Dietary Phosphate Load Research Articles

The Effect of Dietary Phosphate Load on Urinary Supersaturation and Phosphate Metabolism in Non-Stone-Forming Asian Individuals

Introduction: Phosphate ion is common in the core of urinary stones and may initiate stone formation. However, the precise role of phosphate in the initiation of stone formation remains obscure. We assessed the effects of dietary phosphate load on urinary stone risk and phosphate metabolism. Methods: Ten non-stone-forming healthy volunteers completed this randomized, crossover study. Each subject was provided a high- or low-phosphate diet for 3 days. After a 2-day equilibration period with a moderate-phosphate diet, the participants received a low- or high-phosphate diet for another 3 days. Serum, fecal, and 24-h urine samples were collected at the end of each intervention. Results: High dietary phosphate load increased urinary phosphate excretion, and low dietary phosphate decreased urinary phosphate excretion. In addition, urine pH was lower and supersaturation (SS) index of uric acid (UA) was higher after a high-phosphate diet. There was no significant difference in the SS index for calcium oxalate, brushite and hydroxyapatite, or 24-h urinary citrate between the high and the low dietary phosphate. Also, no significant change was observed in fecal phosphate excretion after a high- or low-phosphate diet. The serum phosphate level increased after a high-phosphate diet, but there was no difference in serum phosphate between low-phosphate and moderate-phosphate diets. Conclusion: High dietary phosphate load led to higher urinary phosphate excretion, a higher SS index of UA, and lower urine pH. Stone formers should be advised to limit the intake of high-phosphate source diet, including high-protein diets and phosphate-based food additives.

#1447 Calcimimetics improve impaired cardiac function and contractility in chronic phosphate loading by activating the CaSR/cAMP signaling cascade

Abstract Background and Aims High phosphate loading stimulate the synthesis of PTH and FGF23 and is associated with increased cardiovascular (CV) mortality. In hemodialysis patients, the administration of calcimimetics led to reductions in PTH and FGF23 and the latter was associated with a lower rate of CV events. We have previously shown that mice with a high dietary phosphate load show elevated PTH and FGF23 levels and develop impaired systolic cardiac function, which could be improved by calcimimetics. Calcimimetics are allosteric activators of the calcium-sensing receptor (CaSR). Phosphate (Pi) was shown to inactivate the parathyroid CaSR at concentrations >1.4 mM Pi. Whether calcimimetics contribute to CV event reduction indirectly via lowering PTH and FGF23 or directly via activation of the cardiac CaSR is unknown. Method Wild-type mice were fed a high phosphate diet (HPD) ± etelcalcetide (Etl) or a normal phosphate diet (NPD), cardiac function was assessed by echocardiography and Millar catheterization, and cardiac tissue was harvested for histology and RNAseq analyses. In addition, isolated adult mouse cardiomyocytes (AMCM) were stimulated ex vivo with PTH, FGF23 or Pi, contractility and calcium handling were measured with the addition of Etl and activity analyses were performed. Results In addition to the positive effect on HPD-induced systolic cardiac dysfunction, Etl improved impaired LV contractility and reduced fibrosis. RNAseq analyses revealed reduced Ca, PKA and cAMP signaling by HPD. Ex vivo stimulation of AMCM with PTH and FGF23 had no functional effects. In contrast, Pi significantly worsened contractility and Ca handling, which was blunted by Etl co-stimulation. Downstream of cardiac CaSR, Pi reduced the formation of cAMP, which led to PKA-dependent dephosphorylation of PLN and subsequently to lower Serca2a activity, which was ultimately responsible for the reduced contractility. Etl led to improved cardiomyocyte contractility via increased cAMP synthesis and increased PLN phosphorylation and Serca2a activity. Conclusion Our data suggest that Etl ameliorates the Pi-induced pathologic cardiac phenotype associated with high phosphate load via direct activation of CaSR/cAMP signaling cascade, resulting in improvement of cardiomyocyte contractility.

Intensive Nutritional Counseling and Education for Management of Hyperphosphatemia in Hemodialysis Patients at Al-Khor Hospital- Hamad Medical Corporation - State of Qatar

Objectives: To assess the dietary phosphate intake of hemodialysis patients with hyperphosphatemia and the effects of a dietetic intervention focused on limiting dietary phosphate load. Design: Cross-sectional dietary phosphate intake assessment and prospective intervention study. Setting: Hospital hemodialysis units of AL-Khor hospital – Hamad Medical Corporation, Qatar. Subjects: sixteen stable adult hemodialysis patients, who had phosphorus serum levels ≥1.6 mmol/L. Intervention: Analysis of dietary composition and of the effects of individual dietetic counseling to reduce phosphorus intake while preserving the same or improving protein intake. Main outcome measures: Differences in nutrient intake between pre and post-dietary intervention among hyperphosphatemia patients, and changes in phosphorus–protein ratio, and serum phosphate, after the dietetic intervention. Results: Significant differences in nutrient intake including energy, protein, and phosphorus were detected after the intervention. After dietetic intervention in the hyperphosphatemia patients, a decrease in the dietary phosphate–protein ratio (28.9 -13.4 mg/g, P <0.05) also occurred. Serum phosphate showed a trend of a significant decrease after the dietary intervention (2.2mmol/L-1.68mmol/L), P < 0.05). Conclusion: Individual intensive nutritional education and counseling may be useful in reducing phosphate load and improving serum phosphorus with a positive effect on nutrient intake. A phosphate-controlled diet has a role in an integrated therapeutic approach to hyperphosphatemia and positive calcium-phosphorus balance in hemodialysis patients.

Inactivation of Osteoblast PKC Signaling Reduces Cortical Bone Mass and Density and Aggravates Renal Osteodystrophy in Mice with Chronic Kidney Disease on High Phosphate Diet.

Chronic kidney disease (CKD) frequently leads to hyperphosphatemia and hyperparathyroidism, mineral bone disorder (CKD-MBD), ectopic calcifications and cardiovascular mortality. PTH activates the osteoanabolic Gαs/PKA and the Gαq/11/PKC pathways in osteoblasts, the specific impact of the latter in CKD-MBD is unknown. We generated osteoblast specific Gαq/11 knockout (KO) mice and established CKD-MBD by subtotal nephrectomy and dietary phosphate load. Bone morphology was assessed by micro-CT, osteoblast function by bone planar scintigraphy at week 10 and 22 and by histomorphometry. Osteoblasts isolated from Gαq/11 KO mice increased cAMP but not IP3 in response to PTH 1-34, demonstrating the specific KO of the PKC signaling pathway. Osteoblast specific Gαq/11 KO mice exhibited increased serum calcium and reduced bone cortical thickness and mineral density at 24 weeks. CKD Gαq/11 KO mice had similar bone morphology compared to WT, while CKD Gαq/11-KO on high phosphate diet developed decreased metaphyseal and diaphyseal cortical thickness and area, as well as a reduction in trabecular number. Gαq/11-KO increased bone scintigraphic tracer uptake at week 10 and mitigated tracer uptake in CKD mice at week 22. Histological bone parameters indicated similar trends. Gαq/11-KO in osteoblast modulates calcium homeostasis, bone formation rate, bone morphometry, and bone mineral density. In CKD and high dietary phosphate intake, osteoblast Gαq/11/PKC KO further aggravates mineral bone disease.

Interleukin-36α as a potential biomarker for renal tubular damage induced by dietary phosphate load.

Excessive intake of phosphate has been known to induce renal tubular damage and interstitial inflammation, leading to acute kidney injury or chronic kidney disease in rodents and humans. However, sensitive and early biomarkers for phosphate‐induced kidney damage remain to be identified. Our previous RNA sequencing analysis of renal gene expression identified interleukin‐36α (IL‐36α) as a gene significantly upregulated by dietary phosphate load in mice. To determine the time course and dose dependency of renal IL‐36α expression induced by dietary phosphate load, we placed mice with or without uninephrectomy on a diet containing either 0.35%, 1.0%, 1.5%, or 2.0% inorganic phosphate for 10 days, 4 weeks, or 8 weeks and evaluated renal expression of IL‐36α and other markers of tubular damage and inflammation by quantitative RT‐PCR, immunoblot analysis, and immunohistochemistry. We found that IL‐36α expression was induced in distal convoluted tubules and correlated with phosphate excretion per nephron. The increase in IL‐36α expression was simultaneous with but more robust in amplitude than the increase in tubular damage markers such as Osteopontin and neutrophil gelatinase‐associated lipocalin, preceding the increase in expression of other inflammatory cytokines, including transforming growth factor‐α, interleukin‐1β, and transforming growth factor‐β1. We conclude that IL‐36α serves as a marker that reflects the degree of phosphate load excreted per nephron and of associated kidney damage.

Racial Differences in the Associations Between Food Insecurity and Fibroblast Growth Factor 23 in the Coronary Artery Risk Development in Young Adults Study

Food insecurity is associated with consumption of phosphate additive-laden processed food and beverage products, which could result in higher levels of fibroblast growth factor 23 (FGF23) to compensate for the increased dietary phosphate load. We sought to determine whether food insecurity is associated with higher levels of FGF23. We stratified analyses by race since differences may occur between food insecurity and diet quality across races. The longitudinal community-based Coronary Artery Risk Development in Young Adults Study recruited from 4 US centers: Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA, during the cohort inception in 1985/1986. This analysis included 3,421 black and white participants from Coronary Artery Risk Development in Young Adults follow-up years 20, 25, and 30 who were enrolled in the study between the ages of 18 and 30 years. Econometric fixed effects models stratified by race that adjust by design for all time-invariant covariates were used to model the longitudinal association of food insecurity, defined as the self-reported ability to afford desired quantity and quality of food. The main outcome of interest was changing to the highest quartile of plasma FGF-23 concentrations. During follow-up, 29% of blacks and 14% of whites experienced change in food security. Developing food insecurity was associated with a 1.48 greater odds of increasing to the highest quartile of FGF23 (95% confidence interval 1.02-2.15) among blacks; however, there was no significant longitudinal association among whites (odds ratio=1.14, 95% confidence interval 0.67-1.95). Among blacks, food insecurity was associated with an increase in levels of FGF23. Although phosphate consumption was presumed to mediate the association between food insecurity and FGF23 levels, we were unable to directly test this pathway.

Calciprotein particles regulate fibroblast growth factor-23 expression in osteoblasts

Fibroblast growth factor-23 (FGF23) is a hormone indispensable for maintaining phosphate homeostasis. In response to phosphate intake, FGF23 is secreted from osteocytes/osteoblasts and acts on the kidney to increase urinary phosphate excretion. However, the mechanism by which these cells sense phosphate intake remains elusive. Calciprotein particles are nanoparticles of calcium-phosphate precipitates bound to serum protein fetuin-A and are generated spontaneously in solution containing calcium, phosphate, and fetuin-A to be dispersed as colloids. In cultured osteoblastic cells, increase in either calcium or phosphate concentration in the medium induced FGF23 expression, which was dependent on calciprotein particle formation. When transition of calcium-phosphate precipitates from the amorphous phase to the crystalline phase was blocked by bisphosphonate, the calciprotein particle size was reduced and FGF23 expression was augmented, suggesting that small calciprotein particles containing amorphous calcium-phosphate precipitates function as a more potent FGF23 inducer than larger calciprotein particles containing crystalline calcium-phosphate precipitates. In mice, bolus phosphate administration by oral gavage transiently increased circulating calciprotein particle levels followed by a modest increase in FGF23 expression and serum FGF23 levels. However, continuous dietary phosphate load induced robust and persistent increase in circulating calciprotein particles and FGF23 levels. We confirmed by invivo imaging that calciprotein particles injected intravenously extravasated into the bone marrow and were deposited on the inner surface of the bone, indicating that these particles have direct access to osteoblasts. Thus, we propose that osteoblasts induce FGF23 expression and secretion when they sense an increase in extracellular calciprotein particles following phosphate ingestion.

Phosphate and Cardiovascular Disease beyond Chronic Kidney Disease and Vascular Calcification.

Phosphate is essential for life but its accumulation can be detrimental. In end-stage renal disease, widespread vascular calcification occurs as a result of chronic phosphate load. The accumulation of phosphate is likely to occur long before the rise in serum phosphate above the normal range since several observational studies in both general population and early-stage CKD patients have identified the relationship between high-normal serum phosphate and adverse cardiovascular outcomes. Consumption of food high in phosphate increases both fasting and postprandial serum phosphate and habitual intake of high phosphate diet is associated with aging, cardiac hypertrophy, endothelial dysfunction, and subclinical atherosclerosis. The decline in renal function and dietary phosphate load can increase circulating fibroblast growth factor-23 (FGF-23) which may have a direct impact on cardiomyocytes. Increased FGF-23 levels in both CKD and general populations are associated with left ventricular hypertrophy, congestive heart failure, atrial fibrillation, and mortality. Increased extracellular phosphate directly affects endothelial cells causing cell apoptosis and vascular smooth muscle cells (VSMCs) causing transformation to osteogenic phenotype. Excess of calcium and phosphate in the circulation can promote the formation of protein-mineral complex called calciprotein particles (CPPs). In CKD, these CPPs contain less calcification inhibitors, induce inflammation, and promote VSMC calcification.

Abstract P303: Racial Differences in the Associations Between Food Insecurity and Fibroblast Growth Factor 23 (FGF23) in The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Introduction: Elevated Fibroblast Growth Factor 23 (FGF23) - an endocrine hormone linked to cardiovascular and kidney disease outcomes - is a compensatory response to high dietary phosphate load or chronic kidney disease. Large quantities of inorganic phosphates additives are found in processed foods, and food insecurity is associated with higher consumption of processed foods. Hypothesis: We hypothesized that developing food insecurity is associated with an increase in FGF23. Methods: We included CARDIA study participants with a stored plasma sample available from at least two consecutive exams at years 20, 25, and 30 (N=3,421). Food insecurity was assessed through a single question about ability to afford quantity and quality of food. FGF23 levels were assessed using a commercial c-terminal ELISA. Due to a strong right skew in FGF23 levels, we divided FGF23 in quartiles and compared the highest quartile to the combined lower three quartiles using logistic regression. Econometric fixed effects models that adjust by design for all time-invariant covariates were used to model the longitudinal association between simultaneous within-person change in food insecurity and FGF23. Due to an interaction between food insecurity and race ( p =0.002), we stratified by race. Results: About 29% of blacks and 14% of whites experienced change in food insecurity during follow-up. Developing food insecurity was associated with a 1.46 greater odds of increasing to the highest quartile of FGF23 (95% CI: 1.02,2.10) among blacks; however, there was no significant longitudinal association among whites (OR=1.05; 95% CI: 0.62,1.77). Conclusions: Using models that tightly control for all time-invariant confounding, we found that developing food insecurity was associated with increases in FGF23 among blacks. The differential increases in blacks as compared to whites may be due to differences in dietary changes in response to developing food insecurity. Previous research has shown racial differences in dietary quality by food insecurity.

Stratégies visant à réduire la phosphatémie dans la maladie rénale chronique

Chronic kidney disease is known to be associated with phosphate retention. The mechanisms are complex and the early increase in serum phosphate levels in chronic kidney disease is not strictly related to the dietary phosphate load or to the degree of phosphate retention. It also implicates the activity of intestinal sodium–phosphate cotransporters, the degree of bone turnover and the retention and/or phosphate release from the skeleton, and the feedback mechanisms regulating the phosphaturia. Indeed, the increase in serum phosphate levels is only a reflection of underlying complex mechanisms, and many important factors play a role including parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23), and others. Hyperphosphatemia increases the risk of cardiovascular morbidity and mortality in chronic kidney disease as well as in subjects with normal renal function. Oral phosphate binders are prescribed in patients with chronic kidney disease and in those treated by dialysis, to prevent intestinal absorption of dietary phosphate and reduce serum phosphate. In prospective observational studies, they have been shown to decrease all-cause and cardiovascular mortality risk. However, different problems have been associated with currently available phosphate binders including the induction of a positive calcium balance and impaired outcomes with calcium-based phosphate binders or increased costs with non-calcium-based phosphate binders. Iron-based phosphate binders represent a new class of phosphate binders. The aim of this article is to provide an update review of the pathophysiological mechanisms leading and maintaining elevated serum phosphate levels in patients with chronic kidney disease and patients in dialysis, and the educational, nutritional, and therapeutic strategies that can be undertaken to control the hyperphosphatemia.

Concordance of dietary sodium intake and concomitant phosphate load: Implications for sodium interventions

Background and aimsBoth a high dietary sodium and high phosphate load are associated with an increased cardiovascular risk in patients with chronic kidney disease (CKD), and possibly also in non-CKD populations. Sodium and phosphate are abundantly present in processed food. We hypothesized that (modulation of) dietary sodium is accompanied by changes in phosphate load across populations with normal and impaired renal function. Methods and ResultsWe first investigated the association between sodium and phosphate load in 24-h urine samples from healthy controls (n = 252), patients with type 2 diabetes mellitus (DM, n = 255) and renal transplant recipients (RTR, n = 705). Secondly, we assessed the effect of sodium restriction on phosphate excretion in a nondiabetic CKD cohort (ND-CKD: n = 43) and a diabetic CKD cohort (D-CKD: n = 39). Sodium excretion correlated with phosphate excretion in healthy controls (R = 0.386, P < 0.001), DM (R = 0.490, P < 0.001), and RTR (R = 0.519, P < 0.001). This correlation was also present during regular sodium intake in the intervention studies (ND-CKD: R = 0.491, P < 0.001; D-CKD: R = 0.729, P < 0.001). In multivariable regression analysis, sodium excretion remained significantly correlated with phosphate excretion after adjustment for age, gender, BMI, and eGFR in all observational cohorts. In ND-CKD and D-CKD moderate sodium restriction reduced phosphate excretion (31 ± 10 to 28 ± 10 mmol/d; P = 0.04 and 26 ± 11 to 23 ± 9 mmol/d; P = 0.02 respectively). ConclusionsDietary exposure to sodium and phosphate are correlated across the spectrum of renal function impairment. The concomitant reduction in phosphate intake accompanying sodium restriction underlines the off-target effects on other nutritional components, which may contribute to the beneficial cardiovascular effects of sodium restriction.(f) Registration numbers: Dutch Trial Register NTR675, NTR2366.

Moderator's view: Phosphate binders in chronic kidney disease patients: a clear ‘No’ at the moment, but stay tuned

Particularly because the risk of harm cannot be safely excluded, the use of phosphate binders in chronic kidney disease (CKD) patients demands caution. Yet, the clinical inertia concerning phosphate burden is unjustified. Inorganic, phosphate esters added to preserve food represent an important component of dietary phosphate load. These compounds are easily absorbable and have a measurable effect on serum phosphate, and therefore their use should be avoided in CKD patients. The ongoing CKD Optimal management with Binders and NicotinamidE (COMBINE) study, applying chelation by phosphate binders and intestinal Na-P channel blockade by nicotinamide, will establish whether this combination may effectively reduce serum phosphate and fibroblast growth factor 23 in pre-dialysis CKD patients and produce improvements in surrogate measures of cardiovascular and renal damages. On the other hand, the ANSWER study will ascertain whether phosphate reduction by sevelamer carbonate may have an antiproteinuric effect in CKD patients with residual proteinuria despite effective blockade of the renin-angiotensin system. At this stage of knowledge, the use of phosphate binders in pre-dialysis CKD patients cannot be recommended. Ongoing studies will tell us whether the application of these drugs may have beneficial health effects in CKD patients at the pre-dialysis stage.

High Dietary Phosphate Intake Induces Development of Ectopic Calcifications in a Murine Model of Familial Tumoral Calcinosis

Familial tumoral calcinosis is characterized by ectopic calcifications due to persistent hyperphosphatemia. The most common genetic cause of the disease is mutations in GALNT3, encoding a glycosyltransferase involved in a posttranslational modification of fibroblast growth factor 23 (FGF23). The Galnt3 knockout mouse we developed was hyperphosphatemic due to low intact Fgf23 levels, but did not develop any apparent calcifications on a standard rodent diet. We therefore tested the hypothesis that a further challenge with a high phosphate diet could induce ectopic calcifications in Galnt3 knockout mice. Mice were fed either normal (0.6%) or high (1.65%) phosphate diet for 20 weeks beginning from weaning at 3 weeks. The high phosphate diet did not affect serum phosphorus concentration. However, regardless of the dietary phosphate contents, serum phosphorus levels were consistently elevated in Galnt3 knockout mice. The mice on the high phosphate diet had slightly low serum calcium, but significantly high alkaline phosphatase, parathyroid hormone (PTH), and calcium in the kidney. Although none of Galnt3 knockout mice on the normal phosphate diet developed calcifications, calcifications appeared in approximately one-half of the mice on the high phosphate diet by 12 weeks. Calcified masses were most often found around the neck and on the back and as large as 9.9 mm in length. These data indicate that dietary phosphate load has major impact on the development of ectopic calcifications in tumoral calcinosis.

Sevelamer Hydrochloride Binds Phosphate Released from Phytate in Chicks Fed 1α-Hydroxy Cholecalciferol

Hyperphosphatemia in animal models of human renal disease has been linked to increased risk of death. Phosphate binders (e.g., sevelamer hydrochloride) and plant-based, low phosphate diets are used to reduce dietary phosphate load; however, animal models show that treatment with active forms of vitamin D(3) (e.g., calcitriol, a renal disease therapy) renders plant phytate phosphate available for absorption. Using an established chick model, the effectiveness of sevelamer in preventing the apparent absorption of liberated phytate phosphate during active vitamin D use was investigated in two separate experiments. One-day-old chicks were fed ad libitum a basal diet containing deficient levels of inorganic phosphate (0.13%), but adequate in total phosphate (0.40%, 0.23% as phytate phosphate), with or without the inclusion of sevelamer hydrochloride (a phosphate binder), available inorganic phosphate, or active vitamin D as 1α-(OH) D(3). Plasma phosphate (mg/dL), total bone ash (%), and weight gain (g). Adding inorganic phosphate (0.36%) or 1α-(OH) D(3) increased plasma phosphate 49% and 48%, respectively (P < .0001), and bone ash 23% and 19%, respectively (P < .001). The addition of 1% sevelamer to the basal diet with added inorganic phosphate or 1α-(OH) D(3) significantly decreased plasma phosphate by 28% and 20%, respectively (P < .01). Active vitamin D increased the availability of phytate phosphate for intestinal absorption in an animal model; however, sevelamer effectively reduced the availability of phosphate liberated from phytate. These data imply that sevelamer has phytate phosphate binding efficacy.

Phosphate homeostasis and the renal-gastrointestinal axis

Transport of phosphate across intestinal and renal epithelia is essential for normal phosphate balance, yet we know less about the mechanisms and regulation of intestinal phosphate absorption than we do about phosphate handling by the kidney. Recent studies have provided strong evidence that the sodium-phosphate cotransporter NaPi-IIb is responsible for sodium-dependent phosphate absorption by the small intestine, and it might be that this protein can link changes in dietary phosphate to altered renal phosphate excretion to maintain phosphate balance. Evidence is also emerging that specific regions of the small intestine adapt differently to acute or chronic changes in dietary phosphate load and that phosphatonins inhibit both renal and intestinal phosphate transport. This review summarizes our current understanding of the mechanisms and control of intestinal phosphate absorption and how it may be related to renal phosphate reabsorption; it also considers the ways in which the gut could be targeted to prevent, or limit, hyperphosphatemia in chronic and end-stage renal failure.

Fibroblast growth factor 23: the making of a hormone

Fibroblast growth factor 23 (FGF23) modulates serum phosphate and 1alpha,25-dihydroxyvitamin D3 levels. FGF23 expression is in turn regulated by 1alpha,25-dihydroxyvitamin D3 and dietary phosphate load, and is strikingly elevated during renal progression. In this issue, Nagano and colleagues report that FGF23 can be modulated by intermittently high dietary phosphate in the presence of compromised renal function.

Distinctive features of dietary phosphate supply

Dietary phosphate has profound effects on growth and renal handling of the compound. On the basis of changes in growth rate and food intake, after alterations in phosphate load, our laboratory previously suggested that these effects are mediated by intestinal signals (Landsman A, Lichtstein D, Bacaner M, and Ilani A. Br J Nutr 86: 217-223, 2001). The aim of this study was to further evaluate the role of dietary phosphate on food intake and appetite and specific organ growth, and to test for the presence of a serum factor that may affect renal phosphate handling in phosphate-resupplied rats. The experimental design was based on a comparison between groups of rats receiving identical low-phosphate diets but drinking water containing either phosphate or chloride. We show that 1) changes in food intake after alterations in phosphate load occurred in parallel with variations in digestive system distention, suggesting that dietary phosphate has also a direct effect on appetite; 2) dietary phosphate-dependent growth has a specific effect on the growth of liver and epididymal fat; and 3) serum of rats supplied with phosphate contains a factor that inhibits sodium-dependent phosphate transport in a model of renal proximal tubule cells. Collectively, these observations are in accord with the hypothesis that factor(s) emanating from the digestive system in response to dietary phosphate load may be involved in growth, appetite and renal handling of phosphate.

Length of interdialytic interval influences serum calcium and phosphorus concentrations

Higher levels of serum phosphorus and calcium are associated with increased haemodialysis (HD) patient mortality. Both of these factors act synergistically to promote vascular smooth muscle differentiation to an osteoblast-like phenotype and subsequent vascular calcification. The aim of this study was to investigate the influence of interdialytic interval on serum levels, as well as the influence of oral calcium-based phosphate binder load on the magnitude of the observed differences. We studied 100 patients undergoing HD three times per week, over a 2 week period. Haemoglobin, albumin, calcium and phosphate were measured pre-dialysis before each HD session. Oral phosphate binder usage was recorded. All patients were treated with dialysate containing 1.25 mEq/l calcium. Both mean serum phosphate and calcium were higher after the long interdialytic interval (1.59+/-0.05 vs 1.45+/-0.04 mmol/l, P = 0.0005, and 2.46+/-0.03 vs 2.4+/-0.02 mmol/l, P = 0.001, for serum phosphate and uncorrected calcium, respectively). There were no significant differences in haemoglobin or serum albumin, indicating that variable dilution from an increased hydration status in the long interdialytic interval was unlikely to contribute to these observed differences. A total of 74 patients were treated with calcium-containing binders and 26 patients with sevelamer. Patients on sevelamer did not exhibit the observed cyclical increase in serum calcium seen in patients on calcium-containing binders (mean difference in serum calcium 0.09+/-0.01 mmol/l in the calcium-treated group vs 0.01+/-0.01 mmol/l in the sevelamer-treated patients, P = 0.0004). The increase in serum calcium after the long interval as compared with the short interval was proportional to the daily amount of the oral calcium-containing binder load ingested (r = 0.63, P<0.0001). Cyclical differences in interdialytic interval and overall exposure to both dietary phosphate and oral calcium load influence serum levels. This may have consequences for registry reporting, therapy modulation and potentially the pathogenesis of accelerated vascular calcification seen in HD patients.

Dietary habits and counseling focused on phosphate intake in hemodialysis patients with hyperphosphatemia

To evaluate the dietary habits of hemodialysis patients with hyperphosphatemia and the effects of a dietetic intervention focused on limiting dietary phosphate load. Cross-sectional dietary evaluation and prospective intervention study. Hospital hemodialysis units of Pisa and Pistoia, Italy. Subjects Forty-three stable adult hemodialysis patients, 20 of whom had phosphorus serum levels >5.5 mg/dL. Analysis of dietary composition and of the effects of individual dietetic counseling in an attempt to reduce phosphorus intake while preserving the same protein intake. Differences in nutrient intake between normophosphatemic and hyperphosphatemic patients, and changes in dietary phosphorus and phosphorus-protein ratio, serum phosphate, and calcium-phosphate product after dietetic intervention. No major differences in nutrient intake were detected between hyperphosphatemia and normophosphatemia patients, apart from a lower phosphorus-protein ratio (13.1 +/- 1.7 versus 14.1 +/- 2.1 mg/g, P < .05) in the former. After dietetic intervention in the hyperphosphatemia patients, phosphate and calcium intake decreased significantly (by 100 mg on average), whereas dietary protein did not change. A further decrease of the dietary phosphate-protein ratio (12.5 +/- 1.8 mg/g, P < .05) also occurred. Serum phosphate showed a trend to decrease in the intervention group, whereas the serum calcium-phosphate product decreased significantly (from 66.8 +/- 13.1 to 61.0 +/- 13.8 mg2 /dL2 , P < .05). In compliant and motivated patients, individual dietetic counseling may be useful in reducing phosphate load and in limiting the phosphate burden related to an adequate protein intake, with a potentially favorable impact on calcium-phosphate retention. A phosphate-controlled diet has a role in an integrated therapeutic approach to hyperphosphatemia and positive calcium-phosphorus balance in hemodialysis patients.

Dietary habits and counseling focused on phosphate intake in hemodialysis patients with hyperphosphatemia

ObjectiveTo evaluate the dietary habits of hemodialysis patients with hyperphosphatemia and the effects of a dietetic intervention focused on limiting dietary phosphate load.DesignCross-sectional dietary evaluation and prospective intervention study.SettingHospital hemodialysis units of Pisa and Pistoia, Italy.SubjectsForty-three stable adult hemodialysis patients, 20 of whom had phosphorus serum levels >5.5 mg/dL.InterventionAnalysis of dietary composition and of the effects of individual dietetic counseling in an attempt to reduce phosphorus intake while preserving the same protein intake.Main outcome measuresDifferences in nutrient intake between normophosphatemic and hyperphosphatemic patients, and changes in dietary phosphorus and phosphorus-protein ratio, serum phosphate, and calcium-phosphate product after dietetic intervention.ResultsNo major differences in nutrient intake were detected between hyperphosphatemia and normophosphatemia patients, apart from a lower phosphorus-protein ratio (13.1 ± 1.7 versus 14.1 ± 2.1 mg/g, P < .05) in the former. After dietetic intervention in the hyperphosphatemia patients, phosphate and calcium intake decreased significantly (by 100 mg on average), whereas dietary protein did not change. A further decrease of the dietary phosphate-protein ratio (12.5 ± 1.8 mg/g, P < .05) also occurred. Serum phosphate showed a trend to decrease in the intervention group, whereas the serum calcium-phosphate product decreased significantly (from 66.8 ± 13.1 to 61.0 ± 13.8 mg2/dL2, P < .05).ConclusionsIn compliant and motivated patients, individual dietetic counseling may be useful in reducing phosphate load and in limiting the phosphate burden related to an adequate protein intake, with a potentially favorable impact on calcium-phosphate retention. A phosphate-controlled diet has a role in an integrated therapeutic approach to hyperphosphatemia and positive calcium-phosphorus balance in hemodialysis patients. To evaluate the dietary habits of hemodialysis patients with hyperphosphatemia and the effects of a dietetic intervention focused on limiting dietary phosphate load. Cross-sectional dietary evaluation and prospective intervention study. Hospital hemodialysis units of Pisa and Pistoia, Italy. Forty-three stable adult hemodialysis patients, 20 of whom had phosphorus serum levels >5.5 mg/dL. Analysis of dietary composition and of the effects of individual dietetic counseling in an attempt to reduce phosphorus intake while preserving the same protein intake. Differences in nutrient intake between normophosphatemic and hyperphosphatemic patients, and changes in dietary phosphorus and phosphorus-protein ratio, serum phosphate, and calcium-phosphate product after dietetic intervention. No major differences in nutrient intake were detected between hyperphosphatemia and normophosphatemia patients, apart from a lower phosphorus-protein ratio (13.1 ± 1.7 versus 14.1 ± 2.1 mg/g, P < .05) in the former. After dietetic intervention in the hyperphosphatemia patients, phosphate and calcium intake decreased significantly (by 100 mg on average), whereas dietary protein did not change. A further decrease of the dietary phosphate-protein ratio (12.5 ± 1.8 mg/g, P < .05) also occurred. Serum phosphate showed a trend to decrease in the intervention group, whereas the serum calcium-phosphate product decreased significantly (from 66.8 ± 13.1 to 61.0 ± 13.8 mg2/dL2, P < .05). In compliant and motivated patients, individual dietetic counseling may be useful in reducing phosphate load and in limiting the phosphate burden related to an adequate protein intake, with a potentially favorable impact on calcium-phosphate retention. A phosphate-controlled diet has a role in an integrated therapeutic approach to hyperphosphatemia and positive calcium-phosphorus balance in hemodialysis patients.