How COVID-19 Impacts the Kidneys

Over 40% of admitted patients with COVID-19 show signs of abnormal kidney function such as albuminuria or hematuria. (1–3) A study on 701 patients found increased serum creatinine, blood urea nitrogen, and reduced glomerular filtration in more than 13-14%, as further signs of kidney impairment. The development of acute kidney injury was reported in 5% of patients. (1)

In contrast, a recently published study from Italy focusing on the management of acute kidney injury (AKI) in COVID-19 estimates that AKI occurs in 20 - 40% of critically ill patients admitted to the ICU. (2)

The impact of COVID-19 on the kidneys appears to be multifactorial. Prefactors from comorbidities of COVID-19, such as cardiovascular diseases, hypertension, chronic kidney disease (CKD), and diabetes can be seen as contributors for the development of kidney impairment and AKI. (1,2,4) Diao et al. suggests that additional conditions are especially responsible for glomerular damages occurring in COVID-19 pathogenesis (5).

Kidney injuries can result from medication or effects of the disease such as acute respiratory distress, cytokine storm, and disseminated coagulation (1,2). The latter leads to thrombic events in various veins and can cause (micro-) thrombic events in the kidney as well. (2,4,6)

Direct infection of kidney tissue with SARS-CoV-2 was suspected at the beginning of the pandemic as a reason for kidney involvement. The angiotensin-converting enzyme 2 (ACE2), which is targeted by the virus for cell-entry, is abundant in kidney tissue such as podocytes with even higher expression rates as in the lungs. (1,7–9)

In more recent pathological studies, the authors considered orthogonal analytic approaches to identify viral infections of kidney tissue. Immunohistochemical investigations were paired with electron microscopy and other methods to address uncertainties in either method. (4,5) The researchers were able to confirm previous findings and identify infection of the kidney tubules (5). Virus particles were identified in endothelial cells and podocytes, too (4).

Kidney infection appears to follow respiratory tract and vascular infections as viral SARS-CoV-2 RNA was detected in the liver and kidney in patients with viremia (6,10). Followed by ACE2 promoted cell entry, the virus may promote fibrosis, cell apoptosis, and microvascular changes in the kidney. A local cytokine storm and complement deposition were also described as local effects in infected kidney tissue, leading to tubular damages. (5)

A study published in Cell proved that SARS-CoV-2 can directly infect human blood vessel and kidney organoids. Knowing that SARS-CoV-2 utilizes ACE2 for cell entry, the authors were able to reduce viral growth of SARS-CoV-2 in Vero E6 cells by more than 1000-fold by use of clinical-grade human recombinant soluble ACE2. (10)

References

1. Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney International. 2020;97:829–38. 
2. Ronco C, Reis T, Husain-Syed F. Management of acute kidney injury in patients with COVID-19. The Lancet Respiratory Medicine. 2020;S2213260020302290.
3. Gross O, Moerer O, Weber M, Huber TB, Scheithauer S. COVID-19-associated nephritis: early warning for disease severity and complications? The Lancet. 2020;395:e87–8.
4. Bradley BT, Maioli H, Johnston R, Chaudhry I, Fink SL, Xu H, et al. Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series. The Lancet. 2020;S0140673620313052.
5. Diao B, Wang C, Wang R, Feng Z, Tan Y, Wang H, et al. Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection [Internet]. Infectious Diseases (except HIV/AIDS); 2020 Mar. Available from: medrxiv.org/lookup/doi/10.1101/2020.03.04.20031120
6. Wichmann D, Sperhake J-P, Lütgehetmann M, Steurer S, Edler C, Heinemann A, et al. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study. Ann Intern Med [Internet]. 2020 [cited 2020 May 12]; Available from: annals.org/aim/fullarticle/2765934/autopsy-findings-venous-thromboembolism-patients-covid-19-prospective-cohort-study
7. Harris RC. Podocyte ACE2 protects against diabetic nephropathy. Kidney International. 2012;82:255–6.
8. Su H, Yang M, Wan C, Yi L-X, Tang F, Zhu H-Y, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney International. 2020;98:219–27.
9. Kissling S, Rotman S, Gerber C, Halfon M, Lamoth F, Comte D, et al. Collapsing glomerulopathy in a COVID-19 patient. Kidney International. 2020;98:228–31.
10. Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, Stahl M, et al. Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Cell. 2020;181:905-913.e7.