Epidemiology and Outcomes of AKI Treated With Continuous Kidney Replacement Therapy: The Multicenter CRRTnet Study.

Rationale & Objective: Continuous kidney replacement therapy (CKRT) is the predominant form of acute kidney replacement therapy used for critically ill adult patients with acute kidney injury (AKI). Given the variability in CKRT practice, a contemporary understanding of its epidemiology is necessary to improve care delivery. Study Design: Multicenter, prospective living registry. Setting & Population: 1,106 critically ill adults with AKI requiring CKRT from December 2013 to January 2021 across 5 academic centers and 6 intensive care units. Patients with pre-existing kidney failure and those with coronavirus 2 infection were excluded. Exposure: CKRT for more than 24 hours. Outcomes: Hospital mortality, kidney recovery, and health care resource utilization. Analytical Approach: Data were collected according to preselected timepoints at intensive care unit admission and CKRT initiation and analyzed descriptively. Results: Patients' characteristics, contributors to AKI, and CKRT indications differed among centers. Mean (standard deviation) age was 59.3 (13.9) years, 39.7% of patients were women, and median [IQR] APACHE-II (acute physiologic assessment and chronic health evaluation) score was 30 [25-34]. Overall, 41.1% of patients survived to hospital discharge. Patients that died were older (mean age 61 vs. 56.8, P < 0.001), had greater comorbidity (median Charlson score 3 [1-4] vs. 2 [1-3], P < 0.001), and higher acuity of illness (median APACHE-II score 30 [25-35] vs. 29 [24-33], P = 0.003). The most common condition predisposing to AKI was sepsis (42.6%), and the most common CKRT indications were oliguria/anuria (56.2%) and fluid overload (53.9%). Standardized mortality ratios were similar among centers. Limitations: The generalizability of these results to CKRT practices in nonacademic centers or low-and middle-income countries is limited. Conclusions: In this registry, sepsis was the major contributor to AKI and fluid management was collectively the most common CKRT indication. Significant heterogeneity in patient- and CKRT-specific characteristics was found in current practice. These data highlight the need for establishing benchmarks of CKRT delivery, performance, and patient outcomes. Data from this registry could assist with the design of such studies.

Extracorporeal Immunomodulation Treatment and Clinical Outcomes in ICU COVID-19 Patients.

To evaluate safety and clinical outcomes of extracorporeal immunomodulation treatment with a selective cytopheretic device (SCD) in COVID-19 ICU patients with multiple organ failure. DESIGN: Two-center, prospective, single-arm treatment clinical trial. SETTING: ICUs at two academic medical centers between September 2020 and July 2021. PATIENTS: Twenty-two COVID-10 patients in the ICU with acute respiratory distress syndrome who required mechanical ventilation. Nearly all included patients in the intervention group except one had acute kidney injury requiring continuous renal replacement therapy (CRRT). Sixteen subjects meeting enrollment criteria were selected as contemporaneous controls from a concurrent prospective registry CRRT trial. INTERVENTION: Treatment with an SCD integrated into a continuous renal replacement extracorporeal blood circuit for up to 10 days to provide autologous leukocyte cell processing to immunomodulate the hyperinflammatory disease state of COVID-19. MEASUREMENTS AND MAIN RESULTS: SCD treatment in COVID-19 ICU patients with multiple organ failure demonstrated an acceptable safety profile with no device-related serious adverse events. Treatment of these patients resulted in the selective removal of highly activated circulating leukocytes as determined by flow cytometry. Significant reductions were observed in the elevated plasma levels of eight cytokines and biomarkers, including interleukin (IL)6, IL15, IL10, and soluble ST2, which are predictive of mortality in COVID-19 patients. Significant improvements of leukocytosis and Po2/Fio2 ratios occurred during treatment not observed in the control group. SCD-treated subjects had a reduction in 60-day mortality of 50% compared with 81% in the control cohort. The subjects who received greater than 96 hours of SCD treatment, per protocol, had a further reduction in mortality to 31% (p < 0.012). CONCLUSIONS: Extracorporeal immunomodulation therapy with an SCD demonstrated safety without any device-related serious adverse events. As a rescue therapy in COVID-19 ICU patients progressing to multiple organ failure despite maximal pharmacologic and organ support interventions, SCD treatment resulted in improved clinical outcomes. This autologous leukocyte cell processing technology may provide a new approach in the treatment of unremitting hyperinflammation of COVID-19.

Characteristics and outcomes of prisoners hospitalized due to COVID-19 disease.

BACKGROUND: Correctional facilities have faced unique challenges during the COVID-19 pandemic. A COVID-19 outbreak was reported in the Federal Medical Center (FMC) in Lexington, Kentucky, a prison for inmates requiring medical and mental care. The main objective of this study was to examine clinical characteristics and outcomes of prisoners vs. non-prisoners admitted to the hospital due to COVID-19 disease. MATERIALS AND METHODS: We did a retrospective, comparative cohort study of 86 consecutive COVID-19 patients admitted to the University of Kentucky hospital between March 1 and June 1, 2020. Among these, 37 patients were inmates from a single local FMC and 49 were non-inmates. RESULTS: Mean (SD) age of the cohort was 59.1 (14.5) years, 68.6% were male and 61.6% white. All inmates were men. No significant differences in age or race were observed between inmates and non-inmates. Hypertension (81%), obesity (62%), COPD/asthma (43%), diabetes (41%), coronary artery diseases (38%), and chronic kidney disease (22%) were among the most common comorbidities prevalent in inmates. Inmates had overall higher serum creatinine and C-reactive protein, more proteinuria, and lower platelet counts at the time of hospital admission when compared to non-inmates. Incidence of acute kidney injury (AKI) was more frequent in inmates (68 vs. 38% in non-inmates, p = 0.008). Overall, patients who developed AKI had higher acuity of illness with more requirement of ICU care and mechanical ventilation. Kidney replacement therapy (KRT) was provided to 12.8% of patients. Inpatient mortality occurred in 15.1% of patients and was not different in inmates vs. non-inmates (13.5 vs. 16.3%, p = 0.862). All survivors became independent of KRT, and ~ 1 of 10 survivors had a reduction of eGFR ≥ 25% from baseline by the time of discharge, which was more frequent in inmates vs. non-inmates, 15.6 vs. 2.4%, p = 0.042, respectively. CONCLUSION: Inmates represent a vulnerable population with prevalent comorbidity and susceptibility to COVID-19. When compared to non-inmates with COVID-19, inmates exhibited higher incidence of AKI and, for survivors, less kidney recovery by the time of hospital discharge. Surveillance of long-term sequela of COVID-19 is warranted in this susceptible inmate population.

Incidence and Outcomes of Acute Kidney Injury in COVID-19: A Systematic Review.

BACKGROUND AND OBJECTIVES: The recent worldwide pandemic of COVID-19 has been a serious, multidimensional problem that has left a detrimental worldwide impact on individuals of all ages and several organ systems. The typical manifestation of kidney involvement is acute kidney injury (AKI); however, there is a lack of consensus data regarding AKI epidemiology in COVID-19. This systematic literature review aims to bridge this knowledge gap. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: MEDLINE and Cochrane library were systematically searched for the literature related to AKI in COVID-19 patients of all ages. MedRxIV was searched for relevant unpublished manuscripts. Two reviewers independently assessed the literature on the incidence of AKI and mortality, extracting the need for kidney replacement therapy (KRT). RESULTS: Sixty studies (n = 43,871 patients) were included in this review. The pooled incidence of AKI among COVID-19 patients was 19.45% (95% confidence intervals [95% CI]: 14.63-24.77%), while the pooled incidence of AKI COVID-19 patients requiring KRT was 39.04% (16.38-64.57%). The pooled proportion of COVID+ patients was significantly lower at 8.83% (5.64% to 12/66%). The overall mortality of COVID-19 patients was calculated to be 17.71% (95% CI: 11.49-24.93%), while the mortality among patients with AKI was higher at 54.24% (95% CI: 44.70-63.63%). CONCLUSION: This comprehensive systematic review summarizes the available literature pertaining to AKI epidemiology in COVID-19 patients and highlights the incidence, associated mortality, and the need for KRT in this susceptible population.

AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19.

BACKGROUND: AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT). METHODS: We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients. RESULTS: A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1-123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission. CONCLUSIONS: AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.

Characteristics and Outcomes of Individuals With Pre-existing Kidney Disease and COVID-19 Admitted to Intensive Care Units in the United States.

RATIONALE & OBJECTIVE: Underlying kidney disease is an emerging risk factor for more severe coronavirus disease 2019 (COVID-19) illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing chronic kidney disease (CKD) and investigated the association between the degree of underlying kidney disease and in-hospital outcomes. STUDY DESIGN: Retrospective cohort study. SETTINGS & PARTICIPANTS: 4,264 critically ill patients with COVID-19 (143 patients with pre-existing kidney failure receiving maintenance dialysis; 521 patients with pre-existing non-dialysis-dependent CKD; and 3,600 patients without pre-existing CKD) admitted to intensive care units (ICUs) at 68 hospitals across the United States. PREDICTOR(S): Presence (vs absence) of pre-existing kidney disease. OUTCOME(S): In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/cardiac arrest, thromboembolic events, major bleeds, and acute liver injury (secondary). ANALYTICAL APPROACH: We used standardized differences to compare patient characteristics (values>0.10 indicate a meaningful difference between groups) and multivariable-adjusted Fine and Gray survival models to examine outcome associations. RESULTS: Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median of 4 [IQR, 2-9] days for maintenance dialysis patients; 7 [IQR, 3-10] days for non-dialysis-dependent CKD patients; and 7 [IQR, 4-10] days for patients without pre-existing CKD). More dialysis patients (25%) reported altered mental status than those with non-dialysis-dependent CKD (20%; standardized difference=0.12) and those without pre-existing CKD (12%; standardized difference=0.36). Half of dialysis and non-dialysis-dependent CKD patients died within 28 days of ICU admission versus 35% of patients without pre-existing CKD. Compared to patients without pre-existing CKD, dialysis patients had higher risk for 28-day in-hospital death (adjusted HR, 1.41 [95% CI, 1.09-1.81]), while patients with non-dialysis-dependent CKD had an intermediate risk (adjusted HR, 1.25 [95% CI, 1.08-1.44]). LIMITATIONS: Potential residual confounding. CONCLUSIONS: Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies in this vulnerable population.

Outcomes of critically ill solid organ transplant patients with COVID-19 in the United States.

National data on patient characteristics, treatment, and outcomes of critically ill coronavirus disease 2019 (COVID-19) solid organ transplant (SOT) patients are limited. We analyzed data from a multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units (ICUs) at 68 hospitals across the United States from March 4 to May 8, 2020. From 4153 patients, we created a propensity score matched cohort of 386 patients, including 98 SOT patients and 288 non-SOT patients. We used a binomial generalized linear model (log-binomial model) to examine the association of SOT status with death and other clinical outcomes. Among the 386 patients, the median age was 60 years, 72% were male, and 41% were black. Death within 28 days of ICU admission was similar in SOT and non-SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70-1.22). Other outcomes and requirement for organ support including receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were also similar between groups. There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non-SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97-1.85]). Death and organ support requirement were similar between SOT and non-SOT critically ill patients with COVID-19.