#4980 THE ROLE OF EARLY ACUTE KIDNEY REPLACEMENT THERAPY (AKRT) IN THE PROGNOSIS OF PATIENTS WITH COVID-19: A RANDOMIZED CLINICAL TRIAL
Authors: de Oliveira Paula Gabriela Sousa , Yokota Lais Gabriela , Zamoner Welder , Balbi Andre , Ponce Daniela 
Published: June 2023

Abstract

Background and Aims
The COVID-19 pandemic has increased the burden of morbidity and mortality worldwide and in its moderate to severe forms is associated with serious complications such as Acute Kidney Injury (AKI). AKI related to COVID-19 appears to be multifactorial and the AKI incidence is around 20%, with the need for dialysis in up to 40-50% of critically ill patients. So far, there has been no evidence of benefit from early dialysis in different contexts of AKI. In the context of COVID-19 it is possible that the indication of early dialysis support can help and improve outcomes with inflammation and volume control. The objective of the study was to evaluate the role of early acute kidney replacement therapy (AKRT) in the context of COVID-19.

Method
We analyzed 108 patients from a randomized open-label clinical trial with AKI 3 according to the KDIGO 2012 criteria, with severe acute respiratory syndrome with confirmed COVID-19 (RT- PCR technique or serology), admitted from March 2020 to May 2021 in a reference public hospital in the State of São Paulo (Brazil). Patients were randomized to early AKRT indication (either cytokine storm or fluid balance cumulative greater than 3% of body weight) or standard indication (classic indications or systemic demand and renal capacity imbalance). Cytokine storm was characterized as uninterrupted fever (38ºC or more) for at least 12 hours and exclusion criteria were patients younger than 18 years, pregnant women, chronic kidney disease (CKD) stages 4 and 5, kidney transplant recipients. Patients were randomized in blocks for allocation to groups and the primary outcome was hospital mortality. The study was approved by the research ethics committee, registered in the Brazilian Clinical Trials Registry. Seeking a detection of a 20% mortality difference between the standard and early groups, the required sample size would be 48 patients per group and was assumed an alpha error of 5%. All analyzes were performed using SPSS 28.0.1.1 (15).

Results
108 patients were included in the intention-to-treat analyses (41 in the early group and 67 in the standard group). 66,7% were men, 86,9% white, mean of age was 62,56 ± 14,25 years, 93,9% in intensive care unit, 100% in mechanical ventilation (MV) and 93,5% in use of vasoactive drugs. The most common comorbidities were hypertension (68,5%), diabetes (39,8%) and obesity (52,8%). Hematuria (47,9%) and proteinuria (74,7%) were common. The P/F ratio, ATN-ISS e APACHE II scores mean were, respectively, 145,40 ± 67,70; 0,75 ± 0,12 e 20,04 ± 6,64. 51,9% of the sample had a cytokine storm and the overall mortality was 87%. The standard and early groups were similar in gender, race, comorbidities, severity, medications, and laboratory markers of severity as well as catheter site, system coagulation, number of dialysis sessions and mortality (63,8% in the standard vs 36,2% in the early, p = 0,32). There was a difference in age e modality of dialysis between the groups with lower mean of age (57,78 ± 14,24 years vs 65,49±13,54) and more continuous dialysis (66,7% vs 33,3%, p&lt;0,01) in the early group. Hypertension (68,9% vs 31,1% p = 0,051), CKD (80% vs 20% p = 0,038) and dyslipidemia (80,8% vs 19,2%, p = 0,52) were more common in the standard. The early group had a longer ICU stay (20,26±20,93 days vs 13,22±11,34, p = 0,053), lower maximum creatinine (3,88±1,88 vs 5,24±2,46, p = 0,004) and lower ATN-ISS (0,72±0,12 vs 0,78±0,12, p = 0,017). In the survival analysis, a better hospital survival trend was observed in the early group, but with no statistically significant difference (p = 0,061). Use of angiotensin converting enzyme inhibitor (ACEI), 42,9% vs 13,8, p = 0,008, and longer time in MV (28,71±12,48 days vs 13,42±13,99, p&lt;0,001) were associated with lower mortality. In the logistic regression, use of ACEI (OR 0,007, 95% CI 0-0,29, p = 0,009), MV time (OR 0,93, 95% CI 0,88-0,99, p = 0,023) and higher APACHE II (OR 1,28, 95%CI 1,02-1,6, p = 0,03) were associated with mortality.

Conclusion
It was observed that the use of ACEI, longer ventilation time and APACHE II score were associated with mortality, while early AKRT indication had no impact in survival of patients.