Risk of acute kidney injury in critically-ill patients with COVID-19 compared with seasonal influenza: a retrospective cohort study

Abstract

Background: The SARS-CoV-2 virus can bind to angiotensin-converting enzyme 2 receptors on host renal cells and may cause acute kidney injury (AKI). The comparative risks of AKI in patients severely ill with COVID-19 and influenza A have not been examined.

Methods: This is a retrospective cohort study including patients with positive PCR results for SARS-CoV-2 or influenza A virus admitted to the intensive care units (ICUs) of 15 public hospitals in Hong Kong between 1st January 2013 and 30th April 2023. Patients who were already on chronic dialysis or had missing values in the confounder model were excluded. Data were retrieved from Hong Kong Hospital Authority's electronic healthcare records. The primary outcome was incident AKI during ICU stay. Secondary outcomes included acute kidney disease (AKD) and hospital mortality. All analyses were examined in multivariable regression adjusting for potential confounders (age, sex, baseline eGFR, PaO2/FiO2 ratio, baseline comorbidities, APACHE IV predicted risk of death, Charlson Comorbidity Index, emergent hospital admission, admission from elderly home, reason for ICU admission, presence of bacterial co-infections, use of medications [including vasopressors, antiviral medications, steroids and nephrotoxic antibiotics], as well as anaemia and leucocytosis). Patients were matched in a 1:1 ratio using a propensity score generated based on the full confounder model. The analyses were repeated using inverse probability weighting and in propensity-score matched cohorts.

Findings: A total of 5495 ICU patients were identified. After excluding 1093 (19.9%) patients who met the exclusion criteria and 74 (1.3%) patients who had one or more missing values in the logistic regression model, a total of 4328 patients were included in the final analysis, with 2787 (64.4%) patients who tested positive for SARS-CoV-2 reverse transcription (RT)-PCR and 1541 (35.6%) patients who tested positive for influenza A virus RT-PCR. The comorbidity burden was greater in patients with COVID-19 (Charlson Comorbidity Index 3 [2-4] vs. 3 [1-4]), but the median APACHE IV predicted risk of death was significantly lower (0.19 [0.08-0.38] vs. 0.25 [0.11-0.52]). A total of 1053 (37.8%) patients with COVID-19 and 828 (53.7%) patients with influenza A developed AKI of any stage during ICU stay. In adjusted analysis, the risk of AKI was significantly lower in patients with COVID-19 compared with influenza A (adjusted odds ratio 0.51, 95% confidence interval 0.42-0.61, P < 0.0001]. The risk of stage 3 AKI and AKD were also significantly lower in patients with COVID-19. These results remained robust in multiple pre-planned sensitivity analyses including inverse probability weighting and propensity score matching.

Interpretation: Our results suggest that the risk of AKI in patients severely ill with COVID-19 was lower than in patients with influenza A. The burden of concurrent organ failure complicating respiratory viral infections, such as the higher disease-attributable risk of AKI associated with influenza, should be clarified.

Funding: An unrestricted philanthropic donation from Mr and Mrs Laurence Tse, The Wai Im Charitable Foundation, Chan Sui Kau Family Benefits and Charitable Foundation, So Ka Wing and Lee Sau Ying Charitable Foundation, Mr & Mrs Tam Wing Fun Edmund Renal Research Fund, the Theme-Based Research Scheme of the Research Grants Council, Hong Kong Special Administrative Region, The Government of the Hong Kong Special Administrative Region; Programme of Enhancing Laboratory Surveillance and Investigation of Emerging Infectious Diseases and Antimicrobial Resistance for the Department of Health of the Hong Kong Special Administrative Region Government; Emergency COVID-19 Project, Major Projects on Public Security, National Key Research and Development Program; Emergency Collaborative Project of Guangzhou Laboratory; the National Key Research and Development Program of China; Sanming Project of Medicine in Shenzhen China; and the High Level-Hospital Program, Health Commission of Guangdong Province, China.

Keywords: Acute kidney injury; COVID-19; Influenza; Intensive care unit; Organ failure; SARS-CoV-2.

Fig. 1

Study flow. A total of 5495 patients were admitted to the ICUs during the study period. After excluding 1093 (19.9%) patients who met the exclusion criteria and 74 (1.3%) patients who had missing data, a total of 4328 patients were included in the final analysis. Abbreviations: APACHE–Acute Physiology and Chronic Health Evaluation; COVID-19–coronavirus disease 2019; ICU, intensive care unit.

Fig. 2

eGFR levels from baseline to 12 months after ICU admission. The mean level and 95% confidence interval of eGFR at 4 time-points, including baseline, worst during ICU stay, 6 months and 12 months from ICU admission, in patients with COVID-19 (blue dots) and patients with influenza A (red dots) are presented for all patients (Panel A, N = 4328) and patients with AKI only (Panel B, N = 1881). Abbreviations: AKI, acute kidney injury; COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate; ICU, intensive care unit.

Fig. 3

Forest plot of subgroup analyses. The subgroup analyses was adjusted using the full confounder model (Model 3). There were no significant effect modification of the lower risks of AKI in patients with COVID-19 by factors including age, sex, baseline eGFR, Charlson Comorbidity Index, APACHE IV predicted risk of death, and history of diabetes. Abbreviations: APACHE-IV, Acute physiology and chronic health evaluation IV; CI, confidence interval; COVID-19–coronavirus disease 2019; eGFR, estimated glomerular filtration rate.

Fig. 4

Time-to-dialysis curves of patients with COVID-19 and influenza A. Time-to-event curves for the outcomes of all-cause mortality (Panel a), dialysis (Panel b), and combined outcome (Panel c) from ICU admission to 180 days. COVID-19 (blue line) compared with influenza A (red line) was associated with lower risks of the individual and composite outcomes (P for all log-rank tests <0.05). The number of censoring cases was presented in brackets. Abbreviation: COVID-19, coronavirus disease 2019; ICU, intensive care unit.