In hospital risk factors for acute kidney injury and its burden in patients with Sars-Cov-2 infection: a longitudinal multinational study

Abstract

Acute kidney injury (AKI) is associated with increased mortality in most critical settings. However, it is unclear whether its mild form (i.e. AKI stage 1) is associated with increased mortality also in non-critical settings. Here we conducted an international study in patients hospitalized with SARS-CoV-2 infection aiming 1. to estimate the incidence of AKI at each stage and its impact on mortality 2. to identify AKI risk factors at admission (susceptibility) and during hospitalization (exposures) and factors contributing to AKI-associated mortality. We included 939 patients from medical departments in Moscow (Russia) and Padua (Italy). In-hospital AKI onset was identified in 140 (14.9%) patients, mainly with stage 1 (65%). Mortality was remarkably higher in patients with AKI compared to those without AKI (55 [39.3%] vs. 34 [4.3%], respectively). Such association remained significant after adjustment for other clinical conditions at admission (relative risk [RR] 5.6; CI 3.5- 8.8) or restricting to AKI stage 1 (RR 3.2; CI 1.8–5.5) or to subjects with AKI onset preceding deterioration of clinical conditions. After hospital admission, worsening of hypoxic damage, inflammation, hyperglycemia, and coagulopathy were identified as hospital-acquired risk factors predicting AKI onset. Following AKI onset, the AKI-associated worsening of respiratory function was identified as the main contributor to AKI-induced increase in mortality risk. In conclusion, AKI is a common complication of Sars-CoV2 infection in non-intensive care settings where it markedly increases mortality risk also at stage 1. The identification of hospital-acquired risk factors and exposures might help prevention of AKI onset and of its complications.

COVID-19-associated AKI

“…The association between AKI and increased mortality in COVID-19 was evident in the earliest reports [ 50 ]. It is now widely accepted that even mild AKI (stage 1) confers increased risk of mortality and risk increases as the severity of AKI increases [ 11 ▪ , 20 ▪ , 44 ]. Cohort studies have shown an in-hospital mortality of around 40% of all patients with any AKI [ 11 ▪ , 44 ], which increases to 62% for patients with AKI in ICU [ 20 ▪ ].…”

“…It is now widely accepted that even mild AKI (stage 1) confers increased risk of mortality and risk increases as the severity of AKI increases [ 11 ▪ , 20 ▪ , 44 ]. Cohort studies have shown an in-hospital mortality of around 40% of all patients with any AKI [ 11 ▪ , 44 ], which increases to 62% for patients with AKI in ICU [ 20 ▪ ]. The attributable mortality of AKI in COVID-19 is not well characterised and it remains unclear to what extent AKI is playing a causative role in risk for death or merely reflective of disease severity.…”

“…A recent study by Morieri et al showed that AKI was independently associated with increased mortality in a non-ICU setting (i.e. before a patient had clinically deteriorated to the point of ICU admission) and concluded causation over association [ 44 ]. However, there were many potential confounders and any exact contribution of AKI to risk of death will be inevitably context dependent including influences on clinician decision making.…”

“…Clinical AKI risk factors on admission with COVID-19 are largely related to severity of the COVID-19 disease. This includes clinical parameters, such as high respiration rate (>20) and hypoxia; and blood biochemistry, such as high inflammatory markers (interleukin, IL-6, C-reactive protein, fibrinogen, high neutrophil:lymphocyte ratio, low albumin) and evidence of end-organ damage (high lactate, deranged liver function tests, increased amylase and lactate dehydrogenase) [ 11 ▪ , 19 , 44 ]. Admission proteinuria is also associated with increased risk of AKI, and may be a marker for subclinical kidney injury [ 7 , 45 ].…”

“…The risks for AKI as an inpatient are less well characterised but potentially include inappropriate fluid management at either extreme (either hypervolaemia secondary to excessive fluid resuscitation or hypovolaemia from conservative fluid management or over-diuresis), nephrotoxin exposure and other organ failure and their treatment [ 44 , 48 ▪ ]. Of the patients admitted to ICU, 59.2–81% and 39.2–43% of patients required vasopressor support and mechanical ventilation, respectively [ 19 , 20 ▪ ].…”