COVID-19 And Kidney Injury

COVID-19 and Acute Kidney Injury The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), began in December 2019 and has affected millions of people worldwide life, but many aspects of the disease remain unclear. Current data show that many hospitalized COVID-19 patients suffer from proteinuria, hematuria, or kidney damage in the form of acute kidney injury (AKI).

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AKI is especially prevalent in severe and critically ill COVID-19 patients and is a predictor of mortality. The pathophysiology of AKI in COVID-19 is unclear. Early reports from histopathological examination of necropsy kidney tissue showed the presence of SARS-CoV-2 viral particles in tubular cells and podocytes, suggesting direct viral infection, and acute tubular necrosis, which may also be associated with rhabdomyolysis AKI and glomerular disease. As of today, only remdesivir is authorized to treat COVID-19. Ongoing research investigates the potential of antiviral and anti-inflammatory drugs, as well as the safety and efficacy of commonly used drugs such as renin-angiotensin-aldosterone system blockers. This review discusses the incidence of AKI and its relationship with prognosis while highlighting the possible mechanisms of AKI and suggesting organ protection measures to prevent the development of kidney damage.

In December 2019, a cluster of pneumonia cases caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei Province, China. The disease, now officially named coronavirus disease 2019 (COVID-19), spread rapidly from Wuhan to other cities around the world. As of June 10, 2020, there were more than 7.5 million confirmed cases of COVID-19 worldwide, with 423,000 deaths (1), and an estimated mortality rate of 2.3% (2). The main manifestations of COVID-19 are fever, dry cough, dyspnea, and diarrhea, although its presentation may include asymptomatic infection, respiratory system damage, multiorgan failure, and high mortality (3). Although respiratory failure is the most prominent feature of severe disease, the second most commonly reported organ infected by COVID-19 is the kidney (4). In this review, we discuss the epidemiology and prognostic value of the development of acute kidney injury (AKI) in COVID-19, focusing on possible pathophysiology and preventive approaches that could guide clinical practice during this emerging crisis.

Epidemiological study on acute kidney injury caused by COVID-19

Epidemiology of Acute Kidney Injury in COVID-19 In each series of hospitalized COVID-19 cases, the incidence of kidney injury varied widely, with a reported highest incidence of 69% (5). Importantly, a meta-analysis of 3,062 COVID-19 patients found that the incidence of abnormal renal function was 25.5% Currently, the true incidence of AKI in hospitalized patients with COVID-19 is unknown. In a cohort of 701 COVID-19 patients, the incidence of AKI was 5.1% (7). In another group of 467 people, this was 4.7% (8). However, a retrospective analysis of early data from Wuhan showed that AKI occurred in 27% of 85 hospitalized COVID-19 cases (9), which is consistent with the meta-analysis results (6).

Regardless, all reports consistently observed a higher incidence of AKI in critically ill patients. Very early data showed that AKI occurred in 29% of 52 Chinese critically ill patients (10). In another study, AKI occurred in 23% of patients admitted to the ICU compared with none in non-ICU care (11). A recent report from Bellevue Hospital Center in New York showed that 44 of 105 COVID-19 patients in the ICU had AKI, 40 of whom required renal replacement therapy (12). Another recent retrospective study in China reported renal injury in 70% of severe and critically ill patients (4).

The incidence of AKI among non-survivors was also very high. Two retrospective studies from Wuhan reported AKI in 50% (13) and 25% (14) of 54 and 113 non-survivors, respectively. Although AKI occurred at a median of 15 days [13.0–19.5] after onset, early signs of renal dysfunction occurred significantly earlier in the course of the disease. Of note, a high proportion of patients had symptoms of renal dysfunction on admission, with proteinuria in 65% to 44%, hematuria in 44% to 27%, and serum Increased creatinine (7, 8, 15). Among 333 patients with COVID-19 in China, 251 (75%) developed renal complications such as proteinuria, hematuria, and AKI. The study excluded patients with baseline CKD or suspected CKD who had an abnormal urine test within 3 months of admission (8), which strongly suggested that the renal abnormalities found were related to COVID-19. Considering that the median duration from onset to admission was 9 to 10 days (7, 8), it is plausible that renal damage begins even before admission. However, most reports so far have come from China, and information from other ethnic groups and groups is needed.

In addition, evolving treatments may also affect epidemiology.

Characteristics of AKI

Renal injury in AKI caused by COVID-19 is characterized by elevated serum creatinine levels, proteinuria, hematuria, and AKI, and some patients require renal replacement therapy (RRT) (8). Overall, AKI was defined according to KDIGO criteria (7, 8, 101517), while different definitions of kidney injury were also used, including reduced eGFR (4) and extended criteria (8). AKI was stage 1 in 18%, stage 2 in 32%, and stage 3 in 50% of patients (8). High proteinuria and hematuria rates were found in hospitalized COVID-19 patients. Among 333 hospitalized COVID-19 patients, proteinuria was present in 65.5% and hematuria in 41.7% (8) and was associated with mortality in intensive care unit (ICU) patients (18). Kidney involvement was also evident on CT imaging; mean CT values and CT texture analysis parameters were significantly lower in patients with COVID-19 than in healthy controls without kidney disease (15).

Various renal pathological changes have been observed in patients with COVID-19 infection. Histopathological analysis of autopsies from six COVID-19 patients with renal involvement revealed the presence of viral particles in proximal tubules and podocytes, with varying degrees of acute tubular necrosis and lymphocytic infiltration (9) (Figure 1). In any event, it should be noted that the key findings on pathological examination revealed prominent proximal acute tubular injury manifested by vacuolar degeneration, loss of brush borders, aggregation of red blood cells, absence of platelets or fibrin embolism, and occasionally even necrosis, This is consistent with acute tubular necrosis (ATN) (19). Thus, the predominant form of AKI in SARS-CoV-2 infection appears to be intrarenal AKI.

Of note, pigmented casts with high levels of creatine kinase have also been found in non-survivors of COVID-19, findings consistent with rhabdomyolysis (19), while some collapsing glomerulopathy and crescents have also been reported cases of body proliferative glomerulonephritis (20, 21). Although renal involvement is strongly associated with higher mortality, the high resolution of renal manifestations in survivors also supports that ATN may be the primary renal injury (8).

AKI Outcomes in Patients with New Coronary Pneumonia

AKI has been associated with increased mortality in patients with COVID-19. In a study including 193 patients with COVID-19, the mortality rate of patients who developed AKI was 5.3 times that of patients who did not develop AKI (15). A Wuhan study in a cohort of 701 hospitalized patients showed that stage 2 AKI was independently associated with in-hospital death (7). Patients with stage 3 AKI had a more than the 4-fold higher risk of mortality (hazard ratio 9.81, 95% CI: 5.46-17.65) (7). A dose-dependent relationship between the AKI stage and death is also supported by other cohorts (8). In another report, 32 of 33 COVID-19 patients who developed AKI did not survive (13).

Renal dysfunction due to proteinuria and hematuria also predicted prognosis in the absence of AKI criteria. The incidence of proteinuria and hematuria in critically ill patients is almost twice that of moderately ill patients (proteinuria 81% vs 44%, hematuria 69% vs 33%) (8).

Among 333 COVID-19 patients, the mortality rate in patients with renal involvement (including hematuria, proteinuria, and AKI) was more than 9 times higher than in patients without renal involvement (11.2% and 1.2%, respectively) (8). In contrast, severe cases (including fatal cases) had significantly higher peak levels of BUN and creatinine than non-severe COVID-19 cases and non-COVID-19 (15). Although still within the normal range (87 μmol/L vs 68 μmol/L), the median creatinine on admission was significantly higher in non-survivors than in survivors (16).

Kidney damage is also common with heart damage, possibly because both are predictors of serious disease. The incidence of AKI has been reported to be 26-fold higher in patients with cardiac injury than in patients without cardiac injury (8.5% vs 0.3%) (17).

Consistent with the high incidence of AKI, RRT is the second most common organ support in critically ill patients with COVID-19, after ventilator support. According to a report from China, 17% of critically ill patients (9 of 52) received RRT (10). In another report from New York, 38% of COVID-19 patients (40 of 105) in the ICU required RRT (12).

According to the UK ICNARC report (May 1, 2020), 23% of critically ill patients with COVID-19 (1163 of 5139 patients) required renal support. Among patients receiving renal support, nearly 75% died in intensive care.

Of note, only 5.3% of patients required RRT Figure 1. Healthy kidney tissue expression of viral entry receptors ACE2 and TMPRSS2 and histopathological findings during COVID-19 infection.

ACE2 and TMPRSS are highly expressed in kidney tissue, especially in proximal tubules. This allows the coronavirus to attach to tubular cells and infect kidney tissue. Various histopathological findings were observed in the kidneys of patients with COVID-19. Both the direct involvement of the virus and the activation of the immune system play a role in the pathological outcome.

ACE2: angiotensin-converting enzyme 2, TMPRSS2: transmembrane serine protease 2. patients had the severe renal disease before admission, suggesting that baseline chronic kidney disease (CKD) played only a minor role in the need for RRT

Similar to the ICNARC report, survival in patients requiring RRT was also extremely poor in the small report. In one study, 8 of 9 patients who received RRT did not survive (7), while in another study, 10 of 10 patients did not survive (13).

Based on current evidence, both the development of renal dysfunction and the need for RRT are predictors of very poor prognosis and can be used to assess likely outcomes in a clinical setting.

However, according to one study, remission of kidney injury was common among survivors: 68% of patients with proteinuria (111 of 116) and 44% of patients with hematuria (44 of 102) had remission after COVID-19. Negative (8). Furthermore, 18% of patients with AKI (4 of 22) had complete recovery of renal function at follow-up, with a mean recovery time of 6 days (8). Critical illness was a negative risk factor for AKI recovery, while age ≥ 60 years, pre-hospital ACEI/ARB treatment, and AKI were negative risk factors for hematuria remission (8). Larger cohort studies are needed to better understand renal outcomes in patients with COVID-19-associated AKI.

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