Publications

BACKGROUND AND OBJECTIVES

Frailty is common among patients on hemodialysis and associated with adverse outcomes. However, little is known about changes in frailty over time and the factors associated with those changes.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS

To address these questions, we examined 762 participants in the A Cohort to Investigate the Value of Exercise/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD cohort study, among whom frailty was assessed at baseline and 12 and 24 months. We used ordinal generalized estimating equations analyses and modeled frailty (on a scale from zero to five possible components) and death during follow-up.

RESULTS

The mean frailty score at baseline was 1.9, and the distribution of frailty scores was similar at each evaluation. However, most participants' scores changed, with patients improving almost as often as worsening (overall change, 0.2 points per year; 95% confidence interval, 0.1 to 0.3). Hispanic ethnicity (0.6 points per year; 95% confidence interval, 0.0 to 1.1) and diabetes (0.7 points per year; 95% confidence interval, 0.3 to 1.0) were associated with higher frailty scores and higher serum albumin concentration with lower frailty scores (-1.1 points per g/dl; 95% confidence interval, -1.5 to -0.7). In addition, patients whose serum albumin increased over time were less likely to become frail, with each 1-g/dl increase in albumin associated with a 0.4-point reduction in frailty score (95% confidence interval, -0.80 to -0.05). To examine the underpinnings of the association between serum albumin and frailty, we included serum IL-6, normalized protein catabolic rate, and patient self-report of hospitalization within the last year in a second model. Higher IL-6 and hospitalization were statistically significantly associated with worse frailty at any point and worsening frailty over time, whereas normalized protein catabolic rate was not independently associated with frailty.

CONCLUSIONS

There was substantial year to year variability in frailty scores, with approximately equal numbers of patients improving and worsening. Markers of inflammation and hospitalization were independently associated with worsening frailty. Studies should examine whether interventions to address inflammation or posthospitalization rehabilitation can improve the trajectory of frailty.

BACKGROUND/AIMS

Asian Indians have a high prevalence of vitamin D deficiency and metabolic syndrome. Vitamin D deficiency is associated with an increased risk of cardiovascular disease and diabetes.

METHODS

We performed a cross-sectional study of 150 Asian Indians (50% male) from the San Francisco Bay Area. We assessed the association between 25-OH vitamin D (25-OHD) levels and vitamin D deficiency with body composition (anthropometric and radiographic measures) and metabolic outcomes.

RESULTS

In both men and women, the presence of vitamin D deficiency was associated with higher systolic (p = 0.004) and diastolic (p = 0.01) blood pressure, and fasting glucose (p = 0.01). Only in women, vitamin D deficiency status was associated with higher body mass index (BMI), waist-to-hip ratio, visceral fat area, and hepatic fat content after adjusting for age, income, and physical activity level. In women, 25-OHD was also associated with fasting glucose after adjusting for age, income, and physical activity and further adjusting for BMI and waist circumference (β -2.1, 95% CI -0.86 to -0.01, p = 0.04). This association between vitamin D deficiency and metabolic parameters was not significant in men.

CONCLUSIONS

A lower level of 25-OHD and vitamin D deficiency were associated with higher levels of metabolic factors among Asian Indians. Our findings suggest that 25-OHD metabolism may differ by the distribution of adipose tissue and involve previously unexplored pathways accounting for the variability in the role of vitamin D in cardiovascular disease.

Niemann-Pick C1-like 1 (NPC1L1) plays a critical role in the enterohepatic absorption of free cholesterol. Cellular cholesterol depletion induces the transport of NPC1L1 from the endocytic recycling compartment to the plasma membrane (PM), and cholesterol replenishment causes the internalization of NPC1L1 together with cholesterol via clathrin-mediated endocytosis. Although NPC1L1 has been characterized, the other proteins involved in cholesterol absorption and the endocytic recycling of NPC1L1 are largely unknown. Most of the vesicular trafficking events are dependent on the cytoskeleton and motor proteins. Here, we investigated the roles of the microfilament and microfilament-associated triple complex composed of myosin Vb, Rab11a, and Rab11-FIP2 in the transport of NPC1L1 from the endocytic recycling compartment to the PM. Interfering with the dynamics of the microfilament by pharmacological treatment delayed the transport of NPC1L1 to the cell surface. Meanwhile, inactivation of any component of the myosin Vb.Rab11a.Rab11-FIP2 triple complex inhibited the export of NPC1L1. Expression of the dominant-negative mutants of myosin Vb, Rab11a, or Rab11-FIP2 decreased the cellular cholesterol uptake by blocking the transport of NPC1L1 to the PM. These results suggest that the efficient transport of NPC1L1 to the PM is dependent on the microfilament-associated myosin Vb.Rab11a.Rab11-FIP2 triple complex.