Rachelle Bross

Understanding Sources of Dietary Phosphorus in the Treatment of Patients with Chronic Kidney Disease

In individuals with chronic kidney disease, high dietary phosphorus (P) burden may worsen hyperparathyroidism and renal osteodystrophy, promote vascular calcification and cardiovascular events, and increase mortality. In addition to the absolute amount of dietary P, its type (organic versus inorganic), source (animal versus plant derived), and ratio to dietary protein may be important. Organic P in such plant foods as seeds and legumes is less bioavailable because of limited gastrointestinal absorption of phytate-based P. Inorganic P is more readily absorbed by intestine, and its presence in processed, preserved, or enhanced foods or soft drinks that contain additives may be underreported and not distinguished from the less readily absorbed organic P in nutrient databases. Hence, P burden from food additives is disproportionately high relative to its dietary content as compared with natural sources that are derived from organic (animal and vegetable) food proteins. Observational and metabolic studies indicate nutritional and longevity benefits of higher protein intake in dialysis patients. This presents challenges to providing appropriate nutrition because protein and P intakes are closely correlated. During dietary counseling of patients with chronic kidney disease, the absolute dietary P content as well as the P-to-protein ratio in foods should be addressed. Foods with the least amount of inorganic P, low P-to-protein ratios, and adequate protein content that are consistent with acceptable palatability and enjoyment to the individual patient should be recommended along with appropriate prescription of P binders. Provision of in-center and monitored meals during hemodialysis treatment sessions in the dialysis clinic may facilitate the achievement of these goals.

Association of Malnutrition-Inflammation Score With Quality of Life and Mortality in Hemodialysis Patients: A 5-Year Prospective Cohort Study

BACKGROUND The Malnutrition-Inflammation Score (MIS), an inexpensive and easy-to-assess score of 0 to 30 to examine protein-energy wasting (PEW) and inflammation, includes 7 components of the Subjective Global Assessment, body mass index, and serum albumin and transferrin concentrations. We hypothesized that MIS risk stratification of hemodialysis (HD) patients in predicting outcomes is better than its components or laboratory markers of inflammation. STUDY DESIGN 5-Year cohort study. SETTING & PARTICIPANTS We examined 809 stable HD outpatients and followed them for up to 5 years (October 2001 to December 2006). PREDICTORS MIS and other nutritional and inflammatory markers. OUTCOMES & MEASUREMENTS Prospective all-cause mortality, health-related quality of life using the 36-Item Short Form Health Survey (SF-36), and tests of body composition. RESULTS The MIS correlated with logarithm of serum interleukin 6 level (r = +0.26; P < 0.001), logarithm of C-reactive protein level (r = +0.16; P < 0.001), and several measures of nutritional status. Patients with a higher MIS had lower SF-36 scores. After multivariate adjustment for case-mix and other measures of PEW, HD patients in the second (3 to 4), third (5 to 7), and fourth (>or=8) quartiles of MIS had worse survival rates than those in the first (0 to 2) quartile (P < 0.001). Each 2-unit increase in MIS was associated with a 2-fold greater death risk, ie, adjusted death hazard ratio of 2.03 (95% confidence interval, 1.76 to 2.33; P < 0.001). Cubic spline survival models confirmed linear trends. Adding MIS to the constellation of age, sex, race/ethnicity, and vintage significantly improved the area under the receiver operating characteristic curve developed for predicting mortality (0.71 versus 0.67; P < 0.001). LIMITATIONS Selection bias and unknown confounders. CONCLUSIONS In HD patients, the MIS is associated with inflammation, nutritional status, quality of life, and 5-year prospective mortality. The mortality predictability of the MIS appears equal to serum interleukin 6 and somewhat greater than C-reactive protein levels. Controlled trials are warranted to examine whether interventions to improve the MIS can also improve clinical outcomes in HD patients.

Mid-Arm Muscle Circumference and Quality of Life and Survival in Maintenance Hemodialysis Patients

BACKGROUND AND OBJECTIVES Maintenance hemodialysis (MHD) patients with larger body or fat mass have greater survival than normal to low mass. We hypothesized that mid-arm muscle circumference (MAMC), a conveniently measured surrogate of lean body mass (LBM), has stronger association with clinical outcomes than triceps skinfold (TSF), a surrogate of fat mass. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS The associations of TSF, MAMC, and serum creatinine, another LBM surrogate, with baseline short form 36 quality-of-life scores and 5-year survival were examined in 792 MHD patients. In a randomly selected subsample of 118 subjects, LBM was measured by dual-energy x-ray absorptiometry. RESULTS Dual-energy x-ray absorptiometry-assessed LBM correlated most strongly with MAMC and serum creatinine. Higher MAMC was associated with better short form 36 mental health scale and lower death hazard ratios (HRs) after adjustment for case-mix, malnutrition-inflammation-cachexia syndrome, and inflammatory markers. Adjusted death HRs were 1.00, 0.86, 0.69, and 0.63 for the first to fourth MAMC quartiles, respectively. Higher serum creatinine and TSF were also associated with lower death HRs, but these associations were mitigated after multivariate adjustments. Using median values of TSF and MAMC to dichotomize, combined high MAMC with either high or low TSF (compared with low MAMC/TSF) exhibited the greatest survival, i.e., death HRs of 0.52 and 0.59, respectively. CONCLUSIONS Higher MAMC is a surrogate of larger LBM and an independent predictor of better mental health and greater survival in MHD patients. Sarcopenia-correcting interventions to improve clinical outcomes in this patient population warrant controlled trials.

Association of Dietary Phosphorus Intake and Phosphorus to Protein Ratio with Mortality in Hemodialysis Patients

BACKGROUND AND OBJECTIVES Epidemiologic studies show an association between higher predialysis serum phosphorus and increased death risk in maintenance hemodialysis (MHD) patients. The hypothesis that higher dietary phosphorus intake and higher phosphorus content per gram of dietary protein intake are each associated with increased mortality in MHD patients was examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Food frequency questionnaires were used to conduct a cohort study to examine the survival predictability of dietary phosphorus and the ratio of phosphorus to protein intake. At the start of the cohort, Cox proportional hazard regression was used in 224 MHD patients, who were followed for up to 5 years (2001 to 2006). RESULTS Both higher dietary phosphorus intake and a higher dietary phosphorus to protein ratio were associated with significantly increased death hazard ratios (HR) in the unadjusted models and after incremental adjustments for case-mix, diet, serum phosphorus, malnutrition-inflammation complex syndrome, and inflammatory markers. The HR of the highest (compared with lowest) dietary phosphorus intake tertile in the fully adjusted model was 2.37. Across categories of dietary phosphorus to protein ratios of <12, 12 to <14, 14 to <16, and > or =16 mg/g, death HRs were 1.13, 1.00 (reference value), 1.80, and 1.99, respectively. Cubic spline models of the survival analyses showed similar incremental associations. CONCLUSIONS Higher dietary phosphorus intake and higher dietary phosphorus to protein ratios are each associated with increased death risk in MHD patients, even after adjustments for serum phosphorus, phosphate binders and their types, and dietary protein, energy, and potassium intakes.

Association of serum prealbumin and its changes over time with clinical outcomes and survival in patients receiving hemodialysis

BACKGROUND In patients receiving maintenance hemodialysis (MHD), a low serum prealbumin is an indicator of protein-energy wasting. OBJECTIVE We hypothesized that baseline serum prealbumin correlates independently with health-related quality of life (QoL) and death and that its change over time is a robust mortality predictor. DESIGN Associations and survival predictability of serum prealbumin at baseline and its changes over 6 mo were examined in a 5-y (2001-2006) cohort of 798 patients receiving MHD. RESULTS Patients with serum prealbumin >or= 40 mg/dL had greater mid-arm muscle circumference but lower percentage of total body fat. Both serum interleukin-6 and dietary protein intake correlated independently with serum prealbumin. Measures of QoL indicated better physical health, physical function, and functionality with higher prealbumin concentrations. Although baseline prealbumin was not superior to albumin in predicting survival, in both all and normoalbuminemic (albumin >or= 3.5 g/dL; n = 655) patients, prealbumin < 20 mg/dL was associated with higher death risk in adjusted models, but further adjustments for inflammatory cytokines mitigated the associations. In 412 patients with baseline prealbumin between 20 and 40 mg/dL whose serum prealbumin was remeasured after 6 mo, a >or=10-mg/dL fall resulted in a death hazard ratio of 1.37 (95% CI: 1.02, 1.85; P = 0.03) after adjustment for baseline measures, including inflammatory markers. CONCLUSIONS Even though baseline serum prealbumin may not be superior to albumin in predicting mortality in MHD patients, prealbumin concentrations <20 mg/dL are associated with death risk even in normoalbuminemic patients, and a fall in serum prealbumin over 6 mo is independently associated with increased death risk.

Dietary Potassium Intake and Mortality in Long-term Hemodialysis Patients

BACKGROUND Hyperkalemia has been associated with higher mortality in long-term hemodialysis (HD) patients. There are few data concerning the relationship between dietary potassium intake and outcome. STUDY DESIGN The mortality predictability of dietary potassium intake from reported food items estimated using the Block Food Frequency Questionnaire (FFQ) at the start of the cohort was examined in a 5-year (2001-2006) cohort of 224 HD patients in Southern California using Cox proportional hazards regression. SETTING & PARTICIPANTS 224 long-term HD patients from 8 DaVita dialysis clinics. PREDICTORS Dietary potassium intake ranking using the Block FFQ. OUTCOMES 5-year survival. RESULTS HD patients with higher potassium intake had greater dietary energy, protein, and phosphorus intakes and higher predialysis serum potassium and phosphorus levels. Greater dietary potassium intake was associated with significantly increased death HRs in unadjusted models and after incremental adjustments for case-mix, nutritional factors (including 3-month averaged predialysis serum creatinine, potassium, and phosphorus levels; body mass index; normalized protein nitrogen appearance; and energy, protein, and phosphorus intake) and inflammatory marker levels. HRs for death across the 3 higher quartiles of dietary potassium intake in the fully adjusted model (compared with the lowest quartile) were 1.4 (95% CI, 0.6-3.0), 2.2 (95% CI, 0.9-5.4), and 2.4 (95% CI, 1.1-7.5), respectively (P for trend = 0.03). Restricted cubic spline analyses confirmed the incremental mortality predictability of higher potassium intake. LIMITATIONS FFQs may underestimate individual potassium intake and should be used to rank dietary intake across the population. CONCLUSIONS Higher dietary potassium intake is associated with increased death risk in long-term HD patients, even after adjustments for serum potassium level; dietary protein; energy, and phosphorus intake; and nutritional and inflammatory marker levels. The potential role of dietary potassium in the high mortality rate of HD patients warrants clinical trials.

Comparing body composition assessment tests in long-term hemodialysis patients.

BACKGROUND Protein-energy wasting is common in chronic kidney disease and is associated with decreases in body muscle and fat stores and poor outcomes. The accuracy and reliability of field methods to measure body composition is unknown in this population. STUDY DESIGN Cross-sectional observational study. SETTING & PARTICIPANTS 118 maintenance hemodialysis patients were seen at the General Clinical Research Center at Harbor-UCLA Medical Center, Torrance, CA. INDEX TESTS Triceps skinfold, near-infrared interactance, and bioelectrical impedance analysis using the Segal, Kushner, and Lukaski equations. REFERENCE TEST Dual-energy x-ray absorptiometry (DEXA). RESULTS Participants (42% women, 52% with diabetes, 40% African Americans, and 38% Hispanics) were aged 49.4 +/- 11.5 (mean +/- SD) years, and had undergone dialysis therapy for 41.1 +/- 32.9 months. Body mass index was 27.0 +/- 6.0 kg/m(2). Using DEXA as the reference test, the bioelectrical impedance analysis-Kushner equation, triceps skinfold, and near-infrared interactance were most accurate of the index tests in estimating total-body fat percentage, whereas bioelectrical impedance analysis-Segal equation and bioelectrical impedance analysis-Lukaski equation overestimated total body fat percentage. Bland-Altman analyses and difference plots showed that bioelectrical impedance analysis-Kushner and near-infrared interactance were most similar to the reference test. Bioelectrical impedance analysis-Kushner, triceps skinfold, and near-infrared interactance had the smallest mean differences from DEXA, especially in women (1.6%, 0.7%, and 1.2%, respectively). Similar results were observed in African American participants (n = 47). LIMITATIONS Measurements were performed 1 day after a hemodialysis treatment, leading to more fluid retention, which may have affected the reference and index tests differently. CONCLUSIONS Using DEXA as the reference test, both near-infrared interactance and bioelectrical impedance analysis-Kushner method yield more consistent estimates of total body fat percentage in maintenance hemodialysis patients compared with the other index tests. Near-infrared interactance is not affected by skin color. Field methods with portable devices may provide adequate precision.

Quality-of-Life and Mortality in Hemodialysis Patients: Roles of Race and Nutritional Status

BACKGROUND AND OBJECTIVES Maintenance hemodialysis (MHD) patients often have protein-energy wasting, poor health-related quality of life (QoL), and high premature death rates, whereas African-American MHD patients have greater survival than non-African-American patients. We hypothesized that poor QoL scores and their nutritional correlates have a bearing on racial survival disparities of MHD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined associations between baseline self-administered SF36 questionnaire-derived QoL scores with nutritional markers by multivariate linear regression and with survival by Cox models and cubic splines in the 6-year cohort of 705 MHD patients, including 223 African Americans. RESULTS Worse SF36 mental and physical health scores were associated with lower serum albumin and creatinine levels but higher total body fat percentage. Spline analyses confirmed mortality predictability of worse QoL, with an almost strictly linear association for mental health score in African Americans, although the race-QoL interaction was not statistically significant. In fully adjusted analyses, the mental health score showed a more robust and linear association with mortality than the physical health score in all MHD patients and both races: death hazard ratios for (95% confidence interval) each 10 unit lower mental health score were 1.12 (1.05-1.19) and 1.10 (1.03-1.18) for all and African American patients, respectively. CONCLUSIONS MHD patients with higher percentage body fat or lower serum albumin or creatinine concentration perceive a poorer QoL. Poor mental health in all and poor physical health in non-African American patients correlate with mortality. Improving QoL by interventions that can improve the nutritional status without increasing body fat warrants clinical trials.

Racial and ethnic differences in mortality of hemodialysis patients: role of dietary and nutritional status and inflammation.

Background: Racial/ethnic disparities prevail among hemodialysis patients. We hypothesized that significant differences exist between Black and non-Hispanic and Hispanic White hemodialysis patients in nutritional status, dietary intake and inflammation, and that they account for racial survival disparities. Methods: In a 6-year (2001–2007) cohort of 799 hemodialysis patients, we compared diet and surrogates of nutritional-inflammatory status and their mortality-predictabilities between 279 Blacks and 520 Whites using matched and regression analyses and Cox with cubic splines. Results: In age-, gender- and diabetes-matched analyses, Blacks had higher lean body mass and serum prealbumin, creatinine and homocysteine levels than Whites. In case-mix-adjusted analyses, dietary intakes in Blacks versus Whites were higher in energy (+293 ± 119 cal/day) and fat (+18 ± 5 g/day), but lower in fiber (–2.9 ± 1.3 g/day) than Whites. In both races, higher serum albumin, prealbumin and creatinine were associated with greater survival, whereas CRP and IL-6, but not TNF-α, were associated with increased mortality. The highest (vs. lowest) quartile of IL-6 was associated with a 2.4-fold (95% CI: 1.3–3.8) and 4.1-fold (2.2–7.2) higher death risk in Blacks and Whites, respectively. Conclusions: Significant racial disparities exist in dietary, nutritional and inflammatory measures, which may contribute to hemodialysis outcome disparities. Testing race-specific dietary and/or anti-inflammatory interventions is indicated.

Dietary Assessment of Individuals with Chronic Kidney Disease

Examining the quality and quantity of food intake by appropriate methods is critical in the management of patients with chronic kidney disease (CKD). The four commonly used dietary assessment methods in CKD patients include short‐term dietary recalls, several days of food records with or without dietary interviews, urea kinetic based estimates such as protein nitrogen appearance calculation, and food histories including food screeners and food frequency questionnaires (FFQ). There are a number of strengths and limitations of these dietary assessment methods. Accordingly, none of the four methods is suitable in and of itself to give sufficiently accurate dietary information for all purposes. Food frequency questionnaires, which is the preferred method for epidemiological studies, should be used for dietary comparisons of patients within a given population rather than individual assessment. Food histories including FFQ and dietary recalls may underestimate important nutrients, especially in CKD patients. Given the large and increasing number of dialysis patients and work responsibilities of renal dietitians, routine analysis of dietary records and recalls is becoming less feasible. Ongoing and future studies will ascertain additional strengths and limitations of dietary assessment methods in CKD populations including the assessment of food intake during an actual hemodialysis treatment.