Faculty Bibliography

RATIONALE & OBJECTIVE/OBJECTIVE:Despite national efforts, the uptake of home dialysis (peritoneal dialysis or home hemodialysis) remains low. Characteristics of the built environment may differentially impact home dialysis use. STUDY DESIGN/METHODS:Retrospective cohort study (2010-2019). SETTING & PARTICIPANTS/METHODS:1,103,695 adults (aged≥18 years) initiating dialysis in the US Renal Data System. EXPOSURE/METHODS:We examined 3 built environment domains based on residential ZIP code: (1) medically underserved areas (MUAs), defined as neighborhoods with limited primary care access; (2) distance to the nearest dialysis facility; and (3) distribution of housing characteristics (structure and overcrowding). OUTCOME/RESULTS:Uptake of home dialysis modalities at dialysis initiation. ANALYTICAL APPROACH/METHODS:We quantified associations between built environment characteristics and home dialysis initiation using multilevel logistic regression stratified by urbanicity type (urban, suburban, small-town, and rural). RESULTS:Among adults initiating dialysis, 40.8% lived in MUAs. Across ZIP codes, the mean percentage of overcrowded housing was 4.2% (SD, 4.7%), and the percentage of detached housing was 61.1% (SD, 21.1%); mean distance to the nearest dialysis facility was 5.5km (SD, 9.1km). Living in MUAs was associated with reduced home dialysis use only in urban (OR, 0.94; 95% CI, 0.91-0.96) and suburban (OR, 0.92; 95% CI, 0.89-0.94) areas. Similarly, housing overcrowding was associated with decreased home dialysis use only in urban (OR, 0.88; 95% CI, 0.86-0.89) and suburban (OR, 0.91; 95% CI, 0.90-0.93) areas. Longer distance to a dialysis facility was the most salient neighborhood factor associated with increased home dialysis use in small towns (OR, 1.14; 95% CI, 1.12-1.16) and rural areas (OR, 1.17; 95% CI, 1.15-1.19). LIMITATIONS/CONCLUSIONS:Housing characteristics were measured at the ZIP code level. CONCLUSIONS:Built environment characteristics associated with home dialysis uptake vary by urbanicity. Policies should address built environment barriers that are specific to urbanicity level. For example, increasing the frequency of dialysate delivery schedules could address housing space constraints in urban and suburban areas, and promoting home dialysis might be more effective for patients living far from dialysis centers in small-town and rural areas.

INTRODUCTION/UNASSIGNED:The prognostic value of the discrepancy between the estimated glomerular filtration rate (eGFR) using cystatin C (eGFRcys) and creatinine (eGFRcr) in recently hospitalized adults remains poorly understood. METHODS/UNASSIGNED:We characterized the difference between eGFRcys and eGFRcr, at 3 months after discharge, in 1534 hospitalized adults; 767 (50%) with acute kidney injury (AKI) matched 1:1 with patients who did not develop AKI. We used survival analysis to determine the associations between having lower eGFRcys than eGFRcr with risk of end-stage kidney disease (ESKD), major atherosclerotic cardiac events (MACE), heart failure hospitalization, and death after a a median follow-up of 4.7 years. RESULTS/UNASSIGNED:for interaction with AKI all > 0.1). CONCLUSION/UNASSIGNED:Our findings suggest that the eGFRcys-eGFRcr discrepancy may serve as a valuable prognostic marker in recently hospitalized patients, informing risk stratification and potential interventions.

AIMS/OBJECTIVE:To characterize trends in obesity and prescriptions for glucagon-like peptide-1 receptor agonists (GLP-1RAs) across body mass index (BMI) categories among US youth and adults with type 1 diabetes (T1D) from 2008 to 2023. MATERIALS AND METHODS/METHODS:Patients with T1D were identified using a validated algorithm using de-identified electronic health record (EHRs) data from 33 US health systems. BMI categories were based on age- and sex-specific percentiles for youth (2-19 years) and World Health Organization cut points for adults (≥20 years). Trends in obesity and GLP1-RA prescriptions were characterized by BMI categories among youth and adults with T1D from 2008-2011 to 2020-2023. RESULTS:From 2008-2011 to 2020-2023, the prevalence of obesity among youth with T1D increased from 18.1% (95% confidence interval [CI], 17.3%-18.9%) to 26.0% (25.2%-26.8%) (p-for-trend < 0.001). Among adults with T1D, the prevalence of obesity rose from 30.5% (30.0%-31.0%) in 2008-2011 to 38.1% (37.8%-38.5%) in 2020-2023 (p-for-trend < 0.001). Obesity was highest in Black and Hispanic youth and adults, and racial and ethnic disparities persisted over time. Over the last 15-year period, GLP-1RA prescriptions significantly increased across all BMI categories in a dose-response manner among both youth and adults with T1D (all p-for-trend < 0.001). CONCLUSIONS:Over the last 15-year period, obesity has reached epidemic levels in US youth and adults with T1D, with significant disparities among racial and ethnic minoritized populations. These findings, coupled with the increase in GLP-1RA prescriptions, underscore the urgent need for data on GLP-1RAs' safety and effectiveness and guidance for obesity management in T1D.

BACKGROUND:Plant-based diets are associated with a lower risk of cardiovascular disease (CVD). Proteomics may improve our understanding of the biological pathways underlying these associations. OBJECTIVES/OBJECTIVE:Using large-scale proteomics, we aimed to examine if plant-based diet-related proteins, which have been previously identified, are associated with incident CVD and subtypes of CVD in the Atherosclerosis Risk in Communities (ARIC) Study and Framingham Heart Study (FHS) Offspring cohort. METHODS:Discovery analyses were based on 9,078 participants free of CVD at ARIC visit 3 (1993-1995). Cox proportional hazards regression was used to evaluate the associations between plant-based diet-related proteins and incident CVD, coronary heart disease, heart failure, and stroke. Replication analyses were based on 1,279 participants without CVD in FHS Offspring cohort. RESULTS:In the ARIC Study, over a median follow-up of 21 years, there were 3,167 CVD events. At a false discovery rate (FDR) <0.05, 26 out of 73 plant-based diet-related proteins were significantly associated with incident CVD, after adjusting for important confounders. 18, 1, and 0 proteins were associated with heart failure, stroke, and coronary heart disease, respectively. Three, and 2 additional proteins were associated with CVD, and heart failure risk in FHS Offspring cohort at the nominal threshold (p value <0.05). Soluble advanced glycosylation end product-specific receptor (AGER) was inversely associated with incident CVD whereas thrombospondin-2 (THBS2) and N-terminal pro-BNP (NT-proBNP) was positively associated with incident CVD. THBS2 was positively associated with incident heart failure, whereas neuronal growth factor regulator 1 (NEGR1) and insulin-like growth factor-binding protein 1 (IGFBP1) was inversely associated. CONCLUSION/CONCLUSIONS:These proteins highlight several pathways that could explain plant-based diets-CVD associations.

BACKGROUND:Individuals who report meeting weekly moderate to vigorous physical activity (MVPA) guidelines have lower risk of atrial fibrillation (AF). However existing studies have relied on subjective questionnaires or short-duration (<1 week) objective assessments using accelerometry. The objective of this research was to investigate an association between MVPA levels and the incidence of AF, utilizing long-term, free-living accelerometry data. METHODS:1-year Fitbit data, in addition to survey and electronic health record (EHR) data, were extracted from the NIH All of Us (AoU) research database. Cox proportional hazards regression was used to model the association of average MVPA and incident AF over a five-year follow-up period. RESULTS:, 41±12 complete weeks of Fitbit wear). 97 individuals (0.6%) experienced incident AF in the five-year follow-up period. Every additional hour of MVPA was associated with 8% lower AF risk (HR = 0.92 [0.86,0.99], p=0.02). In a subset of 10533 participants with genomic data, this association persisted after adjustment for AF genetic risk score. CONCLUSIONS:Higher amounts of objectively measured MVPA, measured using free-living, long-term accelerometry data, were inversely associated with risk of incident AF, independent of clinical and genetic risk factors.

The timely and rational institution of therapy is a key step towards reducing the global burden of chronic kidney disease (CKD). CKD is a heterogeneous entity with varied aetiologies and diverse trajectories, which include risk of kidney failure but also cardiovascular events and death. Developments in the past decade include substantial progress in CKD risk prediction, driven in part by the accumulation of electronic health records data. In addition, large randomized clinical trials have demonstrated the effectiveness of sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists in reducing adverse events in CKD, greatly expanding the options for effective therapy. Alongside angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, these classes of medication have been proposed to be the four pillars of CKD pharmacotherapy. However, all of these drug classes are underutilized, even in individuals at high risk. Leveraging prognostic estimates to guide therapy could help clinicians to prescribe CKD-related therapies to those who are most likely to benefit from their use. Risk-based CKD management thus aligns patient risk and care, allowing the prioritization of absolute benefit in determining therapeutic selection and timing. Here, we discuss CKD prognosis tools, evidence-based management and prognosis-guided therapies.

INTRODUCTION/BACKGROUND:The number of assays on proteomic platforms has grown rapidly. The leading platforms, SomaScan and Olink, have strengths and limitations. Comparisons of precision on the latest platforms-SomaScan 11k and Olink Explore HT-have not yet been established. METHODS:Among 102 participants in the Atherosclerosis Risk in Communities Study (mean age 74 years, 53% women, 47% Black), we used split plasma samples to measure platform precision. CV and Spearman correlations were calculated for each assay. Cross-platform agreement was assessed for overlapping proteins. RESULTS:SomaScan 11k demonstrated a median correlation of 0.85 for the 10 778 assays and a median CV of 6.8%, similar precision to earlier versions. The 5420 assays on Olink Explore HT exhibited a median correlation of 0.65 and median CV of 35.7%, which was higher than observed in its predecessors (e.g., 19.8% for Olink Explore 3072). Precision of Olink assays was inversely correlated with the percentage of samples above the limit of detection (LOD) (r = -0.77). Upon replacing Olink values below the LOD with values half the LOD, the median correlation for Olink assays measured in duplicate increased to 0.79; the median CV decreased to 13.3%. The distribution of between-platform correlations for the 4443 overlapping proteins had peaks at r approximately 0 and at r approximately 0.8. One-tenth of the protein pairs had cross-platform correlations r ≥ 0.8. CONCLUSIONS:Precision of these 2 proteomics platforms in human plasma has diverged as the coverage has increased. These results highlight the need for careful consideration in platform selection based on specific research requirements.