Participant Experience with Protocol Research Kidney Biopsies in the Kidney Precision Medicine Project.

BACKGROUND: Kidney biopsies are procedures commonly performed in clinical nephrology and are increasingly used in research. In this study we aimed to evaluate the experiences of participants who underwent research kidney biopsies in the Kidney Precision Medicine Project (KPMP). METHODS: KPMP research participants with acute kidney injury (AKI) or chronic kidney disease (CKD) were enrolled at nine recruitment sites in the United States between September 2019 to January 2023. At 28 days post-biopsy, participants were invited to complete a survey to share their experiences, including: motivation to participate in research; comprehension of informed consent; pain and anxiety during and after the biopsy procedure; overall satisfaction with KPMP participation; and impact of the study on their lives. The survey was developed in collaboration with the KPMP Community Engagement Committee and the Institute of Translational Health Sciences at the University of Washington. RESULTS: 111 participants completed the survey, 23 enrolled for AKI and 88 for CKD. Median age was 61 (IQR 48-67) years, 43% were women, 28% were Black, and 18% were of Hispanic ethnicity. Survey respondents most commonly joined KPMP to help future patients (59%). The consent form was understood by 99% and 97% recognized their important role in the study. Pain during the biopsy was reported by 50%, at a median level of 1 (IQR 0-3) on a 0-10 scale. Anxiety during the biopsy was described by 64% at a median level of 3 (IQR 1-5) on a 0-10 scale. More than half conveyed that KPMP participation impacted their diet, physical activity, and how they think about kidney disease. CONCLUSIONS: KPMP survey respondents were most commonly motivated to participate in research protocol kidney biopsies by altruism, with excellent understanding of the informed consent process.

Prognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19.

RATIONALE & OBJECTIVE: Acute kidney injury (AKI) is common in patients with coronavirus disease 2019 (COVID-19) and associated with poor outcomes. Urinary biomarkers have been associated with adverse kidney outcomes in other settings and may provide additional prognostic information in patients with COVID-19. We investigated the association between urinary biomarkers and adverse kidney outcomes among patients hospitalized with COVID-19. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients hospitalized with COVID-19 (n=153) at 2 academic medical centers between April and June 2020. EXPOSURE: 19 urinary biomarkers of injury, inflammation, and repair. OUTCOME: Composite of KDIGO (Kidney Disease: Improving Global Outcomes) stage 3 AKI, requirement for dialysis, or death within 60 days of hospital admission. We also compared various kidney biomarker levels in the setting of COVID-19 versus other common AKI settings. ANALYTICAL APPROACH: Time-varying Cox proportional hazards regression to associate biomarker level with composite outcome. RESULTS: Out of 153 patients, 24 (15.7%) experienced the primary outcome. Twofold higher levels of neutrophil gelatinase-associated lipocalin (NGAL) (HR, 1.34 [95% CI, 1.14-1.57]), monocyte chemoattractant protein (MCP-1) (HR, 1.42 [95% CI, 1.09-1.84]), and kidney injury molecule 1 (KIM-1) (HR, 2.03 [95% CI, 1.38-2.99]) were associated with highest risk of sustaining primary composite outcome. Higher epidermal growth factor (EGF) levels were associated with a lower risk of the primary outcome (HR, 0.61 [95% CI, 0.47-0.79]). Individual biomarkers provided moderate discrimination and biomarker combinations improved discrimination for the primary outcome. The degree of kidney injury by biomarker level in COVID-19 was comparable to other settings of clinical AKI. There was evidence of subclinical AKI in COVID-19 patients based on elevated injury biomarker level in patients without clinical AKI defined by serum creatinine. LIMITATIONS: Small sample size with low number of composite outcome events. CONCLUSIONS: Urinary biomarkers are associated with adverse kidney outcomes in patients hospitalized with COVID-19 and may provide valuable information to monitor kidney disease progression and recovery.

Integrating Patient Priorities with Science by Community Engagement in the Kidney Precision Medicine Project.

The Kidney Precision Medicine Project (KPMP) is a multisite study designed to improve understanding of CKD attributed to diabetes or hypertension and AKI by performing protocol-driven kidney biopsies. Study participants and their kidney tissue samples undergo state-of-the-art deep phenotyping using advanced molecular, imaging, and data analytical methods. Few patients participate in research design or concepts for discovery science. A major goal of the KPMP is to include patients as equal partners to inform the research for clinically relevant benefit. The purpose of this report is to describe patient and community engagement and the value they bring to the KPMP. Patients with CKD and AKI and clinicians from the study sites are members of the Community Engagement Committee, with representation on other KPMP committees. They participate in KPMP deliberations to address scientific, clinical, logistic, analytic, ethical, and community engagement issues. The Community Engagement Committee guides KPMP research priorities from perspectives of patients and clinicians. Patients led development of essential study components, including the informed consent process, no-fault harm insurance coverage, the ethics statement, return of results plan, a "Patient Primer" for scientists and the public, and Community Advisory Boards. As members across other KPMP committees, the Community Engagement Committee assures that the science is developed and conducted in a manner relevant to study participants and the clinical community. Patients have guided the KPMP to produce research aligned with their priorities. The Community Engagement Committee partnership has set new benchmarks for patient leadership in precision medicine research.

Comparison of strain measurement from multimodality tissue tracking with strain-encoding MRI and harmonic phase MRI in pulmonary hypertension.

BACKGROUND: Pixel-based multimodality tissue tracking (MTT) is a new noninvasive method for the quantification of cardiac deformation from cine image of MRI. The aim of this study is to validate bi-ventricular strain measurement by MTT compared to strain-encoding (SENC) MRI and harmonic phase (HARP) MRI in pulmonary hypertension (PH) patients. METHODS: In 45 subjects (30 PH patients and 15 normal subjects), RV and LV peak global longitudinal strains (Ell) were measured from long axis 4 chamber view using MTT. LV peak global circumferential strains (Ecc) by MTT were measured from short axis. For validation, RV and LV Ell by MTT were compared to measures by SENC-MRI from short axis, and LV Ecc by MTT was compared to measures by short axis tagged MRI analysis (HARP). Reproducibility of MTT was also determined. RESULTS: MTT quantified RV Ell correlated closely to those of SENC (r=0.72, p<0.001), with good limits of agreement. LV Ell quantified by MTT showed moderate correlation with SENC (r=0.57, p=0.001), and LV Ecc by MTT also showed moderate correlation with HARP (-16.9±4.1 vs -14.3±3.5, p<0.001 for all, r=0.60, p<0.001). RV Ell negatively correlated with RVEF (r=-0.53, p=0.001) and also positively correlated with mean PAP in PH patients (r=0.60, p=0.001). Strain measurement by MTT showed high reproducibility. CONCLUSIONS: We demonstrate that MTT is a reproducible tool for quantification of cardiac deformation using cine images in PH patients. Hence, it could serve as a new rapid and comprehensive technique for clinical assessment of regional cardiac function.

Cardiac MR findings and potential diagnostic pitfalls in patients evaluated for arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiomyopathy characterized by fibrofatty replacement of the myocardium, ventricular tachycardia, and ventricular dysfunction that affects primarily the right ventricle (RV). This disease is not common but can be seen more frequently in young adults, and clinical manifestations range from no symptoms to lethal arrhythmia and sudden death. The diagnosis of ARVC is challenging and is based on the recently revised international task force criteria. Given the strengths of cardiac magnetic resonance (MR) imaging for depicting the RV, this modality plays an important role in the diagnosis of ARVC. Functional and structural abnormalities of the RV depicted with cardiac MR imaging constitute major and minor criteria in the revised task force criteria. Since the ARVC program was established at our center in 1998, there has been an increased awareness of a number of normal variants that are commonly misinterpreted as showing evidence for ARVC. On the basis of our clinical experience, the overdiagnosis of ARVC appears to reflect two fundamental problems: (a) a lack of awareness of diagnostic criteria that identify major and minor variables to be used for the diagnosis of ARVC, and (b) a lack of familiarity with the normal variants and mimics that may be misinterpreted as showing evidence of ARVC. The purpose of this article is to review the typical patterns of ventricular involvement in ARVC at cardiac MR imaging and to compare those with the patterns of normal variants and other diseases that can mimic ARVC. Online supplemental material is available for this article.

Functional volumetric MRI in assessing treatment response to intra-arterial therapy of primary and secondary liver tumors.

The assessment of tumor response after intra-arterial therapy (IAT) is useful to determine treatment success, to guide future treatments, and to predict patient outcome. Changes in tumor size in the axial plane after transarterial therapies might be delayed with the traditional criteria, whereas cellular tumor changes can be detected earlier by functional metrics such as vascular enhancement and cellular integrity in the entire tumor volume. Magnetic resonance imaging has become an important tool in the evaluation of early tumor response with the introduction of new techniques, such as diffusion-weighted imaging and apparent diffusion coefficient maps, and the development of advanced software to quantify vascular enhancement after IATs. This review discusses the role of treatment response by functional volumetric imaging after IAT in patients with primary and secondary liver tumors.

Imaging of the patient with a biliary tract or primary liver tumor.

Cross-sectional imaging can be useful in the diagnosis of biliary tract and primary liver tumors. Hepatobiliary tumors are diverse in growth patterns, histologic types and tumor location. A fundamental understanding of the imaging features of hepatobiliary tumors is critical for diagnosis, staging and treatment. Knowledge about various manifestations and mimickers of biliary and primary liver tumors is essential for tumor diagnosis and suitable management. Magnetic resonance imaging and computed tomography technology continues to rapidly evolve and these tools not only aid in evaluation and treatment, but also can potentially define response to therapy and overall patient prognosis.

Oncologic applications of diffusion-weighted MRI in the body.

Diffusion-weighted MRI (DWI) allows the detection of malignancies in the abdomen and pelvis. Lesion detection and characterization using DWI largely depends on the increased cellularity of solid or cystic lesions compared with the surrounding tissue. This increased cellularity leads results in restricted diffusion as indicated by reduction in the apparent diffusion coefficient (ADC). Low pretreatment ADC values of several malignancies have been shown to be predictive of better outcome. DWI can assess response to systemic or regional treatment of cancer at a cellular level and will therefore detect successful treatment earlier than anatomical measures. In this review, we provide a brief technical overview of DWI, discuss quantitative image analysis approaches, and review studies which have used DWI for the purpose of detection and characterization of malignancies as well as the early prediction of treatment response.

Principles and applications of diffusion-weighted imaging in cancer detection, staging, and treatment follow-up.

Diffusion-weighted imaging relies on the detection of the random microscopic motion of free water molecules known as Brownian movement. With the development of new magnetic resonance (MR) imaging technologies and stronger diffusion gradients, recent applications of diffusion-weighted imaging in whole-body imaging have attracted considerable attention, especially in the field of oncology. Diffusion-weighted imaging is being established as a pivotal aspect of MR imaging in the evaluation of specific organs, including the breast, liver, kidney, and those in the pelvis. When used in conjunction with apparent diffusion coefficient mapping, diffusion-weighted imaging provides information about the functional environment of water in tissues, thereby augmenting the morphologic information provided by conventional MR imaging. Detected changes include shifts of water from extracellular to intracellular spaces, restriction of cellular membrane permeability, increased cellular density, and disruption of cellular membrane depolarization. These findings are commonly associated with malignancies; therefore, diffusion-weighted imaging has many applications in oncologic imaging and can aid in tumor detection and characterization and in the prediction and assessment of response to therapy.