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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 -
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 -
Annals of the New York Academy of... Oct 2013High serum phosphate is linked to poor health outcome and mortality in chronic kidney disease (CKD) patients before or after the initiation of dialysis. Therefore,... (Review)
Review
High serum phosphate is linked to poor health outcome and mortality in chronic kidney disease (CKD) patients before or after the initiation of dialysis. Therefore, maintenance of normal serum phosphate levels is a major concern in the clinical care of this population with dietary phosphorus restriction and/or use of oral phosphate binders considered to be the best corrective care. This review discusses (1) evidence for an association between serum phosphate levels and bone and cardiovascular disease (CVD) in CKD patients as well as progression of kidney disease itself; (2) the relationship between serum phosphate and dietary phosphorus intake; and (3) implications from these data for future research. Increasing our understanding of the relationship between altered phosphorus metabolism and disease in CKD patients may clarify the potential role of excess dietary phosphorus as a risk factor for disease in the general population.
Topics: Atherosclerosis; Bone Diseases; Cardiovascular Diseases; Disease Progression; Humans; Hyperparathyroidism; Phosphates; Phosphorus, Dietary; Renal Insufficiency, Chronic
PubMed: 23876096
DOI: 10.1111/nyas.12201 -
Annals of the New York Academy of... Oct 2013Recent epidemiologic studies have linked higher serum phosphorus concentrations to cardiovascular disease (CVD) events and mortality. This association has been... (Review)
Review
Recent epidemiologic studies have linked higher serum phosphorus concentrations to cardiovascular disease (CVD) events and mortality. This association has been identified in the general population and in those with chronic kidney disease (CKD). The risk of adverse outcomes appears to begin with phosphorus concentrations within the upper limit of the normal reference range. Multiple experimental studies have suggested pathogenetic mechanisms that involve direct and indirect effects of high phosphorus concentrations to explain these associations. Drawing from these observations, guideline-forming agencies have recommended that serum phosphorus concentrations be maintained within the normal reference range in patients with CKD and that dietary phosphorus restriction or use of intestinal phosphate binders should be considered to achieve this goal. However, outside the dialysis population, the links between dietary phosphorus intake and serum phosphorus concentrations, and dietary phosphorus intake and CVD events, are uncertain. With specific reference to the nondialysis populations, this review discusses the available data linking dietary phosphorus intake with serum phosphorus concentrations and CVD events.
Topics: Cardiovascular Diseases; Humans; Phosphates; Phosphorus, Dietary; Renal Insufficiency, Chronic
PubMed: 24117725
DOI: 10.1111/nyas.12283 -
The American Journal of Clinical... Feb 2014
Topics: Cardiovascular Diseases; Female; Humans; Male; Mortality; Nutrition Surveys; Phosphorus, Dietary
PubMed: 24381089
DOI: 10.3945/ajcn.113.080259 -
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 -
Nutrients Sep 2022Dietary phosphorus restrictions are usually recommended for people on haemodialysis, although its impact on patient-relevant outcomes is uncertain. We aimed to evaluate...
Dietary phosphorus restrictions are usually recommended for people on haemodialysis, although its impact on patient-relevant outcomes is uncertain. We aimed to evaluate the association between total phosphorus intake and its sources with mortality in haemodialysis. Phosphorus intake was ascertained within the DIET-HD study in 8110 adults on haemodialysis. Adjusted Cox regression analyses were conducted to evaluate the association between the total and source-specific phosphorus (plant-, animal-, or processed and other sources) with mortality. During a median 3.8 years of follow-up, there were 2953 deaths, 1160 cardiovascular-related. The median phosphorus intake was 1388 mg/day. Every standard deviation (SD) (896 mg/day) increase in total phosphorus was associated with higher all-cause mortality [hazard ratio (HR), 1.16; 95% confidence intervals (CI), 1.06-1.26] and cardiovascular mortality (HR, 1.18; 95% CI, 1.03-1.36). Every SD (17%) increase in the proportion of phosphorus from plant sources was associated with lower all-cause mortality (HR, 0.95; 95% CI, 0.90-0.99). Every SD (9%) increase in the proportion of phosphorus from the processed and other sources was associated with higher all-cause mortality (HR, 1.06; 95% CI, 1.02-1.10). A higher total phosphorus intake was associated with increased all-cause and cardiovascular death. This association is driven largely by the phosphorus intake from processed food. Plant based phosphorus was associated with lower all-cause mortality.
Topics: Animals; Cardiovascular Diseases; Diet; Phosphorus; Phosphorus, Dietary; Prospective Studies; Renal Dialysis; Risk Factors
PubMed: 36235716
DOI: 10.3390/nu14194064 -
Advances in Nutrition (Bethesda, Md.) Jan 2014A major role of the kidneys is to maintain phosphorus homeostasis. High serum phosphorus has been linked to all-cause and cardiovascular mortality in chronic kidney... (Comparative Study)
Comparative Study Review
A major role of the kidneys is to maintain phosphorus homeostasis. High serum phosphorus has been linked to all-cause and cardiovascular mortality in chronic kidney disease (CKD) both before and after initiation of renal replacement therapy. Considering the clinical implications of uncontrolled hyperphosphatemia, maintenance of phosphorus concentrations within an optimum range is standard of care in this patient population. Recently, the epidemiologic associations between serum phosphorus and worse outcome have been extended to the general population. This becomes even more important in view of the increasing dietary phosphorus intake in the American diet due in large part to the greater consumption of foods processed with phosphate additives. A greater understanding of mechanisms and epidemiology of altered phosphorus metabolism and disease in CKD may help clarify the possible role of excess dietary phosphorus as a health risk factor in the general population.
Topics: Animals; Bone Resorption; Cardiovascular Diseases; Congresses as Topic; Evidence-Based Medicine; Food Additives; Food, Preserved; Humans; Hyperphosphatemia; Kidney; Models, Biological; Phosphorus, Dietary; Renal Insufficiency; Renal Insufficiency, Chronic
PubMed: 24425728
DOI: 10.3945/an.113.004655