Intestinal Absorption Of Phosphorus Research Articles

MAPK signaling pathway participates in the regulation of intestinal phosphorus and calcium absorption in broiler chickens via 1,25-dihydroxyvitamin D3

Four experiments were performed to investigate the role of the mitogen-activated protein kinase (MAPK) signaling pathway in intestinal absorption of phosphorus (P) and calcium (Ca) in broiler chickens. Experiment 1 assessed how dietary levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) influence the gene expression of intestinal P and Ca transporters in broilers. Experiment 2 evaluated the effects of 1,25(OH)2D3 administered via intraperitoneal injection on the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways. Experiments 3 and 4 investigated the effect of ERK and p38MAPK inhibitors on the expression of intestinal P and Ca transporters. The findings demonstrated that broilers (1-21 days old) fed a 1,25(OH)2D3-deficient diet (0.625 µg/kg) exhibited reduced body weight, tibia P and Ca levels, and mRNA levels of P transporters (NaPi-IIb, PiT-1, and PiT-2), Ca transporters (NCX1, PMCA1b, and CaBP-D28k), vitamin D receptors (VDR), ERK, and p38MAPK in the duodenum (Experiment 1) (P < 0.05). By comparison, the growth, bone quality, and mRNA levels of genes (except for duodenal NaPi-IIb) in broilers were similar to those in broilers fed the control diet when dietary 1,25(OH)2D3 was adequate (5 µg/kg) (Experiment 1) (P > 0.05). After intraperitoneal injection of 1,25(OH)2D3, the mRNA level of jejunal NaPi-IIb and the protein level of p-p38MAPK/t-p38MAPK in broilers (9-14 days old) decreased (P < 0.05), whereas the mRNA level of CaBP-D28k and the protein level of p-ERK/t-ERK increased (Experiment 2) (P < 0.05). The mRNA and protein expression of jejunal NaPi-IIb and the protein expression of CaBP-D28k in broilers (9-17 days old) treated with the ERK inhibitor PD98059 were greater than those in the control group (Experiment 3) (P < 0.05). Similarly, compared with control broilers, broilers (9-17 days old) treated with the p38MAPK inhibitor SB203580 showed elevated mRNA expression of jejunal NaPi-IIb and CaBP-D28k (Experiment 4) (P < 0.05). These results suggest that adequate supplementation with 1,25(OH)2D3 (5 µg/kg) can restore broiler growth and bone quality by upregulating the transcription of genes involved in intestinal P and Ca absorption. Additionally, the ERK and p38MAPK signaling pathways are implicated in the modulatory effect of 1,25(OH)2D3 on the absorption of P and Ca in broilers.

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.

#5123 EFFICACY AND SAFETY OF PATIROMER IN THE TREATMENT OF CHRONIC HYPERKALEMIA IN ASTURIAS: THE K-ASTUR STUDY

Abstract Background and Aims Hyperkalemia is a frequent problem in patients with chronic kidney disease (CKD), especially in those on hemodialysis (HD) and confers increased morbidity and mortality. It is common to carry out urgent HD sessions or increase the number of weekly sessions due to toxic hyperkalemia. Hyperkalemia also prevents the administration or adequate titration of drugs such as renin-angiotensin-aldosterone system (RAAS) inhibitors despite the evidence of their cardiovascular benefits and on the progression of CKD. New drugs have recently entered the market that can help treat chronic hyperkalemia. The aim of the present study was to analyse the efficacy and safety of Patiromer in patients with CKD Method Multicenter, prospective, clinical practice study in patients with CKD stages 3-5. Patiromer was administered with the indication of chronic hyperkalemia. Epidemiological and clinical data were analyzed; the evolution of serum potassium and elements involved in bone and mineral metabolism were taken into account. Results Finally, 52 patients (71±12 years old, 75% male, 63% diabetic, 54% with heart failure, and 42% receiving RAAS inhibitors) were included in the study. Regarding CKD, 17% were in stage 3b, 31% in stage 4, 38% in stage 5 (not on dialysis) and 13% were on HD. Of the 52 patients included, 46 reached 6 months of follow-up, 2 died, 2 underwent a kidney transplant and 2 were transferred to another center. The initial dose of Patiromer was in all cases 8.4 g administered orally in a single dose. Only one patient required doubling the dose because the therapeutic objectives were not achieved. Taking Patiromer was associated with a decrease in the levels of serum potassium of 27% (5.9 vs 4.6 mEq/L; P&amp;lt;0.001), a decrease that was more pronounced in the first month of treatment. There were no changes in the concentration of serum calcium and magnesium. We did find a decrease of 18% in serum phosphorus (5.1 vs 4.2 mg/dl; P 0.022), with no changes in dieto r phosphate binders. Patiromer was well tolerated and only 2 patients reported mild constipation; none discontinued the medication due to adverse effects. Conclusion Patiromer is effective and safe in reducing serum potassium concentrations. Due to its calcium content, it is possible that it favors the reduction in phosphoremia due to a decrease in the intestinal absorption of phosphorus. The use of this drug can help us control potassium levels in patients with CKD, properly titrate the use of ISRAAs, and even reduce the number of HD sessions or dialysis emergencies in some patients.

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.

Effects of Vitamin D on the Renin-Angiotensin System and Acute Childhood Pneumonia.

Vitamin D promotes kidney calcium reabsorption and regulates calcium and phosphate metabolism, as well as the intestinal absorption of calcium and phosphorus and bone mineralization events. Vitamin D is also known for its immunomodulatory properties. It has been shown in the literature that the active form of vitamin D, 1,25-dihydroxyvitamin D, performs multiple functions in the adaptive and innate immune system, as well as acting on the endothelial membrane. Recent evidence shows that vitamin D is a negative endocrine modulator of the renin-angiotensin system (RAS), with protection from diseases leading to lung damage, such as pneumonia caused by various pathogens. Vitamin D support associated with the use of antibiotics could be crucial to counteract these infectious diseases.

Selective vitamin D receptor activator Paricalcitol and its potential benefits in hemodialysis patients with secondary hyperparathyroidism

Currently, the incidence and prevalence of chronic kidney disease (CKD) are increasing annually worldwide, and clinical data show that CKD patients commonly experience relative vitamin D insufficiency or deficiency. Secondary hyperparathyroidism (SHPT) is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients. SHPT is an adaptive and in many cases ultimately maladaptive process that develops in response to declining kidney function, impaired phosphate excretion, failure to bioactivate vitamin D and hypocalcemia. SHPT is characterized by persistently elevated levels of parathyroid hormone (PTH) and complicated by important disturbances in mineral metabolism. Maintaining the level of vitamin D and parathyroid hormone concentrations in the target range reduce its associated complications (e.g., fractures, chronic kidney disease and cardiovascular calcification). Effective therapeutic interventions are highly desirable if the morbidity and mortality associated with uncontrolled SHPT are to be reduced. Major renal guidelines recommend use of vitamin D for secondary hyperparathyroidism in chronic kidney disease. However, because of the difficulties associated with lowering PTH while simultaneously controlling serum levels of calcium and phosphorous, traditional therapies for managing SHPT have several limitations. Selective vitamin D receptor activator paricalcitol mainly targets vitamin D receptors (VDR) in the parathyroid glands, has less effect on VDR in the intestine and other tissues, inhibits PTH strongly, triggers less hypercalcemia, and has less effect on intestinal absorption of calcium, phosphorus and bone metabolism and significantly lowers renin levels, albuminuria and blood pressure, which is supported by the results of most studies conducted over these decades. The article is devoted to the problem of treatment of patients with SHPT inpatient with renal replacement therapy with program hemodialysis.

Intestinal Phosphorus Absorption in Moderate CKD and Healthy Adults Determined Using a Radioisotopic Tracer.

Reducing intestinal phosphorus absorption is a cornerstone in CKD-MBD management. Yet, knowledge gaps include how CKD pathophysiology affects intestinal phosphorus absorption. In vivo rodent studies suggest that intestinal phosphorus absorption remains inappropriately normal in early-moderate CKD, despite declining 1,25-dihydroxyvitamin D (1,25D). We measured intestinal phosphorus absorption in patients with moderate CKD versus healthy adults using a direct radiotracer method. Patients with CKD and healthy adults matched for age, sex, and race were enrolled in this 8-day controlled diet study: the first 6 days outpatient and the final 2 days inpatient. Oral and intravenous doses of 33P and serial blood and urine sampling determined intestinal phosphorus absorption during the final 2 days. Secondary outcomes included fasting biochemistries and 24-hour urine phosphorus (uP). In total, n=8 patients with CKD (eGFR=29-55 ml/min per 1.73 m2) and n=8 matched healthy controls completed the study. On a controlled diet, no difference in fractional intestinal phosphorus absorption was detected between patients with CKD and healthy adults (0.69 versus 0.62, respectively; P=0.52), and this was similar for 24-hour uP (884 versus 935 mg/d, respectively; P=0.70). Fractional intestinal phosphorus absorption was not significantly related to 24-hour uP. Patients with CKD had higher serum intact PTH and intact FGF23 and lower 1,25D. The relationship between 1,25D and fractional intestinal phosphorus absorption was not statistically significant. Intestinal phosphorus absorption with typical dietary intake did not differ in patients with moderate CKD compared with controls, despite lower serum 1,25D levels. In this setting, a relationship between 24-hour uP and fractional or absolute intestinal absorption was not evident. Further investigation is needed to determine what factors influence intestinal phosphorus absorption in CKD and the apparent lack of compensation by the intestine to limit phosphorus absorption in the face of declining kidney function and reduced 1,25D. Whether this is evident across a range of dietary phosphorus intakes, as well as CKD severity, also needs to be determined. Phosphorus Absorption in Healthy Adults and in Patients with Moderate Chronic Kidney Disease, NCT03108222.

Intestinal phosphorus absorption: recent findings in translational and clinical research.

The purpose of this review is to discuss recent findings in intestinal phosphorus absorption pathways, particularly the contributions of paracellular versus transcellular absorption, and the differential findings from studies using in vitro versus in vivo techniques of assessing phosphorus absorption in experimental animal studies. Experimental animal studies show that in vivo effects of low phosphorus diets, 1,25D, and chronic kidney disease on intestinal phosphorus absorption efficiency contradict effects previously established ex vivo/in vitro. Recent in vivo studies also suggest that the paracellular pathway accounts for the majority of phosphorus absorption in animals across very low to high luminal phosphate concentrations. The data from experimental animal studies correspond to recent human studies showing the effectiveness of targeted inhibition of paracellular phosphate absorption. Additionally, recent human studies have demonstrated that NaPi-2b inhibition alone does not appear to be effective in lowering serum phosphate levels in patients with chronic kidney disease. Pursuit of other transcellular phosphate transporter inhibitors may still hold promise. In vivo animal and human studies have added to our understanding of intestinal phosphorus absorption pathways, regulation, and mechanisms. This is beneficial for developing effective new strategies for phosphate management in patients with chronic kidney disease.

Estimated intestinal absorption of phosphorus and its deposition in chosen tissues, bones and feathers of chickens receiving chromium picolinate or chromium nanoparticles in diet.

The aim of the study was to determine whether the level and form of Cr in the diet of chickens influences its accumulation in tissues as well as intestinal absorption of P and its deposition in tissues. The experiment was carried out on 405 one-day-old male Ross 308 chickens that were randomly divided into five treatment groups. Control group was fed the diet without supplemental chromium; experimental groups were fed the diet with 3 or 6 mg/kg chromium picolinate (Cr-Pic) and with 3 or 6 mg/kg chromium nanoparticles (Cr-NP). Chromium was found to accumulate in the tissues of the ileum, liver, breast muscle, bones skin and in feathers of chickens. Chromium deposited in the ileum of chickens does not affect the ex vivo estimated intestinal absorption of P. The use of Cr in the diet of chickens carries the risk of lowering P levels in femur.

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.

Kidney Disease Progression Does Not Decrease Intestinal Phosphorus Absorption in a Rat Model of Chronic Kidney Disease-Mineral Bone Disorder.

The Cy/+ rat has been characterized as a progressive model of chronic kidney disease-mineral bone disorder (CKD-MBD). We aimed to determine the effect of kidney disease progression on intestinal phosphorus absorption and whole-body phosphorus balance in this model. A total of 48 Cy/+ (CKD) and 48 normal littermates (NL) rats were studied at two ages: 20 weeks and 30 weeks, to model progressive kidney function decline at approximately 50% and 20% of normal kidney function. Sodium-dependent and sodium-independent intestinal phosphorus absorption efficiency were measured by the in situ jejunal ligated loop method using 33 P radioisotope. Our results show that CKD rats had slightly higher sodium-dependent phosphorus absorption compared to NL rats, and absorption decreased from 20 to 30 weeks. These results are in contrast to plasma 1,25OH2 D, which was lower in CKD rats. Gene expression of the major intestinal phosphorus transporter, NaPi-2b, was not different between CKD and NL rats in the jejunum but was lower in CKD rats versus NL rats in the duodenum. Jejunal ligated loop phosphorus absorption results are consistent with percent net phosphorus absorption results obtained from metabolic balance: higher net percent phosphorus absorption values in CKD rats compared with NL, and lower values in 30-week-olds compared with 20-week-olds. Phosphorus balance was negative (below zero) in CKD rats, significantly lower in 30-week-old rats compared with 20-week-old rats, and lower in CKD rats compared with NL rats at both ages. These results demonstrate no reduction in intestinal phosphorus absorption with progression of CKD despite lower 1,25OH2 D status when assessed by an in situ ligated loop test, which is in contrast to the majority of in vitro studies, and if confirmed in further studies, could challenge the physiological relevance of in vitro findings. © 2019 American Society for Bone and Mineral Research.

Approach to the patient with vitamin D-deficient osteomalacia due to X-linked agammaglobulinemia

Osteomalacia is a metabolic bone disease characterized by impaired mineralization of bone matrix. VitaminD deficiency contributes to a decrease in the efficiency of intestinal calcium and phosphorus absorption, resulting in secondary hyperparathyroidism and an inadequate calcium-phosphorus product, thereby causing osteomalacia. We present a patient who was diagnosed as vitamin D-deficient osteomalacia due to X-linked agammaglobulinemia (XLA), and the genetic analysis of the BTK gene revealed a missense mutation (c.82C>T). It should be attached great importance to etiological analysis of osteomalacia, and XLA may also be a cause of vitamin D deficiency. Key words: Osteomalacia; Vitamin D deficiency; X-linked agammaglobulinemia

3318 Phosphorus Absorption in Healthy Adults and in Patients with Moderate Chronic Kidney Disease

OBJECTIVES/SPECIFIC AIMS: The aim of this study is to compare intestinal phosphorus absorption in healthy adults and moderate stage chronic kidney disease patients in the context of a controlled feeding study METHODS/STUDY POPULATION: Participants are 30-75 years old and include 10 healthy subjects and 10 moderate-staged CKD patients. Each subject pool will be enrolled in a 9-day study period including 7 days of controlled feeding of a 1500 mg phosphorus diet. Following the controlled feeding, two days of absorption tests will take place (oral and IV tests) utilizing radioisotopic phosphorus to calculate fractional absorption efficiency. RESULTS/ANTICIPATED RESULTS: Current enrollment has produced 7 total matched subject (current n = 14/20). Four of the 7 pairs of completed subjects are female and 3 of 7 are black. Preliminary kinetic modeling data from the first enrolled subject show a moderate CKD patient with fractional absorption of 0.375. With forthcoming analyses, we expect that this fractional absorption result will not be statistically different from this subject’s matched pair, nor will each groups average absorption be different from the other. Additionally, we expect absorption to be maintained even with changes in secondary outcomes measures in serum (FGF23, 1,25-dihydroxyvitamin D, parathyroid hormone, and total phosphorus) in CKD patients. DISCUSSION/SIGNIFICANCE OF IMPACT: Lack of statistical difference in fractional phosphorus absorption between gropus would support that intestinal phosphorus absorption is inappropriately normal in CKD patients compared to healthy adults, despite evidence of abnormal phosphorus homeostatic mechanisms. Future studies will consider the effect of dietary P restriction, the most common nutrition intervention in moderate stage CKD, on fractional absorption efficiency in CKD.

Effect of dietary phosphorus intake and age on intestinal phosphorus absorption efficiency and phosphorus balance in male rats

Intestinal phosphorus absorption is an important component of whole-body phosphorus metabolism, and limiting dietary phosphorus absorption is particularly of interest as a therapeutic target in patients with chronic kidney disease to manage mineral bone disorders. Yet, mechanisms and regulation of intestinal phosphorus absorption have not been adequately studied and discrepancies in findings exist based on the absorption assessment technique used. In vitro techniques show rather consistent effects of dietary phosphorus intake level and age on intestinal sodium-dependent phosphate transport. But, the few studies that have used in vivo techniques conflict with these in vitro studies. Therefore, we aimed to investigate the effects of dietary phosphorus intake level on phosphorus absorption using the in situ ligated loop technique in three different aged rats. Male Sprague-Dawley rats (n = 72), were studied at 10-, 20-, and 30-weeks-of-age on a low (0.1%), normal (0.6%), or high (1.2%) phosphorus diet in a 3x3 factorial design (n = 8/group). Rats were fed their assigned diet for 2-weeks prior to absorption testing by jejunal ligated loop as a non-survival procedure, utilizing 33P radioisotope. Metabolic cages were used for determination of calcium and phosphorus balance over the final four days prior to sacrifice, and blood was collected at the time of sacrifice for biochemistries. Our results show that phosphorus absorption was higher in 10-week-old rats compared with 20- and 30-week-olds and this corresponded to higher gene expression of the major phosphate transporter, NaPi-2b, as well as higher whole-body phosphorus balance and net phosphorus absorption. Dietary phosphorus intake level did not affect jejunal phosphorus absorption or NaPi-2b gene expression. Our results contrast with studies utilizing in vitro techniques, but corroborate results of other rodent studies utilizing in situ or in vivo methods. Thus, there is need for additional studies that employ more physiological methods of phosphorus absorption assessment.

Intestinal Phosphorus Absorption in Chronic Kidney Disease.

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.

Bone remodeling through a phosphate metabolism.

Phosphorus is the second abundant mineral stored in bones, and disturbance of phosphate metabolisms results in various disease developments such as hypophosphatemic rickets. Blood phosphorus levels are regulated by dietary intake or its absorption from intestine, proximal tubular reabsorption, and number of factors plays roles for maintaining phosphate homeostasis. Vitamin D stimulates intestinal phosphorus absorption, and phosphorus promotes FGF23 secretion from osteocytes. FGF23 inhibits Cyp27b1, an enzyme to produce an active vitamin D3, 1,25(OH)2D3, through FGF receptor/Klotho complex. In this review, I will discuss about the roles of Enpp1 in regulating the FGF23-Klotho-vitamin D axis and bones.

Vitamin D and male reproductive system.

Vitamin D deficiency is a highly prevalent worldwide condition and affects people of all ages. The most important role of vitamin D is the regulation of intestinal calcium absorption and metabolism of calcium and phosphorus to maintain muscle and bone homeostasis. Furthermore, in recent years it has been discovered that the vitamin D receptor (VDR) is widely distributed in many organs and tissues where vitamin D can perform other actions that include the modulation of the immune response, insulin secretion, anti-proliferative effect on cells of vascular smooth muscle, modulation of the renin-angiotensin-aldosterone system and regulates cell growth in several organs. The VDR is widely distributed in the male reproductive system. Vitamin D induces changes in the spermatozoa's calcium and cholesterol content and in protein phosphorylation to tyrosine/threonine residues. These changes could be involved in sperm capacitation. Vitamin D seems to regulate aromatase expression in different tissues. Studies analyzing seasonal variations of sex steroids in male populations yield conflicting results. This is probably due to the wide heterogeneity of the populations included according to age, systemic diseases and obesity.

Fibroblast growth factor-23 and phosphorus related factors in young Japanese women: a cross-sectional study.

Phosphorus homeostasis is determined by dietary intake, intestinal absorption, and renal tubular reabsorption of phosphorus. Serum fibroblast growth factor-23 (FGF-23) is considered to be a sensitive early biomarker of disordered phosphorus metabolism in both patients with chronic kidney diseases and healthy subjects. However, the number of studies evaluating serum FGF-23 concentrations in healthy subjects is limited. The objective of this cross-sectional study was to examine the relationship between serum FGF-23 concentrations and phosphorus related factors in 182 young Japanese women (mean age, 19.5±0.4 years). We found that higher serum concentrations of inorganic phosphorus and lower serum concentrations of 1,25-dihydroxy vitamin D as well as lower fat but higher phosphorus and calcium intake were weakly but significantly associated with high serum concentrations of FGF-23, adjusted for postmenarcheal age and body weight. These results suggested that in young Japanese women, serum FGF-23 might be indicative of phosphorus nutrition status. However, it is worthy of note that maturity factors, including postmenarcheal age and physical attributes, such as body weight, might be related to serum FGF-23 concentrations.

Effect of dietary phosphorus on intestinal phosphorus absorption in growing Holstein steers

The effect of dietary P intake on intestinal P absorption was evaluated in growing Holstein steers. Diets varying in P content (0.15, 0.27, 0.36, and 0.45%, DM basis) were fed to 8 steers (174±10kg of BW) fitted with permanent duodenal and ileal cannulas in a replicated 4×4 Latin square with 14-d periods. Ytterbium-labeled corn silage and cobalt-EDTA were used as particulate and liquid phase markers, respectively, to measure digesta flow. Duodenal and ileal samples and spot urine samples were collected every 9 h from d 11 to 14. Total fecal collection was conducted on d 11 to 14 with fecal bags. Blood samples were collected from the coccygeal vessel on d 14. Feed, digesta, and fecal samples were analyzed for total P and inorganic P. Data were analyzed using PROC GLIMMIX in SAS with a model including treatment, square, period, and interaction of treatment and square. Preplanned contrasts were used to evaluate linear and quadratic treatment effects. Results were reported as least squares means. Dry matter intake (mean=4.90kg/d, 2.8% of BW) and apparent DM digestibility (mean=78.1%) were unaffected by treatment. Duodenal and ileal flow of total P increased linearly with increasing P intake (13.4, 18.5, 23.0, and 27.4g/d; 6.80, 7.87, 8.42, and 10.4g/d). Increasing P intake increased the quantity of P absorbed from the small intestine linearly (6.96, 11.1, 14.6, and 17.2g/d), but absorption efficiency was unchanged (mean=59.6%). Phosphorus was absorbed on a net basis from the large intestine, but this was not affected by treatment and was a small proportion of total P absorption. Blood inorganic P increased linearly with increased dietary P (4.36, 6.31, 7.68, and 8.5mg/dL) and salivary P secretion was unchanged (mean=5.79g/d), suggesting that rumen function was prioritized during short-term P deficiency. These data showing an absence of change in absorption efficiency and salivary P secretion in the face of short-term P deficiency may be used to improve published models of P digestion, absorption, and metabolism.

Dietary management of hyperphosphatemia in chronic kidney disease

Abstract Dysregulation of phosphate homeostasis occurs in chronic kidney disease (CKD). Hyperphosphatemia is an ongoing challenge in treating CKD patients. Restriction of dietary proteins remains one of the cornerstones of nutritional management of CKD patients foods from animal sources are rich in organic phosphorus. Foods sources including certain beverages like colas, enhanced meats, frozen meals, snack bars, processed or spreadable cheeses, instant food products, and refrigerated bakery products are rich in inorganic phosphorus. Phosphate additives added to foods further increases the phosphorus burden. It is estimated that the intestinal absorption of inorganic phosphorus is usually more than 90% compared to only 40%–60% from that of the organic phosphorus. Phosphates from animal food are more readily absorbed compared to that present in plant foods sources as majority of it is present in the form of phytate and hence not readily absorbed. Intensive nutritional counseling regarding phosphorus content of foods, their bioavailability with an emphasis on consumption of a mixed diet including foods from animal sources and plant sources high in phytate. While limiting or avoiding the intake from foods very high in phosphorus to protein ratio and foods rich in phosphorus additives but with an adequate protein content to avoid malnutrition, reinforcement on dietary compliance and judicious use of phosphorus binders are important for the better management of hyperphosphatemia in CKD. Methods like soaking foods in water and boiling them helps in reducing the dietary phosphorus content per gram of protein in foods.