Nazanin Noori

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.

The Obesity Paradox and Mortality Associated With Surrogates of Body Size and Muscle Mass in Patients Receiving Hemodialysis

OBJECTIVE To determine whether dry weight gain accompanied by an increase in muscle mass is associated with a survival benefit in patients receiving maintenance hemodialysis (HD). PATIENTS AND METHODS In a nationally representative 5-year cohort of 121,762 patients receiving HD 3 times weekly from July 1, 2001, through June 30, 2006, we examined whether body mass index (BMI) (calculated using 3-month averaged post-HD dry weight) and 3-month averaged serum creatinine levels (a likely surrogate of muscle mass) and their changes over time were predictive of mortality risk. RESULTS In the cohort, higher BMI (up to 45) and higher serum creatinine concentration were incrementally and independently associated with greater survival, even after extensive multivariate adjustment for available surrogates of nutritional status and inflammation. Dry weight loss or gain over time exhibited a graded association with higher rates of mortality or survival, respectively, as did changes in serum creatinine level over time. Among the 50,831 patients who survived the first 6 months and who had available data for changes in weight and creatinine level, those who lost weight but had an increased serum creatinine level had a greater survival rate than those who gained weight but had a decreased creatinine level. These associations appeared consistent across different demographic groups of patients receiving HD. CONCLUSION In patients receiving long-term HD, larger body size with more muscle mass appears associated with a higher survival rate. A discordant muscle gain with weight loss over time may confer more survival benefit than weight gain while losing muscle. Controlled trials of muscle-gaining interventions in patients receiving HD are warranted.

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.

Serum creatinine as a marker of muscle mass in chronic kidney disease: results of a cross‐sectional study and review of literature

BackgroundHigher muscle mass is associated with better outcomes and longevity in patients with chronic disease states. Imaging studies such as dual-energy X-ray absorptiometry (DEXA) are among the gold standard methods for assessing body fat and lean body mass (LBM), approximately half of which is comprised of skeletal muscle mass. Elaborate imaging devices, however, are not commonly available in routine clinical practice and therefore easily accessible and cost-effective, but reliable muscle mass biomarkers are needed. One such marker is serum creatinine, derived from muscle-based creatine, which is inexpensive and ubiquitously available, and it can serve as a biomarker of skeletal muscle mass in human subjects.Methods and resultsIn 118 hemodialysis patients, we found that the 3-month averaged serum creatinine concentration correlated well with DEXA-measured LBM. The recent literature regarding serum creatinine as a surrogate of muscle mass is summarized, as is the literature concerning the use of other measures of muscle mass, such as plasma gelsolin and actin, and urinary creatinine excretion. We have also reviewed the role of dietary meat intake in serum creatinine variability along with several biomarkers of dietary meat intake (creatine, carnitine, carnosine, ophidine, anserine, 3-methyl-l-histidine and 1-methylhistidine).ConclusionIn summary, none of these biomarkers was studied in CKD patients. We advance the hypothesis that in both health and disease, under steady state, serum creatinine can serve as a reliable muscle mass biomarker if appropriate adjustment for full or residual kidney function and dietary meat intake is undertaken.

Glycemic Control and Survival in Peritoneal Dialysis Patients with Diabetes Mellitus

BACKGROUND AND OBJECTIVES The optimal target for glycemic control has not been established for diabetic peritoneal dialysis (PD) patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined mortality-predictability of hemoglobin A1c random serum glucose in a contemporary cohort of diabetic PD patients treated in DaVita dialysis clinics July 2001 through June 2006 with follow-up through June 2007. RESULTS We identified 2798 diabetic PD patients with A1c data. Serum glucose correlated with A1C (r=0.51). Adjusted all-cause death hazard ratio and 95% confidence interval for baseline A1c increments of 7.0 to 7.9%, 8.0 to 8.9%, 9.0 to 9.9%, and ≥10%, compared with 6.0 to 6.9% (reference), were 1.13 (0.97 to 1.32), 1.05 (0.88 to 1.27), 1.06 (0.84 to 1.34), and 1.48 (1.18 to 1.86); and for time-averaged A1c values were 1.10 (0.96 to 1.27), 1.28 (1.07 to 1.53), 1.34 (1.05 to 1.70), and 1.81 (1.33 to 2.46), respectively. The A1c-mortality association was modified by hemoglobin level such that higher all-cause mortality was evident only in nonanemic patients. Similar but non-significant trends in cardiovascular death risk was found across A1c increments. Adjusted all-cause death HR for time-averaged blood glucose 150 to 199, 200 to 249, 250 to 299, and ≥300 mg/dl, compared with 60 to 99 mg/dl (reference), were 1.02 (0.70 to 1.47), 1.12 (0.77 to 1.63), 1.45 (0.97 to 2.18), and 2.10 (1.37 to 3.20), respectively. CONCLUSIONS Poor glycemic control appears associated incrementally with higher mortality in PD patients. Moderate to severe hyperglycemia is associated with higher death risk especially in certain subgroups.

Total and individual coronary artery calcium scores as independent predictors of mortality in hemodialysis patients.

Many traditional and nontraditional risk factors contribute to vascular calcification among maintenance hemodialysis (MHD) patients. It is not clear whether coronary artery calcification (CAC) delineates a higher mortality risk independent of known risk factors. We examined 6-year (10/2001–9/2007) survival of 166 MHD patients, aged 53 ± 13 years, with baseline CAC scores. Patients were grouped into four CAC groups: 0, 1–100, 101–400, and 400+. The 101–400 and 400+ groups were associated with a significantly higher adjusted risk of death than CAC 0 with hazard ratios (HR) 8.5 (95% CI: 1.1–48.1, p = 0.02) and 13.3 (95% CI: 1.3–65.1, p = 0.01), respectively, independent of demographics, comorbidity, lipids and other cardiovascular risks, surrogates of bone disease, nutritional and inflammatory markers and dialysis dose. Total CAC [HR 6.7 (1.1–21.5, p = 0.03)] followed by the presence of CAC in the left main [4.6 (2.2–9.8, p = 0.001)] and left anterior descending artery [4.3 (2.1–14.2, p = 0.001)] were strong independent predictors of mortality even after adjusting for above covariates. Total and vessel-specific CAC predict mortality in MHD patients independent of traditional and nontraditional risk factors.

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.