COVID-19 and Renal Replacement Therapies

Although Severe Acute Respiratory Syndrome CoronaVirus (SARS-CoV-2) infection primarily manifests as an acute pulmonary disease (COronaVirus Disease 2019; COVID-19) and respiratory failure with interstitial and alveolar pneumonia, it frequently affects multiple organs, including the kidneys, heart, gut, and nervous system. Acute kidney injury (AKI) is emerging as a common and important sequela of COVID-19, with rates as high as 33-43% among hospitalized patients [1]. In case of respiratory failure, AKI affects over 50% of patients admitted to the intensive care unit (ICU) [2]. Among critically ill patients, AKI frequently manifests as a severe oligo-anuric phenotype and imposes the use of renal replacement therapy (RRT) [3, 4]. In fact, RRT is frequently required to treat ICU patients with severe COVID-19 related AKI (C-19-AKI), and different modalities have been described in the literature (Continuous RRT-CRRT; Intermittent Hemodialysis-IHD; Peritoneal Dialysis-PD) [3]. Specifically, careful management of fluid balance and electrolyte disorders has been found to be beneficial in patients with severe C-19-AKI requiring RRT [5]. Not surprisingly, C-19-AKI requiring RRT is also associated with a particularly poor outcome. In fact, renal failure is now a well-established independent risk factor linked with increased in-hospital mortality [3, 4]. A recent study involving COVID-19 patients found that 63% of the patients exhibited proteinuria, 19% had an elevated plasma creatinine level, and 27% had an elevated urea nitrogen level [6]. During the first pandemic peak, 451 adult COVID-19 patients admitted to ICUs at the Karolinska University Hospital showed an overall incidence of AKI of 43.7% (9.5% had AKI grade I, 8.9% AKI grade II, and 25.3% experienced AKI grade III) [7]. Compared to non-AKI patients, AKI patients had a prolonged, doubled, length of stay, higher SAPS III scores, and 18.2% received CRRT while on ICU [7]. Even if the overall 30-day mortality for the COVID-19 cohort was 19.1% (and 23.1% at 60 days), mortality of AKI patients was much higher (42.6%) compared to patients with no-AKI (8.7%). As expected, mortality was proportional to the severity of AKI being 27.9% in grade I, 40.0% in grade II, and 49.1% in grade III [7]. Finally, 45.1% of those who received CRRT died up until the end of follow-up, showing that mortality in the CRRT group was significantly higher than in non-CRRT patients with a hazard ratio of 2.59 (confidence interval, CI 1.73-3.86, P ≤ 0.001) [7]. Interestingly, predictors of hospital mortality for CRRT patients were a higher age at admission, being 55 (IQR 52-64) years in survivors vs. 63 (IQR 58-68) years in nonsurvivors, weight change during hospital stay, being -10.5 (-15.3 to 6.7)% in survivors and -1.2 (-4.1 to +0.7)% in nonsurvivors, and a higher baseline creatinine value [7]. These data show that older subjects with accumulation of fluid excess and preinfection renal disfunction showed the worse outcomes. Mortality appeared to be highly variable in different publications. In one Italian report of COVID-19 patients, it was 38.9% and 52.9% for AKI patients and for those who received CRRT, respectively [8]. In a second report, AKI incidence was 22.6% with a mortality of 63% [9]. In a cohort of nearly 4000 hospitalized patients in New York, 76% of the 976 ICU patients had AKI, 19% received RRT and in-hospital mortality in the AKI group was 50% [10]. The largest prospective study on RRT in C-19-AKI is the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID), a multicenter cohort study at 67 geographically diverse hospitals across the USA [1]. A total of 3099 patients were included in the analysis and 637 of them patients (20.6%) developed AKI requiring RRT within 14 days following ICU admission. Patients with RRT were similar in age to patients without AKI-RRT and were more likely to have comorbidities (e.g., diabetes mellitus, hypertension, and chronic kidney disease-CKD), and to have greater severity of illness on arrival to the ICU, including higher rates of invasive mechanical ventilation and treatment with vasopressors. In the 637 AKI-RRT patients, the median time from ICU admission to RRT initiation was 4 days (IQR 2-7 days), and in 52.4% of the cases the modality was CRRT. The remaining modalities included intermittent hemodialysis in 30.0%, “hybrid” RRT (a CRRT conducted for <12 h/day) in 14.9%, and PD in 1.3%. CKD was associated with a higher risk of AKI-RRT (odds ratio, 5.63), and additional patient-specific risk factors for AKI-RRT included sex (men at higher risk), nonwhite race, hypertension, diabetes mellitus, higher body mass index, lower PaO2: FiO2 ratio on ICU admission, and d-dimer >2500 ng/mL on ICU admission. Among the 637 patients with AKI-RRT, 28-day mortality was 54.9%. Older age, receipt of two or more vasopressors at the time of RRT initiation, and severe oliguria (urine output <100 mL/day) at the time of RRT initiation were each associated with a higher risk of 28-day mortality, whereas CKD stage 4 or 5 was associated with a lower risk of 28-day mortality. Among the 216 patients discharged, 33.8% remained RRT dependent on discharge [1]. A recent large meta-analysis on AKI and RRT in COVID-19 patients analyzed 58 observational studies and 22, 671 patients [11]. The pooled AKI incidence rate was 12.3% and 39% among the ICU patients. A total of 12 studies reported that AKI incidence among deceased patients was 42.0%. Furthermore, in 7 studies, among 1588 AKI patients, the proportions of stage 1, 2, and 3 AKI were 36.3%, 20.7%, and 43.0%, respectively. RRT was used to treat 939 out of 17, 664 COVID-19 patients in 39 selected studies, for a pooled application rate of 5.4% and in the overall ICU patients RRT use was 16.3% [11].