Balancing nutrition and serum phosphorus in maintenance dialysis.

Elevated serum phosphorus levels are common in patients with chronic kidney disease and are associated with heart and vascular disease, conditions that in turn are associated with increased mortality. Accurately managing phosphorus intake by restricting dietary protein alone can prove challenging because protein from different sources can contain varying amounts of available phosphorus. Additives used in processed foods frequently are high in inorganic phosphorus, which is readily absorbed, compounding this difficulty. Recent evidence suggests that dietary protein restriction in some cases may do more harm than good in some patients treated with maintenance hemodialysis because protein restriction can lead to protein-energy wasting, which is associated with increased mortality. Accordingly, phosphorus binders are important for managing hyperphosphatemia in dialysis patients. Managing hyperphosphatemia in patients with late-stage chronic kidney disease requires an individualized approach, involving a combination of adequate dietary advice, phosphate-binder use, and adjustments to dialysis prescription. We speculate that increased use of phosphate binders could allow patients to eat more protein-rich foods and that communicating this to patients might increase their perception of their need for phosphate binders, providing an incentive to improve adherence. The aim of this review is to discuss the challenges involved in maintaining adequate nutrition while controlling phosphorus levels in patients on maintenance hemodialysis therapy.

Phosphorus Counting Table for the control of serum phosphorus levels without phosphate binders in hemodialysis patients.

BACKGROUND AND AIMS: Hyperphosphatemia constitutes one of the major problems faced by patients with chronic kidney disease, and nourishment plays a significant role in its control. The present study aimed to evaluate the maintenance of phosphorus serum levels by observing measurements before and after an intervention using the Phosphorus Counting Table (PCT), in hemodialysis patients lacking phosphate binder use. METHODS: The assessment included fifty individuals on hemodialysis who underwent phosphate binder suspension 30 days prior to the intervention. The participants received food and nutrition education on the PCT tool, which assists in the control of dietary phosphorus intake, and followed its instructions for two months. Fasting blood samples were collected at three moments for phosphorus, total calcium, and parathyroid hormone (PTH) analysis. The study sample was initially analyzed as a whole, then sub-classified into two groups: adherence and non-adherence. RESULTS: At the end of the study, no significant difference in serum phosphorus was observed in the total and the adherence groups (p > 0.05). The non-adherence group showed a substantial increase of 0.74 mg/dL in serum phosphorus levels and 6.16 mg2/dL2 in the calcium-phosphorus product after the intervention. Meanwhile, the calcium-phosphorus product improved from 56.42 ± 11.49 mg2/dL2 to 51.05 ± 10.67 mg2/dL2 in the adherence group. Serum calcium levels did not change throughout the study in the three groups. A significant increment in PTH serum levels was observed at the end of the study in all groups. CONCLUSION: The PCT showed to be efficient in the maintenance of serum phosphorus in the individuals who adhered well to the tool, without the administration of phosphate binders. Such a method can assist in patient adherence to treatment and enables better diet flexibility. The present trial was registered under the Brazilian Clinical Trials Registry (Rebec). Registration number: RBR-2vzd48.

The Healthy Hearts and Kidneys (HHK) study: Design of a 2×2 RCT of technology-supported self-monitoring and social cognitive theory-based counseling to engage overweight people with diabetes and chronic kidney disease in multiple lifestyle changes.

Patients with complex chronic diseases usually must make multiple lifestyle changes to limit and manage their conditions. Numerous studies have shown that education alone is insufficient for engaging people in lifestyle behavior change, and that theory-based behavioral approaches also are necessary. However, even the most motivated individual may have difficulty with making lifestyle changes because of the information complexity associated with multiple behavior changes. The goal of the current Healthy Hearts and Kidneys study was to evaluate, different mobile health (mHealth)-delivered intervention approaches for engaging individuals with type 2 diabetes (T2D) and concurrent chronic kidney disease (CKD) in behavior changes. Participants were randomized to 1 of 4 groups, receiving: (1) a behavioral counseling, (2) technology-based self-monitoring to reduce information complexity, (3) combined behavioral counseling and technology-based self-monitoring, or (4) baseline advice. We will determine the impact of randomization assignment on weight loss success and 24-hour urinary excretion of sodium and phosphorus. With this report we describe the study design, methods, and approaches used to assure information security for this ongoing clinical trial. Clinical Trials.gov Identifier: NCT02276742.

Twenty-Four-Hour Urine Phosphorus as a Biomarker of Dietary Phosphorus Intake and Absorption in CKD: A Secondary Analysis from a Controlled Diet Balance Study.

BACKGROUND AND OBJECTIVES: Twenty-four-hour urine phosphorus is commonly used as a surrogate measure for phosphorus intake and absorption in research studies, but its reliability and accuracy are unproven in health or CKD. This secondary analysis sought to determine the reliability and accuracy of 24-hour urine phosphorus as a biomarker of phosphorus intake and absorption in moderate CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Eight patients with stage 3-4 CKD participated in 2-week balance studies with tightly controlled phosphorus and calcium intakes. Thirteen 24-hour urine collections per patient were analyzed for variability and reliability of 24-hour urine phosphorus and phosphorus-to-creatinine ratio. The accuracy of 24-hour urine phosphorus to predict phosphorus intake was determined using a published equation. The relationships of 24-hour urine phosphorus with phosphorus intake, net absorption, and retention were determined. RESULTS: There was wide day-to-day variation in 24-hour urine phosphorus within and among subjects (coefficient of variation of 30% and 37%, respectively). Two 24-hour urine measures were needed to achieve ≥75% reliability. Estimating dietary phosphorus intake from a single 24-hour urine resulted in underestimation up to 98% in some patients and overestimation up to 79% in others. Twenty-four-hour urine phosphorus negatively correlated with whole-body retention but was not related to net absorption. CONCLUSIONS: From a sample of eight patients with moderate CKD on a tightly controlled dietary intake, 24-hour urine phosphorus was highly variable and did not relate to dietary phosphorus intake or absorption, rather it inversely related to phosphorus retention.

Effect of Treatment of Metabolic Acidosis on Vascular Endothelial Function in Patients with CKD: A Pilot Randomized Cross-Over Study.

BACKGROUND AND OBJECTIVES: We examined the effect of alkali replacement for metabolic acidosis on vascular endothelial function in patients with CKD. METHODS: We performed a pilot, prospective, open-label 14-week crossover study examining the effect of oral sodium bicarbonate treatment on vascular function in 20 patients with an eGFR of 15-44 ml/min per 1.73 m2 with low serum bicarbonate levels (16-21 mEq/L). Each period was 6 weeks in duration with a 2-week washout period in between. Patients were treated to goal serum bicarbonate of ≥23 mEq/L. The primary end point was change in brachial artery flow-mediated dilation (FMD) between treatment and control conditions. Secondary end points included changes in markers of inflammation, bone turnover, mineral metabolism, and calcification. RESULTS: Eighteen patients completed the study and were included in the primary efficacy analysis. The mean (SD) age and eGFR were 59 (12) years and 26 (8) ml/min per 1.73 m2, respectively. Serum bicarbonate increased significantly with sodium bicarbonate treatment (+2.7±2.9 mEq/L, P≤0.001), whereas there was no change in bicarbonate levels in the control group. FMD significantly improved after sodium bicarbonate therapy (mean±SD, FMD baseline: 4.1%±4.1%; 6 weeks: 5.2%±2.9%; P=0.04) There was no significant change in FMD in the control group (mean±SD, FMD baseline: 4.6%±3.1%; 6 weeks: 4.1%±3.4%; P=0.20). Compared with control, sodium bicarbonate treatment resulted in a significant increase in FMD (mean, 1.8%; 95% confidence interval, 0.3 to 3.3; P=0.02). There was no significant change in bone markers or serum calcification propensity with treatment. Serum phosphorus and intact fibroblast growth factor 23 increased significantly during treatment. CONCLUSIONS: Treatment of metabolic acidosis with sodium bicarbonate significantly improved vascular endothelial function in patients with stages 3b and 4 CKD.

Association of Serum Phosphorus Concentration with Mortality and Graft Failure among Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: Hyperphosphatemia in kidney transplant recipients has been shown to predict poorer graft and patient survival. However, studies examining hypophosphatemia are scarce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To evaluate the association of serum phosphorus level with patient and graft survival, we performed a retrospective multicenter cohort study. Between January of 1997 and August of 2012, 2786 kidney transplant recipients (41.7±11.4 years; 59.3% men; 73.5% living donors; 26.1% with diabetes; 3.8% with prior history of cardiovascular disease) were classified into seven groups according to serum phosphorus levels 1 year after transplantation, with intervals of 0.5 mg/dl (lowest group, <2.5 mg/dl; highest group, ≥5.0 mg/dl; reference group, 3.5-3.99 mg/dl). Survival analysis was performed by defining baseline time point as 1 year after transplantation. RESULTS: During median follow-up of 78.5 months, 60 patient deaths and 194 cases of graft loss occurred. In multivariate analysis, both lowest and highest serum phosphorus groups were associated with higher mortality, compared with the reference group (hazard ratio [HR], 4.82; 95% confidence interval [95% CI], 1.36 to 17.02; P=0.01; and HR, 4.24; 95% CI, 1.07 to 16.84; P=0.04, respectively). Higher death-censored graft loss was observed in the lowest and highest groups (HR, 3.32; 95% CI, 1.42 to 7.79; P=0.01; and HR, 2.93; 95% CI, 1.32 to 6.49; P=0.01, respectively), despite eGFR exhibiting no difference between the lowest group and reference group (65.4±19.3 versus 61.9±16.7 ml/min per 1.73 m2; P=0.33). Moreover, serum phosphorus showed a U-shape association with patient mortality and graft failure in restricted cubic spline curve analysis. CONCLUSIONS: Serum phosphorus level 1 year after transplantation exhibits a U-shape association with death-censored graft failure and patient mortality in kidney transplant patients characterized by relatively high rate of living donor transplant and low incidence of diabetes and prior cardiovascular disease compared with Western countries.

Association of Parameters of Mineral Bone Disorder with Mortality in Patients on Hemodialysis according to Level of Residual Kidney Function.

BACKGROUND AND OBJECTIVES: The relationship between mineral and bone disorders and survival according to residual kidney function status has not been previously studied in patients on hemodialysis. We hypothesized that residual kidney function, defined by renal urea clearance, modifies the association between mineral and bone disorder parameters and mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The associations of serum phosphorus, albumin-corrected calcium, intact parathyroid hormone, and alkaline phosphatase with all-cause mortality were examined across three strata (<1.5, 1.5 to <3.0, and ≥3.0 ml/min per 1.73 m2) of baseline residual renal urea clearance using Cox models adjusted for clinical characteristics and laboratory measurements in 35,114 incident hemodialysis patients from a large United States dialysis organization over the period of 2007-2011. RESULTS: A total of 8102 (23%) patients died during the median follow-up of 1.3 years (interquartile range, 0.6-2.3 years). There was an incremental mortality risk across higher serum phosphorus concentrations, which was pronounced among patients with higher residual renal urea clearance (Pinteraction=0.001). Lower concentrations of serum intact parathyroid hormone were associated with higher mortality among patients with low residual renal urea clearance (i.e., <1.5 ml/min per 1.73 m2), whereas higher concentrations showed a higher mortality risk among patients with greater residual renal urea clearance (i.e., ≥1.5 ml/min per 1.73 m2; Pinteraction<0.001). Higher serum corrected total calcium and higher alkaline phosphatase concentrations consistently showed higher mortality risk (Ptrend<0.001 for both) irrespective of residual renal urea clearance strata (Pinteraction=0.34 and Pinteraction=0.53, respectively). CONCLUSIONS: Residual kidney function modified the mortality risk associated with serum phosphorus and intact parathyroid hormone among incident hemodialysis patients. Future studies are needed to examine whether taking account for residual kidney function into the assessment of mortality risk associated with serum phosphorus and intact parathyroid hormone improves patient management and clinical outcomes in the hemodialysis population.

Cardiovascular Phenotypes in Children with CKD: The 4C Study.

BACKGROUND AND OBJECTIVES: Cardiovascular disease is the most important comorbidity affecting long-term survival in children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Cardiovascular Comorbidity in Children with CKD Study is a multicenter, prospective, observational study in children ages 6-17 years old with initial GFR of 10-60 ml/min per 1.73 m2. The cardiovascular status is monitored annually, and subclinical cardiovascular disease is assessed by noninvasive measurements of surrogate markers, including the left ventricular mass index, carotid intima-media thickness, and central pulse wave velocity. We here report baseline data at study entry and an explorative analysis of variables associated with surrogate markers. RESULTS: A total of 737 patients were screened from October of 2009 to August of 2011 in 55 centers in 12 European countries, and baseline data were analyzed in 688 patients. Sixty-four percent had congenital anomalies of the kidney and urinary tract; 26.1% of children had uncontrolled hypertension (24-hour ambulatory BP monitoring; n=545), and the prevalence increased from 24.4% in CKD stage 3 to 47.4% in CKD stage 5. The prevalence of left ventricular hypertrophy was higher with each CKD stage, from 10.6% in CKD stage 3a to 48% in CKD stage 5. Carotid intima-media thickness was elevated in 41.6%, with only 10.8% of patients displaying measurements below the 50th percentile. Pulse wave velocity was increased in 20.1%. The office systolic BP SD score was the single independent factor significantly associated with all surrogate markers of cardiovascular disease. The intermediate end point score (derived from the number of surrogate marker measurements >95th percentile) was independently associated with a diagnosis of congenital anomalies of the kidney and urinary tract, time since diagnosis of CKD, body mass index, office systolic BP, serum phosphorus, and the hemoglobin level. CONCLUSIONS: The baseline data of this large pediatric cohort show that surrogate markers for cardiovascular disease are closely associated with systolic hypertension and stage of CKD.

Diet Soda Consumption and Risk of Incident End Stage Renal Disease.

BACKGROUND AND OBJECTIVES: Diet soda consumption is common in the United States and is associated with impaired glucose metabolism, diabetes, and metabolic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We prospectively analyzed diet soda consumption, assessed by food frequency questionnaire at baseline (1987-1989) and a follow-up examination (1993-1995), and incident ESRD through December 31, 2012 in the Atherosclerosis Risk in Communities study (n=15,368). RESULTS: Baseline mean age of participants was 54 years, 55% were female, and 27% were black. The majority of participants (43.5%) consumed <1 glass/wk of diet soda; 17.8% consumed 1-4 glasses/wk; 25.3% consumed 5-7 glasses/wk; and 13.5% consumed >7 glasses/wk. Over a median follow-up of 23 years, 357 incident ESRD cases were observed. Relative to <1 glass/wk of diet soda, consuming 1-4 glasses/wk, 5-7 glasses/wk, and >7 glasses/wk, respectively, was associated with 1.08-times (95% confidence interval [95% CI], 0.75 to 1.55), 1.33-times (95% CI, 1.01 to 1.75), and 1.83-times (95% CI, 1.01 to 2.52) higher risk of ESRD after adjusting for age, sex, race-center, education level, smoking status, physical activity, total caloric intake, eGFR, body mass index category, diabetes, systolic BP, and serum uric acid (P value for trend <0.001). Results were similar after additional adjustment for dietary acid load, diet quality, dietary sodium, dietary fructose, sugar-sweetened beverages, and dietary phosphorus. Risk estimates were similar by body mass index category (P value for interaction = 0.82), but the association between diet soda and ESRD was only significant for those who were overweight or obese at baseline. Sugar-sweetened beverage consumption was not significantly associated with ESRD in the fully adjusted model. CONCLUSIONS: Diet soda consumption was associated with higher ESRD risk in this general population sample. Further research is necessary to validate these findings in other study populations and to examine potential mechanisms through which diet soda could impact kidney disease.

Conhecimento de hiperfosfatemia e quelante de fósforo em hemodialíticos / Knowledge about hyperphosphatemia and phosphate binder at hemodialysis

Introdução: O controle do fósforo sérico é um desafio no tratamento de pacientes em hemodiálise. A orientação dietética e o uso adequado de quelantes são a base do tratamento e seu sucesso depende essencialmente da habilidade do paciente em entender e aderir ao plano dietético e ao uso dos quelantes. Objetivo: Avaliar o conhecimento sobre hiperfosfatemia e uso de quelantes de fósforo de pacientes em hemodiálise. Método: Estudo transversal que avaliou 74 pacientes em hemodiálise, por meio de questionário preestabelecido sobre conhecimento da hiperfosfatemia, uso de quelantes, alimentos ricos em fósforo, e aspectos relacionados ao tratamento da hiperfosfatemia. Os parâmetros laboratoriais Kt/V, níveis séricos de paratormônio (PTH), fósforo (P), cálcio (Ca) e produto cálcio/fósforo (CaxP) foram identificados. Os dados foram apresentados como porcentagens ou média e desvio padrão. Para avaliação dos fatores associados à hiperfosfatemia, utilizou-se a regressão de Poisson, adotando nível de significância adotado de 5%. Resultados: Cerca de 40,3% dos pacientes faziam uso de quelantes de fósforo, 36,6% apresentavam níveis séricos de PTH elevados, 36% de hiperfosfatemia e 28% estavam com o produto Ca x P inadequado. A maioria conhecia os efeitos da hiperfosfatemia (52%) e sua relação causal com a alimentação (82,2%), sendo capazes de identificar os alimentos ricos em fósforo (60%). O uso de quelantes junto às refeições foi apontado por 88% dos pacientes. O insucesso no tratamento da hiperfosfatemia foi atribuído ao consumo de dieta rica em fósforo por 70,9% dos pacientes. Conclusão: A maioria dos pacientes possuía conhecimento sobre a hiperfosfatemia, contudo, apresentou baixa adesão às recomendações dietéticas.(AU)

Introduction: The control of serum phosphorus is a challenge in the treatment of hemodialysis patients. Dietary guidance and the proper use of chelating agents are the mainstay of treatment, its success depends primarily on the patient's ability to understand and adhere to the dietary plan and the use of chelators. Objective: To assess the knowledge of hyperphosphatemia and use of phosphate binders in hemodialysis patients treated. Methods: A cross-sectional study evaluated 74 patients in hemodialysis, through preestablished questionnaire on knowledge of hyperphosphatemia, use of binders, phosphorus-rich foods, and aspects related to the treatment of hyperphosphatemia. The laboratory parameters Kt / V, serum levels of parathyroid hormone (PTH), phosphorus (P), calcium (Ca) and product calcium / phosphorus (Ca x P) were identified. The data were presented as percentages or means and standard deviations. To evaluate the factors associated with hyperphosphatemia were used Poisson regression, with a level of significance of 5%. Results: About 40.3% of patientes made use of phosphorus binders, 36.6% had elevated serum PTH, 36% of hyperphosphatemia and 28% had inadequate Ca x P product. Most knew the effects of hyperphosphatemia (52%) and their causal relationship with food (82.2%), being able to identify foods rich in phosphorus (60%). The use of binders with meals was reported by 88% of patients. The failure in the treatment of hyperphosphatemia has been attributed to the consumption of a diet rich in phosphorus by 70.9% of patients. Conclusion: Most patients had knowledge of hyperphosphatemia, however showed poor adherence to dietary recommendations.(AU)