Screening for hospitalization and nutritional risks among community-dwelling older persons.

BACKGROUND: The potential for the use of nutritional screening to identify older persons at risk of hospitalization has not been contrasted with the use of tools developed for predicting hospital admissions. OBJECTIVE: Our goal was to compare the associations of items from the Level II Nutrition Screen (LII) and the Probability of Repeated Admissions (P(ra)) questionnaire with the outcome of hospitalization. DESIGN: This was a cohort study of participants in a Medicare managed-risk health plan who completed both the LII and P(ra) (n = 386). All hospitalizations within 1 y of screening were recorded. Hierarchical multivariate logistic regression was used to model associations with hospitalization. RESULTS: P(ra) items that retained significant associations with hospitalization were self-reported health, hospitalization in the past year, and >6 doctor visits in the past year (positive predictive value: 20%; sensitivity: 53.1; specificity: 69.7). LII items that retained significant associations with hospitalization were eating problems and polypharmacy (positive predictive value: 17.9%; sensitivity: 58.0; specificity: 56.3). Those persons designated by the P(ra) score as being at high risk of hospitalization (P(ra) > or = 0.30, 75th percentile) were also more likely to report weight loss, polypharmacy, consumption of a special diet, and functional limitation on the LII. CONCLUSIONS: Retained items from the P(ra) and the LII were comparable in identifying participants at risk of hospitalization. These observations suggest that nutritional risk factors such as eating problems, weight loss, and consumption of special diets should be considered in the management of older persons at risk of hospitalization, irrespective of the screening approach selected.

The relationship between body mass index and self-reported functional limitation among older adults: a gender difference.

OBJECTIVES: To determine whether there is a gender difference in how body mass index (BMI) relates to self-reported functional limitation. Also, to evaluate whether the method of categorizing BMI changes the observed results. DESIGN: Cross-sectional cohort study. SETTING: Rural Pennsylvania. PARTICIPANTS: A total of 7,120 male (n = 3,312) and female (n = 3,808) community-dwelling older adults enrolled in a Medicare managed-risk contract. MEASUREMENTS: All subjects completed a modified Level II Nutrition Risk Screen upon enrollment in the health plan. Height and weight were obtained by nursing personnel during an enrollment clinic visit. Subjects who reported 10 or more pounds weight loss in the previous 6 months were excluded. Logistic regression was used to evaluate the relationship between BMI and self-reported functional limitation separately for each sex, adjusting for age, depression, and polypharmacy. Two schemes were used to categorize BMI: equally distributed sex-specific quintiles and arbitrary division based on National Institutes of Health (NIH) Obesity Guidelines. RESULTS: How BMI relates to functional limitation depends upon both sex and method of categorizing BMI. When BMI was considered in gender-specific quintiles, women in the highest quintile of BMI had increased risk of functional impairment; there was no relationship between BMI and functional limitation for men. When BMI was categorized by the NIH obesity guidelines, both men and women with BMI >40 had significantly increased risk of functional limitation. CONCLUSIONS: The mechanisms behind gender discrepancy in self-reported functional limitation remain unclear. Studies may need to consider men and women separately, because how BMI relates to function depends on gender. Further research is needed to evaluate how changes in weight and body composition during middle and old age affect functional status.

Up-regulation of multidrug resistance P-glycoprotein via nuclear factor-kappaB activation protects kidney proximal tubule cells from cadmium- and reactive oxygen species-induced apoptosis.

Cadmium-mediated toxicity of cultured proximal tubule (PT) cells is associated with increased production of reactive oxygen species (ROS) and apoptosis. We found that cadmium-dependent apoptosis (Hoechst 33342 and annexin V assays) decreased with prolonged CdCl(2) (10 microM) application (controls: 2.4 +/- 1.6%; 5 h: +5.1 +/- 2.3%, 20 h: +5.7 +/- 2.5%, 48 h: +3.3 +/- 1.0% and 72 h: +2.1 +/- 0.4% above controls), while cell proliferation was not affected. Reduction of apoptosis correlated with a time-dependent up-regulation of the drug efflux pump multidrug resistance P-glycoprotein (mdr1) in cadmium-treated cells ( approximately 4-fold after 72 h), as determined by immunoblotting with the monoclonal antibody C219 and measurement of intracellular accumulation of the fluorescent probe calcein +/- the mdr1 inhibitor PSC833 (0.5 microM). When mdr1 inhibitors (PSC833, cyclosporine A, verapamil) were transiently added to cells with mdr1 up-regulation by pretreatment for 72 h with cadmium, cadmium-induced apoptosis increased significantly and to a percentage similar to that obtained in cells with no mdr1 up-regulation (72-h cadmium: 5.2 +/- 0.9% versus 72-h cadmium + 1-h PSC833: 7.2 +/- 1.4%; p < or = 0.001). Cadmium-induced apoptosis and mdr1 up-regulation depended on ROS, since co-incubation with the ROS scavengers N-acetylcysteine (15 mM) or pyrrolidine dithiocarbamate (0.1 mM) abolished both responses. Moreover, cadmium- and ROS-associated mdr1 up-regulation was linked to activation of the transcription factor NF-kappaB; N-acetylcysteine, pyrrolidine dithiocarbamate, and the IkappaB-alpha kinase inhibitor Bay 11-7082 (20 microM) prevented both, mdr1 overexpression and degradation of the inhibitory NF-kappaB subunit, IkappaB-alpha, induced by cadmium. The data show that 1) cadmium-mediated apoptosis in PT cells is associated with ROS production, 2) ROS increase mdr1 expression by a process involving NF-kappaB activation, and 3) mdr1 overexpression protects PT cells against cadmium-mediated apoptosis. These data suggest that mdr1 up-regulation, at least in part, provides anti-apoptotic protection for PT cells against cadmium-mediated stress.

Cadmium-mediated oxidative stress in kidney proximal tubule cells induces degradation of Na+/K(+)-ATPase through proteasomal and endo-/lysosomal proteolytic pathways.

The mechanisms of cadmium (Cd)-dependent nephrotoxicity were studied in a rat proximal tubule (PT) cell line. CdCl(2) (5 microM) increased the production of reactive oxygen species (ROS), as determined by oxidation of dihydrorhodamine 123 to fluorescent rhodamine 123. The levels of ubiquitin-conjugated cellular proteins were increased by Cd in a time-dependent fashion (maximum at 24-48 h). This was prevented by coincubation with the thiol antioxidant N-acetylcysteine (NAC, 15 mM). Cd also increased apoptosis (controls: 2.4+/-1.6%; Cd: 8.1+/-1.9%), but not necrosis (controls: 0.5 +/- 0.3%; Cd: 1.4+/- 2.5%). Exposure of PT cells with Cd decreased protein levels of the catalytic subunit (alpha1) of Na+/K(+)-ATPase, a long-lived membrane protein (t(1/2)>48 h) that drives reabsorption of ions and nutrients through Na(+)-dependent transporters in PT. Incubation of PT cells for 48 h with Cd decreased Na+/K(+)-ATPase alpha1-subunit, as determined by immunoblotting, by approximately 50%, and NAC largely prevented this effect. Inhibitors of the proteasome such as MG-132 (20 microM) or lactacystin (10 microM), as well as lysosomotropic weak bases such as chloroquine (0.2 mM) or NH(4)Cl (30 mM), significantly reduced the decrease of Na(+)/K(+)-ATPase alpha1-subunit induced by Cd, and in combination abolished the effect of Cd on Na+/K(+)-ATPase. Immunofluorescence labeling of Na+/K(+)-ATPase showed a reduced expression of the protein in the plasma membrane of Cd-exposed cells. After addition of lactacystin and chloroquine to Cd-exposed PT cells, immunoreactive material accumulated into intracellular vesicles. The data indicate that micromolar concentrations of Cd can increase ROS production and exert a toxic effect on PT cells. Oxidative damage increases the degradation of Na+/K(+)-ATPase through both the proteasomal and endo-/lysosomal proteolytic pathways. Degradation of oxidatively damaged Na+/K(+)-ATPase may contribute to the 'Fanconi syndrome'-like Na(+)-dependent transport defects associated with Cd-nephrotoxicity.