MAJOR ADVERSE EVENTS IN CRITICALLY ILL PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME

Abstract

Acute kidney injury (AKI) is common among patients with COVID-19 or sepsis. The incidence of AKI may increase when these patients develop acute respiratory distress syndrome (ARDS), which is often associated with poorer patient outcomes and higher mortality rates. Major adverse kidney events (MAKEs) - a composite of the need for renal replacement therapy (RRT), a decline in eGFR of <75% from baseline, or all- cause mortality - are considered a reliable long-term measure of AKI's impact on patient outcomes.

This thesis aimed to evaluate the existing evidence regarding the incidence and risk factors of AKI in COVID-19 patients with ARDS. Additionally, it sought to determine the incidence and clinical risk factors of MAKE-365 in patients with AKI, both with and without COVID-19 ARDS. The thesis also examined the associations between novel kidney biomarkers (including plasma Cystatin C, urinary NGAL, urinary [TIMP- 2]*[IGFBP-7], and urinary CCL-14) and MAKE-365 in ICU patients with sepsis and AKI. Lastly, it evaluated the predictive capabilities of these kidney biomarkers in combination with clinical predictive models for MAKE-365.

Firstly, a systematic review and meta-analysis were conducted to examine the incidence and risk factors of AKI in COVID-19 patients with ARDS. This review, which included 31 studies, found a higher incidence of AKI in COVID-19 patients with ARDS compared to those without. The study identified several risk factors associated with worse outcomes, including advanced age, male gender, and pre-existing conditions such as hypertension, diabetes, obesity, and CKD.

Secondly, a retrospective cohort study was carried out on ARDS patients to assess the occurrence of MAKEs up to 365 days post-ICU admission in both non-COVID-19 and COVID-19 cohorts. The incidence of MAKE-365 was more common in the non- COVID-19 cohort. CKD and high bilirubin levels were identified as predictors for MAKE-365 in both cohorts, with additional risk factors such as older age and diabetes in the COVID-19 cohort and lower albumin levels in the non-COVID-19 cohort.

Finally, another retrospective cohort study was conducted to assess MAKE-365 development and evaluate the predictive ability of kidney biomarkers for MAKE-365 in septic patients, regardless of ARDS status. The prevalence of MAKE-365 was higher in septic patients with AKI, irrespective of ARDS status. Among the evaluated biomarkers, urinary [TIMP-2]*[IGFBP-7] showed the most promise for predicting MAKE-365, particularly when combined with the clinical prediction model.

Overall, this thesis underscores the importance of identifying patients at risk of MAKE- 365 development in critically ill patients using clinical predictors in conjunction with kidney biomarkers. However, the utility of these biomarker combinations must be confirmed in larger, external prospective cohorts to ensure the findings' generalizability and specificity to the patient population used in this study.