CCL14 Predicts Oliguria and Dialysis Requirement in Patients with Moderate to Severe Acute Kidney Injury.

INTRUDUCTION: AKI is a frequent complication in critical illness and portends poor outcome. CCL14 has been validated to predict persistent severe AKI in critically ill patients. We examined the association of CCL14 with urine output within 48 hours. METHODS: In pooled data from 2 studies of critically ill patients with KDIGO stage 2-3 AKI, CCL14 was measured by NEPHROCLEAR™CCL14 Test on the Astute 140® Meter, and divided to low, intermediate and high categories (1.3 and 13 ng/mL). Average hourly urine output over 48 hours, stage 3 AKI per urine output criterion on day 2, and composite of dialysis or death within 7 days were examined using multivariable mixed, and logistic regression models. RESULTS: Of the 497 subjects with median age of 65 [56-74] years, 49% (242/497) were on diuretics. CCL14 concentration was low in 219 (44%), intermediate in 217 (44%), and high in 61 (12%) patients. In mixed regression analysis, urine output trajectory over time was different within each CCL14 risk category based on diuretic use due to significant three-way interaction (p < 0.001). In logistic regression analysis CCL14 risk category was independently associated with low urine output on day 2 (KDIGO stage 3) adjusted for diuretic use and baseline clinical variables and composite of dialysis or death within 7 days (adjusted for urine output within 48 hours of CCL14 measurement). CONCLUSIONS: CCL14 measured in patients with moderate to severe AKI is associated with urine output trajectory within 48 hours, oliguria on day 2, and dialysis within 7 days.

Effect of Changing Estimated Glomerular Filtration Rate Formula on Sugammadex Use and Pulmonary Complications for African American and non-African American Patients.

BACKGROUND: Sugammadex is associated with fewer postoperative pulmonary complications than is neostigmine reversal of neuromuscular blockade. However, the Food and Drug Administration-approved package insert states that its use is "not recommended" in severe renal impairment, separately defined as creatinine clearance <30 mL/min. Recently, the formula for estimating glomerular filtration rate (GFR) was updated to remove the race variable. Compared to the prior formula, the new consensus equation lowers the estimated GFR for African American patients and raises it for everyone else. We sought to determine how this change could differently impact the use of sugammadex, and thus the rate of pulmonary complications, for both African American and non-African American patients. METHODS: We used Monte Carlo simulation models to estimate the difference in pulmonary complications that would be suffered by patients when the change in creatine clearance calculated from the estimated GFR (using the old race-based and new race-neutral Chronic Kidney Disease Epidemiology Collaboration formulas) crossed the 30 mL/min threshold, which would require a change in sugammadex or neostigmine use. RESULTS: We found that 0.22% (95% confidence interval 0.14%-0.36%) of African American patients' creatinine clearance would drop from above to below 30 mL/min making sugammadex not recommended and 0.19% (0.16%-0.22%) of non-African American patients would have creatinine clearance increase to >30 mL/min making sugammadex now recommended. Based on our model, we estimate that African American patients would suffer (count [95% confidence interval]) 3 [0.4-6] more pulmonary complications per 100,000 African American patients who received rocuronium or vecuronium through the change from sugammadex to neostigmine reversal to comply with labeling recommendations. Conversely, the same change in formulas would reduce the number of non-African American patients suffering pulmonary complications by 3 [2-4] per 100,000. CONCLUSIONS: The recent change in GFR formulas may potentially be associated with an increase in postoperative pulmonary complications in African American patients and a decrease in postoperative pulmonary complications in non-African American patients through GFR-driven changes in sugammadex use.

Abrupt Decline in Estimated Glomerular Filtration Rate after Initiating Sodium-Glucose Cotransporter 2 Inhibitors Predicts Clinical Outcomes: A Systematic Review and Meta-Analysis.

BACKGRUOUND: The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined. METHODS: We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis. RESULTS: We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group. CONCLUSION: Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.

Framework for virtual education of COVID-19 vaccines for Mandarin-speaking learners: an educational intervention module.

BACKGROUND: In the United States, patients with limited English proficiency face significant barriers to comprehending and acting upon health-related information, particularly during the COVID-19 pandemic. The ability of health professionals to communicate COVID-19-related information to Mandarin-speaking patients has proved critical in discussions about vaccine efficacy, side effects, and post-vaccine protection. METHODS: The authors created a one-hour educational module to help Mandarin-speaking medical students better convey COVID-19 vaccine information to Mandarin-only speakers. The module is composed of an educational guide, which introduced key terminology and addressed commonly asked questions, and pre- and post-surveys. The authors recruited 59 Mandarin-speaking medical students all of whom had previously completed a medical Mandarin elective. The module and surveys were distributed and completed in August 2021. Data analysis measured the change in aggregate mean for subjective five-point Likert-scale questions and change in percent accuracy for objective knowledge-based questions. RESULTS: 86.4% of participants were primary English speakers with variable levels of Mandarin proficiency. The educational module significantly improved participants' subjective comfort level in discussing the COVID-19 vaccine in English and Mandarin. The largest improvement in both English and Mandarin was demonstrated in participants' ability to explain differences between the COVID-19 vaccines, with an aggregate mean improvement of 0.39 for English and 1.48 for Mandarin. Survey respondents also demonstrated increased percent accuracy in knowledge-based objective questions in Mandarin. CONCLUSIONS: This module provides Mandarin-learning medical students with skills to deliver reliable information to the general population and acts as a model for the continued development of educational modules for multilingual medical professionals.

Midline catheters in patients with advanced chronic kidney disease.

BACKGROUND: Midline catheters (midlines) are increasingly used in patients with advanced chronic kidney disease (CKD). OBJECTIVE: This study describes current practice and acute complications associated with midlines in CKD patients. DESIGNS, SETTING, AND PARTICIPANTS: Trained abstractors at 66 hospitals from the Michigan Hospital Medicine Safety (HMS) Consortium collected data on a sample of patients who received a midline during hospitalization. Patients were classified as having advanced CKD if their estimated glomerular filtration rate was <45 mL/min/1.73 m2 . MAIN OUTCOME AND MEASURES: Midline recipients with advanced CKD were compared to those without advanced CKD by patient, provider, and device characteristics, and by the occurrence of acute complications including major (e.g., upper extremity deep vein thrombosis [UE-DVT] and catheter-related bloodstream infection [CRBSI]) or minor (e.g., catheter occlusion, catheter dislodgement, infiltration, superficial thrombophlebitis, and leaking at insertion site) events. Multivariable mixed effects logistic regression was used to evaluate the association between catheter-related complications and stage of CKD. RESULTS: Of 21,415 midline recipients, 5272 (24.6%) had advanced CKD, while 16,143 (75.4%) did not. Most midlines were single lumen (90.5%) and remained in place for a median of 6 days. A major or minor midline complication occurred in 804 (15.3%) patients with and 2239 (14.4%) patients without advanced CKD (adjusted odds ratios = 1.04; 95% confidence interval: 0.94-1.14). Among patients with advanced CKD, CRBSI occurred in 13 patients (0.2%) and UE-DVT occurred in 65 patients (1.2%). The proportion of advanced CKD among midline recipients and the frequency of midline-related complications varied across hospitals (interquartile range [IQR] = 19.2% to 29.8% [median = 25.0%] and IQR = 11.0%-18.9% [median = 15.4%], respectively).

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.

Oxygen Delivery Thresholds During Cardiopulmonary Bypass and Risk for Acute Kidney Injury.

BACKGROUND: Postoperative acute kidney injury (AKI) in cardiac surgery patients is multifactorial and associated with low oxygen delivery (DO2) during cardiopulmonary bypass. METHODS: Cardiac surgical patients undergoing full cardiopulmonary bypass between May 1, 2016 and December 31, 2021 were included, whereas those on preoperative dialysis, undergoing circulatory arrest procedures, or lacking minute-to-minute physiologic data were excluded. A 5-minute running average of indexed DO2 (DO2i, mL/min/m2) was calculated ([pump flow] × [hemoglobin] × 1.36 [hemoglobin saturation] + 0.003 [arterial oxygen tension]/body surface area). AKI was defined using established Kidney Disease: Improving Global Outcomes criteria. The threshold of nadir DO2i on the effect of AKI was estimated using risk-adjusted Constrained Broken-Stick models. RESULTS: Postoperative AKI occurred among 1155 patients (29.4%), with 276 (7.0%) having stage 2 to 3 AKI. The median nadir DO2i was lower for those with (vs without) AKI (197.9 mL/min/m2 [interquartile range {IQR}, 166.3-233.2] vs 217.2 mL/min/m2 [IQR, 184.5-252.2], P < .001) and stage 2 to 3 AKI relative to stage 1 or none (186.9 mL/min/m2 [IQR, 160.1-220.5] vs 213.8 mL/min/m2 [IQR, 180.4-249.4]). In risk-adjusted analyses the estimated threshold for nadir DO2i was 231.2 mL/min/m2 (95% CI, 173.6-288.8) for any AKI and 103.3 (95% CI, 68.4-138.3) for stage 2 to 3 AKI. CONCLUSIONS: Decreasing nadir DO2i was associated with an increased risk of AKI. The identified nadir DO2i thresholds suggest management and treatment of nadir DO2i during cardiopulmonary bypass may decrease a patient's postoperative AKI risk.

Genetic predisposition may not improve prediction of cardiac surgery-associated acute kidney injury.

Background: The recent integration of genomic data with electronic health records has enabled large scale genomic studies on a variety of perioperative complications, yet genome-wide association studies on acute kidney injury have been limited in size or confounded by composite outcomes. Genome-wide association studies can be leveraged to create a polygenic risk score which can then be integrated with traditional clinical risk factors to better predict postoperative complications, like acute kidney injury. Methods: Using integrated genetic data from two academic biorepositories, we conduct a genome-wide association study on cardiac surgery-associated acute kidney injury. Next, we develop a polygenic risk score and test the predictive utility within regressions controlling for age, gender, principal components, preoperative serum creatinine, and a range of patient, clinical, and procedural risk factors. Finally, we estimate additive variant heritability using genetic mixed models. Results: Among 1,014 qualifying procedures at Vanderbilt University Medical Center and 478 at Michigan Medicine, 348 (34.3%) and 121 (25.3%) developed AKI, respectively. No variants exceeded genome-wide significance (p < 5 × 10-8) threshold, however, six previously unreported variants exceeded the suggestive threshold (p < 1 × 10-6). Notable variants detected include: 1) rs74637005, located in the exonic region of NFU1 and 2) rs17438465, located between EVX1 and HIBADH. We failed to replicate variants from prior unbiased studies of post-surgical acute kidney injury. Polygenic risk was not significantly associated with post-surgical acute kidney injury in any of the models, however, case duration (aOR = 1.002, 95% CI 1.000-1.003, p = 0.013), diabetes mellitus (aOR = 2.025, 95% CI 1.320-3.103, p = 0.001), and valvular disease (aOR = 0.558, 95% CI 0.372-0.835, p = 0.005) were significant in the full model. Conclusion: Polygenic risk score was not significantly associated with cardiac surgery-associated acute kidney injury and acute kidney injury may have a low heritability in this population. These results suggest that susceptibility is only minimally influenced by baseline genetic predisposition and that clinical risk factors, some of which are modifiable, may play a more influential role in predicting this complication. The overall impact of genetics in overall risk for cardiac surgery-associated acute kidney injury may be small compared to clinical risk factors.

Enhancing the Cardiovascular Safety of Hemodialysis Care Using Multimodal Provider Education and Patient Activation Interventions: Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: End-stage kidney disease (ESKD) is treated with dialysis or kidney transplantation, with most patients with ESKD receiving in-center hemodialysis treatment. This life-saving treatment can result in cardiovascular and hemodynamic instability, with the most common form being low blood pressure during the dialysis treatment (intradialytic hypotension [IDH]). IDH is a complication of hemodialysis that can involve symptoms such as fatigue, nausea, cramping, and loss of consciousness. IDH increases risks of cardiovascular disease and ultimately hospitalizations and mortality. Provider-level and patient-level decisions influence the occurrence of IDH; thus, IDH may be preventable in routine hemodialysis care. OBJECTIVE: This study aims to evaluate the independent and comparative effectiveness of 2 interventions-one directed at hemodialysis providers and another for patients-in reducing the rate of IDH at hemodialysis facilities. In addition, the study will assess the effects of interventions on secondary patient-centered clinical outcomes and examine factors associated with a successful implementation of the interventions. METHODS: This study is a pragmatic, cluster randomized trial to be conducted in 20 hemodialysis facilities in the United States. Hemodialysis facilities will be randomized using a 2 × 2 factorial design, such that 5 sites will receive a multimodal provider education intervention, 5 sites will receive a patient activation intervention, 5 sites will receive both interventions, and 5 sites will receive none of the 2 interventions. The multimodal provider education intervention involved theory-informed team training and the use of a digital, tablet-based checklist to heighten attention to patient clinical factors associated with increased IDH risk. The patient activation intervention involves tablet-based, theory-informed patient education and peer mentoring. Patient outcomes will be monitored during a 12-week baseline period, followed by a 24-week intervention period and a 12-week postintervention follow-up period. The primary outcome of the study is the proportion of treatments with IDH, which will be aggregated at the facility level. Secondary outcomes include patient symptoms, fluid adherence, hemodialysis adherence, quality of life, hospitalizations, and mortality. RESULTS: This study is funded by the Patient-Centered Outcomes Research Institute and approved by the University of Michigan Medical School's institutional review board. The study began enrolling patients in January 2023. Initial feasibility data will be available in May 2023. Data collection will conclude in November 2024. CONCLUSIONS: The effects of provider and patient education on reducing the proportion of sessions with IDH and improving other patient-centered clinical outcomes will be evaluated, and the findings will be used to inform further improvements in patient care. Improving the stability of hemodialysis sessions is a critical concern for clinicians and patients with ESKD; the interventions targeted to providers and patients are predicted to lead to improvements in patient health and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT03171545; https://clinicaltrials.gov/ct2/show/NCT03171545. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46187.

Serial Urinary C-C Motif Chemokine Ligand 14 and Risk of Persistent Severe Acute Kidney Injury.

To assess the added prognostic value of serial monitoring of urinary C-C motif chemokine ligand 14 (uCCL14) over that of single measurements, which have been shown to be prognostic for development of persistent severe acute kidney injury (AKI) in critically ill patients. DESIGN: Retrospective observational study. SETTING: Data derived from two multinational ICU studies (Ruby and Sapphire). PATIENTS: Critically ill patients with early stage 2-3 AKI. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed three consecutive uCCL14 measurements at 12-hour intervals after diagnosis of stage 2-3 AKI by Kidney Disease Improving Global Outcomes criteria. Primary outcome was persistent severe AKI, defined as 72 consecutive hours of stage 3 AKI, death, or receipt of dialysis prior to 72 hours. uCCL14 was measured using the NEPHROCLEAR uCCL14 Test on the Astute 140 Meter (Astute Medical, San Diego, CA). Based on predefined, validated cutoffs, we categorized uCCL14 as: low (≤ 1.3 ng/mL), medium (> 1.3 to ≤ 13 ng/mL), or high (> 13 ng/mL). Seventy-five of 417 patients with three consecutive uCCL14 measurements developed persistent severe AKI. Initial uCCL14 category strongly correlated with primary endpoint and, in most cases (66%), uCCL14 category was unchanged over the first 24 hours. Compared with no change and accounting for baseline category, decrease in category was associated with decreased odds of persistent severe AKI (odds ratio [OR], 0.20; 95% CI, 0.08-0.45; p < 0.001) and an increase in category with increased odds (OR, 4.04; 95% CI, 1.75-9.46; p = 0.001). CONCLUSIONS: In one-third of patients with moderate to severe AKI uCCL14 risk category altered over three serial measurements and such changes were associated with altered risk for persistent severe AKI. Serial CCL-14 measurement may detect progression or resolution of underlying kidney pathology and help refine AKI prognosis.

Limited clinical utility for GWAS or polygenic risk score for postoperative acute kidney injury in non-cardiac surgery in European-ancestry patients.

BACKGROUND: Prior studies support a genetic basis for postoperative acute kidney injury (AKI). We conducted a genome-wide association study (GWAS), assessed the clinical utility of a polygenic risk score (PRS), and estimated the heritable component of AKI in patients who underwent noncardiac surgery. METHODS: We performed a retrospective large-scale genome-wide association study followed by a meta-analysis of patients who underwent noncardiac surgery at the Vanderbilt University Medical Center ("Vanderbilt" cohort) or Michigan Medicine, the academic medical center of the University of Michigan ("Michigan" cohort). In the Vanderbilt cohort, the relationship between polygenic risk score for estimated glomerular filtration rate and postoperative AKI was also tested to explore the predictive power of aggregating multiple common genetic variants associated with AKI risk. Similarly, in the Vanderbilt cohort genome-wide complex trait analysis was used to estimate the heritable component of AKI due to common genetic variants. RESULTS: The study population included 8248 adults in the Vanderbilt cohort (mean [SD] 58.05 [15.23] years, 50.2% men) and 5998 adults in Michigan cohort (56.24 [14.76] years, 49% men). Incident postoperative AKI events occurred in 959 patients (11.6%) and in 277 patients (4.6%), respectively. No loci met genome-wide significance in the GWAS and meta-analysis. PRS for estimated glomerular filtration rate explained a very small percentage of variance in rates of postoperative AKI and was not significantly associated with AKI (odds ratio 1.050 per 1 SD increase in polygenic risk score [95% CI, 0.971-1.134]). The estimated heritability among common variants for AKI was 4.5% (SE = 4.5%) suggesting low heritability. CONCLUSION: The findings of this study indicate that common genetic variation minimally contributes to postoperative AKI after noncardiac surgery, and likely has little clinical utility for identifying high-risk patients.

In-Hospital and 1-Year Mortality Trends in a National Cohort of US Veterans with Acute Kidney Injury.

BACKGROUND AND OBJECTIVES: AKI, a frequent complication among hospitalized patients, confers excess short- and long-term mortality. We sought to determine trends in in-hospital and 1-year mortality associated with AKI as defined by Kidney Disease Improving Global Outcomes consensus criteria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study used data from the national Veterans Health Administration on all patients hospitalized from October 1, 2008 to September 31, 2017. AKI was defined by Kidney Disease Improving Global Outcomes serum creatinine criteria. In-hospital and 1-year mortality trends were analyzed in patients with and without AKI using Cox regression with year as a continuous variable. RESULTS: We identified 1,688,457 patients and 2,689,093 hospitalizations across the study period. Among patients with AKI, 6% died in hospital, and 28% died within 1 year. In contrast, in-hospital and 1-year mortality rates were 0.8% and 14%, respectively, among non-AKI hospitalizations. During the study period, there was a slight decline in crude in-hospital AKI-associated mortality (hazard ratio, 0.98 per year; 95% confidence interval, 0.98 to 0.99) that was attenuated after accounting for patient demographics, comorbid conditions, and acute hospitalization characteristics (adjusted hazard ratio, 0.99 per year; 95% confidence interval, 0.99 to 1.00). This stable temporal trend in mortality persisted at 1 year (adjusted hazard ratio, 1.00 per year; 95% confidence interval, 0.99 to 1.00). CONCLUSIONS: AKI associated mortality remains high, as greater than one in four patients with AKI died within 1 year of hospitalization. Over the past decade, there seems to have been no significant progress toward improving in-hospital or long-term AKI survivorship.

Continuous Renal Replacement Therapy among Patients with COVID-19 and Acute Kidney Injury.

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) is a common complication among patients with COVID-19 and acute respiratory distress syndrome. Reports suggest that COVID-19 confers a pro-thrombotic state, which presents challenges in maintaining hemofilter patency and delivering continuous renal replacement therapy (CRRT). We present our initial experience with CRRT in critically ill patients with COVID-19, emphasizing circuit patency and the association between fluid balance during CRRT and respiratory parameters. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Retrospective chart review of 32 consecutive patients with COVID-19 and AKI managed with continuous venovenous hemodiafiltration with regional citrate anticoagulation (CVVHDF-RCA) according to the University of Michigan protocol. Primary outcome was mean CRRT circuit life per patient during the first 7 days of CRRT. We used simple linear regression to assess the relationship between patient characteristics and filter life. We also explored the relationship between fluid balance on CRRT and respiratory parameters using repeated measures modeling. RESULTS: Patients' mean age was 54.8 years and majority were Black (75%). Comorbidities included hypertension (90.6%), obesity (70.9%) diabetes (56.2%), and chronic kidney disease (40.6%). Median CRRT circuit life was 53.5 [interquartile range 39.1-77.6] hours. There was no association between circuit life and inflammatory or pro-thrombotic laboratory values (ferritin p = 0.92, C-reactive protein p = 0.29, D-dimer p = 0.24), or with systemic anticoagulation (p = 0.37). Net daily fluid removal during the first 7 days of CRRT was not associated with daily (closest recorded values to 20:00) PaO2/FIO2 ratio (p = 0.21) or positive end-expiratory pressure requirements (p = 0.47). CONCLUSIONS: We achieved adequate CRRT circuit life in COVID-19 patients using an established CVVHDF-RCA protocol. During the first 7 days of CRRT therapy, cumulative fluid balance was not associated with improvements in respiratory parameters, even after accounting for baseline fluid balance.

The Role of Race on Acute Kidney Injury After Cardiac Surgery.

BACKGROUND: Acute kidney injury (AKI) frequently complicates cardiac surgery and is more common among Black patients. We evaluated determinants of race-based differences in AKI rates. METHODS: Serum creatinine-based criteria were used to identify adult cardiac surgical patients having postoperative AKI in the Perfusion Measures and Outcomes (PERForm) Registry (July 1, 2014, to June 30, 2019). Patient characteristics, operative details, and outcomes were compared by race (Black vs White) after excluding patients with preoperative dialysis, missing preoperative or postoperative creatinine, or other races. A mixed effects model (adjusting for demographics, comorbidities, surgical factors) used hospital as a random effect to predict postoperative stage 2 or 3 AKI. Propensity score analyses were conducted to evaluate robustness of the primary analyses. RESULTS: The study cohort included 34 520 patients (8% Black). More Black patients than White patients were female (43% vs 27%, P < .001), and had hypertension (93% vs 87%, P < .001) and diabetes mellitus (51% vs 41%, P < .001). Acute kidney injury of stage 2 or greater occurred in 1697 patients (5%), more often among Black than White patients (8% vs 5%, P < .001). Intraoperatively, Black patients had lower nadir hematocrits (23 vs 26, P < .001), and were more likely to be given transfusions (22% vs 14%, P < .001). After adjustment, Black race (compared with White) independently predicted odds for postoperative AKI (adjusted odds ratio 1.50; 95% confidence interval, 1.26 to 1.78). The multivariable findings were similar in propensity score analyses. CONCLUSIONS: Despite accounting for differences in risk factors and intraoperative practices, Black patients had a 50% increased odds for having moderate-severe postoperative AKI compared with White patients. Additional evaluations are warranted to identify potential targets to address racial disparities in AKI outcomes.

Generalizability of an acute kidney injury prediction model across health systems.

Delays in the identification of acute kidney injury (AKI) in hospitalized patients are a major barrier to the development of effective interventions to treat AKI. A recent study by Tomasev and colleagues at DeepMind described a model that achieved a state-of-the-art performance in predicting AKI up to 48 hours in advance.1 Because this model was trained in a population of US Veterans that was 94% male, questions have arisen about its reproducibility and generalizability. In this study, we aimed to reproduce key aspects of this model, trained and evaluated it in a similar population of US Veterans, and evaluated its generalizability in a large academic hospital setting. We found that the model performed worse in predicting AKI in females in both populations, with miscalibration in lower stages of AKI and worse discrimination (a lower area under the curve) in higher stages of AKI. We demonstrate that while this discrepancy in performance can be largely corrected in non-Veterans by updating the original model using data from a sex-balanced academic hospital cohort, the worse model performance persists in Veterans. Our study sheds light on the importance of reproducing artificial intelligence studies, and on the complexity of discrepancies in model performance in subgroups that cannot be explained simply on the basis of sample size.

Telavancin pharmacokinetics in patients with chronic kidney disease receiving haemodialysis.

BACKGROUND: Telavancin is a lipoglycopeptide antibiotic with limited pharmacokinetic data to guide drug dosing in patients receiving haemodialysis. OBJECTIVES: This study characterized telavancin pharmacokinetics in patients receiving haemodialysis. PATIENTS AND METHODS: This was a Phase IV, prospective, open-label, single-centre, crossover pharmacokinetic study (ClinicalTrials.gov: NCT02392208). Eight subjects with end-stage kidney disease requiring maintenance haemodialysis (mean ±â€ŠSD: 47 ±â€Š20 years, 69.5 ±â€Š17.1 kg) received 5 mg/kg telavancin IV 3 h before starting a 3.5 hour haemodialysis treatment with a high-permeability haemodialyser (haemodialysis period). After a 14 day washout period, a second 5 mg/kg dose was administered post-haemodialysis (control period). Telavancin plasma concentrations were measured over a 2 day period after each dose and non-compartmental pharmacokinetic analyses were performed. RESULTS: The geometric mean (GM) of telavancin overall clearance was 11.2 mL/h/kg (intrinsic clearance and dialytic clearance) in the haemodialysis period and 5.9 mL/h/kg (off-haemodialysis clearance) in the control period [GM ratio (GMR) = 1.89; 90% CI: 1.70-2.10; P < 0.01]. The GM t½ was 13.1 h when haemodialysis occurred 3 h post-dosing in the haemodialysis period but extended to 20.9 h with post-haemodialysis dosing in the control period (GMR = 0.63; 90% CI: 0.54-0.73; P < 0.01). The GM of telavancin plasma concentrations removed by haemodialysis was 27.7%. The GMR of peak plasma concentration and volume of distribution of the haemodialysis period and the control period were 0.88 (90% CI: 0.79-0.98; P = 0.08) and 1.17 (90% CI: 1.05-1.30; P = 0.048), respectively. CONCLUSIONS: Haemodialysis with high-permeability haemodialysers removes telavancin considerably (∼⅓ of body load). Telavancin 5 mg/kg every 48 h post-haemodialysis dosing is recommended, but dose adjustments may be warranted if haemodialysis starts within 3 h of telavancin administration.