Urinary Phosphorus Excretion Research Articles

Association of urinary calcium and phosphorus excretion with renal disease progression in type 2 diabetes

ObjectivesDiabetes is associated with a high incidence of microvascular disease, including nephropathy. The current study aimed to investigate the association of urinary calcium and phosphorus excretion with chronic kidney disease (CKD) progression in type 2 diabetes mellitus. MethodsA total of 159 T2DM patients with chronic kidney disease (CKD stage G1-G4) were retrospectively included. Patients were categorized into three groups according to the tertiles of 24-h urinary calcium and phosphorus excretion, respectively. Clinical parameters and laboratory findings were compared among the three groups. Cox proportional hazards models were used to estimate the associations of urinary calcium and phosphorus excretion with CKD progression and adjusted for baseline eGFR, urinary protein excretion, mean arterial pressure, and use of RAAS inhibitor. A cubic spline curve was used to explore the association between urinary calcium excretion and CKD progression, as well as urinary phosphorus excretion and CKD progression. Moreover, the subgroup effects of urinary calcium and phosphorus excretion on CKD progression were estimated using Cox regression. CKD progression was defined as double of baseline serum creatinine or occurrence of ESRD. ResultsDuring a median of 18.23 months of follow-up, the composite renal outcomes were noted in 27%. Cumulative renal outcomes were significantly lower in the highest tertile of urinary calcium excretion and phosphorus excretion in Kaplan-Meier analyses. The multivariate Cox proportional hazards regression analyses indicated that both the highest tertile of urinary calcium and phosphorus excretion was associated with a lower risk for CKD progression compared with the lowest tertile. Restricted cubic spline analyses of the association between urinary calcium excretion and CKD progression indicated a linear association. Additionally, there was also a linear association between urinary phosphorus excretion and CKD progression. Subgroup analyses showed that higher urinary phosphorus excretion was particularly associated with a lower risk of CKD progression in non-diabetic kidney disease (NDKD) patients. ConclusionHigher urinary calcium and phosphorus excretion were associated with decreased risk of CKD progression in T2DM patients.

Renal Phosphate Wasting Due to Tumor-Induced (Oncogenic) Osteomalacia

Osteomalacia is a widely prevalent bone disorder that is caused by an imbalance in body calcium and phosphate. Tumor-induced osteomalacia (TIO) is a rare form of osteomalacia that is associated with mesenchymal tumors. It is caused by overproduction of fibroblast growth factor 23 (FGF-23), a hormone involved in phosphate regulation.A 59-year-old male with a history of factor V Leiden mutation, pulmonary embolism, and deep vein thrombosis was diagnosed with oncogenic osteomalacia in 2008 following laboratory findings significant for low phosphorus and elevated FGF-23 levels. He underwent a resection of a right suprascapular notch mass with the biopsy confirming a phosphaturic mesenchymal tumor. He was maintained on oral phosphorus and calcitriol replacements with a regular follow-up with oncology and nephrology. Eight years later, the patient’s phosphorus levels started declining despite replacement. A repeat test showed FGF-23 levels once again elevated. A whole-body magnetic resonance imaging (MRI) scan showed no significant findings. The patient was continued on oral replacement therapy with a close follow-up. Two years later, urine phosphorus excretion was elevated at 2494 mg per 24 hours with low plasma phosphorus (1.2 mg/dL) and an elevated FGF-23 level of 1005 relative units (RU)/mL. A repeat MRI of the right shoulder revealed a mass in the supraspinatus muscle and another in the spinal glenoid notch. The masses were resected and the biopsy was consistent with a recurrence of the phosphaturic mesenchymal tumor. Follow-up serum phosphate levels remained in the normal range.FGF-23 plays a critical role in bone mineralization through the regulation of phosphate levels. Overproduction, as seen in mesenchymal tumors, results in hyperphosphaturia, hypophosphatemia, and low calcitriol levels. While the definitive treatment of TIO involves the resection of the mesenchymal tumor, localization of the tumor is often challenging given its small size and slow growth. This leads to delayed diagnosis and treatment. For individuals whose tumor cannot be resected or detected, burosumab is the preferred form of therapy. Interestingly, FGF-23 is shown to have a potential cardiovascular (CV) morbidity and mortality through various mechanisms like activation of myocardial FGF-23 receptors, endothelial dysfunction, inflammation, and altered phosphorus and vitamin D metabolisms. While studies have shown possible FGF-23 effects on CV outcomes in patients with chronic kidney disease, this has not been proven in cases of TIO.

Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers

Backgrounds:Previous studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs).MethodsBiobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied. Urinary EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry.ResultsUrine excretion of calcium, oxalate, phosphorus, and calcium oxalate supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion, whereas excretion of EVs expressing FGF23 negatively (P < 0.05) correlated with both urinary calcium and phosphorus excretion. Urinary EVs with markers of HIP1 and ANO4 correlated negatively (P < 0.05) with clinical stone events and basement membrane calcifications on papillary tip biopsies.ConclusionsUrinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.

MO121ASSOCIATION BETWEEN BONE MINERAL DENSITY, BODY COMPOSITION AND SERUM SCLEROSTIN IN MALE STONE-FORMERS

Abstract Background and Aims Reduced bone mineral density (BMD) has been observed in stone-formers (SF). Although obesity is considered a protective factor for bone health due to increased mechanical load, the role of muscle mass (lean) or body fat remains controversial. Sclerostin, an antagonist of the Wnt signaling pathway, is secreted by osteocytes and its actions involve the inhibition of bone formation, FGF23 stimulation, and increased urinary calcium and phosphorus excretion. Recent studies also indicate its association with body composition. The aim of the present study was to evaluate the relationship between BMD and body composition with serum sclerostin levels in male SF. Method This is a retrospective study, based on medical records of SF with available data of BMD and body composition, serum and urinary biochemistry and hormonal measurements including sclerostin. BMD had been assessed at lumbar spine (L1-L4), femoral neck (FN) and total femur (TF) and body composition (fat and lean mass) in a dual energy X-ray absorptiometry (DXA). Results Fifty-five male SF (37.2 ± 9.3 years) were included. Patients were divided into tertiles according to the percentage of body fat (T1, n = 19, 8.7-20.0 %; T2, n = 20, 20.1-26.0 %; T3, n = 16, 26.1-38.0 %). There was no statistical difference in BMD in any of the sites between these tertiles. Higher urinary sodium and serum sclerostin were observed in T3 versus T1 (280 ± 93 vs 199 ± 75 mEq/day, p &amp;lt;0.05; 33.6 ± 14.7 vs 24.7 ± 8.3 pmol/L, p&amp;lt;0.05, respectively). There was an inverse association between serum sclerostin and lean mass (β= -0.30, p=0.001) and direct association with fat mass (β=0.40, p=0.001), urinary calcium and phosphorus (β=0.29, p=0.02; β=0.32, p=0.01). In a multivariate linear regression model, lean mass was an independent predictor of BMD at L1-L4, FN and TF (β= 0.70, p&amp;lt;0.001; β=0.70, p&amp;lt;0.001; β=0.57, p=0.00, respectively) and at the TF there was also an inverse association between body fat and PTH (β= –0.51, p= 0.03; β= –0.25, p= 0.03). Conclusion These data suggest that male SF with a higher percentage of body fat had higher levels of serum sclerostin, which were directly associated with calciuria and phosphaturia but not with BMD. In addition, lean mass was an independent predictor of BMD. Further studies are needed to determine long-term effects of serum sclerostin levels upon bone formation in SF.

MO593CONTROLLING DIETARY PHOSPHORUS IN CHRONIC KIDNEY DISEASE STAGES 1 AND 2 DECREASES PROTEINURIA AND PREVENTS DECLINE IN RENAL FUNCTION

Abstract Background and Aims High phosphorus intake is known to cause renal and vascular calcification and renal tubular injury and albuminuria. Dietary phosphorus restriction is therapeutic for controlling disordered phosphorus homeostasis and for improving cardiovascular outcomes in CKD. However, early restriction of dietary phosphorus is not advocated Aim: To evaluate if early control of dietary phosphorus ameliorates proteinuria, prevents decline in glomerular filtration rate and prevents increase in FGF-23 Method One year longitudinal study on 79 CKD patients in stages 1 and 2. eGFR, serum creatinine , phosphorus, calcium, FGF-23, soluble α-Klotho iPTH FGF 23, blood pressure, were evaluated and compared with 35 controls. 3 days dietary intake was taken using standard methodology on first visit, 6 and 12 months. CKD patients were grouped based on dietary phosphorus intake: Group 1 (n 42): normal phosphorous intake (&amp;lt;1000mg/day) and Group 2 (n=37; 17 in CKD 1; 20 CKD 2): high phosphorous intake (&amp;gt;1000mg/d). Patients in Group 2 were educated on high and low phosphorus foods and counselled to avoid fresh and frozen and processed meat, eggs, nuts and seeds, chocolates, packaged food, phosphorus-containing food additives and counselled to adopt a plant-based diet, for low phosphorus availability/absorption diet with directed diet plan. Lentils and pulses, milk and milk products (hard cheese, ice-creams, custards, cottage cheese, pudding, yoghurt), bran and whole wheat cereals were restricted up to 1-2 servings a day Data were analysed using SPSS. Results At baseline there was no significant difference in the GFR (group1 85.00±18.64 ml/min vs group 2 82.53±16.30ml/min), serum creatinine between groups. In group2 ; GFR, sKlotho, serum phosphorus and FGF-23 correlated significantly with dietary phosphorus intake. In group 2, FGF-23, Serum phosphorus, dietary protein and phosphorus intake were significantly higher and sKlotho was significantly lower than group 1. There was significant difference in serum phosphorus (p 0.000), iPTH, (p 0.004), FGF23 (p0.000), Klotho (p0.000), urinary protein (p0.000), dietary protein (Group 1 37.57±3.40; Group 248.79±5.86 p 0.000) and phosphorus (Group 1868.96±69.99 mg/d and Group 2 1312.26±137.57 mg/d p 0.000) intake and dietary phosphorous to protein ratio (p 0.000) between groups 1 and 2.. After dietary intervention in group 2 GFR increased from 80.93±15.34 to 84.11±15.38 in six months and to 87.43±18.27 ml/min at 12 months p 0.012, and urinary protein declined to 22.01±3.39 mg/mL. FGF 23 declined from 60.67±6.26 to 58.00±7.07 to 53.29±9.48 pg/mL at 12 months. Urinary phosphorus excretion increased from 574.37±214.22 to 624.64±137.67 at 12 months. Dietary phosphorus protein to ratio reduced from 27.16±4.35 to24.75±4.34 p 0.000 at 12 months Conclusion CKD patients should be cautioned and counselled on their first visit on the impact of dietary phosphorus intake on the progression of CKD and development of CVD.

Sporadic Pseudohypoparathyroidism 1B in Monozygotic Twins: Insights Into the Pathogenesis of Methylation Defects

Background: Pseudohypoparathyroidism (PHP) 1B is an imprinting disorder characterized by renal resistance to parathyroid hormone (PTH) without Albright Hereditary Osteodystrophy (AHO). PHP1B is associated with methylation defects at the GNAS differentially methylated regions (DMRs). In sporadic cases with PHP1B, the mechanistic basis of methylation defects remains to be solved, except in rare cases with uniparental disomy of chromosome 20. In addition, to date, monozygotic twin cases with sporadic PHP1B have not been reported. Clinical Case: The patients were 26-year-old Japanese female monozygotic twins. They had been born to nonconsanguineous parents after an uneventful pregnancy. Both twins had common biochemical features, including hypocalcemia, hyperphosphatemia, elevated PTH levels, and impaired urinary excretion of phosphorus and cAMP in response to teriparatide. They showed no signs of AHO. The serum calcium levels of their parents and brother were within the normal range, and family history was unremarkable. Based on these findings, the twins were diagnosed with PHP1B. Targeted bisulfite sequencing of the GNAS DMRs in all family members revealed almost complete gain-of-methylation at the NESP55 DMR, and loss-of-methylation at the AS, XL, and A/B DMRs in the twins, but not in other family members. Except for the GNAS locus, we did not find clear methylation defects in other imprinted genome loci in the twins. Methylation defects at the GNAS locus were further confirmed by methylation-sensitive restriction enzyme-qPCR. Whole-genome sequencing of the twins showed no pathogenic variants in the GNAS exons encoding the Gs alpha subunit. No large deletions or insertions were found at the STX16 locus or in the region from AS exon 5 to XL. Based on the SNP genotyping results, large paternal isodisomies in the GNAS DMRs were unlikely. Collectively, these results suggested that the twins had concordant methylation defects that are seen in the sporadic form of PHP1b. We speculate that an early developmental event before the twin splitting is responsible for the abnormal methylation of the GNAS DMRs. Conclusion: We report, for the first time, monozygotic twins with sporadic PHP1B who were phenotypically and epigenetically concordant. Our comprehensive molecular genetic analyses have thus far ruled out the previously described genetic defects underlying PHP1B. The current findings provide new insights into the mechanistic basis of the GNAS methylation defects in sporadic PHP1B.

Dominant factors of the phosphorus regulatory network differ under various dietary phosphate loads in healthy individuals

Background The purpose of this study was to explore the contribution of each factor of the phosphorus metabolism network following phosphorus diet intervention via Granger causality analysis. Methods In this study, a total of six healthy male volunteers were enrolled. All participants sequentially received regular, low-, and high-phosphorus diets. Consumption of each diet lasted for five days, with a 5-day washout period between different diets. Blood and urinary samples were collected on the fifth day of consumption of each diet at 9 time points (00:00, 04:00, 08:00, 10:00, 12:00, 14:00, 16:00, 20:00, 24:00) for measurements of serum levels of phosphate, calcium, PTH, FGF23, BALP, α-Klotho, and 1,25 D and urinary phosphorus excretion. Granger causality and the centrality of the above variables in the phosphorus network were analyzed by pairwise panel Granger causality analysis using the time-series data. Results The mean age of the participants was 28.5 ± 2.1 years. By using Granger causality analysis, we found that the α-Klotho level had the strongest connection with and played a key role in influencing the other variables. In addition, urinary phosphorus excretion was frequently regulated by other variables in the network of phosphorus metabolism following a regular phosphorus diet. After low-phosphorus diet intervention, serum phosphate affected the other factors the most, and the 1,25 D level was the main outcome factor, while urinary phosphorus excretion was the most strongly associated variable in the network of phosphorus metabolism. After high-phosphorus diet intervention, FGF23 and 1,25 D played a more critical role in active regulation and passive regulation in the Granger causality analysis. Conclusions Variations in dietary phosphorus intake led to changes in the central factors involved in phosphorus metabolism.

Effect of animal and plant protein intake on urinary phosphorus excretion in healthy young women

Effect of animal and plant protein intake on urinary phosphorus excretion in healthy young women

274 Determination of phosphorus requirement of lactating sows based on 24-hour urinary phosphorus excretion

Abstract The objective was to determine phosphorus (P) requirement of lactating sows using 24-hour urinary P excretion as the response criteria. The underlying assumption was that urinary P remains low and constant until the requirements are met then increases as P consumption increases. Thirty-six crossbred PIC Camborough sows (parity 3 to 7) were randomly assigned to 1 of 6 corn-soybean-meal diets with increasing dietary total P (tP) levels (0.40, 0.48, 0.56, 0.64, 0.72, and 0.80%) and a constant calcium (Ca) to tP ratio (1.25:1). Diets were fed from breeding until the end of lactation. Urine and blood samples were collected on days 4 and 18 of lactation and analyzed for P and Ca concentrations. Data were analyzed using MIXED and NLIN procedures of SAS. Phosphorus requirements were estimated using a broken-line regression model. Plasma Ca (ranging from 12.1 to 10.3 mg/dL) was not affected by dietary treatments, and was maintained within the normal physiological range on day 4 and 18 of lactation. Plasma P (ranging from 2.9 to 6.4 mg/dL) linearly increased (P &amp;lt; 0.05) with increasing dietary tP levels on day 4 and 18 of lactation. Only sows fed the 0.40% tP diet failed to maintain plasma P concentrations within the normal physiological range. Clinical signs of P and Ca deficiencies were not observed. Differences in sow and litter performance among treatments were not detected. A nonlinear response of urinary P excretion to dietary P intake was observed. Based on a broken-line linear model fit to 24-hour urinary P excretion, minimum tP requirements of sows at day 4 and 18 of lactation were 0.47 and 0.54%, respectively. In conclusion, 24-hour urine P excretion provided sensitive criteria for estimates of tP requirements in lactating sows. Efforts to adjust heteroscedasticity for animals fed dietary P above the estimated requirement need further evaluation.

Urinary Phosphate Excretion and Microvascular Function in a Population-Based Cohort

Urinary Phosphate Excretion and Microvascular Function in a Population-Based Cohort

Cálcio, fósforo, fração de excreção urinária de fósforo e paratormônio em cães com leishmaniose visceral

The kidneys perform an essential role in the regulation of serum phosphorus concentration. In visceral leishmaniasis (VL), the decline of the glomerular filtration rate leads to hyperphosphatemia, whose primary consequence is the development of secondary renal hyperparathyroidism. This study aimed to determine the concentration of serum phosphorus, ionized calcium (Cai), urinary fractional excretion of phosphorus (uFEP), and parathormone (PTH) in azotemic and non-azotemic dogs with VL and evaluate the uFEP as a marker of secondary renal hyperparathyroidism. The study comprised 31 dogs, divided into 24 sick animals and 07 healthy animals used as a control group (GC). The sick animals were classified into groups as azotemic (GA) and non-azotemic (GNA). The serum levels of phosphorus, creatinine, Cai, and the plasma levels of PTH were measured and compared between groups. The uFEP was calculated using values of serum and urinary levels of phosphorus and creatinine. The Kruskal-Wallis test with a 0.05 significance level was used, followed by the Mann-Whitney test as a post hoc test, with a 0.016 significance level. The levels of serum phosphorus were higher in the GA group, whereas for the PTH, the GNA and GA groups demonstrated high values compared to the GC. The uFEP was significantly higher in the GA when compared to the GNA, although there was no statistical difference between the GC and the GNA. The uFEP showed to be a late marker of chronic kidney disease and secondary hyperparathyroidism in dogs with visceral leishmaniasis.

Race, Ancestry, and Vitamin D Metabolism: The Multi-Ethnic Study of Atherosclerosis.

A comprehensive characterization of racial/ethnic variations in vitamin D metabolism markers may improve our understanding of differences in bone and mineral homeostasis and the risk of vitamin D-related diseases. Describe racial/ethnic differences in vitamin D metabolism markers and their associations with genetic ancestry. In a cross-sectional study within the Multi-Ethnic Study of Atherosclerosis (MESA), we compared a comprehensive panel of vitamin D metabolism markers across self-reported racial/ethnic groups of Black (N = 1759), White (N = 2507), Chinese (N = 788), and Hispanic (N = 1411). We evaluated associations of proportion African and European ancestry with this panel of markers in Black and Hispanic participants using ancestry informative markers. Latent class analysis evaluated associations between patterns of vitamin D measurements with race/ethnicity. Compared with Black participants, White participants had significantly higher serum concentrations of 25-hydroxyvitamin D and fibroblast growth factor-23; lower concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D; circulating vitamin D metabolite ratios suggesting lower CYP27B1 and higher CYP24A1 activity; higher urinary concentrations of calcium and phosphorus with higher urinary fractional excretion of phosphorus; and differences in vitamin D binding globulin haplotypes. Higher percent European ancestry was associated with higher 25-hydroxyvitamin D and lower parathyroid hormone concentrations among Black and Hispanic participants. Latent classes defined by vitamin D measurements reflected these patterns and differed significantly by race/ethnicity and ancestry. Markers of vitamin D metabolism vary significantly by race/ethnicity, may serve to maintain bone and mineral homeostasis across ranges of 25-hydroxyvitamin D production, and be attributable, at least partly, to genetic ancestry.

586-P: Characteristics of 24-Hour Urinary Electrolyte Excretion and Its Correlation with Renal Function in Type 2 Diabetics

Objective: There are few studies on the characteristics of 24-hour urinary electrolyte excretion in patients with type 2 diabetes mellitus (T2DM),and it is unclear whether the level of 24-hour urinary electrolyte excretion is related to poor renal prognosis.This study aimed to explore associations between 24-hour urinary electrolyte excretion and renal function in T2DM patients. Methods: A total of 479 patients with T2DM in our hospital from 2018 to 2019 were enrolled. According to the estimated glomerular filtration rate (eGFR), patients were divided into normal group(eGFR≥90 mL/min/1.73m`2,n=317)and abnormal group(eGFR&amp;lt;90 mL/min/1.73m`2,n=162). The correlation between 24-hour urinary electrolyte excretion and eGFR in T2DM patients was analyzed. In addition, the 24-hour urine electrolyte excretion was compared with gender, diabetic duration, and HbA1c. Results: The levels of 24-hour urinary potassium, sodium and chlorine excretion in abnormal group were higher than normal group, the levels of calcium and phosphorus excretion were lower. Therein, levels of sodium(P=0.037) and calcium (P&amp;lt;0.001) had significant difference. The levels of 24-hour urinary potassium, sodium, chloride, calcium and phosphorus excretion in the male group were higher than female group, among which potassium (P&amp;lt;0.001), sodium (P=0.001), chloride (P=0.002), and phosphorus (P&amp;lt;0.001) were statistically significant. In addition, duration of disease and HbAlc was not related to 24-hour Urinary Electrolyte Excretion. Conclusion:There is a certain correlation between 24-hour urinary electrolyte excretion in T2DM and renal function. With the increase of 24-hour urinary sodium excretion and decrease of urinary calcium excretion, eGFR decreased, which was related to gender. Therefore, in patients with T2DM of the same gender, 24-hour urinary sodium and calcium excretion may be useful metabolic parameters for predicting poor renal prognosis, which needs further study. Disclosure Y. Wang: None. N. Li: None. L. Bu: None. H. Sun: None. B. Zhu: None. H. Li: None. S. Qu: None. Funding National Key Research and Development Program of China (2018YFC1314100); National Natural Science Foundation of China (81970677)

EOS789, a novel pan-phosphate transporter inhibitor, is effective for the treatment of chronic kidney disease–mineral bone disorder

Chronic kidney disease is characterized as impaired renal function along with the imbalance and dysregulation of mineral metabolism; recognized as chronic kidney disease-mineral and bone disorder. Hyperphosphatemia, characterized by altered phosphate homeostasis along with elevated fibroblast growth factor-23 and intact parathyroid hormone, is such an alteration of mineral metabolism. We discovered a novel inhibitor, EOS789, that interacts with several sodium-dependent phosphate transporters (NaPi-IIb, PiT-1, and PiT-2) known to contribute to intestinal phosphate absorption. This inhibitor dose-dependently increased the fecal phosphorus excretion rate and inversely decreased the urinary phosphorus excretion rate in normal rats, suggesting inhibition of intestinal phosphorus absorption. In rats with adenine-induced hyperphosphatemia, EOS789 markedly decreased the serum phosphate, fibroblast growth factor-23, and intact parathyroid hormone below values found in normal control rats. Notably, this pan-phosphate transporter inhibitor exhibited a more potent effect on serum phosphate than a NaPi-IIb-selective inhibitor in rats with hyperphosphatemia indicating that PiT-1 and PiT-2 play important roles in intestinal phosphate absorption. Moreover, in a long-term study, EOS789 sustained the suppression of serum phosphorus in parallel with fibroblast growth factor-23 and intact parathyroid hormone and ameliorated ectopic calcification of the thoracic aorta. Additionally, EOS789 treatment also ameliorated kidney deterioration in rats with progressive kidney injury, probably due to the strict phosphate control. Thus, EOS789 has potent efficacy against hyperphosphatemia and its complications and could provide a significant benefit to patients who are ineffectively treated with phosphate binders.

Fibroblast Growth Factor 23 and the Last Mile.

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphorus balance by enhancing urinary phosphorus excretion and inhibiting the synthesis of 1,25-dihydroxyvitamin D [1,25(OH)2D] ([1][1]). Its discovery and characterization could be considered a triumph for precision

Conventional and novel impacts of ferric citrate on iron deficiency anemia and phosphorus metabolism in rats.

Ferric citrate is an oral iron-based phosphate binder, being known to affect iron status and improve iron deficiency anemia (IDA) in chronic kidney disease (CKD) patients. We examined whether oral administration of ferric citrate could change iron status and improve anemia without affecting phosphorus metabolism in iron deficiency anemia rats. In Normal rat study, normal rats were fed a diet containing 0.3 or 3% ferric citrate for 11 days for setting the dose and administration period of ferric citrate. The effects of ferric citrate on iron status- and phosphorus metabolism-related parameters were evaluated using blood and urine samples. Next, an iron deficiency anemia was induced by feeding iron-depleted diet in rats. After 7 days of starting the iron-depleted diet, 0.3% ferric citrate was administered for 7 days by dietary admixture. Iron status- and phosphorus metabolism-related parameters were evaluated with blood and urine samples. In Normal rat study, 3% ferric citrate treatment increased serum iron level and transferrin saturation (TSAT), and decreased serum phosphorus level, intact fibroblast growth factor 23 (iFGF23) level, and urinary phosphorus excretion, but 0.3% ferric citrate treatment showed no effects. On the other hand, in Iron deficiency anemia rat study, 0.3% ferric citrate treatment increased iron status-related parameters and improved anemia, but did not show any apparent changes in phosphorus metabolism-related parameters. In conclusion, ferric citrate could have hematopoietic effects without affecting phosphorus metabolism, and could be a potential option for the treatment of IDA in patients without CKD.

Efficacy and safety of calcium carbonate in normophosphataemic patients with chronic kidney disease Stages 3 and 4.

BackgroundDisordered bone and mineral metabolism are a common complication of chronic kidney disease (CKD). Phosphate binders are often prescribed in advanced CKD, when hyperphosphataemia develops. Little is known about the role of these drugs in earlier stages, when serum phosphorus levels are kept in the normal range by increased urinary excretion.MethodsA retrospective, controlled observational study was conducted on a cohort of 78 pre-dialysis patients. Subjects had CKD Stage 3 or 4, normal serum phosphorus levels and increased urinary fractional excretion of phosphate. Thirty-eight patients receiving calcium carbonate for 24 months were compared with 40 patients under no phosphate binders, regarding mineral metabolism parameters and vascular calcification scores.ResultsCalcium carbonate decreased mean urinary fractional excretion of phosphate and median 24-h urine phosphorus, whereas no significant change was seen in the control group. Mean serum phosphorus and median serum intact parathyroid hormone (iPTH) remained stable in treated patients but increased in the control group. Vascular calcification, assessed by Kauppila and Adragão scores, worsened under calcium carbonate with no significant change in the control group.ConclusionsCalcium carbonate reduced urinary phosphate excretion and prevented the rise in phosphorus and iPTH serum levels in a cohort of normophosphataemic pre-dialysis patients. However, treatment was associated with increased vascular calcification, suggesting that calcium-based phosphate binders are not a safe option for CKD patients.

The association of dietary phosphorus with blood pressure: results from a secondary analysis of the PREMIER trial.

Inconsistent findings exist for the association between dietary phosphorus intake and blood pressure (BP). We examined the longitudinal association between urinary excretion and dietary intake of phosphorus (total, plant, animal, and added) with BP.This is a secondary analysis of PREMIER, a randomized behavioral intervention study in adults (25–79y) with BP, measured at six months, as the primary outcome. We classified total phosphorus intake from dietary recalls into plant, animal, and added phosphorus. We modeled six month change of phosphorus intake (from 24h dietary recalls, N = 622) and excretion (from 24h urine collection, N = 564) on BP, using linear regression crude and adjusted for intervention, age, race, sex, income, education, study site, and change in energy intake (kcal/d), sodium intake (mg/d), fitness (heart rate, bpm), and DASH diet index.Baseline phosphorus intake was 1154 mg/d (95%CI 1126, 1182) with 38%, 53%, and 10% from plant, animal, and added phosphorus, respectively. Total phosphorus intake was not associated with significant changes in BP. Increased urinary phosphorus excretion was associated with a significant increase in DBP [0.14 mmHg/100 mg (0.01, 0.28), adjusted]. In several analyses, phosphorus type (plant, animal, or added) significantly modified the association between phosphorus intake and BP. For example, added phosphorus (but not plant or animal) was associated with increases in SBP and DBP, 1.24 mmHg/100 mg (0.36, 2.12) and 0.83 mmHg/100 mg (0.22, 1.44), respectively, crude.These findings suggest that the type of phosphorus may modify the association between phosphorus intake and BP. Trial registration (clinicaltrials.gov).

The Percentage of Dietary Phosphorus Excreted in the Urine Varies by Dietary Pattern in a Randomized Feeding Study in Adults

Urinary phosphorus excretion has been proposed as a recovery biomarker of dietary phosphorus intake. However, it is unclear whether phosphorus excretion is constant across a range of dietary and nondietary factors. We assessed whether percentage urinary phosphorus excretion is constant across 3 dietary patterns in the Dietary Approaches to Stop Hypertension (DASH) trial. DASH is a completed feeding study of 459 prehypertensive and stage 1 hypertensive adults (52% male, 56% black). After a 3-wk run-in on a typical American (control) diet, participants were randomly assigned to the control diet, a diet rich in fruits and vegetables (FV diet), or a diet rich in fruits, vegetables, and low-fat dairy with reduced saturated fat and cholesterol (DASH diet) for 8 wk. We estimated the percentage phosphorus excretion as urinary phosphorus excretion (from 24 h urine) divided by phosphorus intake (from analyzed food composites). Differences between group means for all 3 diets were compared by ANOVA followed by pairwise comparisons with Tukey's honest significant difference test. At the end of the intervention, the mean phosphorus intake was 1176 mg/d (95% CI: 1119, 1233 mg/d), 1408 mg/d (1352, 1464 mg/d), and 2051 mg/d (1994, 2107 mg/d) in the control, FV, and DASH diet, respectively (P<0.001, all comparisons). The mean phosphorus excretion was 734 mg/d (682, 787 mg/d), 705 mg/d (654, 756 mg/d), and 872 mg/d (820, 923 mg/d) in the control, FV, and DASH diet, respectively (P=0.74 control vs. FV, P<0.001 all other comparisons). The mean percentage phosphorus excretion was 63% (60%, 67%), 51% (48%, 54%), and 43% (39%, 46%) in the control, FV, and DASH diet, respectively (P<0.001, all comparisons). These findings in prehypertensive and stage 1 hypertensive adults strongly suggest that urinary phosphorus excretion should not be used as a recovery biomarker for dietary phosphorus intake, given the wide range of urinary phosphorus excretion across dietary patterns. This trial is registered at clinicaltrials.gov as NCT0000054.

Dietary phosphorus intake and blood pressure in adults: a systematic review of randomized trials and prospective observational studies

Elevated blood pressure (BP) is a major cause of preventable disease in the United States and around the world. It has been postulated that phosphorus intake may affect BP, with some studies suggesting a direct and others an inverse association. We systematically reviewed the literature on the association of dietary phosphorus with BP in adults and performed a qualitative synthesis. We included randomized and nonrandomized behavioral intervention and feeding studies (intervention studies) and prospective observational studies that measured dietary phosphorus intake or urinary phosphorus excretion and BP. We excluded studies of supplements, children, or individuals with major medical conditions. We searched PubMed, Embase, Cochrane Trials, and clinicaltrials.gov on 1 June, 2017 and 22 August, 2018. We assessed studies' risk of bias in their assessment of phosphorus exposure and BP. We reviewed 4759 publications and included 14 intervention studies (2497 participants), 3 prospective observational cohorts (17,795 participants), and 2 ongoing trials. No included intervention studies were designed specifically to achieve a phosphorus contrast. Two studies found a significant positive association of dietary phosphorus with systolic BP, 4 a significant inverse association, and 8 no significant association. Four studies found a significant inverse association with diastolic BP and 10 no significant associations. Two cohorts found lower risk of incident hypertension comparing the highest with the lowest quintiles of phosphorus intake and 1 found no significant difference: HR: 0.86 (95% CI: 0.75, 0.98); HR: 0.83 (95% CI: 0.68, 1.02); and HR: 0.75 (95% CI: 0.45, 1.27), respectively. We found no consistent association between total dietary phosphorus intake and BP in adults in the published literature nor any randomized trials designed to examine this association. This trial was registered at www.crd.york.ac.uk/prospero/ as CRD42017062489.