Posthospital Multidisciplinary Care for AKI Survivors: A Feasibility Pilot.

Rationale & Objective: Innovative models are needed to address significant gaps in kidney care follow-up for acute kidney injury (AKI) survivors. Study Design: This quasi-experimental pilot study reports the feasibility of the AKI in Care Transitions (ACT) program, a multidisciplinary approach to AKI survivor care based in the primary care setting. Setting & Participants: The study included consenting adults with stage 3 AKI discharged home without dialysis. Interventions: The ACT intervention included predischarge education from nurses and coordinated postdischarge follow-up with a primary care provider and pharmacist within 14 days. ACT was implemented in phases (Usual Care, Education, ACT). Outcomes: The primary outcome was feasibility. Secondary outcomes included process and clinical outcomes. Results: In total, 46 of 110 eligible adults were enrolled. Education occurred in 18/18 and 14/15 participants in the Education and ACT groups, respectively. 30-day urine protein evaluation occurred in 15%, 28%, and 87% of the Usual Care, Education, and ACT groups, respectively (P < 0.001). Cumulative incidence of provider (primary care or nephrologist) and laboratory follow-up at 14 and 30 days was different across groups (14 days: Usual care 0%, Education 11%, ACT 73% [P < 0.01]; 30 days: 0%, 22%, and 73% [P < 0.01]). 30-day readmission rates were 23%, 44%, and 13% in the Usual Care, Education, and ACT groups, respectively (P = 0.13). Limitations: Patients were not randomly assigned to treatment groups. The sample size limited the ability to detect some differences or perform multivariable analysis. Conclusions: This study demonstrated the feasibility of multidisciplinary AKI survivor follow-up beginning in primary care. We observed a higher cumulative incidence of laboratory and provider follow-up in ACT participants. Trial Registration: ClinicalTrials.gov (NCT04505891). Plain-Language Summary: Abrupt loss of kidney function in hospitalized patients, acute kidney injury (AKI), increases the chances of long-term kidney disease and a worse health care experience for patients. One out of 3 people who experience AKI do not get the follow-up kidney care they need. We performed a pilot study to test whether a program that facilitates structured AKI follow-up in primary care called the AKI in Care Transitions (ACT) program was possible. ACT brings together the unique expertise of nurses, doctors, and pharmacists to look at the patient's kidney health plan from all angles. The study found that the ACT program was possible and led to more complete kidney care follow-up after discharge than the normal approach to care.

Comprehensive Acute Kidney Injury Survivor Care: Protocol for the Randomized Acute Kidney Injury in Care Transitions Pilot Trial.

BACKGROUND: Innovative care models are needed to address gaps in kidney care follow-up among acute kidney injury (AKI) survivors. We developed the multidisciplinary AKI in Care Transitions (ACT) program, which embeds post-AKI care in patients' primary care clinic. OBJECTIVE: The objective of this randomized pilot trial is to test the feasibility and acceptability of the ACT program and study protocol, including recruitment and retention, procedures, and outcome measures. METHODS: The study will be conducted at Mayo Clinic in Rochester, Minnesota, a tertiary care center with a local primary care practice. Individuals who are included have stage 3 AKI during their hospitalization, do not require dialysis at discharge, have a local primary care provider, and are discharged to their home. Patients unable or unwilling to provide informed consent and recipients of any transplant within 100 days of enrollment are excluded. Consented patients are randomized to receive the intervention (ie, ACT program) or usual care. The ACT program intervention includes predischarge kidney health education from nurses and coordinated postdischarge laboratory monitoring (serum creatinine and urine protein assessment) and follow-up with a primary care provider and pharmacist within 14 days. The usual care group receives no specific study-related intervention, and any aspects of AKI care are at the direction of the treating team. This study will examine the feasibility of the ACT program, including recruitment, randomization and retention in a trial setting, and intervention fidelity. The feasibility and acceptability of participating in the ACT program will also be examined in qualitative interviews with patients and staff and through surveys. Qualitative interviews will be deductively and inductively coded and themes compared across data types. Observations of clinical encounters will be examined for discussion and care plans related to kidney health. Descriptive analyses will summarize quantitative measures of the feasibility and acceptability of ACT. Participants' knowledge about kidney health, quality of life, and process outcomes (eg, type and timing of laboratory assessments) will be described for both groups. Clinical outcomes (eg, unplanned rehospitalization) up to 12 months will be compared with Cox proportional hazards models. RESULTS: This study received funding from the Agency for Health Care Research and Quality on April 21, 2021, and was approved by the Institutional Review Board on December 14, 2021. As of March 14, 2023, seventeen participants each have been enrolled in the intervention and usual care groups. CONCLUSIONS: Feasible and generalizable AKI survivor care delivery models are needed to improve care processes and health outcomes. This pilot trial will test the ACT program, which uses a multidisciplinary model focused on primary care to address this gap. TRIAL REGISTRATION: ClinicalTrials.gov NCT05184894; https://www.clinicaltrials.gov/ct2/show/NCT05184894. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48109.

Acute Kidney Injury Survivor Care Following Hospital Discharge: A Mixed-Methods Study of Nephrologists and Primary Care Providers.

Rationale & Objective: Widespread delivery of high-quality care for acute kidney injury (AKI) survivors after hospital discharge requires a multidisciplinary team. We aimed to compare management approaches between nephrologists and primary care providers (PCPs) and explored strategies to optimize collaboration. Study Design: Explanatory sequential mixed-methods study using a case-based survey followed by semi-structured interviews. Setting & Participants: Nephrologists and PCPs providing AKI survivor care at 3 Mayo Clinic sites and the Mayo Clinic Health System were included. Outcomes: Survey questions and interviews elucidated participants' recommendations for post-AKI care. Analytical Approach: Descriptive statistics were used to summarize survey responses. Qualitative data analysis used deductive and inductive strategies. A connecting and merging approach was used for mixed-methods data integration. Results: 148 of 774 (19%) providers submitted survey responses (24/72 nephrologists and 105/705 PCPs). Nephrologists and PCPs recommended laboratory monitoring and follow-up with a PCP shortly after hospital discharge. Both indicated that the need for nephrology referral, and its timing should be dictated by clinical and non-clinical patient-specific factors. There were opportunities for improvement in medication and comorbid condition management in both groups. Incorporation of multidisciplinary specialists (eg, pharmacists) was recommended to expand knowledge, optimize patient-centered care, and alleviate provider workload. Limitations: Survey findings may have been affected by non-response bias and the unique challenges facing clinicians and health systems during the COVID-19 pandemic. Participants were from a single health system, and their views or experiences may differ from those in other health systems or serving different populations. Conclusions: A multidisciplinary team-based model of post-AKI care may facilitate implementation of a patient-centered care plan, improve adherence to best practices, and reduce clinician and patient burden. Individualizing care for AKI survivors based on clinical and non-clinical patient-specific factors is needed to optimize outcomes for patients and health systems.

Pharmacogenomics and beyond! Customized pharmacotherapy for solid organ transplant recipients.

Solid organ transplant recipients are reliant on immunosuppressive drugs, which have a narrow therapeutic index, and are concurrently vulnerable to adverse drug events due to comorbidity burden and the complexity of their medication regimens. Urgent management of post-transplant complications often falls to the generalist clinician or critical care specialist. The purpose of this narrative review is to discuss innovations and bedside applications of pharmacogenomics and therapeutic drug monitoring applied to immunosuppression and agents frequently encountered in transplant recipients. Medication formulations will be given specific attention, as interchange is frequently required in the acute care setting. Bioassays quantifying immune system activity will be described with practical applications. A structured approach to addressing drug-drug, drug-gene, and drug-drug-gene interactions will be modeled using a case-based approach synthesizing pharmacogenomics, therapeutic drug monitoring, pharmacokinetics, and pharmacodynamic principles.

Pharmacist-provider collaborative visits after hospital discharge in a comprehensive acute kidney injury survivor model.

BACKGROUND: Postdischarge follow-up in primary care is an opportunity for pharmacists to re-evaluate medication use in acute kidney injury (AKI) survivors. Of the emerging AKI survivor care models described in literature, only one involved a pharmacist with limited detail about the direct impact. OBJECTIVE: This study aimed to describe pharmacist contributions to a comprehensive postdischarge AKI survivorship program in primary care (the AKI in Care Transitions [ACT] program). METHODS: The ACT program was piloted from May to December of 2021 at Mayo Clinic as a bundled care strategy for patients who survived an episode of AKI and were discharged home without the need for hemodialysis. Patients received education and care coordination from nurses before discharge and later completed postdischarge laboratory assessment and clinician follow-up in primary care. During the follow-up encounter, patients completed a 30-minute comprehensive medication management visit with a pharmacist focusing on AKI survivorship considerations. Medication therapy recommendations were communicated to a collaborating primary care provider (PCP) before a separate 30-minute visit with the patient. PCPs had access to clinical decision support with evidence-based post-AKI care recommendations. Medication-related issues were summarized descriptively. RESULTS: Pharmacists made 28 medication therapy recommendations (median 3 per patient, interquartile range 2-3) and identified 14 medication discrepancies for the 11 patients who completed the pilot program, and 86% of the medication therapy recommendations were acted on by the PCP within 7 days. Six recommendations were made to initiate renoprotective medications, and 5 were acted on (83%). CONCLUSION: During the pilot phase of a multifaceted transitional care program for AKI survivors, pharmacists' successfully identified and addressed multiple medication therapy problems, including for renally active drugs. These results demonstrate the potential for pharmacist-provider collaborative visits in primary care to improve safe and effective medication use in AKI survivors.

High-Dose Methotrexate in Patients With Lymphoma: Predictors of a Complicated Course.

PURPOSE: High-dose methotrexate (HDMTX; > 500 mg/m2) is an important component of lymphoma therapy. Serum MTX monitoring at 48 hours is the standard approach to identify those at increased risk of developing MTX toxicity. Our aim was to characterize the incidence of complications and their association with MTX levels. METHODS: A retrospective review of our institutional electronic medical record was conducted to identify patients with lymphoma who received HDMTX between January 1, 2002, and December 31, 2018. We characterized the incidence of acute kidney injury (AKI), intensive care unit (ICU) admission, length of hospital stay (LOS), and 30-day mortality across 48-hour MTX levels. To establish an association between 48-hour MTX levels and the complications listed, we performed chi-square analysis for dichotomous variables and Kruskal-Wallis for nonparametric data. Receiver operator characteristic curve analysis was performed to identify the MTX level where AKI grade ≥ 2 was more likely. Multivariate logistic regression analysis was performed to identify risk factors for this MTX level. RESULTS: We identified 642 patients with 2,804 cycles of HDMTX. The incidence of AKI was 19.1% with AKI grade ≥ 2 making up 21% of cases. Rates of AKI, ICU admission, and 30-day mortality are associated with elevated 48-hour MTX levels. There was a significant increase in median LOS with elevated MTX levels (P < .001). Receiver operator characteristic curve analysis for AKI grade ≥ 2 demonstrated a 48-hour MTX level threshold of 1.28 µmol/L. Multivariate logistic regression analysis revealed age, male sex, elevated body surface area, higher MTX dose, monotherapy, and first cycle as independent factors. CONCLUSION: Elevated MTX levels are associated with a significant increased rate of AKI, ICU admission, prolonged LOS, and 30-day mortality. Elevated 48-hour MTX levels, particularly > 1.28 µmol/L, should alert clinicians for complications and to initiate measures to reduce MTX levels.

A Systematic Review and Meta-Analysis Evaluating Geographical Variation in Outcomes of Cancer Patients Treated in ICUs.

The reported mortality rates of cancer patients admitted to ICUs vary widely. In addition, there are no studies that examined the outcomes of critically ill cancer patients based on the geographical regions. Therefore, we aimed to evaluate the mortality rates among critically ill cancer patients and provide a comparison based on geography. DATA SOURCES: PubMed, EMBASE, and Web of Science. STUDY SELECTION: We included observational studies evaluating adult patients with cancer treated in ICUs. We excluded non-English studies, those with greater than 30% hematopoietic stem cell transplant or postsurgical patients, and those that evaluated a specific type of critical illness, stage of malignancy, or age group. DATA EXTRACTION: Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. Studies were classified based on the continent in which they were conducted. Primary outcomes were ICU and hospital mortality. We pooled effect sizes by geographical region. DATA SYNTHESIS: Forty-six studies were included (n = 110,366). The overall quality of studies was moderate. Most of the published literature was from Europe (n = 22), followed by North America (n = 9), Asia (n = 8), South America (n = 5), and Oceania (n = 2). Pooled ICU mortality rate was 38% (95% CI, 33-43%); the lowest mortality rate was in Oceania (26%; 95% CI, 22-30%) and highest in Asia (51%; 95% CI, 44-57%). Pooled hospital mortality rate was 45% (95% CI, 41-49%), with the lowest in North America (37%; 95% CI, 31-43%) and highest in Asia (54%; 95% CI, 37-71%). CONCLUSIONS: More than half of cancer patients admitted to ICUs survived hospitalization. However, there was wide variability in the mortality rates, as well as the number of available studies among geographical regions. This variability suggests an opportunity to improve outcomes worldwide, through optimizing practice and research.

Optimising transitions of care for acute kidney injury survivors: protocol for a mixed-methods study of nephrologist and primary care provider recommendations.

INTRODUCTION: Acute kidney injury (AKI) affects nearly 20% of all hospitalised patients and is associated with poor outcomes. Long-term complications can be partially attributed to gaps in kidney-focused care and education during transitions. Building capacity across the healthcare spectrum by engaging a broad network of multidisciplinary providers to facilitate optimal follow-up care represents an important mechanism to address this existing care gap. Key participants include nephrologists and primary care providers and in-depth study of each specialty's approach to post-AKI care is essential to optimise care processes and healthcare delivery for AKI survivors. METHODS AND ANALYSIS: This explanatory sequential mixed-methods study uses survey and interview methodology to assess nephrologist and primary care provider recommendations for post-AKI care, including KAMPS (kidney function assessment, awareness and education, medication review, blood pressure monitoring and sick day education) elements of follow-up, the role of multispecialty collaboration, and views on care process-specific and patient-specific factors influencing healthcare delivery. Nephrologists and primary care providers will be surveyed to assess recommendations and clinical decision-making in the context of post-AKI care. Descriptive statistics and the Pearson's χ2 or Fisher's exact test will be used to compare results between groups. This will be followed by semistructured interviews to gather rich, qualitative data that explains and/or connects results from the quantitative survey. Both deductive analysis and inductive analysis will occur to identify and compare themes. ETHICS AND DISSEMINATION: This study has been reviewed and deemed exempt by the Institutional Review Board at Mayo Clinic (IRB 20-0 08 793). The study was deemed exempt due to the sole use of survey and interview methodology. Results will be disseminated in presentations and manuscript form through peer-reviewed publication.

Development and Feasibility of a Multidisciplinary Approach to AKI Survivorship in Care Transitions: Research Letter.

Background: Acute kidney injury (AKI) survivors are at heightened risk for poor short- and long-term health outcomes. Even among those who recover after an AKI episode, the risk for chronic kidney disease is 4- to 6-fold higher than in patients without AKI, underscoring the importance of identifying methods to improve AKI survivorship. Objective: The purpose of this report was to describe the development and feasibility of a novel multidisciplinary approach to caring for AKI survivors at care transitions (ACT). Design: Observational process improvement initiative. Setting: Single academic medical center in the United States. Patients: The studied population was adults with stage 3 AKI not discharging on dialysis who were established with a primary care provider (PCP) at our institution. Methods: An electronic health record tool was developed prior to implementation to identify AKI survivors. The ACT program encompassed engaging patients in the hospital, delivering education by nephrology-trained nurses before discharge, completing recommended laboratory testing after discharge, and conducting structured kidney-focused follow-up with a pharmacist and a PCP within 7 to 14 days after discharge. Patients could be referred for nephrology evaluation at the discretion of the PCP. Results: Preliminary data demonstrated that most AKI survivors of interest could be identified, educated, and followed up with this model. This strategy appeared feasible, scalable, and maximized the unique expertise of each member of the multidisciplinary team. Limitations: Small sample size, future assessment of process, clinical, and patient-reported outcomes needed. Conclusions: The multidisciplinary ACT workflow supported by clinical decision support was feasible and addressed gaps in existing care transition models. Team-based care delivery in primary care appears to be a mechanism to extend the capacity for kidney health monitoring for AKI survivors.

Contexte: Les patients qui survivent à un épisode d'insuffisance rénale aiguë (IRA) courent un risque plus élevé de mauvais résultats cliniques à court et à long terme. Même chez les patients qui se rétablissent, le risque de progression vers l'insuffisance rénale chronique (IRC) demeure de quatre à six fois plus élevé que chez les patients n'ayant jamais eu d'épisode d'IRA. Il est donc essentiel d'identifier des méthodes permettant d'améliorer la survie à un épisode d'IRA. Objectif: L'objectif de cette étude était de décrire l'élaboration et la faisabilité d'une nouvelle approche multidisciplinaire pour la prise en charge des survivants d'un épisode d'IRA en transition de soins (Approche multidisciplinaire en Transition de Soins­AmTS). Type d'étude: Initiative d'amélioration des processus menée par observation. Cadre: Un seul centre médical universitaire aux États-Unis. Sujets: La population étudiée était constituée d'adultes atteints d'IRA de stade 3 sans traitements de dialyse à leur sortie et qui avaient été mis en contact avec un fournisseur de soins primaires (FSP) dans l'établissement. Méthodologie: Avant la mise en œuvre de l'intervention, un outil de dossier de santé électronique a été développé pour identifier les survivants à un épisode d'IRA. Le programme de l'AmTS comprenait la participation des patients pendant leur séjour à l'hôpital, une formation donnée par des infirmières formées en néphrologie avant le congé, les tests de laboratoire recommandés après la sortie de l'hôpital et un suivi structuré axé sur la santé rénale avec un pharmacien et un FSP dans les 7 à 14 jours suivant la sortie de l'hôpital. Il a été laissé à la discrétion des FSP d'aiguiller ou non leurs patients pour une évaluation en néphrologie. Résultats: Des données préliminaires ont démontré qu'il était possible d'identifier, d'informer et d'assurer le suivi de la plupart des sujets d'intérêt (des survivants à un épisode d'IRA) avec ce modèle. Cette stratégie a semblé réalisable, évolutive et apte à optimiser l'expertise individuelle des membres de l'équipe multidisciplinaire. Limites: Faible taille de l'échantillon; une évaluation future du processus, des résultats cliniques et des résultats rapportés par les patients est nécessaire. Conclusion: Le processus de cette AmTS soutenue par une aide à la prise de décision clinique s'est avéré réalisable et a permis de combler les lacunes des modèles de transition des soins existants. Dans le contexte des soins primaires, la prestation de soins en équipe semble être un mécanisme permettant d'étendre la capacité de surveillance de la santé rénale des survivants à un épisode d'IRA.

Critically Ill Patients Treated for Chimeric Antigen Receptor-Related Toxicity: A Multicenter Study.

OBJECTIVES: To report the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. DESIGN: Retrospective cohort study. SETTING: Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative. PATIENTS: Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019. INTERVENTIONS: Demographics, toxicities, specific interventions, and outcomes were collected. RESULTS: One-hundred five patients treated with axicabtagene ciloleucel required ICU admission for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome during the study period. At the time of ICU admission, the majority of patients had grade 3-4 toxicities (66.7%); 15.2% had grade 3-4 cytokine release syndrome and 64% grade 3-4 immune effector cell-associated neurotoxicity syndrome. During ICU stay, cytokine release syndrome was observed in 77.1% patients and immune effector cell-associated neurotoxicity syndrome in 84.8% of patients; 61.9% patients experienced both toxicities. Seventy-nine percent of patients developed greater than or equal to grade 3 toxicities during ICU stay, however, need for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) was uncommon. Immune Effector Cell-Associated Encephalopathy score less than 3 (69.7%), seizures (20.2%), status epilepticus (5.7%), motor deficits (12.4%), and cerebral edema (7.9%) were more prevalent. ICU mortality was 8.6%, with only three deaths related to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Median overall survival time was 10.4 months (95% CI, 6.64-not available mo). Toxicity grade or organ support had no impact on overall survival; higher cumulative corticosteroid doses were associated to decreased overall and progression-free survival. CONCLUSIONS: This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.

Use of sublingual tacrolimus in adults undergoing hematopoietic cell transplant: A pilot study.

INTRODUCTION: Orally administered tacrolimus is widely used in hematopoietic cell transplant patients, but multiple clinical situations may arise rendering oral administration infeasible. The undesirable sequelae of intravenous administration, including toxicity, challenges with administration and cost call for innovative solutions to conserve existing supply and optimize safety and efficacy of medication delivery. We sought to demonstrate feasibility of sublingual tacrolimus use and estimate a sublingual-to-oral (SL:PO) conversion ratio in the hematopoietic cell transplant setting. METHODS: Ten adults undergoing allogeneic hematopoietic cell transplant received tacrolimus 0.04 mg/kg/dose twice daily. Initial doses were given via sublingual route and a steady state trough level was collected after 4 consecutive doses. Participants were then switched to oral tacrolimus, the dose adjusted for a goal trough 8-12ng/mL, and another steady state trough was drawn. Total daily dose was divided by trough concentration for each route to determine the dosing ratio of SL:PO. RESULTS: Median trough level following sublingual administration was 11.3 ng/mL. Three of these were within goal, 3 were low (4.7-6.4 ng/mL) and 4 were elevated (15.9-18.6 ng/mL). Median SL:PO ratio was 1.02. In 5 participants the SL:PO ratio was <1 (range 0.57-0.94) and in 5 the ratio was ≥1 (range 1.10-1.92). No significant barriers or intolerance to sublingual tacrolimus use were noted. CONCLUSIONS: Results demonstrate reliable absorption with sublingual tacrolimus use in patients undergoing hematopoietic cell transplant. Sublingual administration may allow for avoidance of the undesirable complications of IV tacrolimus, such as increased toxicities, required hospitalization for continuous infusion, risk of dose conversion and dilution errors and increased cost.Trial Registry name: Use of Sublingual Tacrolimus in Adult Blood and Marrow Transplant Patients, NCT04041219https://clinicaltrials.gov/ct2/show/NCT04041219?term=NCT04041219&draw=2&rank=1.

Incidence of Serum Creatinine Monitoring and Outpatient Visit Follow-Up among Acute Kidney Injury Survivors after Discharge: A Population-Based Cohort Study.

INTRODUCTION: Acute kidney injury (AKI) affects 20% of hospitalized patients and worsens outcomes. To limit complications, post-discharge follow-up and kidney function testing are advised. The objective of this study was to evaluate the frequency of follow-up after discharge among AKI survivors. METHODS: This was a population-based cohort study of adult Olmsted County residents hospitalized with an episode of stage II or III AKI between 2006 and 2014. Those dismissed from the hospital on dialysis, hospice, or who died within 30 days after discharge were excluded. The frequency and predictors of follow-up, defined as an outpatient serum creatinine (SCr) level or an in-person healthcare visit after discharge were described. RESULTS: In the 627 included AKI survivors, the 30-day cumulative incidence of a follow-up outpatient SCr was 80% (95% confidence interval [CI]: 76% and 83%), a healthcare visit was 82% (95% CI: 79 and 85%), or both was 70% (95% CI: 66 and 73%). At 90 days and 1 year after discharge, the cumulative incidences of meeting both follow-up criteria rose to 82 and 91%, respectively. Independent predictors of receiving both an outpatient SCr assessment and healthcare visit within 30 days included lower estimated glomerular filtration rate at discharge, higher comorbidity burden, longer length of hospitalization, and greater maximum AKI severity. Age, sex, race/ethnicity, education level, and socioeconomic status did not predict follow-up. CONCLUSIONS: Among patients with moderate to severe AKI, 30% did not have follow-up with a SCr and healthcare visit in the 30-day post-discharge interval. Follow-up was associated with higher acuity of illness rather than demographic or socioeconomic factors.

Relationship between uric acid and kidney function in adults at risk for tumor lysis syndrome.

Uric acid drives acute kidney injury in tumor lysis syndrome (TLS). This study investigated the relationship between uric acid and changes in estimated glomerular filtration rate (eGFR) in adults at risk for TLS. Linear regression was used to evaluate the relationship between uric acid area under the curve (AUC) and percent change in eGFR from baseline at hospital dismissal, 1 and 3 months. In 210 included participants, each 100 mg*hour/dL increase in 24 h AUC was associated with an average decline in eGFR at hospital dismissal of 9% (95%CI 3, 15) in univariate analysis. Each 100 mg*hour/dL increase in 24 h AUC was independently associated with an average decline in eGFR of 8% (95%CI 2, 13) at 1 month after dismissal. Additional research is needed to confirm these findings and determine whether treatments that reduce overall uric acid exposure improve kidney outcomes. Preserving kidney health could favorably impact cancer treatment eligibility, tolerability, and outcomes.

Risk for Significant Kidney Function Decline After Acute Kidney Injury in Adults With Hematologic Malignancy.

INTRODUCTION: Acute kidney injury (AKI) affects 30% of adults hospitalized with hematologic malignancy. Little is known about the long-term impact on kidney outcomes in this population despite the close relationship between kidney function and malignancy treatment eligibility. The purpose of this population-based cohort study was to determine the effect of AKI on kidney function in the year following a new diagnosis of acute leukemia or lymphoma. METHODS: Participants were adults hospitalized within 3 weeks of malignancy diagnosis. Baseline kidney function was determined and AKI diagnosed using standardized criteria. Cox proportional hazard modeling examined the relationship between AKI and a ≥30% decline in estimated glomerular filtration rate (eGFR) from baseline in the 1 year following hospitalization as the primary endpoint. RESULTS: AKI occurred in 33% of 1064 participants, with 70% of episodes occurring within 48 hours of hospitalization, and significantly increased risk for a ≥ 30% decline in eGFR (hazard ratio [HR] 2.7, 95% confidence interval [CI] 2.2-3.5) and incident chronic kidney disease (HR 2.2, 95% CI 1.7-2.8). AKI remained a significant predictor of eGFR decline in subgroup and multivariable analyses (adjusted HR 1.9, 95% CI 1.4-2.7). A ≥ 30% decline in eGFR increased the risk for death within 1 year in participants with AKI (HR 2.1, 95% CI 1.3-3.3). CONCLUSION: Results aid in identifying individuals at highest risk for poor outcomes and highlight the need for research involving interventions that preserve kidney function from the time of initial hospitalization with a hematologic malignancy into the postdischarge period.

Ideal Body Weight-Based Dosing of Rabbit Antithymocyte Globulin for Cost Minimization in Kidney Transplantation.

INTRODUCTION: Contemporary dosing strategies for rabbit anti-thymocyte globulin (rATG) in kidney transplantation aim to reduce cumulative exposure, minimizing long-term adverse events. The use of ideal body weight-based dosing has been trialed, however concern for increased rejection post-transplant exists due to lower doses of rATG. Research Questions: The primary aim of this study was to compare rejection rates between rATG dosing protocols using actual body weight and ideal body weight and secondarily to evaluate cost savings following protocol implementation. DESIGN: This was a retrospective study surrounding implementation of an ideal body weight-based dosing protocol for rATG. We compared 75 kidney transplant recipients in whom rATG was dosed based on actual body weight (pre-protocol group) to 64 in whom dosing was based on ideal body weight (post-protocol group), following a nine-month washout. RESULTS: The mean cumulative rATG dose in the pre-protocol group was 6.3 mg/kg of actual body weight. When ideal body weight was used in the post-protocol group, the mean dose was 4.5 mg/kg of actual body weight. The rejection rate was 18.7% pre-protocol and 23.4% postprotocol, which did not represent a statistically significant difference (p = 0.491). The actual annual cost savings after protocol implementation exceeded $162,000, approximately $2,500 per patient. CONCLUSION: Results suggest ideal body weight-based dosing of rATG may reduce exposure and cost, without significantly impacting the risk of rejection in kidney transplant recipients. More studies are needed to confirm these findings.

Characteristics and Outcome of Periengraftment Respiratory Distress Syndrome after Autologous Hematopoietic Cell Transplant.

Rationale: The periengraftment respiratory distress syndrome (PERDS) is an early important cause of morbidity following autologous hematopoietic cell transplantation (HCT). There are few contemporary data describing PERDS. Objectives: To determine prevalence, risk factors, and outcomes of PERDS after autologous HCT. Methods: This was a historical cohort study of adults undergoing autologous HCT at Mayo Clinic, Rochester, Minnesota, between 2005 and 2016. PERDS was defined as 1) respiratory failure requiring supplemental oxygen within 5 days on either side of the neutrophil engraftment date, 2) new pulmonary opacities on chest imaging, and 3) exclusion of an infectious or cardiac etiology to explain the clinical presentation. Results: Of 3,473 patients undergoing autologous HCT, 167 (4.8%) developed PERDS. Radiographic changes preceded engraftment in 77% of cases. In a multivariable regression model, risk factors for PERDS included female sex (odds ratio [OR], 1.73; P = 0.001), the number of preengraftment platelet transfusions (OR, 1.22; P = 0.002), and more rapid engraftment (OR, 0.72 per day longer; P < 0.001). PERDS cases were more likely to be admitted to the intensive care unit (47.3% vs. 9.5%, P < 0.001) and require intubation (20.4% vs. 1.6%, P < 0.001). In an adjusted 100-day death analysis, those diagnosed with PERDS were more likely to die (hazard ratio, 3.1; 95% confidence interval, 1.5-6.2; P = 0.002). Conclusions: PERDS is a common complication of autologous HCT and is associated with increased mortality and healthcare use. Radiographic evidence of pulmonary involvement precedes hematopoietic recovery. A larger number of platelet transfusions and more rapid engraftment appear to increase risk for PERDS.

The chimeric antigen receptor-intensive care unit (CAR-ICU) initiative: Surveying intensive care unit practices in the management of CAR T-cell associated toxicities.

PURPOSE: A task force of experts from 11 United States (US) centers, sought to describe practices for managing chimeric antigen receptor (CAR) T-cell toxicity in the intensive care unit (ICU). MATERIALS AND METHODS: Between June-July 2019, a survey was electronically distributed to 11 centers. The survey addressed: CAR products, toxicities, targeted treatments, management practices and interventions in the ICU. RESULTS: Most centers (82%) had experience with commercial and non-FDA approved CAR products. Criteria for ICU admission varied between centers for patients with Cytokine Release Syndrome (CRS) but were similar for Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Practices for vasopressor support, neurotoxicity and electroencephalogram monitoring, use of prophylactic anti-epileptic drugs and tocilizumab were comparable. In contrast, fluid resuscitation, respiratory support, methods of surveillance and management of cerebral edema, use of corticosteroid and other anti-cytokine therapies varied between centers. CONCLUSIONS: This survey identified areas of investigation that could improve outcomes in CAR T-cell recipients such as fluid and vasopressor selection in CRS, management of respiratory failure, and less common complications such as hemophagocytic lymphohistiocytosis, infections and stroke. The variability in specific treatments for CAR T-cell toxicities, needs to be considered when designing future outcome studies of critically ill CAR T-cell patients.

Racial differences in breast cancer survival in the Detroit Metropolitan area.

African American (AA) women have poorer breast cancer survival compared to Caucasian American (CA) women. The purpose of this analysis was to determine whether socioeconomic status (SES) and treatment differences influence racial differences in breast cancer survival. The study population included 9,321 women (82% CA, 18% AA) diagnosed with local (63%) or regional (37%) stage disease between 1988 and 1992, identified through the Metropolitan Detroit SEER registry. Data on SES were obtained through linkage with the 1990 Census of Population and Housing Summary Tape and cases were geocoded to census block groups. Pathology, treatment and survival data were obtained through SEER. Cox proportional hazards models were used to compare survival for AA versus CA women after adjusting for age, SES, tumor size, number of involved lymph nodes, and treatment. AA women were more likely to live in a geographic area classified as working poor than were CA women (p<0.001). AA women were less likely to have lumpectomy and radiation and more likely to have mastectomy with radiation (p<0.001). After multivariable adjusted analysis, there were no significant racial differences in survival among women with local stage disease, although AA women with regional stage disease had persistent but attenuated poorer survival compared to CA women. After adjusting for known clinical and SES predictors of survival, AA and CA women who are diagnosed with local disease demonstrate similar overall and breast cancer-specific survival, while race continues to have an independent effect among women presenting at a later stage of disease.