High Phosphorus Intake Research Articles

Association of Intake of Whole Grains with Health Outcomes in the Chronic Renal Insufficiency Cohort Study.

Patients with chronic kidney disease (CKD) are encouraged to choose refined grains instead of whole grains as part of the low-phosphorus diet for managing chronic kidney disease-mineral and bone disorders (CKD-MBD). However, there is no direct evidence indicating that limiting whole grains has a beneficial impact on CKD outcomes. This study analyzed Chronic Renal Insufficiency Cohort data in two ways, namely cross-sectional examination of CKD-MBD biomarkers and prospective examination of health outcomes. A total of 4,067 (cross-sectional) and 4,331 (prospective) participants were included. The primary exposure was reported intake of whole grains (analyzed as servings/day, servings/1,000kcal, and refined grain servings/whole grain servings). CKD-MBD biomarkers included serum phosphorus, fibroblast growth factor-23, parathyroid hormone, calcitriol, and calcium. Outcomes included cardiovascular events, kidney failure, and all-cause mortality. In adjusted models, reported intake of whole grains was associated with higher phosphorus intake and serum phosphorus when assessed crudely (serving/day), but not when analyzed in relation to energy. Higher intake of refined grain relative to whole grains was associated (all models) with higher risk of kidney failure (Model 4: 1.01, 95% CI 1.00 to 1.02; P=0.01, all-cause mortality (Model 4: 1.01, 95% CI 1.00 to 1.01; P=0.01), and cardiovasulcar disease except for the fully adjusted model. Higher dietary density was associated with lower mortality in models adjusted for demographic and clinical factors including kidney function, but not in the fully adjusted model that futher adjusted for dietary factors. Intake of whole grains was not associated with CKD-MBD biomarkers. Intake of whole grains in relation to refined grains was associated with lower risk of cardiovascular disease, kidney failure, and mortality. The results of this study put into question the long-standing practice of restricting whole grains in patients with chronic kidney disease.

The Fate of Phosphate: Assessing Dietary Intake and Urinary Excretion in Swedish Adolescents

BackgroundA high total phosphorus (P) intake has been proposed to promote endothelial dysfunction and atherosclerosis. A diet rich in foods containing P additives could contribute to an excessive intake, potentially reflected as increased concentration of P in urine. ObjectivesThis study aimed to assess the intake of total dietary P, P additives, and its sources and examine their correlation with urinary P in a cross-sectional national study in Swedish adolescents. MethodsWe constructed a database of P additives and applied it to the foods consumed by 3099 participants in the representative school-based dietary survey Riksmaten Adolescents 2016–17. Intake of total dietary P and P additives were assessed using two 24-h recalls. Urinary P was analyzed in a subsample of 756 participants using inductively coupled plasma mass spectrometry. Spearman rank correlation (ρ) was used to assess the association between dietary P intake and urinary P excretion. ResultsThe mean (SD) intake of total P was 1538 (±667) mg/d. Food containing P additives were consumed by 92% of adolescents and the median (IQR) intake was 49 (22–97; range: 0.01–947) mg/d, corresponding to 5% (1%–6%; range: 0%–50%) of total P. The main contributing food to P additives was cola drinks, while the main contributing food group was sausage dishes. Total P intake was weakly correlated with urinary P (ρ = 0.12; P < 0.01) but not with intake of P additives. ConclusionsNearly, all participants consumed P additives, contributing to an average of 5% of total P intake but ranging up to 50%. The intake of total P, but not P additives, was weakly reflected in the urinary P. Access to more comprehensive information on P additives in foods would improve further evaluation of potential health consequences.

Dietary Phosphorus Levels Influence Protein-Derived Uremic Toxin Production in Nephrectomized Male Rats.

Gut microbiota-derived uremic toxins (UT) accumulate in patients with chronic kidney disease (CKD). Dietary phosphorus and protein restriction are common in CKD treatment, but the relationship between dietary phosphorus, a key nutrient for the gut microbiota, and protein-derived UT is poorly studied. Thus, we explored the relationship between dietary phosphorus and serum UT in CKD rats. For this exploratory study, we used serum samples from a larger study on the effects of dietary phosphorus on intestinal phosphorus absorption in nephrectomized (Nx, n = 22) or sham-operated (sham, n = 18) male Sprague Dawley rats. Rats were randomized to diet treatment groups of low or high phosphorus (0.1% or 1.2% w/w, respectively) for 1 week, with serum trimethylamine oxide (TMAO), indoxyl sulfate (IS), and p-cresol sulfate (pCS) analyzed by LC-MS. Nx rats had significantly higher levels of serum TMAO, IS, and pCS compared to sham rats (all p < 0.0001). IS showed a significant interaction between diet and CKD status, where serum IS was higher with the high-phosphorus diet in both Nx and sham rats, but to a greater extent in the Nx rats. Serum TMAO (p = 0.24) and pCS (p = 0.34) were not affected by dietary phosphorus levels. High dietary phosphorus intake for 1 week results in higher serum IS in both Nx and sham rats. The results of this exploratory study indicate that reducing dietary phosphorus intake in CKD may have beneficial effects on UT accumulation.

Higher Renal Net Acid Excretion, but Not Higher Phosphate Excretion, during Childhood and Adolescence Associates with the Circulating Renal Tubular Injury Marker Interleukin-18 in Adulthood.

High dietary phosphorus intake (P-In) and high acid loads may adversely affect kidney function. In animal models, excessive phosphorus intake causes renal injury, which, in humans, is also inducible by chronic metabolic acidosis. We thus examined whether habitually high P-In and endogenous acid production during childhood and adolescence may be early indicators of incipient renal inflammatory processes later in adulthood. P-In and acid-base status were longitudinally and exclusively determined by biomarker-based assessment in 277 healthy children, utilizing phosphate and net acid excretion (NAE) measurements in 24 h urine samples repeatedly collected between the ages of 3 and 17 years. Standard deviation scores (by sex and age) were calculated for anthropometric data and for the urinary biomarkers available within age range 3-17 years. Multivariable linear regression was used to analyze the relations of phosphate excretion and NAE with the adulthood outcome circulating interleukin-18 (IL-18), a marker of inflammation and kidney dysfunction. After adjusting for growth- and adulthood-related covariates and pro-inflammatory biomarkers to rule out confounding by non-renal inflammatory processes, regression models revealed a significant positive relationship of long-term NAE (p = 0.01), but not of long-term phosphate excretion with adult serum IL-18. Similar significant positive regression results were obtained after replacing NAE with 24 h urinary ammonium excretion as the exposition variable. Our results suggest that even moderate elevations in renal ammonia production, as caused by habitually higher acid loading during growth, may affect the intrarenal pro-inflammatory system in the long-term, known to be boosted by acidosis-induced raised ammoniagenesis.

Effects of a single phosphate-enriched test meal on inflammasome activity and postprandial inflammatory markers in healthy subjects.

The consumption of highly processed food is often associated with a high intake of inorganic phosphate. Hyperphosphatemia is accompanied by an inflammatory status in patients with chronic kidney disease. However, the immune response to high phosphorus intake in healthy individuals is largely unknown. Therefore, the aim of the present study was to evaluate the effect of a single phosphate-enriched meal on inflammasome activity and plasma levels of inflammatory markers. The analysis included 28 participants who received a single dose of either 700mg phosphorus or a placebo with a test meal. At baseline, 4 and 8h post-meal, plasma interleukin (IL)-6, IL-1β, IL-10, c-reactive protein (CRP), soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (sgp130) levels were determined. At baseline and 4h post-meal, peripheral blood mononuclear cells were isolated to assess inflammasome activity. Subsequently, the effect of phosphate with or without glucose on IL-6 and IL-1β gene expression and secretion in U937 monocytes was examined. While both groups showed a marked postprandial increase in IL-6 plasma levels, neither plasma levels of IL-6, IL-1β, CRP, IL-10, sIL-6R, and sgp130 nor inflammasome activity were affected by phosphate compared to placebo. In U937 cells, there was also no effect of phosphate on IL-6 expression, but the addition of glucose increased it. Phosphate, however, reduced the IL-1β secretion of these cells. Postprandial inflammatory markers were not affected by dietary phosphate. However, IL-6 plasma levels were markedly increased post-meal, which appears to be a metabolic rather than a pro-inflammatory phenomenon. ClinicalTrials.gov, NCT03771924, date of registration: 11th December 2018, retrospectively registered.

Nutrition and Aging in Dogs and Cats.

Aging is often associated with chronic inflammation and declining health. Both veterinarians and owners of aging dogs and cats are interested in nutritional solutions and strategies to prevent signs of age-related disease, increase longevity, and improve quality of life. Physiological decreases in muscle mass, decreased immunity, and a decrease in sense acuity are some of the changes often seen in otherwise healthy senior pets; however, there may also be an increase in risk for pathologies such as renal, cardiovascular, musculoskeletal, and neoplastic diseases. Aging may also lead to cognitive decline and even cognitive dysfunction. Some nutritional strategies that may be helpful with the prevention and treatment of age-related diseases include supplementation with ω3 polyunsaturated fatty acids and antioxidant nutrients that can help modulate inflammation and benefit osteoarthritis, renal disease, cancer, and more. Supplementation with medium-chain triglycerides shows promise in the treatment of canine cognitive dysfunction as these may be metabolized to ketone bodies that are utilized as analternative energy source for the central nervous system. Additionally, a high intake of dietary phosphorus in soluble and bioavailable forms can lead to renal disease, which is of greater concern in senior pets. There are no published guidelines for nutritional requirements specific to senior pets and as a result, products marketed for senior dogs and cats are highly variable.

Phosphorus - a scoping review for Nordic Nutrition Recommendations 2023.

This scoping review aims to describe the totality of evidence for the role of phosphorus for health-related outcomes as a basis for setting and updating dietary reference values (DRVs). Phosphorus is needed in many biological processes, such as cellular metabolism and bone mineralization. Dietary phosphorus intake exceeds the previous Nordic Nutrition Recommendations (NNR2012) 2-3-fold in the Nordic countries. Intake from food additives is unknown but may play a significant role because the use of phosphate additives is common in the food industry. Bioavailability of phosphorus in plant-based products is lower than animal-based products. Nevertheless, bioavailability of phosphorus additives is higher. The main phosphorus-related health outcomes concern high phosphorus intake mainly from food additives with potential adverse effects on kidney, bone, and cardiovascular health.

A multifaceted assessment of the nutritional status, diet and eating habits of midwives working on a shift schedule in Wrocław, Poland: evaluation of macronutrients, vitamins and minerals in the diets of midwives participating in the study.

The aim of the study was to assess the nutritional status and diet of midwives working on a shift schedule in public hospitals in Wrocław, Poland, and to analyze the variation in their diet according to their working hours (day shift, night shift) and on a non-working day. In the group of 50 midwives, employed in 4 public hospitals in Wrocław weight and body composition, waist and hip circumference, waist-hip-ratio and BMI were assessed. The nutritional habits and quality of the study participants' diets were assessed by 3-days food dietary recall, including 1 day shift day, 1 night shift day, and 1 non-working day. More than half of the subjects were assessed as having excess body weight (BMI ≥25 kg/m2). Thirty percent of participants had BMI ≥25-<30 kg/m2 and 24% BMI ≥30 kg/m2, 70% had a body fat percentage >30%. Fifty-six percent of the diets had an energy value <90% of the subject's total daily energy expenditure. Significantly higher energy value of diets on the night shift day compared to the morning shift day (1959.05±596.09 kcal vs. 1715.36±654.55 kcal, p = 0.01) were observed. The same relationship applied to cholesterol content (349.50±155.33 mg vs. 261.39±190.59 mg, p = 0.002). A high intake of phosphorus and sodium, exceeding the recommended dietary intake, was noticed. The occurrence of a night shift in the shift work schedule is an element of that model that may have a significant impact on the nutritional and health value of shift workers' diets. Therefore, it seems reasonable to implement nutritional education programs promoting healthy eating choices and habits during night work. Int J Occup Med Environ Health. 2023;36(5):618-31.

A High-Phosphorus Diet Moderately Alters the Lipidome and Transcriptome in the Skeletal Muscle of Adult Mice.

A high phosphorus intake has been associated with various metabolic disorders, including chronic kidney disease, cardiovascular disease, and osteoporosis. Recent studies have demonstrated the effects of dietary phosphorus on lipid and glucose metabolism. This study investigated the impact of a high-phosphorus diet on mouse skeletal muscle lipid composition and gene transcription. Adult male mice (n = 12/group) received either a diet with an adequate (0.3%) or a high (1.2%) phosphorus concentration for 6 weeks. The lipidome analysis showed that among the 17 analyzed lipid classes, the concentrations of three classes were reduced in the high phosphorus group compared to the adequate phosphorus group. These classes were phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and lysophosphatidylcholine (LPC) (p < 0.05). Out of the three hundred and twenty-three individual lipid species analyzed, forty-nine showed reduced concentrations, while three showed increased concentrations in the high phosphorus group compared to the adequate phosphorus group. The muscle transcriptome analysis identified 142 up- and 222 down-regulated transcripts in the high phosphorus group compared to the adequate phosphorus group. Gene set enrichment analysis identified that genes that were up-regulated in the high phosphorus group were linked to the gene ontology terms "mitochondria" and "Notch signaling pathway", whereas genes that were down-regulated were linked to the "PI3K-AKT pathway". Overall, the effects of the high-phosphorus diet on the muscle lipidome and transcriptome were relatively modest, but consistently indicated an impact on lipid metabolism.

#4032 RAPAMYCIN AGGRAVATES KIDNEY LESIONS IN RATS FED HIGH PHOSPHATE

Abstract Background and Aims Rapamycin is currently used to prevent rejection after kidney transplantation. mTOR blockade by rapamycin may slow the progression of diabetic kidney disease. Rapamycin promotes phosphaturia by inhibiting renal tubular transport of phosphate. Excessive tubular load of phosphate produces kidney damage by inducing tubular injury and interstitial fibrosis. The aim of this work is to evaluate the effect of rapamycin on kidney pathology in rats fed different phosphate levels. Method Thirty four female Wistar rats were used in this experiment. Rats, aged 2 months at the beginning of the studies, were allotted to 6 groups (n = 4-6). Rats with intact renal function were fed a standard diet containing either nomal (0.6%, NP), low (0.2%, LP) or high (1.2%, HP) phosphate. Half of the groups received placebo treatment (NP, LP, HP) and the other half were treated with rapamycin (NP-Rapa, LP-Rapa, HP-Rapa) at a dose of 1.3 mg/kg/day, for 22 days. Plasma concentrations of urea, creatinine, and phosphate as well as urine creatinine and phosphate were measured by spectrophotometry. Microscopic evaluation of the kidneys was performed in tissue sections fixed with formaldehyde solution and embedded in paraffin. Kidney sections were stained with hematoxylin-eosin, Masson Trichrome, periodic acid Schiff, and Von Kossa staining. Thirty non overlapping fields were evaluated. Chronic interstitial fibrosis and renal calcification were measured with a point counting grid and the result was expressed in percentage. Atrophic tubules were counted and the result was expressed as number of atrophic tubuli/field. Values are expressed as the mean ± standard error (SE). The difference between means was assessed by ANOVA. Fisher LSD test was used as a post-hoc procedure. A correlation study was carried out using the Pearson test. p&amp;lt;0.05 was considered significant. Results Kidney lesions were more severe in rats treated with rapamycin and fed high phosphate diet. Areas of chronic interstitial fibrosis, with interstitial fibrosis and lymphoplasmacytic infiltrate, as well as atrophic tubules with thickened and wrinkled tubular basement membrane, loss of the brush border and flattening of the tubular cell cytoplasm, were observed. Calcification foci, mainly located in the corticomedullary junction, were identified with Von Kossa staining. Treatment with rapamycin did not influence renal function parameters in NP and LP rats but increased plasma creatinine and urea in HP rats. Plasma P concentration tended to decrease after rapamycin treatment. Fractional excretion of P was higher in all the groups treated with rapamycin, and the differences reached significance in HP-Rapa rats. Fractional excretion of P showed an excellent correlation with kidney lesions: chronic interstitial fibrosis (r = 0.822), calcification (r = 0.827) and tubular atrophy (r = 0.855). Conclusion The phosphaturic action of rapamycin aggravates renal lesions in rats fed high phosphate diets. Thus, rapamycin could be deleterious for the kidneys in the context of high phosphorus intake.

Abstract P210: Dietary Calcium and Phosphorus Intakes at Middle Age and Their Associations With Vascular Calcification at Older Age: The Atherosclerosis Risk in Communities (ARIC) Study

Background: High dietary calcium and phosphorus intakes may accelerate vascular calcification. A few studies have explored the association of dietary calcium and phosphorus intakes with vascular calcification but reported inconsistent results. Most studies relied on dietary assessment at one time point and evaluated only coronary artery calcification. Aim: To assess the associations of dietary calcium and phosphorus intakes over two time points during middle age with coronary artery and extra-coronary calcification at older age. Methods: We studied 1,940 ARIC participants who underwent chest CT scans at ≥75 years of age in 2018-19 and completed a 66-item food frequency questionnaire at two earlier visits (1987-89 and 1993-95). We calculated the average of dietary calcium and phosphorus intakes across these two visits. Calcification was quantified as Agatston score in coronary arteries, ascending aorta, descending aorta, aortic valve ring, aortic valve, and mitral valve. We ran multivariable linear (for continuous Agatston score) and logistic regression models (for Agatston score &gt;75 th percentile). Results: The mean dietary calcium and phosphorus intake was 659 mg/day and 1,074 mg/day, respectively. Overall, we did not observe any positive associations of dietary calcium intake with vascular/valvular calcification. Rather, we saw its inverse association with ascending aorta calcification (Figure). In contrast, dietary phosphorus was not associated with the calcification of any vascular beds. The results were largely similar in linear regression models and after excluding 332 participants (17%) taking calcium supplements. Conclusion: Dietary calcium intake at middle age was largely neutral in its association with vascular calcification while showing a mild inverse association with ascending aorta calcification at older age. No evident associations were seen for dietary phosphorus. Our findings do not support a concern that a calcium or phosphorus-rich diet may accelerate vascular calcification.

Acute High Dietary Phosphorus Following Low-Phosphorus Diet Acclimation Does Not Enhance Intestinal Fractional Phosphorus Absorption in Nephrectomized Male Rats.

Dietary phosphorus restriction and phosphorus binders are commonly prescribed for patients with chronic kidney disease (CKD). However, occurrences of non-adherence to these interventions are common. As low-phosphorus (LP) diets have been consistently experimentally shown in vitro to increase intestinal phosphorus absorption efficiency, a bout of non-adherence to diet or binders may cause an unintended consequence of enhanced intestinal phosphorus absorption. Thus, we aimed to determine the effect of a single bout of high-phosphorus (HP) intake after acclimation to a LP diet. Male Sprague Dawley rats with 5/6 nephrectomy (n=36) or sham operation (n=36) were block-randomized to 1 of 3 diets: LP (0.1% P w/w), HP (1.2%), or LP followed by acute HP (LPHP 0.1% then 1.2%). Phosphorus absorption tests were conducted using 33P radioisotope administrated by oral gavage or intravenously (iv). Although the overall two-way ANCOVA model for intestinal fractional phosphorus absorption was non-significant, exploratory comparisons showed intestinal fractional phosphorus absorption efficiency tended to be higher in rats in the LP compared with HP or LPHP groups. Rats in the HP or LPHP groups had higher plasma phosphorus compared with rats in the LP group, but the LPHP group was not different from the HP group. Gene expression of the major intestinal phosphate transporter, NaPi-2b, was lower in the jejunum of rats in the LPHP group compared with rats in the HP group but not different in the duodenum. These results demonstrate that an acute HP load after acclimation to a LP diet does not lead to enhanced intestinal fractional phosphorus absorption efficiency in 5/6 nephrectomized male rats. These data provide evidence against the notion that dietary phosphorus restriction or binder use adversely increases absorption efficiency after a single instance of dietary or binder non-adherence. However, other adverse consequences of fluctuating dietary phosphorus intake cannot be ruled out. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Acidified diet is not effective in preventing hypocalcemia in dairy cows on French commercial farms

The objective of this study was to assess, in the context of typical dairy farms in western France, the preventive effects of prepartum diet acidification (AcD) and mineral intake during late gestation on the incidence of subclinical hypocalcemia (SHC) and subclinical hypophosphatemia (SHP) after calving. We conducted a longitudinal study that followed a cohort of 371 Holstein cows from 26 French dairy farms; of these, 235 cows (15 farms) were supplied with anionic salts during late gestation, and 136 cows (11 farms) were not. Blood samples were collected from 1 to 22 cows per farm (average of 14.3 cows per farm) between 24 and 48 h after calving. Total calcium and inorganic phosphorus concentrations in plasma were then quantified by inductively coupled plasma - optical emission spectrometry. The effects of AcD on the incidence of SHC and SHP were assessed using mixed linear models that evaluated the cow-level factors parity, milk yield index, and individual health events/treatments, and the farm-level factors diet calcium and magnesium content, dietary phosphorus intake, vitamin D supply, diet crude protein content, and duration of AcD, with farm as a random effect. Approximately 55% of cows were diagnosed with SHC (calcium &amp;lt; 2.0 mmol/l, n = 203) and 37% with SHP (inorganic phosphorus &amp;lt; 1.3 mmol/l, n=136). The first model confirmed earlier findings that the risk of SHC is higher with increased parity (P ≤ 0.0001) and revealed a higher risk associated with high milk yield (P = 0.0005), high phosphorus intake (40–60 g/cow per day, OR = 3.5; ≥ 60 g/cow per day, OR = 7.3; P = 0.0003) and high vitamin D supply (≥ 19950 IU/cow per day, OR = 3, P = 0.007). The second model highlighted a greater risk of SHP with increasing parity (P = 0.03) and showed trends for the preventive effects of AcD (OR = 0.4, P = 0.07) and moderate amounts of phosphorus in the diet (OR = 0.4, P = 0.10). Overall, our results do not support the effectiveness of AcD in preventing SHC or SHP under field conditions examined here, probably resulting from insufficient diet acidification.

Zinc and Breast Cancer Survival: A Prospective Cohort Study of Dietary Intake and Serum Levels.

Zinc has been suggested to play a role in breast cancer progression; however, no previous study on zinc levels and the potential effect on breast cancer survival has been conducted. This study investigates recurrence-free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS) in relation to zinc levels, in serum and diet, overall and stratified for phosphorus and selenium levels. The Malmö Diet and Cancer Study, a prospective population-based cohort in Sweden including 17,035 women, was used to identify breast cancer patients diagnosed in the period 1991–2013. Diet was assessed by a validated modified diet history method. A Cox regression analysis yielded hazard ratios (HRs) with 95% confidence intervals adjusted for potential confounders. Out of 1062 patients with invasive breast cancer, 268 recurrences, 205 breast cancer deaths and 228 deaths from other causes were recorded. No overall associations were seen between zinc and RFS, BCSS or OS. However, in women with a high phosphorus intake, a higher BCSS and OS were seen in zinc intake Q2 to Q4 versus Q1; the adjusted HR was 0.41 (0.23–0.73) and 0.64 (0.41–1.00), respectively. The results indicate that the combination of intermediate/high zinc intake and high phosphorus intake may lead to a better breast cancer survival.

Protein and Phosphate Intakes are Associated with Hyperphosphatemia in Hemodialysis Patients at Sanglah Hospital, Bali, Indonesia

Increased chronic kidney disease (CKD) mortality rate is significantly associated with increased blood phosphate levels. Hyperphosphatemia control is one of the main focuses in the management of hemodialysis (HD) patients. A high protein diet has been suggested to prevent malnutrition in hemodialysis patients. However, a high protein and phosphorus diet has the risk of increasing the phosphate level in the blood circulation, leading to a higher mortality rate of hemodialysis patients. This study aimed to prove that the level of protein and phosphate intake is associated with hyperphosphatemia in CKD patients with routine HD. This was cross-sectional analytical study conducted from September to October 2020 on 66 CKD patients who underwent hemodialysis. Subject characteristics and phosphorus and protein intake data were obtained from a questionnaire food recall adapted from the Food and Agriculture Organization of the United Nations. Data consumption patterns were processed using the nutritional survey software to obtain the nutritional values. Data were analyzed using the Chi-Square test to identify the relationship and risk between hyperphosphatemia and diet protein, phosphorus, and protein-phosphorus ratio. The confidence level in this study was 95%. There was a significant relationship between protein and phosphorus intake in hyperphosphatemia in CKD patients. The risk factors for hyperphosphatemia were high phosphorus intake (p=0.018; OR=3.886;95% CI: 1.212–12.460) and adequate protein intake (p=0.035; OR=3.674; 95% CI: 1.049-12.865). This study showed no significant relationship between phosphorus-protein ratio, protein-phosphorus ratio, and hyperphosphatemia incidence. In conclusion, high protein intake and excessive phosphorus intake provide a significant relationship to the incidence of hyperphosphatemia in CKD patients undergoing routine hemodialysis.

Circulating phosphorus concentration and risk of prostate cancer: a Mendelian randomization study

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. To explore the potential causal relation between circulating phosphorus and risk of prostate cancer, we conducted a Mendelian randomization (MR) study. 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. 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. 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.

Use of Micro-CT Imaging to Assess Ventral Mandibular Cortical Thickness and Volume in an Experimental Rodent Model With Chronic High-Phosphorus Intake.

Adverse effects of high dietary phosphorus on bone health have been observed in both animal and human studies. The aim of the investigation was to examine chronic effects of high phosphorus diet on the apical mandibular cortical thickness and volume in a hystricomorph rodent (Octodon degus) using microcomputed tomography. Male degus were randomly divided into two groups fed by different mineral contents from the age of 12 weeks till the age of 17 months. The micro-CT scanning and wall thickness analysis were applied on the region of the mandible exactly under the apices of the 4th premolar tooth, first molar tooth, and second molar tooth in two animals from each group. General overview and mapping of the ventral mandibular bone thickness revealed pronounced bony mandibular protrusions in all the animals fed a high-phosphorus diet with obvious bone thinning apically to the 4th premolar and first and second molar tooth apices. Mandibular bone volume and thickness located apically to the premolar and molars were statistically significantly smaller/thinner in the group fed by a high phosphorus diet. The thinnest bone measured 0.004 mm, where the mandibular 4th premolar tooth almost perforated the mandibular cortex. Similar studies of metabolic bone disease and its influence on alveolar bone were also published in rats and mice. The influence of different environmental, infectious, or metabolic factors on the growing tooth, alveolar bone formation, and bone pathologies must be done experimentally on growing animals. In contrast, degus have continuously growing dentition, and the effect of any of the above listed factors can be studied in this animal model at any age and for longer time periods.

POS-286 ASSESSMENT OF PHOPSHATE INTAKE AND IMPLEMENTATION OF PARENTAL STRUCTURED DIETARY PHOSPHATE EDUCATION IN PEDIATRIC CKD-A PROSPECTIVE STUDY

Hyperphosphatemia is an important co morbidity of chronic kidney disease (CKD) with long term implications on cardiovascular health. The KDOQI 2008 guidelines based on dietary references intakes (DRI) and PRNT [Pediatric Renal Nutrition task force] 2020 guidelines based on suggested daily intakes (SDI) provide recommendations for phosphorus(P) intake in children with CKD. Besides, differences in food culture demands detailed assessment of dietary intake of phosphorus and its sources in children across regions. Data on dietary phosphorus intake and sources in Indian children with CKD has not been systematically studied. The aim of this study was to evaluate for dietary intake and sources of phosphorus with reference to KDOQI and PRNT guidelines and assess the impact of parental structured phosphate education in the management of hyperphosphatemia. This prospective study included children aged 2-18yrs with stage2-5DCKD[calculated sample size 58] recruited from April 2018 to November 2019. Phosphorus intake was assessed by 24 hour dietary recall, analysed using food processor software (version7.4,1999, ESHA,Portland,OR,USA) and interpreted based on KDOQI 2008 and PRNT recommendations. No change in phosphate binders were made during the study period. Parents of those with hyperphosphatemia were subjected to a structured phosphate education comprising of pamphlets in regional languages describing the importance of dietary phosphorus control. A phosphorus pyramid based on Indian foods and phosphorus lowering techniques was formulated (Figure 1) for the parental education. Serum phosphate was monitored once in 2 months for 6 months. Figure 2 depicts the study flow. Seventy of the 75 children screened were recruited [mean age 9.4±3.4 years, CKD2-4:49% (n=34), CKD5/5D:51% (n=36), 27/36 on peritoneal dialysis, 20% vegetarians] with median duration of CKD being 3.8 [IQR2,6] years. The mean daily phosphorus intake was comparable between children with and without hyperphosphatemia [908±279 mg vs 814±302 mg, p=0.1]. Dairy and bakery products were main dietary sources of phosphorus. Based on DRI of KDOQI and SDI of PRNT recommendations, high phosphorus intake was observed in 51%and 64% of the cohort and in 58% and 100% of those with hyperphosphatemia respectively. Hyperphosphatemia was observed in 51% (Stage 2 to 4 CKD:33%; CKD5:67%; CKD5D:55% p=0.6). In 36 parents who received phosphate education, 29 children completed 6 months follow up and serum phosphate levels reduced to normal in 66%. Reduction in serum phosphate was independent of age, stage of CKD, dietary intake of phosphorus or intake of phosphate binders. In children with CKD2-5D,dietary intake of phosphorus is comparable in those with and without hyperphosphatemia. DRI based KDOQI2008 recommendation underestimated dietary phosphate intake compared to SDI based PRNT recommendations. In the majority, parental structured phosphate education using the phosphorus pyramid, is useful in the management of hyperphosphatemia.

Dietary Phosphorus as a Marker of Mineral Metabolism and Progression of Diabetic Kidney Disease.

Phosphorus is an essential nutrient that is critically important in the control of cell and tissue function and body homeostasis. Phosphorus excess may result in severe adverse medical consequences. The most apparent is an impact on cardiovascular (CV) disease, mainly through the ability of phosphate to change the phenotype of vascular smooth muscle cells and its contribution to pathologic vascular, valvular and other soft tissue calcification. Chronic kidney disease (CKD) is the most prevalent chronic disease manifesting with the persistent derangement of phosphate homeostasis. Diabetes and resulting diabetic kidney disease (DKD) remain the leading causes of CKD and end-stage kidney disease (ESRD) worldwide. Mineral and bone disorders of CKD (CKD-MBD), profound derangement of mineral metabolism, develop in the course of the disease and adversely impact on bone health and the CV system. In this review we aimed to discuss the data concerning CKD-MBD in patients with diabetes and to analyze the possible link between hyperphosphatemia, certain biomarkers of CKD-MBD and high dietary phosphate intake on prognosis in patients with diabetes and DKD. We also attempted to clarify if hyperphosphatemia and high phosphorus intake may impact the onset and progression of DKD. Careful analysis of the available literature brings us to the conclusion that, as for today, no clear recommendations based on the firm clinical data can be provided in terms of phosphorus intake aiming to prevent the incidence or progression of diabetic kidney disease.

Randomized Trial of Acute Changes in Plasma Phosphate After Phosphorus-Standardized Meals in Peritoneal Dialysis

IntroductionHyperphosphatemia is associated with increased morbidity and mortality in patients with chronic kidney disease. The aim of this study was to assess whether a meal with high phosphorus content would affect plasma phosphate in the hours that follow among subjects with end-stage kidney disease on peritoneal dialysis.MethodsThis was a single-blinded randomized cross-over trial of 12 subjects on maintenance peritoneal dialysis, in which subjects were randomized to consume a meal with either high or low phosphorus content on 2 separate trial days. On each trial day, plasma phosphate was measured immediately before consumption of the standardized meal and after 1, 2, 3, and 5 hours.ResultsThe mean fasting plasma phosphate at baseline was 1.69 ± 0.22 mmol/l. Plasma phosphate was similar between the 2 meals at baseline, as well as at 1, 2, 3, and 5 hours after consumption. The largest observed difference in plasma phosphate between the 2 meals was 0.15 mmol/l, which occurred 5 hours after consumption (high-phosphorus meal 1.75 ± 0.32 mmol/l vs. low-phosphorus meal 1.60 ± 0.14 mmol/l (P = 0.06)). Using summary analyses for repeated measures, we observed a significant difference in the plasma phosphate between the 2 meals (P = 0.03).ConclusionOur results show that in subjects with end-stage kidney disease, a meal with high phosphorus content has only a negligible effect on plasma phosphate compared to a meal with low phosphorus content. Thus, large increases in plasma phosphate cannot be accounted for by a high intake of phosphorus in the hours before blood sampling.