Plasma Phosphorus Concentrations Research Articles

Nutritional Infertility and Ameliorative Measures in Dairy Animals of Middle Gujarat

Fertility improvement camps were organized in different villages of middle Gujarat covering 1481 breedable cattle and buffaloes with the history of impaired fertility. The reproductive status of animals was ascertained through gynaeco-clinical examination per rectum. Blood sampling (n=305) was done from representative groups of animals to know the nutritional status. All non-infectious infertile animals were dewormed using either Inj. Ivermectin 100 mg s/c or bolus Fenbendazole + Ivermectin 3.0 g orally. Anestrus animals (n=265) were then nutritionally supplemented either with chelated area specific mineral mixture (ASMM, 50-60 g/d/h) or multi-minerals boli - one on alternate day, with and without bypass fat (75-80 g/d/h) for one month along with an advice to improve feeding level, estrus detection and timely breeding. Revisits were made after 2.5-3.0 months to check the reproductive status. The mean blood glucose concentrations were significantly lower (p less than 0.05), while total cholesterol and zinc levels were higher (p less than 0.05) in anestrus than in subestrus and/or repeat breeding cows and buffaloes. Moreover, the plasma total cholesterol levels in buffaloes were just one half to those of cows. Further, the plasma total protein, calcium, phosphorus, magnesium, iron, copper and cobalt concentrations were found to be nonsignificantly higher in repeat breeders than in anestrus or subestrus cows and buffaloes. Calcium was deficient in some 20% animals and calcium: phosphorus ratio varied from 1:1 to 1.8:1 in animals under different areas of study indicating its role in causing infertility in dairy animals. Supplementation of ASMM, multi-mineral boli alone or in combination with bypass fat in pubertal /postpartum anestrus animals resulted in 34-56% estrus induction response and 33-50% conception rate, both being better with mineral plus bypass fat supplementation than minerals alone.

Effects of gelatin prepared from calf bones rich in phosphorus on broiler performance, bone characteristics and digestive enzymes activity

ABSTRACT1. Gelatin prepared from calf bones (GCB) is a novel source of high-quality protein and phosphorus. Its inclusion in broiler chicken diets may improve bone strength, plasma and digestive alkaline phosphatase activity (ALP), phosphorus digestibility and performance of broilers. Therefore, di-calcium phosphate in a corn-soy control diet was replaced with 12, 24, and 36 g/kg of GCB in a completely randomised design with four treatments of six replicates and 10 chicks in each pen. The trial lasted from 1 to 42 d of age.2. Body weight and feed intake were measured weekly. Plasma calcium and phosphorus concentration along with plasma and digestive ALP were assayed throughout the trial. Trypsin, α-amylase, lipase and total protease activity were assayed at 14 and 28 d of age. Tibia ash, calcium and phosphorus content and breaking strength were measured at 14, 28 and 42 d of age. Phosphorus digestibility was measured at 36 d of age.3. Body weight and feed intake showed no significant differences between controls and diets containing 12 and 36 g/kg GCB. Tibia ash and tibia length were increased by supplementation of GCB (P ≤ 0.001). Tibia calcium and phosphorus content were increased by GCB inclusion at 14 d of age (P ≤ 0.001). Digestive alkaline phosphatase activity was increased and trypsin activity was reduced by inclusion of GCB (P ≤ 0.001; P ≤ 0.004). α-amylase activity decreased by inclusion of 12 and 24 g/kg GCB, whereas an increase in α-amylase activity was observed by inclusion of 36 g/kg GCB (P ≤ 0.001). Supplementation of diets with GCB increased phosphorus digestibility (P ≤ 0.01) and suppressed ileum growth during the experimental period.4. Results of the current study showed that phosphorus from gelatin can greatly improve broiler bone characteristics and phosphorus digestibility and complete elimination of inorganic phosphate sources from broiler diets is feasible with inclusion of 36 g/kg high phosphorus gelatin.

Effect of daily milk production levels on plasma calcium, phosphorus and magnesium concentrations in dairy cows

The aim of this study was to determine the serum level of calcium (Ca), phosphorus (P) and magnesium (Mg) and hence determine the relationship and the effect of daily milk production on the mentioned essential macro elements. The metabolism and neurohumoral regulation of Ca, P and Mg are closely related, and the metabolic disorder of one of these electrolytes inevitably affects the metabolism of the other two. The study was carried out in the winter period of animal keeping and nutrition, and it included 63 Holstein-Friesian breed cows in the northern region of Bosnia and Herzegovina, aged 2-9 years in different lactation stages (1-8). The largest number of cows, eighteen of them, were in the second, third and fourth lactation stage, while nine cows were in the first lactation stage. This study was conducted on three different groups of cows corresponding to the amount of daily milk production. First was the group of lower daily milk production n=21, the second group of examined cows was the group of medium daily milk production n=23 and third was the group of higher daily milk production n=19. Ca, P and Mg were determined in blood plasma using the Beckmann spectrophotometer. By examining the obtained results and the dynamics of the tested mineral substances, we point out the different behaviour of the Ca-P relationship in correlation with the different level of daily milk produced. Although the average values ​​of both minerals are lowered with an increase in daily milk production, the analysis of single linear regression shows that there is a negative correlation between P concentration in blood plasma and the amount of daily milk produced, while for Ca it has not been established. Although the concentration of Mg in the blood plasma increases as the daily milk production increases, the analysis of single linear regression does not show a significant interconnection of these two values. Lower average values of Ca and P concentrations in the blood of cows with higher daily milk production may be associated with increased total excretion of these minerals through milk, unlike the cows which daily produced lower amounts of milk.

Calcium metabolism-related hormonal changes in layers experimentally infected with Salmonella Gallinarum

The present study was conducted to investigate the calcium metabolism-related hormonal changes in layers experimentally infected with Salmonella Gallinarum. A total of 20 18-week-old ISA brown layers were purchased from a commercial poultry farm in Kujama farm, Kaduna State, Nigeria. The birds were allowed to acclimatize for a period of 4 weeks prior to commencement of the experiment. On the day of infection with Salmonella Gallinarum, the birds were randomly divided into two groups, infected and control, of 10 birds each. To establish the infection, each bird in the infected group was orally administered 0.5 ml of the inoculum containing 9 × 108 CFU/ml. Similarly, birds in the control group were each administered 0.5 ml normal saline only. Following the inoculation, all experimental birds were closely monitored for clinical signs of fowl typhoid. Blood samples were collected from each group and was dispensed into heparinized bottles for plasma separation at day zero (day 0), 2, 4, 7, 14, 21, 28, 35, and 42 post-infection (pi) and was used for determination of hormones and electrolyte parameters. By day 7 post-infection, all birds in the infected group showed clinical signs typical of fowl typhoid, namely weakness, ruffled feathers, huddling together, somnolence, greenish-yellow diarrhea, weight loss, drop in egg production, decrease in feed and water consumption, and mortality rate (50%). There were, however, significant decrease in plasma calcium and phosphorus concentrations and significant increase in plasma estrogen and parathyroid hormone concentration in the Salmonella Gallinarum-infected layers. In conclusion, the decrease in plasma calcium and phosphorus concentrations observed in the Salmonella Gallinarum experimentally infected layers was a consequence of hepatic, renal, and gastrointestinal lesions and not due to endocrine dysfunction as plasma levels of the hormones did not suggest so.

Effects of profound acidemia on the dynamic glucose and insulin response and plasma potassium and phosphorus concentrations during an intravenous glucose tolerance test in neonatal calves

Acidemia and electrolyte imbalances such as hyperkalemia are common in neonatal calves with diarrhea. Acidemia negatively affects the cellular response to insulin and may therefore result in deranged glucose, potassium, and phosphorus homeostasis. The primary aim of this study was to compare indices that characterize the dynamic glucose and insulin response between acidemic and nonacidemic neonatal diarrheic calves and a healthy control group during an intravenous glucose tolerance test (IVGTT) that consisted of i.v. administration of 0.3 g of glucose per kg of body weight. Secondary aims were to characterize the associated changes in plasma potassium and phosphorus concentrations. The effect of correction of profound acidemia with a sodium bicarbonate containing infusion on these parameters was also assessed. Thirty calves (age ≤21 d) were purposively assigned to one of the following groups: 10 calves with diarrhea and profound acidemia (venous blood pH <7.20) where an IVGTT was performed before and after treatment with sodium bicarbonate, 10 calves with diarrhea and minimal acid-base disturbance (venous blood pH >7.35), and 10 healthy control calves. Profoundly acidemic diarrheic calves (jugular venous blood pH 6.99 ± 0.10) had a similar initial increase in plasma insulin concentration to that in healthy control calves or nonacidemic calves with diarrhea. However, insulin concentrations remained relatively stable in acidemic calves between 15 and 60 min after the start of the IVGTT, whereas a marked decrease in plasma insulin concentrations occurred in all other groups during the same period of time. We conclude that acidemia does not alter cell glucose availability or the dynamic response of glucose, phosphorus, and potassium to insulin; however, acidemia markedly prolongs plasma insulin concentrations following an IVGTT through an unidentified mechanism. Results of this study emphasize the importance of correcting acidemia and metabolic acidosis in neonatal calves with diarrhea.

Changes in white cell estimates and plasma chemistry measurements following oral or external dosing of double-crested cormorants, Phalacocorax auritus, with artificially weathered MC252 oil

Scoping studies were designed whereby double-crested cormorants (Phalacocorax auritus) were dosed with artificially weathered Deepwater Horizon (DWH) oil either daily through oil injected feeder fish, or by application of oil directly to feathers every three days. Preening results in oil ingestion, and may be an effective means of orally dosing birds with toxicant to improve our understanding of the full range of physiological effects of oral oil ingestion on birds. Blood samples collected every 5–6 days were analyzed for a number of clinical endpoints including white blood cell (WBC) estimates and differential cell counts. Plasma biochemical evaluations were performed for changes associated with oil toxicity. Oral dosing and application of oil to feathers resulted in clinical signs and statistically significant changes in a number of biochemical endpoints consistent with petroleum exposure. In orally dosed birds there were statistically significant decreases in aspartate amino transferase (AST) and gamma glutamyl transferase (GGT) activities, calcium, chloride, cholesterol, glucose, and total protein concentrations, and increases in plasma urea, uric acid, and phosphorus concentrations. Plasma electrophoresis endpoints (pre-albumin, albumin, alpha-2 globulin, beta globulin, and gamma globulin concentrations and albumin: globulin ratios) were decreased in orally dosed birds. Birds with external oil had increases in urea, creatinine, uric acid, creatine kinase (CK), glutamate dehydrogenase (GLDH), phosphorus, calcium, chloride, potassium, albumin, alpha-1 globulin and alpha-2 globulin. Decreases were observed in AST, beta globulin and glucose. WBC also differed between treatments; however, this was in part driven by monocytosis present in the externally oiled birds prior to oil treatment.

Serum fibroblast growth factor 23 concentrations in dogs with chronic kidney disease

The aim of this study was to determine if serum fibroblast growth factor (FGF23) concentrations were increased in dogs with chronic kidney disease (CKD). Serum samples submitted to a commercial laboratory were collected over a 15-month period, 14 samples were from dogs with a history of polyuria/polydipsia, azotaemia and low urine specific gravity, 20 samples were from non-azotaemic dogs. Serum FGF23, parathyroid hormone, total calcium and phosphorus, urea and creatinine were measured. Mann-Whitney test was used to determine differences between non-azotaemic and CKD groups; a one-way ANOVA with Tukey pairwise comparisons was used to determine any differences between International Renal Interest Society stages; and regression models were used to determine predictors of International Renal Interest Society stage, serum phosphorus and FGF23 concentrations. The median serum FGF23 concentration of dogs with CKD was 5194.6pg/mL, which was significantly greater (P<0.001) than the median serum FGF23 concentration of non-azotaemic dogs (259.2pg/mL). Log serum FGF23 and age were significantly associated with IRIS stage (P=0.027 and P=0.032 respectively), while log serum phosphorus concentration (P<0.001) was significantly associated with log serum FGF23 concentration. In summary, serum FGF23 concentration is increased in dogs with CKD, and is associated with serum phosphorus concentration. This phosphatonin pathway may be a useful target for the development of future treatments to control plasma phosphorus concentrations in chronic kidney disease.

Comparative effects of human chorionic gonadotropin (hCG) and Ovaprim™ (sGnRHa + domperidone) on the reproductive characteristics of wild-caught male Longspine scraper, Capoeta trutta (Heckel, 1843)

The effectiveness of two different hormonal treatments or a saline control on sperm characteristics, plasma sex steroids and testes histology of male Longspine scraper, Capoeta trutta (Heckel, 1843) collected from the wild and maintained in captivity were tested. Fish injected with Ovaprim™ had significantly increased gonadosomatic index (GSI) and sperm volume, but had decreased spermatozoa concentration and spermatocrit compared with control. Fish injected with hCG had significantly decreased motility duration of their sperm, as well as decreased spermatozoa concentration and spermatocrit. Both treatments increased seminal plasma pH compared with control, while decreases in osmolality of seminal plasma occurred only in Ovaprim™-treated fish.Hormonal treatments altered the seminal plasma sodium (Na+), calcium (Ca2+), magnesium (Mg2+), glucose, phosphorus, urea, creatinine, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) concentrations. However, neither treatment affected the seminal plasma potassium (K+), chloride (Cl−), uric acid, total protein, cholesterol, triglycerides, and aspartate aminotransferase (AST) concentrations.The concentration of 17,20β-dihydroxy-4-pregnen-3-one (DHP) in the plasma was significantly enhanced by Ovaprim™ treatment, but not by hCG. On the other hand, plasma testosterone (T) was significantly elevated by both treatments.Histological examination of the testes revealed stimulation of testicular maturation following treatment with Ovaprim™, with lobules observed that were filled exclusively with a large number of spermatozoa (spz). In summary, hormonal treatments stimulated steroidogenesis and spermiation in male C. trutta, with highest efficiency of the Ovaprim™ treatment. Therefore, it can be concluded that like many other cyprinids, dopamine inhibitory action was operating in C. trutta, thus requiring anti-dopaminergic and hormonal treatments to overcome this in order to maximize steroidogenesis and induction of spermiation. Statement of relevanceThe research I present in this paper is novel, as:•The effectiveness of exogenous hormones on male C. trutta reproduction under controlled conditions;•The effect of hormonal treatment on a wide range of seminal plasma compositions in C. trutta;•Valuable information which will assist commercial facilities in organizing and, spermiation success in this new aquaculture species.

Pharmacokinetic and Pharmacodynamic Properties of Cinacalcet (KRN1493) in Chinese Healthy Volunteers: A Randomized, Open-label, Single Ascending–dose and Multiple-dose, Parallel-group Study

PurposeThe aim of this study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) properties and safety of single and multiple doses of cinacalcet in Chinese healthy volunteers (HVs) for the purposes of a New Drug Application package for the Chinese Food and Drug Administration. MethodsIn this randomized, open-label, single ascending–dose and multiple-dose, parallel-group study, 42 Chinese HVs were randomized to receive a single oral dose of 25, 50, or 100 mg of cinacalcet and multiple doses of 50 mg of cinacalcet once daily for 7 days. Plasma cinacalcet concentrations were analyzed by HPLC-MS/MS. The PK parameters were assessed with noncompartmental analysis. Plasma intact parathyroid hormone, serum calcium, and phosphorus concentrations were measured for PD evaluation. The safety profile was also assessed. Adverse events (AEs) were noted during the study. FindingsOf the 42 randomized HVs, 41 completed the study per protocol; 1 prematurely discontinued the study because of AEs. Cinacalcet has nonlinear PK properties over a dose range of 25 to 100 mg after a single dose. Mean (SD) Cmax values were 7.68 (4.25), 17 (6.33), and 31.3 (16.42) ng/mL with single doses of 25, 50, and 100 mg of cinacalcet, respectively. Mean (SD) AUC0– last values were 58.4 (25.38), 187 (70.7), and 367 (180.03) hr∙ng/mL with single doses of 25, 50, and 100 mg of cinacalcet, respectively. Steady state was attained within 7 doses of successive daily administration of 50 mg of cinacalcet. At steady state, the mean (SD) Cmax and AUC0–last values were 20.6 (9.63) ng/mL and 297 (146.15) ng∙h/mL. The accumulation ratios of Cmax and AUC (AUCτ/AUC0–24) were 1.21 and 1.32. Plasma intact parathyroid hormone and serum calcium concentrations had similar patterns, both decreased after administration of cinacalcet, whether after single dose or multiple doses. A total of 52 AEs were reported in 20 HVs (47.6%). The most frequently reported AEs after single-dose and multiple-dose cinacalcet administration were hypocalcemia, numbness, dizziness, and muscle soreness. No serious AEs were reported. ImplicationsCinacalcet was well tolerated and effective after administration of a single oral dose up to 100 mg and multiple doses of 50 mg of cinacalcet once daily for 7 days. Cinacalcet has nonlinear PK properties over a dose range of 25 to 100 mg after a single dose. PK profiles after multiple doses were similar to those after a single dose with no accumulation. Cinacalcet had similar PK and safety profiles between Chinese and Western HVs at the same dose levels.

Effect of a Ferric Citrate Formulation, a Phosphate Binder, on Oxidative Stress in Chronic Kidney Diseases-Mineral and Bone Disorder Patients Receiving Hemodialysis: A Pilot Study.

A ferric citrate formulation for treating hyperphosphatemia is a new therapeutic that not only suppresses the accumulation of phosphorus in patients with chronic kidney disease-mineral bone disorders (CKD-MBD), but also ameliorates anemia caused by iron deficiency. In contrast, it has been demonstrated that intravenous iron injection markedly increases oxidative stress. This study was designed to investigate the effect of a ferric citrate formulation on oxidative stress in CKD-MBD patients receiving hemodialysis therapy. Fifteen CKD-MBD patients undergoing dialysis were enrolled in this study. The patients were orally administered a ferric citrate formulation for 6 months. Their plasma phosphorus concentrations remained unchanged with the switch from other phosphorus adsorbents to the ferric citrate formulation. In addition, the ferric citrate formulation generally allowed for dose reduction of an erythropoiesis stimulating agent with an increased hematopoietic effect. The average values of plasma ferritin level increased after the introduction of a ferric citrate formulation, but did not exceed 100 (ng/mL). Interestingly, oxidative stress markers did not increase significantly, and anti-oxidative capacity was not significantly decreased at 6 months after the drug administration. Similarly, no change was observed in any inflammation markers. The ferric citrate formulation induces negligible oxidative stress in CKD-MBD patients receiving dialysis under the present clinical condition.

Vitamin D deficiency is a potential risk factor for contrast-induced nephropathy.

Vitamin D deficiency (VDD) is widespread in the general population. Iodinated (IC) or gadolinium-based contrast media (Gd) may decrease renal function in high-risk patients. This study tested the hypothesis that VDD is a predisposing factor for IC- or Gd-induced nephrotoxicity. To this end, male Wistar rats were fed standard (SD) or vitamin D-free diet for 30 days. IC (diatrizoate), Gd (gadoterate meglumine), or 0.9% saline was then administered intravenously and six groups were obtained as the following: SD plus 0.9% saline (Sham-SD), SD plus IC (SD+IC), SD plus Gd (SD+Gd), vitamin D-free diet for 30 days plus 0.9% saline (Sham-VDD30), vitamin D-free diet for 30 days plus IC (VDD30+IC), and vitamin D-free diet for 30 days plus Gd (VDD30+Gd). Renal hemodynamics, redox status, histological, and immunoblot analysis were evaluated 48 h after contrast media (CM) or vehicle infusion. VDD rats showed lower levels of total serum 25-hydroxyvitamin D [25(OH)D], similar plasma calcium and phosphorus concentration, and higher renal renin and angiotensinogen protein expression compared with rats fed SD. IC or Gd infusion did not affect inulin clearance-based estimated glomerular filtration rate (GFR) in rats fed SD but significantly decreased GFR in rats fed vitamin D-free diet. Both CM increased renal angiotensinogen, and the interaction between VDD and CM triggered lower renal endothelial nitric oxide synthase abundance and higher renal thiobarbituric acid reactive substances-to-glutathione ratio (an index of oxidative stress) on VDD30+IC and VDD30+Gd groups. Conversely, worsening of renal function was not accompanied by abnormalities on kidney structure. Additionally, rats on a VDD for 60 days displayed a greater fall in GFR after CM administration. Collectively, our findings suggest that VDD is a potential risk factor for IC- or Gd-induced nephrotoxicity most likely due to imbalance in intrarenal vasoactive substances and oxidative stress.

Selected clinical, biochemical, and electrolyte alterations in anesthetized captive tigers (Panthera tigris) and lions (Panthera leo).

A prospective study to assess changes in selected plasma biochemistry and electrolyte values, plasma insulin and aldosterone concentrations, and electrocardiography (ECG) was performed on eight female captive tigers (Panthera tigris) and three lions (Panthera leo) undergoing general anesthesia for elective laparoscopic ovariectomy. Each animal was sedated with medetomidine (18-25 microg/kg) and midazolam (0.06-0.1 mg/kg) intramuscularly, and anesthesia was induced with ketamine (1.9-3.5 mg/kg) intramuscularly and maintained with isoflurane. Venous blood samples were collected and analyzed for plasma biochemistry parameters and insulin and aldosterone concentrations. An ECG was recorded at the time of each blood sample collection. Mean plasma potassium, glucose, phosphorus, and aldosterone concentrations increased during anesthesia (P < or = 0.05). One tiger developed hyperkalemia (6.5 mmol/L) 2.5 hr after anesthetic induction. Plasma insulin concentrations were initially below the low end of the domestic cat reference interval (72-583 pmol/L), but mean insulin concentration increased (P < or = 0.05) over time compared with the baseline values. Three tigers and two lions had ECG changes that were representative of myocardial hypoxemia. Based on these results, continuous monitoring of clinical and biochemical alterations during general anesthesia in large nondomestic felids is warranted, and consideration should be given to reversal of medetomidine in these animals should significant changes in electrolytes or ECG occur.

Determinants of phosphorus mobilization during hemodialysis

Our recent work proposed a pseudo one-compartment model for describing intradialysis and postdialysis rebound kinetics of phosphorus. In this model, phosphorus is removed directly from a central distribution volume with the rate of phosphorus mobilization from a second, very large compartment proportional to the phosphorus mobilization clearance. Here, we evaluated factors of phosphorus mobilization clearance and postdialysis central distribution volume from 774 patients in the HEMO Study. Phosphorus mobilization clearance and postdialysis central distribution volume were 87 (65, 116) ml/min, median (interquartile range), and 9.4 (7.2, 12.0) liter, respectively. The phosphorus mobilization clearance was significantly higher for male patients than for female patients. Both the phosphorus mobilization clearance and the postdialysis central distribution volume were significantly associated with postdialysis body weight but negatively with the predialysis serum phosphorus concentration. The postdialysis central distribution volume was also significantly associated with age. Overall, the postdialysis central distribution volume was 13.6% of the postdialysis body weight. Thus, the phosphorus mobilization clearance during hemodialysis is higher when predialysis serum phosphorus concentration is low and higher in male patients than in female patients. The central distribution volume of phosphorus is a space approximating the extracellular fluid volume.

Puzzling Phosphorus: Unlikely Results

Discordant plasma phosphorus concentrations (Table 1) were obtained with 2 clinical instruments (concentration range, 4.5–23.8 mg/dL; reference interval, 2.5–4.6 mg/dL) for a 50-year-old woman. Her medical history was positive for idiopathic pulmonary arterial hypertension, chronic kidney disease (stage 1), severe right heart failure, ascites, and thrombocytopenia. During hospitalization, the patient received enteral feeding, cefuroxime, docusate, dronabinol, gabapentin, …

The role of phosphorus in the pathophysiology of chronic kidney disease

To review the human and veterinary literature on the role of phosphorus in the pathophysiology of chronic kidney disease (CKD) and to explore why control of plasma phosphorus concentration is an important goal in the management of patients with this disease. Human and veterinary studies, reviews, clinical reports, textbooks, and recent research findings focused on phosphate homeostasis and CKD patient management. Recent studies using rodent models and human patients with CKD have focused on trying to elucidate the role of the phosphatonins, predominantly fibroblast growth factor-23, in phosphate homeostasis and the pathophysiology of secondary renal hyperparathyroidism (SRHP). Fibroblast growth factor-23 is now considered to be a key regulator of plasma phosphorus concentration in people but has only recently been investigated in companion animal species. Cross-sectional studies of naturally occurring CKD in dogs and cats have shown hyperphosphatemia and SRHP to be highly prevalent and associated with increased morbidity and mortality in these patients. Experimental studies of surgically induced renal impairment in the dog and cat, and cases of naturally occurring CKD have emphasized the ability of renal care diets to modify plasma phosphorus and parathyroid hormone concentrations. Evidence from these studies indicates that maintaining plasma phosphorus concentrations to within the International Renal Interest Society targets for CKD patients improves survival time and reduces clinical manifestations of hyperphosphatemia and SRHP. The maintenance of plasma phosphorus concentrations in to within the International Renal Interest Society targets is recommended in management of CKD patients. The discovery of the phosphatonins has improved understanding of the mechanisms involved in phosphorus homeostasis and SRHP and may lead to improved ability to monitor and manage these patients.

Physiologic volume of phosphorus during hemodialysis: Predictions from a pseudo one‐compartment model

The kinetics of plasma phosphorus concentrations during hemodialysis (HD) are complex and cannot be described by conventional one- or two-compartment kinetic models. It has recently been shown by others that the physiologic (or apparent distribution) volume for phosphorus (Vr-P) increases with increasing treatment time and shows a large variation among patients treated by thrice weekly and daily HD. Here, we describe the dependence of Vr-P on treatment time and predialysis plasma phosphorus concentration as predicted by a novel pseudo one-compartment model. The kinetics of plasma phosphorus during conventional and six times per week daily HD were simulated as a function of treatment time per session for various dialyzer phosphate clearances and patient-specific phosphorus mobilization clearances (K(M)). Vr-P normalized to extracellular volume from these simulations were reported and compared with previously published empirical findings. Simulated results were relatively independent of dialyzer phosphate clearance and treatment frequency. In contrast, Vr-P was strongly dependent on treatment time per session; the increase in Vr-P with treatment time was larger for higher values of K(M). Vr-P was inversely dependent on predialysis plasma phosphorus concentration. There was significant variation among predicted Vr-P values, depending largely on the value of K(M). We conclude that a pseudo one-compartment model can describe the empirical dependence of the physiologic volume of phosphorus on treatment time and predialysis plasma phosphorus concentration. Further, the variation in physiologic volume of phosphorus among HD patients is largely due to differences in patient-specific phosphorus mobilization clearance.

Patient-specific phosphorus mobilization clearance during nocturnal and short daily hemodialysis

The kinetics of plasma phosphorus during different hemodialysis (HD) modalities are incompletely understood. We recently demonstrated that a pseudo one-compartment kinetic model including phosphorus mobilization from various body compartments into extracellular fluids can describe intradialytic and postdialytic rebound kinetics of plasma phosphorus during conventional and short 2-hour HD treatments. In this model, individual patient differences in phosphorus kinetics were characterized by a single parameter, the phosphorus mobilization clearance (K(M)). In this report we determined K(M) in patients treated by in-center nocturnal HD (ICNHD) and short daily HD (SDHD) with low dialyzer phosphate clearance. In the ICNHD study, eight patients underwent 8-hour HD treatments where intradialytic and postdialytic plasma samples were collected; K(M) values were determined by nonlinear regression of plasma concentration as a function of time. In the SDHD study, five patients were studied during 28 treatments for approximately 3 hours. Here, K(M) was calculated using only predialytic and postdialytic plasma phosphorus concentrations. Dialyzer phosphate clearances were 134 ± 20 (mean ± SD) and 95 ± 16 mL/min during ICNHD and SDHD, respectively. K(M) values for the respective therapies were 124 ± 83 and 103 ± 33 mL/min, comparable to those determined previously during conventional and short HD treatments of 98 ± 44 mL/min. When results from ICNHD, SDHD, and previous HD modalities were combined, K(M) was directly correlated with postdialytic body weight (r = 0.38, P = 0.025) and inversely correlated with predialytic phosphorus concentration (r = -0.47, P = 0.005). These findings suggest that phosphorus kinetics during various HD modalities can be described by a pseudo one-compartment model.

Insulin resistance induces medial artery calcification in fructose-fed rats

Osteogenic differentiation of vascular smooth muscle cells (VSMCs) results in medial artery calcification, which is common in diabetes, but the pathogenesis is poorly understood. We aimed to explore the pathophysiological roles of insulin resistance (IR) on medial artery calcification in rats with 10% fructose in drinking water. After 12 weeks of fructose feeding, rats showed severe IR, with increased levels of fasting blood glucose, serum insulin and oral glucose tolerance test (OGTT). Fructose-fed rats showed aortic calcification, increased aortic calcium deposition and irregular elastic fibers in the medial layer of the vessel wall. Moreover, plasma phosphorus concentration, calcium × phosphorus product and alkaline phosphatase (ALP) activity, and aortic calcium content and ALP activity were significantly increased. Fructose feeding increased mRNA levels of osteopontin, type III sodium-dependent phosphate co-transporter, bone morphogenetic protein-2 and the key transcription factor core binding factor alpha 1 in aortic tissue and downregulated mRNA levels of osteoprotegerin and matrix γ-carboxyglutamic acid protein. Fructose feeding decreased protein levels of smooth-muscle lineage markers and induced severe lipid peroxidation injury. IR induced by high fructose feeding could evoke osteogenic transdifferentiation of VSMCs and promote vascular calcification.

Comparative studies on plasma mineral status of cattle in fluoride toxic brackish water zone of Punjab, India

ObjectiveChronic fluoride intoxication or fluorosis is a worldwide health problem in humans and animals. The present research work was aimed to assess the status of copper, zinc, cobalt, manganese, magnesium, calcium and phosphorus in blood of fluorotic cattle in brackish water zone of Punjab. MethodsThe present study was conducted in villages of district Muktsar, a brackish water zone, of Punjab state. Cattle (n=103) showing signs of dental lesions or lameness, from the villages with water fluoride concentration more than 1 ppm, were selected for the study whereas cattle (n=98) from villages with water fluoride concentration less than 1 ppm and with no clinical signs served as control. Blood samples were collected from both the groups and were analysed for minerals. ResultsSignificantly (P < 0.05) higher plasma F concentrations were observed in animals of fluorotic region in comparison to healthy control animals. Concentrations of plasma Ca, Mg, Cu and Zn were significantly lower in cattle of hydrofluorotic region. Plasma phosphorus, iron and iodine concentrations were higher in animals of hydrofluorotic region whereas Mo and Mn did not differ between the two groups. ConclusionsPresent study indicated decrease in certain essential minerals in animals of fluorotic region and such changes may contribute to the toxic effects associated with exposure to excess fluoride and salinity.

Kinetic Model of Phosphorus Mobilization during and after Short and Conventional Hemodialysis

The kinetics of plasma phosphorus (inorganic phosphorus or phosphate) during hemodialysis treatments cannot be explained by conventional one- or two-compartment models; previous approaches have been limited by assuming that the distribution of phosphorus is confined to classical intracellular and extracellular fluid compartments. In this study a novel pseudo one-compartment model, including phosphorus mobilization from a large second compartment, was proposed and evaluated. Clinical data were obtained during a crossover study where 22 chronic hemodialysis patients underwent both short (2-hour) and conventional (4-hour) hemodialysis sessions. The model estimated two patient-specific parameters, phosphorus mobilization clearance and phosphorus central distribution volume, by fitting frequent intradialytic and postdialytic plasma phosphorus concentrations using nonlinear regression. Phosphorus mobilization clearances varied among patients (45 to 208 ml/min), but estimates during short (98 ± 44 ml/min, mean ± SD) and conventional (99 ± 47 ml/min) sessions were not different (P = 0.74) and correlated with each other (concordance correlation coefficient ρ(c) of 0.85). Phosphorus central distribution volumes for each patient (short: 11.0 ± 4.2 L and conventional: 11.9 ± 3.8 L) were also correlated (ρ(c) of 0.45). The reproducibility of patient-specific parameters during short and conventional hemodialysis treatments suggests that a pseudo one-compartment model is robust and can describe plasma phosphorus kinetics under conditions of clinical interest.