Association of Integrated Proteomic and Metabolomic Modules with Risk of Kidney Disease Progression.

Key Points: Integrated analysis of proteome and metabolome identifies modules associated with CKD progression and kidney failure. Ephrin transmembrane proteins and podocyte-expressed CRIM1 and NPNT emerged as central components and warrant experimental and clinical investigation.

Background: Proteins and metabolites play crucial roles in various biological functions and are frequently interconnected through enzymatic or transport processes.

Frailty and Cardiovascular Outcomes in Adults With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale & Objective: Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes in adults with kidney failure requiring dialysis. However, this relationship has not been thoroughly evaluated among those with non-dialysis-dependent CKD.

Study Design: Prospective cohort study.

Association between Depressive Symptom Trajectory and Chronic Kidney Disease Progression: Findings from the Chronic Renal Insufficiency Cohort Study.

Key Points: Depressive symptoms are largely stable over time among individuals with mild-to-moderate CKD. Low educational attainment, cigarette smoking, and poor quality of life are associated with persistent depressive symptoms. Persistent depressive symptoms are associated with nonlinear and rapid decline in kidney function.

Association of Proximal Tubular Secretory Clearance with Long-Term Decline in Cognitive Function.

Background: People with chronic kidney disease (CKD) are at high risk for cognitive impairment and progressive cognitive decline. Retention of protein-bound organic solutes that are normally removed by tubular secretion is hypothesized to contribute to cognitive impairment in CKD.

Methods: We followed 2362 participants who were initially free of cognitive impairment and stroke in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study.

A Comparative Study of Serum Phosphate and Related Parameters in Chronic Kidney Disease between the USA and Japan.

Introduction: Recent studies have suggested a higher incidence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) in the USA than in Japan. Hyperphosphatemia, a possible risk for CVD, may explain this difference; however, international differences in phosphate parameters in CKD have not been well elaborated.

Methods: By using the baseline data from the USA and the Japanese nation-wide, multicenter, CKD cohort studies; the Chronic Renal Insufficiency Cohort Study (CRIC, N = 3,870) and the Chronic Kidney Disease-Japan Cohort Study (CKD-JAC, N = 2,632), we harmonized the measures and compared clinical parameters regarding phosphate metabolism or serum phosphate, fibroblast growth factor-23 (FGF23), and parathyroid hormone (PTH), in the cross-sectional model.

High-Throughput Metabolomics and Diabetic Kidney Disease Progression: Evidence from the Chronic Renal Insufficiency (CRIC) Study.

Introduction: Metabolomics could offer novel prognostic biomarkers and elucidate mechanisms of diabetic kidney disease (DKD) progression. Via metabolomic analysis of urine samples from 995 CRIC participants with diabetes and state-of-the-art statistical modeling, we aimed to identify metabolites prognostic to DKD progression.

Methods: Urine samples (N = 995) were assayed for relative metabolite abundance by untargeted flow-injection mass spectrometry, and stringent statistical criteria were used to eliminate noisy compounds, resulting in 698 annotated metabolite ions.

Social Support in Older Adults With CKD: A Report From the CRIC (Chronic Renal Insufficiency Cohort) Study.

Rationale & Objective: Social support in older adults with chronic kidney disease (CKD) is a potentially modifiable factor that may affect important clinical outcomes such as health-related quality of life, cognitive function, and frailty. However, limited data about the effects of social support in older patients with non-dialysis-dependent CKD exist. Our objective was to evaluate the association of social support with health-related quality of life, cognitive function, and frailty in older adults with CKD.

Association Between Kidney Clearance of Secretory Solutes and Cardiovascular Events: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale & Objective: The clearance of protein-bound solutes by the proximal tubules is an innate kidney mechanism for removing putative uremic toxins that could exert cardiovascular toxicity in humans. However, potential associations between impaired kidney clearances of secretory solutes and cardiovascular events among patients with chronic kidney disease (CKD) remains uncertain.

Study Design: A multicenter, prospective, cohort study.

Health-Related Quality of Life, Depressive Symptoms, and Kidney Transplant Access in Advanced CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale & Objective: Among individuals with chronic kidney disease (CKD), poor self-reported health is associated with adverse outcomes including hospitalization and death. We sought to examine the association between health-related quality-of-life (HRQoL) and depressive symptoms in advanced CKD and subsequent access to the kidney transplant waiting list.

Study Design: Prospective cohort study.

Research-based versus clinical serum creatinine measurements and the association of acute kidney injury with subsequent kidney function: findings from the Chronic Renal Insufficiency Cohort study.

Background: Observational studies relying on clinically obtained data have shown that acute kidney injury (AKI) is linked to accelerated chronic kidney disease (CKD) progression. However, prior reports lacked uniform collection of important confounders such as proteinuria and pre-AKI kidney function trajectory, and may be susceptible to ascertainment bias, as patients may be more likely to undergo kidney function testing after AKI.

Methods: We studied 444 adults with CKD who participated in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study and were concurrent members of a large integrated healthcare delivery system.

Integrating a Medical Home in an Outpatient Dialysis Setting: Effects on Health-Related Quality of Life.

Background: Integrating primary care has been proposed to reduce fragmented care delivery for patients with complex medical needs. Because of their high rates of morbidity, healthcare use, and mortality, patients with end-stage kidney disease (ESKD) may benefit from increased access to a primary care medical home.

Objective: To evaluate the effect of integrating a primary care medical home on health-related quality of life (HRQOL) for patients with ESKD receiving chronic hemodialysis.

Differential network enrichment analysis reveals novel lipid pathways in chronic kidney disease.

Motivation: Functional enrichment testing methods can reduce data comprising hundreds of altered biomolecules to smaller sets of altered biological 'concepts' that help generate testable hypotheses. This study leveraged differential network enrichment analysis methodology to identify and validate lipid subnetworks that potentially differentiate chronic kidney disease (CKD) by severity or progression.

Results: We built a partial correlation interaction network, identified highly connected network components, applied network-based gene-set analysis to identify differentially enriched subnetworks, and compared the subnetworks in patients with early-stage versus late-stage CKD.

Self-reported Medication Adherence and CKD Progression.

Introduction: In the general population, medication nonadherence contributes to poorer outcomes. However, little is known about medication adherence among adults with chronic kidney disease (CKD). We evaluated the association of self-reported medication adherence with CKD progression and all-cause death in patients with CKD.

Facilitating primary care provider use in a patient-centered medical home intervention study for chronic hemodialysis patients.

Patients with chronic kidney disease have a high disease burand may benefit from primary care services and care coord A medical home model with direct access to primary care services is one approach that may address this need, yet has not been examined. As a substudy of the Patient-Centered Outcomes Research Institute (PCORI) patient-centered medical home for kidney disease (PCMH-KD) health system intervention study, we examined the uptake of free primary care physician (PCP) services. The PCORI PCMH-KD study was an initial step toward integrating PCPs, a nurse coordinator, a pharmacist, and community health workers (CHWs) within the health care delivery team.

Effects of Intensive Blood Pressure Treatment on Acute Kidney Injury Events in the Systolic Blood Pressure Intervention Trial (SPRINT).

Background: Treating to a lower blood pressure (BP) may increase acute kidney injury (AKI) events.

Study Design: Data for AKI resulting in or during hospitalization or emergency department visits were collected as part of the serious adverse events reporting process of the Systolic Blood Pressure Intervention Trial (SPRINT).

Setting & Participants: 9,361 participants 50 years or older with 1 or more risk factors for cardiovascular disease.

Risks of Adverse Events in Advanced CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Background: People with advanced chronic kidney disease are at risk for the development of end-stage renal disease (ESRD), but also many other adverse outcomes, including cardiovascular disease (CVD) events and death. Determination of risk factors that explain the variability in prognosis and timing of these adverse outcomes can aid patient counseling and medical decision making.

Study Design: Prospective research cohort.

Coronary Artery Calcification and Risk of Cardiovascular Disease and Death Among Patients With Chronic Kidney Disease.

Importance: Coronary artery calcification (CAC) is highly prevalent in dialysis-naive patients with chronic kidney disease (CKD). However, there are sparse data on the association of CAC with subsequent risk of cardiovascular disease and all-cause mortality in this population.

Objective: To study the prospective association of CAC with risk of cardiovascular disease and all-cause mortality among dialysis-naive patients with CKD.

Predictors and Outcomes of Health-Related Quality of Life in Adults with CKD.

Background And Objectives: Low health-related quality of life is associated with increased mortality in patients with ESRD. However, little is known about demographic and clinical factors associated with health-related quality of life or its effect on outcomes in adults with CKD.

Design, Settings, Participants, & Measurements: Data from 3837 adult participants with mild to severe CKD enrolled in the prospective observational Chronic Renal Insufficiency Cohort and Hispanic Chronic Renal Insufficiency Cohort Studies were analyzed.

Patient and Other Stakeholder Engagement in Patient-Centered Outcomes Research Institute Funded Studies of Patients with Kidney Diseases.

Including target populations in the design and implementation of research trials has been one response to the growing health disparities endemic to our health care system, as well as an aid to study generalizability. One type of community-based participatory research is "Patient Centered-Research", in which patient perspectives on the germane research questions and methodologies are incorporated into the study. The Patient-Centered Outcomes Research Institute (PCORI) has mandated that meaningful patient and stakeholder engagement be incorporated into all applications.

Rationale and design of a patient-centered medical home intervention for patients with end-stage renal disease on hemodialysis.

In the U.S., more than 400,000 individuals with end-stage renal disease (ESRD) require hemodialysis (HD) for renal replacement therapy.

Healthy lifestyle and risk of kidney disease progression, atherosclerotic events, and death in CKD: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

Background: In general populations, healthy lifestyle is associated with fewer adverse outcomes. We estimated the degree to which adherence to a healthy lifestyle decreases the risk of renal and cardiovascular events among adults with chronic kidney disease (CKD).

Study Design: Prospective cohort.

Urinary creatinine excretion, bioelectrical impedance analysis, and clinical outcomes in patients with CKD: the CRIC study.

Background And Objectives: Previous studies in chronic disease states have demonstrated an association between lower urinary creatinine excretion (UCr) and increased mortality, a finding presumed to reflect the effect of low muscle mass on clinical outcomes. Little is known about the relationship between UCr and other measures of body composition in terms of the ability to predict outcomes of interest.

Design, Setting, Participants, & Measurements: Using data from the Chronic Renal Insufficiency Cohort (CRIC), the relationship between UCr, fat free mass (FFM) as estimated by bioelectrical impedance analysis, and (in a subpopulation) whole-body dual-energy x-ray absorptiometry assessment of appendicular lean mass were characterized.