Acute kidney injury (AKI) is commonly reported in critically ill patients with COVID-19. Apart from increasing the degree of severity in the patients it also indicates a poorer prognosis.

The pathophysiological processes that may be involved in AKI can be explained as-

Fluid balance disturbances causing prerenal AKI: Nearly 11% of COVID-19 patients experience at least one gastrointestinal symptom (nausea, vomiting or diarrhea), along with other symptoms of Covid-19. It has been postulated that Cardiomyopathy and acute viral myocarditis can lead to renal venous congestion, hypotension and renal hypoperfusion, ultimately causing a reduction in glomerular filtration rate.

Cytokine release syndrome or rhabdomyolysis causing Toxic tubular damage: Cytokine storm leads to hypoperfusion-related injury of the renal tubules. Viral infection in alveolar cells causes massive engagement of immune cells, producing large amounts of cytokines which can mediate cytokine-mediated AKI.

Rhabdomyolysis has also been reported in patients with COVID-19.

Activation of Angiotensin II pathway: Interaction between SARS-CoV-2 and angiotensin II receptors may facilitate SARS-CoV-2-associated kidney injury. ACE polymorphism and susceptibility to SARS-CoV-2 can explain the development of more severe forms of COVID-19 in different populations.

A complex process driven by virus-mediated injury: Some evidence suggests a direct cytopathic effect of SARS-CoV-2. Previous autopsy data have demonstrated the presence of SARS-CoV-2 in multiple organs, with selective tropism for the kidneys, even in patients without a history of chronic kidney disease or those not critically ill with SARS-CoV-2 infection. Immunofluorescence of kidney specimens has demonstrated the presence of SARS-CoV-2 protein in areas of glomerular epithelial, endothelial and tubular cells, with affinity to glomerular cells.

Early autopsies have confirmed that SARS-CoV-2 directly infects human kidney tubular cells, inducing acute tubular damage via direct cytopathic effect and/or through cytotoxic action of CD68+ interstitial macrophages, together with tubular deposition of complement C5b-9. 

Acute tubular injury has been reported to be the most commonly found injury in autopsy and Kidney biopsy.  A high prevalence of proteinuria has been reported during COVID-19, in numerous clinical reports.  Apart, there are also reports of multiple wedge-shaped kidney infarctions and cases of pauci-immune vasculitis in covid-19 patients.

Endotheliitis, thrombotic events and intravascular coagulation: Disseminated intravascular coagulation (DIC) is characteristic of severe COVID-19 illness. Autopsy reports of patients with COVID-19 have shown prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. 

Unrestrained complement activation induced by the virus has shown to contribute to inflammation, endothelial cell dysfunction, thrombus formation and intravascular coagulation, leading to multiple organ failure and death.

Lung–kidney axis: Toxic overproduction of cytokines in SARS-CoV-2 has been reported to cause alveolar and tubular damage in the lung–kidney axis. Acute respiratory distress syndrome may also cause renal medullary hypoxia and tubular cell damage.

Even heart–kidney axis, or cardiorenal syndrome, have also been reported to contribute to AKI in COVID-19 patients with cardiomyopathy and/or acute viral myocarditis. 

Drug-induced nephrotoxicity: Numerous antibiotics and antivirals used during the treatment of Covid-19 patients have a risk of liver and kidney damage, and renal adverse drug reactions.

Source-Izzedine H, Jhaveri KD. Acute kidney injury in patients with COVID-19: an update on the pathophysiology, Nephrology Dialysis Transplantation, 2021;36(2):224–226. https://doi.org/10.1093/ndt/gfaa184