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Kidney International May 2018Hyperphosphatemia has consistently been shown to be associated with dismal outcome in a wide variety of populations, particularly in chronic kidney disease (CKD).... (Review)
Review
Hyperphosphatemia has consistently been shown to be associated with dismal outcome in a wide variety of populations, particularly in chronic kidney disease (CKD). Compelling evidence from basic and animal studies elucidated a range of mechanisms by which phosphate may exert its pathological effects and motivated interventions to treat hyperphosphatemia. These interventions consisted of dietary modifications and phosphate binders. However, the beneficial effects of these treatment methods on hard clinical outcomes have not been convincingly demonstrated in prospective clinical trials. In addition, exposure to high amounts of dietary phosphate may exert untoward actions even in the absence of overt hyperphosphatemia. Based on this concept, it has been proposed that the same interventions used in CKD patients with normal phosphate concentrations be used in the presence of hyperphosphatemia to prevent rise of phosphate concentration and as an early intervention for cardiovascular risk. This review describes conceptual models of phosphate toxicity, summarizes the evidence base for treatment and prevention of hyperphosphatemia, and identifies important knowledge gaps in the field.
Topics: Animals; Biomarkers; Chelating Agents; Humans; Hyperphosphatemia; Phosphates; Phosphorus, Dietary; Recommended Dietary Allowances; Renal Insufficiency, Chronic; Risk Factors; Risk Reduction Behavior; Treatment Outcome
PubMed: 29580635
DOI: 10.1016/j.kint.2017.11.036 -
Annual Review of Nutrition Aug 2017Although phosphorus is an essential nutrient required for multiple physiological functions, recent research raises concerns that high phosphorus intake could have... (Review)
Review
Although phosphorus is an essential nutrient required for multiple physiological functions, recent research raises concerns that high phosphorus intake could have detrimental effects on health. Phosphorus is abundant in the food supply of developed countries, occurring naturally in protein-rich foods and as an additive in processed foods. High phosphorus intake can cause vascular and renal calcification, renal tubular injury, and premature death in multiple animal models. Small studies in human suggest that high phosphorus intake may result in positive phosphorus balance and correlate with renal calcification and albuminuria. Although serum phosphorus is strongly associated with cardiovascular disease, progression of kidney disease, and death, limited data exist linking high phosphorus intake directly to adverse clinical outcomes. Further prospective studies are needed to determine whether phosphorus intake is a modifiable risk factor for kidney disease.
Topics: Animals; Diet, Western; Humans; Kidney; Phosphorus, Dietary; Renal Insufficiency, Chronic
PubMed: 28613982
DOI: 10.1146/annurev-nutr-071816-064607 -
Nutrients Apr 2021Phosphate is a key uremic toxin associated with adverse outcomes. As chronic kidney disease (CKD) progresses, the kidney capacity to excrete excess dietary phosphate... (Review)
Review
Phosphate is a key uremic toxin associated with adverse outcomes. As chronic kidney disease (CKD) progresses, the kidney capacity to excrete excess dietary phosphate decreases, triggering compensatory endocrine responses that drive CKD-mineral and bone disorder (CKD-MBD). Eventually, hyperphosphatemia develops, and low phosphate diet and phosphate binders are prescribed. Recent data have identified a potential role of the gut microbiota in mineral bone disorders. Thus, parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched in the Th17 cell-inducing taxa segmented filamentous bacteria. Furthermore, the microbiota was required for PTH to stimulate bone formation and increase bone mass, and this was dependent on bacterial production of the short-chain fatty acid butyrate. We review current knowledge on the relationship between phosphate, microbiota and CKD-MBD. Topics include microbial bioactive compounds of special interest in CKD, the impact of dietary phosphate and phosphate binders on the gut microbiota, the modulation of CKD-MBD by the microbiota and the potential therapeutic use of microbiota to treat CKD-MBD through the clinical translation of concepts from other fields of science such as the optimization of phosphorus utilization and the use of phosphate-accumulating organisms.
Topics: Animals; Chelating Agents; Chronic Kidney Disease-Mineral and Bone Disorder; Disease Models, Animal; Disease Progression; Gastrointestinal Microbiome; Holistic Health; Humans; Hyperphosphatemia; Mice; Parathyroid Hormone; Phosphorus, Dietary; Probiotics; Renal Insufficiency, Chronic; Th17 Cells
PubMed: 33924419
DOI: 10.3390/nu13041273 -
Frontiers in Veterinary Science 2021The sustainability of animal production relies on the judicious use of phosphorus (P). Phosphate, the mined source of agricultural phosphorus supplements, is a... (Review)
Review
The sustainability of animal production relies on the judicious use of phosphorus (P). Phosphate, the mined source of agricultural phosphorus supplements, is a non-renewable resource, but phosphorus is essential for animal growth, health, and well-being. P must be provided by efficient and sustainable means that minimize the phosphorus footprint of livestock production by developing precise assessment of the bioavailability of dietary P using robust models. About 60% of the phosphorus in an animal's body occurs in bone at a fixed ratio with calcium (Ca) and the rest is found in muscle. The P and Ca requirements must be estimated together; they cannot be dissociated. While precise assessment of P and Ca requirements is important for animal well-being, it can also help to mitigate the environmental effects of pig farming. These strategies refer to multicriteria approaches of modeling, efficient use of the new generations of phytase, depletion and repletion strategies to prime the animal to be more efficient, and finally combining these strategies into a precision feeding model that provides daily tailored diets for individuals. The industry will need to use strategies such as these to ensure a sustainable plant-animal-soil system and an efficient P cycle.
PubMed: 34901241
DOI: 10.3389/fvets.2021.734365 -
Nutrients Sep 2020Inorganic phosphate (P) plays a critical function in many tissues of the body: for example, as part of the hydroxyapatite in the skeleton and as a substrate for ATP... (Review)
Review
Inorganic phosphate (P) plays a critical function in many tissues of the body: for example, as part of the hydroxyapatite in the skeleton and as a substrate for ATP synthesis. P is the main source of dietary phosphorus. Reduced bioavailability of P or excessive losses in the urine causes rickets and osteomalacia. While critical for health in normal amounts, dietary phosphorus is plentiful in the Western diet and is often added to foods as a preservative. This abundance of phosphorus may reduce longevity due to metabolic changes and tissue calcifications. In this review, we examine how dietary phosphorus is absorbed in the gut, current knowledge about P sensing, and endocrine regulation of P levels. Moreover, we also examine the roles of P in different tissues, the consequences of low and high dietary phosphorus in these tissues, and the implications for healthy aging.
Topics: Biological Availability; Bone and Bones; Healthy Aging; Humans; Phosphates; Phosphorus, Dietary
PubMed: 33007883
DOI: 10.3390/nu12103001 -
The American Journal of Clinical... Feb 2022Recent observational studies have suggested that circulating phosphorus concentrations are positively associated with the risk of prostate cancer. However, little is...
BACKGROUND
Recent observational studies have suggested that circulating phosphorus concentrations are positively associated with the risk of prostate cancer. However, little is known about the causal direction of the association.
OBJECTIVES
To explore the potential causal relation between circulating phosphorus and risk of prostate cancer, we conducted a Mendelian randomization (MR) study.
METHODS
Summary statistics of prostate cancer were obtained from a meta-analysis of genome-wide association studies (GWASs) consisting of 79,148 cases and 61,106 controls. Single-nucleotide polymorphisms (SNPs) associated with serum phosphorus concentration were selected from a GWAS of 291,408 individuals from the UK Biobank. MR analysis was performed using the inverse variance weighted (IVW) method, supplemented with simple median method, weighted median method, maximum likelihood-based method, MR-Egger regression, and the MR pleiotropy residual sum and outlier test. We also performed a meta-analysis of observational studies to assess the associations of dietary phosphorus intake and serum phosphorus concentration with risk of prostate cancer.
RESULTS
In the MR analysis, a total of 125 independent SNPs associated with serum phosphorus concentrations were used as instrumental variables. Genetically predicted serum phosphorus concentrations were associated with a 19% increased risk of prostate cancer (95% CI: 9%, 31%) per 1-SD increment of serum phosphorus by IVW (P = 1.82 × 10-4). Sensitivity analyses using alternative MR methods produced similar positive associations, and no evidence of pleiotropy was detected by MR-Egger regression (P = 0.422). For meta-analysis, 8 studies for dietary phosphorus intake and 4 for serum phosphorus concentrations were included involving a total of 669,080 participants. Consistently, high dietary phosphorus intake and serum phosphorus concentrations were associated with an 8% (95% CI: 4%, 12%) and 7% (95% CI: 1%, 14%) increase in prostate cancer risk, respectively.
CONCLUSIONS
Our study suggested a potential causal relation between circulating phosphorus and risk of prostate cancer. Further studies are warranted to elucidate the underlying mechanism of phosphorus in the development of prostate cancer.
Topics: Biomarkers, Tumor; Genome-Wide Association Study; Humans; Likelihood Functions; Male; Mendelian Randomization Analysis; Meta-Analysis as Topic; Phosphorus; Polymorphism, Single Nucleotide; Prostatic Neoplasms
PubMed: 34617559
DOI: 10.1093/ajcn/nqab342 -
Clinical Journal of the American... Oct 2019
Topics: Cross-Over Studies; Diet; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Phosphates; Phosphorus, Dietary; Renal Dialysis
PubMed: 31519551
DOI: 10.2215/CJN.09640819 -
American Journal of Hematology May 2021Phosphorus has an essential role in cellular and extracellular metabolism; maintenance of normal phosphorus homeostasis is critical. Phosphorus homeostasis can be... (Review)
Review
Phosphorus has an essential role in cellular and extracellular metabolism; maintenance of normal phosphorus homeostasis is critical. Phosphorus homeostasis can be affected by diet and certain medications; some intravenous iron formulations can induce renal phosphate excretion and hypophosphatemia, likely through increasing serum concentrations of intact fibroblast growth factor 23. Case studies provide insights into two types of hypophosphatemia: acute symptomatic and chronic hypophosphatemia, while considering the role of pre-existing conditions and comorbidities, medications, and intravenous iron. This review examines phosphorus homeostasis and hypophosphatemia, with emphasis on effects of iron deficiency and iron replacement using intravenous iron formulations.
Topics: Anemia, Hypochromic; Calcitriol; Ferric Compounds; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Homeostasis; Humans; Hypophosphatemia; Infusions, Parenteral; Iron; Iron Deficiencies; Kidney; Malabsorption Syndromes; Maltose; Osteomalacia; Parathyroid Hormone; Phosphorus; Phosphorus, Dietary
PubMed: 33471363
DOI: 10.1002/ajh.26100 -
Nutrients Sep 2018Chronic kidney disease (CKD) affects approximately 10% of adults worldwide. Dysregulation of phosphorus homeostasis which occurs in CKD leads to development of... (Review)
Review
Chronic kidney disease (CKD) affects approximately 10% of adults worldwide. Dysregulation of phosphorus homeostasis which occurs in CKD leads to development of CKD-Mineral Bone Disorder (CKD-MBD) and contributes to increased morbidity and mortality in these patients. Phosphorus is regulated by multiple hormones (parathyroid hormone (PTH), 1,25-dihyxdroxyvitamin D (1,25D), and fibroblast growth factor 23 (FGF23)) and tissues (kidney, intestine, parathyroid glands, and bone) to maintain homeostasis. In health, the kidneys are the major site of regulation for phosphorus homeostasis. However, as kidney function declines, the ability of the kidneys to adequately excrete phosphorus is reduced. The hormonal changes that occur with CKD would suggest that the intestine should compensate for impaired renal phosphorus excretion by reducing fractional intestinal phosphorus absorption. However, limited studies in CKD animal models and patients with CKD suggest that there may be a break in this homeostatic response where the intestine fails to compensate. As many existing therapies for phosphate management in CKD are aimed at reducing absolute intestinal phosphorus absorption, better understanding of the factors that influence fractional and absolute absorption, the mechanism by which intestinal phosphate absorption occurs, and how CKD modifies these is a much-needed area of study.
Topics: Animals; Bone Density; Bone Diseases; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Homeostasis; Humans; Intestinal Absorption; Intestines; Kidney; Malabsorption Syndromes; Parathyroid Hormone; Phosphorus; Phosphorus, Dietary; Renal Insufficiency, Chronic; Vitamin D
PubMed: 30249044
DOI: 10.3390/nu10101364 -
Scientific Reports May 2021Controversial results have been reported about the association of calcium, magnesium, and phosphorus and stroke risk, but none in China. To investigate the association...
Controversial results have been reported about the association of calcium, magnesium, and phosphorus and stroke risk, but none in China. To investigate the association between dietary calcium, magnesium, phosphorus, and stroke incidence in Chinese adults, we collected data from the China Health and Nutrition Survey (CHNS) from 2004 to 2011, including 6411 participants aged 45-79 years and free of stroke at baseline. Diet was assessed by interviews combining 3-d 24-h food recalls and household food inventory weighing at each survey round. The stroke incident was identified based on the validated self-report. Multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). For 32,024 person-years of follow-up, 179 stroke cases were documented. After adjustment for major lifestyle and dietary risk factors, calcium intake was positively associated with reduced stroke risk, and the HR of stroke comparing extreme quartiles was 0.53 (95% CI 0.29-0.96, P = 0.03). In further stratified analyses, significant heterogeneity across sex strata was found (P = 0.03). Dietary calcium intake among men was more inversely related to stroke, with HRs being 0.33 (95% CI 0.15-0.76, P = 0.02), compared to 1.24 (95% CI 0.46-3.35, P = 0.89) among women. However, no significant association between stroke and magnesium or phosphorus was revealed. Our findings suggest that higher dietary calcium intake was associated with a lower risk of stroke in Chinese adults, particularly in men.
Topics: Aged; Asian People; Calcium; Calcium, Dietary; China; Diet; Dietary Supplements; Female; Humans; Incidence; Magnesium; Male; Middle Aged; Nutrition Surveys; Nutritional Status; Phosphorus; Phosphorus, Dietary; Proportional Hazards Models; Retrospective Studies; Risk Factors; Stroke; Surveys and Questionnaires
PubMed: 34050206
DOI: 10.1038/s41598-021-90388-z