Patient Preferences and Priorities for the Design of an AKI Prevention Trial: Findings from a Consensus Workshop.

INTRODUCTION: High-quality clinical trials are needed to establish the efficacy and safety of novel therapies for acute kidney injury (AKI) prevention. In this consensus workshop, we identified patient and caregiver priorities for recruitment, intervention delivery, and outcomes of a clinical trial of cilastatin to prevent nephrotoxic AKI. METHODS: We included adults with lived experience of AKI, chronic kidney disease, or risk factors for AKI (e.g., critical care hospitalization), and their caregivers. Using a modified nominal group technique approach, we conducted a series of hybrid in-person/virtual discussions covering 3 clinical trial topic areas: (1) consent and recruitment; (2) intervention delivery; and (3) trial outcomes. Participants voted on their top preferences in each topic area, and discussion transcripts were analyzed inductively using conventional content analysis. RESULTS: Thirteen individuals (11 patients, 2 caregivers) participated in the workshop. For consent and recruitment, participants prioritized technology enabled pre-screening and involvement of family members in the consent process. For intervention delivery, participants prioritized measures to facilitate ease of intervention administration and return visits. For trial outcomes, participants identified kidney-related and other clinical outcomes (e.g., AKI, chronic kidney disease, cardiovascular events) as top priorities. Analysis of transcripts provided insight into care team and family involvement in trial-related decisions, implications of allocation to a placebo arm, and impact of participants' experiences of AKI and critical illness. CONCLUSION: Findings from our workshop will directly inform development of a clinical trial protocol of cilastatin for nephrotoxic AKI prevention and can assist others in patient-centered approaches to AKI trial design.

In patients with the kidney-dysfunction triad, facilitated evidence-based care did not reduce hospitalizations at 1 y.

SOURCE CITATION: Vazquez MA, Oliver G, Amarasingham R, et al; ICD-Pieces Study Group. Pragmatic trial of hospitalization rate in chronic kidney disease. N Engl J Med. 2024;390:1196-1206. 38598574.

Advancing Community Care and Access to Follow-up After Acute Kidney Injury Hospitalization: Design of the AFTER AKI Randomized Controlled Trial.

Background: Acute kidney injury (AKI) is a common complication among hospitalized patients with long-term implications including chronic kidney disease (CKD). Although models are available to predict the risk of advanced CKD after AKI, there is limited evidence regarding follow-up for patients with AKI after hospital discharge, resulting in variable follow-up care. A risk-stratified follow-up approach may improve appropriateness and efficiency of management for CKD among patients at risk of declining kidney function following AKI. Objective: The objective was to compare and evaluate the use of a risk-stratified approach to follow-up care vs usual care for patients with AKI after hospital discharge. Design: This study was a pragmatic randomized controlled trial. Setting: This study was conducted in 2 large urban hospitals in Alberta, Canada. Patients: Hospitalized patients with AKI (KDIGO stage 2 or 3) not previously under the care of a nephrologist, expected to survive greater than 90 days being discharged home. Measurements: We will evaluate whether guideline-recommended CKD care processes are initiated within 90 days, including statin use, angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) use in those with proteinuria or diabetes, and nephrologist follow-up if sustained eGFR <30 mL/min/1.73 m2. We will also assess the feasibility of recruitment and the proportion of patients completing the recommended blood and urine tests at 90 days. Methods: Patients with AKI will be enrolled and randomized near the time of hospital discharge. In the intervention group, low risk patients will receive information regarding AKI, medium risk patients will additionally receive follow-up guidance sent to their primary care physician, and high-risk patients will additionally receive follow-up with a nephrologist. Participants in the intervention and usual care group will receive a requisition for urine testing and bloodwork at 90 days following hospital discharge. Telephone follow-up will be conducted for all study participants at 90 days and 1 year after hospital discharge. Bivariate tests of association will be conducted to evaluate group differences at the follow-up time points. Limitations: We expect there may be challenges with recruitment due to the significant co-existence of comorbidity in this population. Conclusions: If the trial shows a positive effect on these processes for kidney care, it will inform larger-scale trial to determine whether this intervention reduces the incidence of long-term clinical adverse events, including CKD progression, cardiovascular events, and mortality following hospitalization with AKI.

Contexte: L'insuffisance rénale aiguë (IRA) est une complication fréquente chez les patients hospitalisés qui peut avoir des conséquences à long terme, notamment l'insuffisance rénale chronique (IRC). Bien que des modèles de prédiction du risque d'IRC avancée après un épisode d'IRA soient disponibles, peu de données existent sur le suivi des patients atteints d'IRA après leur sortie de l'hôpital, ce qui se traduit par une variabilité dans les soins de suivi. Une approche de suivi stratifiée selon le risque d'IRC peut améliorer la qualité et l'efficacité de la prise en charge de l'IRC chez les patients dont la fonction rénale risque de se détériorer après un épisode d'IRA. Objectifs: Évaluer l'utilisation d'une approche de suivi post-hospitalisation stratifiée selon le risque d'IRC chez les patients atteints d'IRA et la comparer aux soins habituels. Conception: Essai contrôlé randomisé pragmatique. Cadre: Deux grands hôpitaux urbains en Alberta (Canada). Sujets: Patients hospitalisés avec une IRA (stade KDIGO 2 ou 3) qui n'étaient pas suivis auparavant par un néphrologue et dont on prévoyait la survie au-delà de 90 jours après leur sortie de l'hôpital. Mesures: Nous évaluerons si, dans les 90 jours suivant le congé, les soins d'IRC habituels recommandés par les lignes directrices seront amorcés, c'est-à-dire l'utilisation de statines, l'utilisation d'IECA/ARA chez les patients souffrant de protéinurie ou de diabète, et le suivi avec un néphrologue pour les patients avec un DFGe inférieur à 30 ml/min/1,73 m2 de façon soutenue. Nous évaluerons également la faisabilité du recrutement et la proportion de patients qui auront effectué les analyses sanguines et urinaires recommandées à 90 jours. Méthodologie: Les patients atteints d'IRA seront recrutés et randomisés au moment de leur sortie de l'hôpital. Dans le groupe d'intervention, les patients présentant un faible risque d'évolution recevront de l'information sur l'IRA, les patients présentant un risque moyennement élevé recevront en plus des conseils de suivi envoyés à leur médecin de premier recours, et les patients présentant un risque élevé feront également l'objet d'un suivi avec un néphrologue. Les participants des groupes intervention et soins habituels recevront une requête pour des analyses de sang et d'urine 90 jours après la sortie de l'hôpital. Un suivi téléphonique sera effectué auprès de tous les participants à l'étude 90 jours et un an après la sortie de l'hôpital. Des tests d'association bivariés seront effectués pour évaluer les différences entre les groupes aux points temporels de suivi. Limites: Nous nous attendons à ce que le recrutement soit difficile, considérant l'importance des comorbidités dans cette population. Conclusion: Si l'essai montre un effet positif sur ces processus de soins rénaux, il informera un essai à plus grande échelle visant à déterminer si cette intervention réduit l'incidence des événements cliniques indésirables à long terme, notamment la progression de l'IRC, les événements cardiovasculaires et la mortalité après une hospitalisation avec épisode d'IRA.

The effect of goal-directed fluid therapy on delayed graft function in kidney transplant recipients: A systematic review and meta-analysis.

Delayed graft function (DGF) is a common post-operative complication with potential long-term sequelae for many kidney transplant recipients, and hemodynamic factors and fluid status play a role. Fixed perioperative fluid infusions are the standard of care, but more recent evidence in the non-transplant population has suggested benefit with goal-directed fluid strategies based on hemodynamic targets. We searched MEDLINE, EMBASE, Cochrane Controlled Trials Registry and Google Scholar through December 2022 for randomized controlled trials comparing risk of DGF between goal-directed and conventional fluid therapy in adults receiving a living or deceased donor kidney transplant. Effect estimates were reported with odds ratios (OR) and pooled using random effects meta-analysis. We identified 4 studies (205 participants) that met the inclusion criteria. The use of goal-directed fluid therapy had no significant effect on DGF (OR 1.37 95% CI, 0.34-5.6; p = 0.52; I2 = 0.11). Subgroup analysis examining effects among deceased and living kidney donation did not reveal significant differences in the effects of fluid strategy on DGF between subgroups. Overall, the strength of the evidence for goal-directed versus conventional fluid therapy to reduce DGF was of low certainty. Our findings highlight the need for larger trials to determine the effect of goal-directed fluid therapy on this patient-centered outcome.

Managing Medications During "Sick Days" in Patients With Diabetes, Kidney, and Cardiovascular Conditions: A Theory-informed Approach to Intervention Design and Implementation.

OBJECTIVES: Our aim in this work was to 1) explore barriers and enablers to patient and health-care provider (HCP) behaviours related to sick-day medication guidance (SDMG), 2) identify theory-informed strategies to advise SDMG intervention design, and 3) obtain perspectives on an eHealth tool for this purpose. METHODS: A qualitative descriptive study using qualitative conventional content analysis was undertaken. Interviews and focus groups were held with patients and HCPs from January 2021 to April 2022. Data were analyzed using the Behaviour Change Wheel and Theoretical Domains Framework to inform intervention design. RESULTS: Forty-eight people (20 patients, 13 pharmacists, 12 family physicians, and 3 nurse practitioners) participated in this study. Three interventions were designed to address the identified barriers and enablers: 1) prescriptions provided by a community-based care provider, 2) pharmacists adding a label to at-risk medications, and 3) built-in prompts for prescribing and dispensing software. Most participants accepted the concept of an eHealth tool and identified pharmacists as the ideal point-of-care provider. Challenges for an eHealth tool were raised, including credibility, privacy of data, medical liability, clinician remuneration and workload impact, and equitable access to use of the tool. CONCLUSIONS: Patients and HCPs endorsed non-technology and eHealth innovations as strategies to aid in the delivery of SDMG. These findings can guide the design of future theory-informed SDMG interventions.

Unsupervised item response theory models for assessing sample heterogeneity in patient-reported outcomes measures.

PURPOSE: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models. METHODS: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics. RESULTS: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease. CONCLUSION: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models' Type I error and statistical power for identifying covariates associated with DIF.

Response shift in coronary artery disease.

PURPOSE: Patients with coronary artery disease (CAD) experience significant angina symptoms and lifestyle changes. Revascularization procedures can result in better patient-reported outcomes (PROs) than optimal medical therapy (OMT) alone. This study evaluates the impact of response shift (RS) on changes in PROs of patients with CAD across treatment strategies. METHODS: Data were from patients with CAD in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease (APPROACH) registry who completed the 16-item Canadian version of the Seattle Angina Questionnaire at 2 weeks and 1 year following a coronary angiogram. Multi-group confirmatory factor analysis (MG-CFA) was used to assess measurement invariance across treatment groups at week 2. Longitudinal MG-CFA was used to test for RS according to receipt of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical therapy (OMT) alone. RESULTS: Of the 3116 patients included in the analysis, 443 (14.2%) received CABG, 2049(65.8%) PCI, and the remainder OMT alone. The MG-CFA revealed a partial-strong invariance across the treatment groups at 2 weeks (CFI = 0.98, RMSEA [90% CI] = 0.05 [0.03, 0.06]). Recalibration RS was detected on the Angina Symptoms and Burden subscale and its magnitude in the OMT, PCI, and CABG groups were 0.32, 0.28, and 0.53, respectively. After adjusting for RS effects, the estimated target changes were largest in the CABG group and negligible in the OMT group. CONCLUSION: Adjusting for RS is recommended in studies that use SAQ-CAN to assess changes in patients with CAD who have received revascularization versus OMT alone.