The aims of this study were to characterize symptom clusters and examine the influence of social determinants of health (SDOH) on symptom cluster membership among people receiving maintenance hemodialysis and experiencing chronic pain. This study utilized baseline data collected from the 643 patients enrolled in the HOPE Consortium Trial designed to test the efficacy of an intervention to reduce chronic pain. Latent profile analyses were performed to characterize symptom clusters. SDOH variables were collected using self-report and the Census Geocoder. Five distinct clusters of symptoms were identified including (1) moderate levels of anxiety, (2) average level of all symptoms, (3) low levels of all symptoms, (4) low levels of anxiety, and (5) high levels of all symptoms. When compared to the symptom cluster with average level of symptoms, higher everyday discrimination scores were associated with higher odds of membership in the clusters reflecting moderate levels of anxiety and high levels of all symptoms. Greater residential segregation was associated with higher odds of being in the low anxiety cluster; and greater income inequality was associated with higher odds of membership in the moderate level anxiety symptom cluster. Multi-level interventions targeting discrimination and those living in areas with the greatest income inequality are warranted to reduce symptom burden and improve quality of life in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov #NCT04571619. PERSPECTIVE STATEMENT: Social determinants of health (SDOH) such as discrimination and income inequality were associated with higher anxiety while segregation resulted in lower levels of anxiety reflecting the complex relationship between SDOH and mental health. Multi-level interventions targeting discrimination and income inequality are warranted to reduce symptom burden in this patient population.

Technology-assisted cognitive-behavioral therapy (CBT) interventions have been conducted for symptoms including depression, pain, and fatigue in patients with chronic illnesses but not in end-stage renal disease (ESRD). The purpose of this study was to pilot the feasibility and acceptability of a technology-assisted CBT intervention in ESRD patients on hemodialysis (HD), share design and implementation lessons learned, and provide preliminary results on changes in select patient-reported symptoms. This was a single-center pilot feasibility study of adult ESRD patients on HD. Study eligibility required clinically elevated levels of at least one symptom (depression, pain, or fatigue). Patients met weekly with a CBT therapist for eight sessions, each 45-60 min, during HD sessions via a video-conferencing platform. Symptom questionnaires were completed at baseline and 3 months follow-up. Of 10 patients screened, 100% screened positive for at least one symptom, 100% of eligible patients consented, and eight (of 10) completed the intervention (mean age 59 years, 50% male, 50% African American). Patient adherence and satisfaction was high, and seven of the eight patients completed all eight prescribed sessions. Minimal interference with HD was reported. Preliminary results indicate no statistically significant changes in depression, fatigue, or pain at follow-up. However, there was small improvement in SF-36 Physical Component score [t(7) = -2.60, p = .035], and four of the six patients (67%) with clinically elevated pain at baseline reported improvement at follow-up. A technology-assisted CBT intervention for ESRD patients was feasible, well-accepted, and required minimal additional resources in the HD setting. Larger, adequately powered clinical trials are needed to evaluate the effect on ESRD patient-reported outcomes.

Lysosomal dysfunction is associated with a number of age-related pathologies that affect all organ systems. While much research has focused on neurodegenerative diseases and aging-induced changes in neurons, much less is known about the impact that aging has on lower urinary tract function. Our studies explored age-dependent changes in the content of endo-lysosomal organelles (i.e., multivesicular bodies, lysosomes, and the product of their fusion, endolysosomes) and age-induced effects on lysosomal degradation in the urothelium, the epithelial tissue that lines the inner surface of the bladder, ureters, and renal pelvis. When examined by transmission electron microscopy, the urothelium from young adult rats (~3 months), mature adult rats (~12 months), and aged rats (~26 months old) demonstrated a progressive age-related accumulation of aberrantly large endolysosomes (up to 7μm in diameter) that contained undigested content, likely indicating impaired degradation. Stereological analysis confirmed that aged endolysosomes occupied approximately 300% more volume than their younger counterparts while no age-related change was observed in multivesicular bodies or lysosomes. Consistent with diminished endolysosomal degradation, we observed that cathepsin B activity was significantly decreased in aged versus young urothelial cell lysates as well as in live cells. Further, the endolysosomal pH of aged urothelium was higher than that of young adult (pH 6.0 vs pH 4.6). Our results indicate that there is a progressive decline in urothelial endolysosomal function during aging. How this contributes to bladder dysfunction in the elderly is discussed.