

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Background: Coronavirus disease is a pandemic that has disrupted many human lives, threatening people’s physical and mental health. Each pandemic wave struck in different ways, infectiveness-wise and mortality-wise. This investigation focuses on critically ill patients affected by the last two variants, Delta and Omicron, and aims to analyse if any difference exists between the two groups. Methods: intensive care unit (ICU) COVID-19 consecutive admissions between 1 October 2021 and 31 March 2022 were recorded daily, and data concerning the patients’ demographics, variants, main comorbidities, ICU parameters on admission, and the outcome were analysed by a univariate procedure and by a multivariate analysis. Results: 65 patients were enrolled, 31 (47.69%) belonging to the Omicron versus 34 (52.31%) to the Delta group. The mortality rate was 52.94% for the Omicron group versus 41.9% for the Delta group. A univariate analysis showed that the Omicron variant was associated with total comorbidities number, Charlson Comorbidity Index (CCI), pre-existing pulmonary disease, vaccination status, and acute kidney injury (AKI). In stepwise multivariate analysis, the total number of comorbidities was positively associated with the Omicron group, while pulmonary embolism was negatively correlated with the Omicron group. Conclusion: Omicron appears to have lost some of the hallmarks of the Delta variant, such as endothelialitis and more limited cellular tropism when it comes to the patients in the ICU. Further studies are encouraged to explore different therapeutic approaches to treat critical patients with COVID-19.

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COVID-19-related acute kidney injury; incidence, risk factors and outcomes in a large UK cohort

Cited by 46 publications

References 38 publications

Comparison of Two Waves of COVID-19 in Critically Ill Patients: A Retrospective Observational Study

Comparison of Two Waves of COVID-19 in Critically Ill Patients: A Retrospective Observational Study

Complement Activation via the Lectin and Alternative Pathway in Patients With Severe COVID-19

COVID-19 Variants in Critically Ill Patients: A Comparison of the Delta and Omicron Variant Profiles

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