Impact of mechanical ventilation on severe acute kidney injury in critically ill patients with and without COVID-19 – a multicentre propensity matched analysis

Perschinka et al. Annals of Intensive Care (2025) 15:17 https://doi.org/10.1186/s13613-025-01424-4 Annals of Intensive Care Open Access RESEARCH Impact of mechanical ventilation on severe acute kidney injury in critically ill patients with and without COVID-19 – a multicentre propensity matched analysis Fabian Perschinka1 , Timo Mayerhöfer1 , Teresa Engelbrecht2, Alexandra Graf2 , Paul Zajic3, Philipp Metnitz3 and Michael Joannidis1* Abstract Background Acute kidney injury (AKI) is common in critically ill patients and is associated with increased morbidity and mortality. Its complications often require renal replacement therapy (RRT). Invasive mechanical ventilation (IMV) and infections are considered risk factors for the occurrence of AKI. The use of IMV and non-invasive ventilation (NIV) has changed over the course of the pandemic. Concomitant with this change in treatment a reduction in the incidences of AKI and RRT was observed. We aimed to investigate the impact of IMV on RRT initiation by comparing critically ill patients with and without COVID-19. Furthermore, we wanted to investigate the rates and timing of RRT as well as the outcome of patients, who were treated with RRT. Results A total of 8,678 patients were included, of which 555 (12.8%) in the COVID-19 and 554 (12.8%) in the control group were treated with RRT. In the first week of ICU stay the COVID-19 patients showed a significantly lower probability for RRT initiation (day 1: p < 0.0001, day 2: p = 0.021). However, after day 7 a reversed HR was found. In mechanically ventilated patients the risk was significantly higher for the initiation of RRT over the entire stay. While in non-COVID-19 patients this was a non-significant trend, in COVID-19 patients the risk for RRT was significantly increased. The median delay between initiation of IMV and requirement of RRT was observed to be longer in COVID19 patients (5 days [IQR: 2–11] vs. 2 days [IQR: 1–5]). The analysis restricted to patients with RRT showed a significantly higher risk for ICU death in patients requiring IMV compared to patients without IMV. Conclusion The analysis demonstrated that IMV as well as COVID-19 are associated with an increased risk for initiation of RRT. The association between IMV and risk of RRT initiation was given for all investigated time intervals. Additionally, COVID-19 patients showed an increased risk for RRT initiation during the entire ICU stay within patients admitted to an ICU due to respiratory disease. In COVID-19 patients treated with RRT, the risk of death was significantly higher compared to non-COVID-19 patients. Keywords Renal replacement therapy, Invasive mechanical ventilation, CARDS, Propensity score matched *Correspondence: Michael Joannidis Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Perschinka et al. Annals of Intensive Care (2025) 15:17 Page 2 of 11 Introduction Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with increased morbidity and mortality. In the AKI-EPI study the requirement of renal replacement therapy (RRT) was as high as 13.5% in critically ill patients [1], while reported rates in patients admitted because of sepsis were even higher [2]. Mortality rates in patients treated with RRT are up to 44% [3]. Sepsis and septic shock are among the most common causes for AKI [4], but the impact of severe viral infections is still unclear. During the COVID-19 pandemic relatively low rates of AKI were reported initially [5]. However, later cohort studies in critically ill patients and meta-analysis showed normal AKI incidences for critically ill patients with relatively high rates of RRT [6, 7]. Since angiotensin converting enzyme 2 (ACE2) receptors are present in the proximal tubular cells, a direct impact of SARS-CoV-2 on the kidneys seemed plausible [8–11]. However autopsy and biopsy studies indicated a rather multifactorial aetiology of AKI [12–15]. Since in respiratory failure COVID-19 primarily affects the lungs, especially in critically ill, lung-kidney interactions as a trigger of AKI may be of particular interest. This is especially true for severe respiratory failure since hypoxemia itself may interfere with renal blood flow [16]. A possible modifiable risk factor for AKI in critically ill patients may be invasive mechanical ventilation (IMV), which was shown in a meta-analysis [17]. At the beginning of the pandemic IMV rates were relatively high because of uncertainty and reports about rapid respiratory deterioration [18, 19]. A high post end-expiratory pressure (PEEP) leads to an increased intrathoracic and intraabdominal pressure and a consequently impaired renal perfusion [20]. As knowledge grew [21], non-invasive ventilation (NIV) strategies became more prominent. Concomitant with this change in treatment a reduction in the incidence of AKI and RRT was observed in cohort studies [22, 23]. The aim of this study was to investigate the association of IMV on RRT by comparing critically ill patients with and without COVID-19 over the first two years of pandemic. Furthermore, we wanted to investigate the rates and timing of RRT as well as the outcome of patients treated with RRT. from January 1, 2020 to December 31, 2021. The registry contains data about demographics, hospital stay, reason for ICU admission (a detailed list of the categories is presented in the Electronic Supplemental Material, ESM Table 1), scores (Simplified Acute Physiology Score [SAPS 3] [24] and Simplified Therapeutic Intervention Scoring System 28 [TISS28] [25]) as well as patients outcome. Data about ICU therapy provided by ASDI contains the following variables: COVID-19 (binary: Yes/ No), time to ICU-mortality as well as time to airway, ventilation mode and renal support for each day on the ICU per patient. Patients were defined to have IMV if they had an endotracheal tube or tracheal cannula at the same time as assisted breathing, Biphasic Positive Airway Pressure (BIPAP), controlled ventilation or high-frequency (HF)-Ventilation in the daily documentation. Hemodialysis (acute) (...truncated)