2.1 COVID-19 infection and acute kidney injury

Progressive acute kidney injury (AKI) is common among hospitalized COVID-19 patients, and is an independent risk factor for mortality. It has been reported that AKI was one of the complications observed in hospitalized COVID-19 patients with its occurrence ranging between 0.5% and 80% (Ng et al., 2020a). The mechanisms underlying COVID-19–associated AKI are unknown. However, proposed mechanisms of kidney injury range from direct viral infection to effects on the renin-angiotensin-aldosterone system, hemodynamic instability, coagulopathy, and cytokine storm. In a systematic review and meta-analysis of outcomes for patients with COVID-19 and AKI among 20 cohorts covering 13,137 hospitalized COVID-19 patients, prevalence of AKI was found to be 17%, out of which 77% experienced severe COVID-19 infection and 52% died (Robbins-Juarez et al., 2020). AKI was associated with increased odds of death among COVID-19 patients (pooled odds ratio 15.27, 95% CI 4.82-48.36), although there was considerable heterogeneity across studies and among different regions in the world. About 5% of all patients in the study required the use of kidney replacement therapy. The study concluded that kidney dysfunction was common among patients with COVID-19, and patients who develop AKI have inferior outcomes (Robbins-Juarez et al., 2020).
Proteinuria and hematuria were common features observed in about 40% of COVID-19 patients on hospital admission (Perico et al., 2020). In one observational study of 5,449 hospitalized patients, the incidence of AKI was 36.6% with 14.3% of patients requiring dialysis and this was even higher in patients admitted at the intensive care unit (Benedetti et al., 2020). Autopsy reports from kidneys of COVID-19 deceased patients revealed acute tubular injury and collapsing glomerulopathy as the most prominent damage to the kidneys (Cheruiyot et al., 2020; Su et al., 2020). Electron microscopy of kidney biopsies revealed viral-like particles in the glomeruli and renal tubules although the particles were not conclusively that of SARS-CoV-2 (Perico et al., 2020; Su et al., 2020). The incidence of AKI in COVID-19 patients was also highlighted in 15 separate studies, with an odds ratio (OR) of 18.5% based on COVID-19 severity (Cheruiyot et al., 2020). The OR for COVID-19 patients with AKI-associated mortality was reported to be as high as 23.95%. In some 710 COVID-19 patients who reported to the hospital, prevalence of elevated markers of renal function such as serum creatinine and blood urea nitrogen (BUN) was 15.5% and 14.1% respectively, with 26.9% of these patients coming in with microscopic hematuria and 44% having proteinuria although the incidence of AKI in these patients was reported as 3.2% (Swai et al., 2020). According to this and other supporting data, AKI is likely associated with worse prognosis in COVID-19 patients and increases their mortality rates (Izzedine and Jhaveri 2021; Taher et al., 2020). In a related retrospective analysis of medical records from 85 COVID-19-positive patients in Wuhan from January 17 to March 3, 2020, 27.06% of the patients developed AKI especially among the elderly (59-92 years old) (Diao et al., 2021). During this study, varying degrees of tubular necrosis, luminal brush border sloughing and vacuole degeneration was observed in a Hematoxylin and Eosin staining of 6 kidney samples as well as the presence of CD68+ macrophages, CD8+ T cells, CD4+ T cells and CD56+ natural killer cells from deceased COVID-19 patients (Diao et al., 2021). In conclusion, COVID-19 infection likely accelerates the development of AKI, especially among elderly patients.