Plasma Phosphate Concentration Research Articles

A de novo PRPF8 pathogenic variant in transient severe hypophosphatemia with delayed puberty and growth failure.

Childhood hypophosphatemia is a rare condition and may be caused by malabsorption, malignancies, or genetic factors. Prolonged hypophosphatemia leads to impaired growth and radiographic signs of rickets. We performed a detailed clinical and genetic evaluation of an adolescent boy with repeatedly low plasma phosphate concentrations (below 0.60 mmol/L), and growth failure. At 14 years, the patient presented with decelerating growth and delayed puberty. Biochemistry showed hypophosphatemia due to increased urinary phosphate loss; kidney function and vitamin D status were normal. Radiographs showed mild metaphyseal changes. A gene panel for known genetic hypophosphatemias was negative. Trio exome analysis followed by Sanger sequencing identified a pathogenic heterozygous de novo stop gain variant in PRPF8 gene, c.5548C>T p.(Arg1850*)., in the conserved RNase H homology domain. PRPF8 encodes the pre-RNA protein 8, which has a role in RNA processing. Heterozygous PRPF8 variants have been associated with retinitis pigmentosa and neurodevelopmental disorders but not with phosphate metabolism. The patient underwent growth hormone (GH) stimulation tests which confirmed GH deficiency. Head MRI indicated partially empty sella. GH treatment was started at 15 years. Surprisingly, phosphate metabolism normalized during GH treatment, suggesting that hypophosphatemia was at least partly secondary to growth hormone deficiency. In conclusion, the evaluation of an adolescent with profound long-term hypophosphatemia revealed a pituitary developmental defect associated with a stop gain variant in PRPF8. Hypophosphatemia alleviated with GH treatment. The pathological PRPF8 variant may contribute to abnormal pituitary development; however, its role in phosphate metabolism remains uncertain.

Efficacy and adverse events of L-Asparaginase administration as a first-line treatment for feline large-cell gastrointestinal lymphoma.

L-Asparaginase (L-Asp) is often used to induce remission in feline large-cell gastrointestinal lymphoma (LCGIL). However, no study has evaluated the efficacy and adverse events following the initial use of this drug as a first-line treatment in feline LCGIL. We retrospectively reviewed medical records of cats with LCGIL treated with L-Asp to induce remission. This study included 43 cats. The response rate (RR) after the first administration of L-Asp was 37.2% (Complete remission: 7.0 %, partial remission: 30.2%). RR was significantly higher in cases with primary gastric lesions (64.3%) than in those with primary intestinal lesions (24.1%) (P=0.018), and it was also higher in cases without anemia (57.1%) than those with anemia (15.0%) (P=0.009). The most common adverse event was hyperammonemia, which occurred in 10 of 12 cases where we could compare plasma ammonia concentrations before and after the first dose of L-Asp. Plasma phosphate concentrations were also significantly increased (P<0.001) within 24 hr after the first dose. Decreased appetite, vomiting, and diarrhea were also observed in five, three, and seven cases, respectively, and Grade 3 or higher gastrointestinal signs were observed as adverse events in three cases. The median overall survival of all cats was 150 days (range, 5-1,065 days), and the median progression-free survival was 104 days (range, 2-978 days). In conclusion, L-Asp was effective to induce remission, and severe adverse events were uncommon in feline LCGIL.

#1228 MOTS-c improves CV and mortality risk prediction in chronic hemodialysis patients: a prospective, multicenter cohort study

Abstract Background and Aims Cardiovascular disease (CVD) is the leading cause of death in patients with end stage kidney disease (ESKD), especially in those undergoing chronic hemodialysis (HD), but correct risk prediction in this setting is often complicated. The mitochondrial open reading frame of 12S rRNA type-C (MOTS-s) is a peptide encoded by mitochondrial DNA, mainly expressed by cardiac and skeletal muscle tissues, which may prevent CVD thanks to its remarkable anti-oxidant capacities. From a clinical point of view, altered circulating MOTS-c levels predict worsen CV outcomes, particularly among diabetic individuals or post-AMI patients. Mitochondrial dysfunction is highly pervasive in HD patients. Starting from this background, we aimed at evaluating the clinical significance and predictive usefulness of measuring circulating MOTS-c in a multicenter cohort of chronic HD patients, beyond common cohort-related risk factors. Method We conducted a prospective, observational study on 94 chronic HD patients. The study endpoint was a composite of all-cause/CV mortality and non-fatal CV events. We identified the cohort-related predictors of the endpoint by logistic and Cox-regression analyses and built prognostic models based on such variables. Performance of such models was tested before and after the inclusion of MOTS-c. 31 healthy patients were employed as controls. MOTS-c was measured in serum using a commercially available ELISA kit. Results MOTS-c levels were more elevated in HD patients than in controls (36.7 [24.9-49.9] vs. 13.8 [10.4-28.7] ng/mL; p &amp;lt; 0.001; Fig. 1) and independently correlated with a history of ischemic heart disease (β = 0.213; p = 0.03), LVMi (β = 0.185; p = 0.05) and phosphate plasma concentration (β = −0.201; p = 0.05). Of note, MOTS-c levels were even more increased in the 53 individuals experiencing the endpoint during a median 26.5. months follow-up (p = 0.01; Fig. 2). MOTS-c predicted the endpoint at either multivariate logistic (OR 1.020; 95% CI 1.011-1.109; p = 0.03) or Cox-regression analyses (HR 1.004; 95% CI 1.000-1.025; p = 0.05) and the addition of this peptide to multivariate models including the other, cohort-related risk factors (age, LVMi, E/e’, diabetes, pulse pressure) remarkably improved the calibration, risk variability explanation (+3%), discrimination (ROC-AUC from 0.727 to 0.743; C-index from 0.658 to 0.700) and, particularly, the overall reclassification capacity (NRI 15.87%; p = 0.01). Conclusion Circulating MOTS-c balance is altered in chronic HD patients. In these individuals, MOTS-c may add significant information to improve CV and mortality risk prediction, on top of traditional and uremia-specific, cohort-related risk variables. Future investigations are needed to extend this preliminary observation in wider HD cohorts.

Risk factors and implications associated with ultrasound-diagnosed nephrocalcinosis in cats with chronic kidney disease.

Microscopic nephrocalcinosis is a common pathological feature of chronic kidney disease (CKD) in cats. Detection of macroscopic nephrocalcinosis using ultrasonography and its implications remain unexplored. Identify risk factors associated with ultrasound-diagnosed nephrocalcinosis and evaluate the influence of nephrocalcinosis on CKD progression. Thirty-six euthyroid client-owned cats with CKD. Prospective cohort study. Cats with CKD with and without ionized hypercalcemia were enrolled for renal ultrasonography. Cats were categorized according to the presence or absence of ultrasound-diagnosed nephrocalcinosis. Binary logistic regression was performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression was assessed using linear mixed models. Ultrasound-diagnosed nephrocalcinosis was evident in 61% of CKD cats overall, with increased prevalence (81%) in those with hypercalcemia. At enrollment, higher blood ionized calcium concentration (odds ratio [OR], 1.27 per 0.1 mg/dL; P = .01), plasma phosphate concentration (OR, 1.16 per 0.1 mg/dL; P = .05), plasma creatinine concentration (OR, 1.29 per 0.1 mg/dL; P = .02) and alanine aminotransferase activity (OR, 2.08 per 10 U/L; P = .04) were independent nephrocalcinosis risk factors. The rate of change in log-transformed fibroblast growth factor-23 differed significantly between groups (P = .04). Cats with CKD and nephrocalcinosis had increasing plasma creatinine concentrations (.03 ± .01 mg/dL/month; P = .04) and phosphate concentrations (.06 ± .02 mg/dL/month; P < .001) and decreasing body weight (.02 ± .01 kg/month; P < .001) over time. Nephrocalcinosis is prevalent in cats with CKD, especially in those with hypercalcemia. This pathological feature appears to be associated with CKD progression in cats.

Inferring personal intake recommendations of phosphorous and potassium for end-stage renal failure patients by simulating with Bayesian hierarchical multivariate model.

Most end-stage renal disease (ESRD) patients face a risk of malnutrition, partly due to dietary restrictions on phosphorous and, in some cases, potassium intake. These restrictions aim to regulate plasma phosphate and potassium concentrations and prevent the adverse effects of hyperphosphatemia or hyperkalemia. However, individual responses to nutrition are known to vary, highlighting the need for personalized recommendations rather than relying solely on general guidelines. In this study, our objective was to develop a Bayesian hierarchical multivariate model that estimates the individual effects of nutrients on plasma concentrations and to present a recommendation algorithm that utilizes this model to infer personalized dietary intakes capable of achieving normal ranges for all considered concentrations. Considering the limited research on the reactions of ESRD patients, we collected dietary intake data and corresponding laboratory analyses from a cohort of 37 patients. The collected data were used to estimate the common hierarchical model, from which personalized models of the patients' diets and individual reactions were extracted. The application of our recommendation algorithm revealed substantial variations in phosphorus and potassium intakes recommended for each patient. These personalized recommendations deviate from the general guidelines, suggesting that a notably richer diet may be proposed for certain patients to mitigate the risk of malnutrition. Furthermore, all the participants underwent either hospital, home, or peritoneal dialysis treatments. We explored the impact of treatment type on nutritional reactions by incorporating it as a nested level in the hierarchical model. Remarkably, this incorporation improved the fit of the nutritional effect model by a notable reduction in the normalized root mean square error (NRMSE) from 0.078 to 0.003. These findings highlight the potential for personalized dietary modifications to optimize nutritional status, enhance patient outcomes, and mitigate the risk of malnutrition in the ESRD population.

Cordymin alleviates osteoporosis induced by hindlimb unloading via regulating the gut - microelements -bone axis --for non-clinical studies

IntroductionThe purpose of this study was to evaluate the protective effects of cordymin on osteoporosis induced by hindlimb unloading(HLU) in rats and whether cordymin can prevent bone loss from HLU.Materials and methodsWe employed the hindlimb suspension rats model to mimic physiological changes concomitant with space travel.The mechanical strength in the femoral neck,cancellous bone volume, gut microbiota structure,serum calcium and phosphorus contents, bone mineral content and bone mineral content can be changed after hindlimb unloading. Oral cordymin was administered for 4 weeks,cordymin treatment significantly increased the mechanical strength through elevated bone volume/tissue volume (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) and decreased trabecular separation (Tb. Sp).ResultsImportantly, 16 S rRNA sequencing showed cordymin treatment regulated the various genera that were imbalanced in hindlimb unloading rats. At the same time,The plasma total calcium and inorganic phosphate concentrations in hindlimb unloading rats decreased and bone mineral content in the lumbar vertebrae and femur increased after treatment with cordymin.ConclusionThese data indicate that the cordymin might exert bone protective effects indirectly via modulating the complex relationship between gut microbiota, microelements and bone loss.

A novel method for automated crystal visualization and quantification in murine folic acid-induced acute kidney injury.

Folic acid (FA)-induced acute kidney injury (FA-AKI) is an increasingly prevalent rodent disease model involving the injection of a high dose of FA that culminates in renal FA crystal deposition and injury. However, the literature characterizing the FA-AKI model is sparse and dated in part due to the absence of a well-described methodology for the visualization and quantification of renal FA crystals. Using widely available materials and tools, we developed a straightforward and crystal-preserving histological protocol that can be coupled with automated imaging for renal FA crystal visualization and generated an automated macro for downstream crystal content quantification. The applicability of the method was demonstrated by characterizing the model in male and female C57BL6/JRj mice after 3 and 30 h of FA treatment. Kidneys from both sexes and timepoints showed a bimodal distribution of FA crystal deposition in the cortical and medullary regions while, compared with males, females exhibited higher renal FA crystal content at the 30-h timepoint accompanied by greater kidney weight and higher plasma urea. Despite comparable plasma phosphate concentrations, FA-AKI resulted in a substantially more elevated plasma intact fibroblast growth factor 23 (FGF23) in females, reflected by a similar pattern in osseous Fgf23 mRNA expression. Therefore, the presented method constitutes a valuable tool for the quantification of renal FA crystals, which can aid the mechanistic characterization of the FA-AKI model and serves as a means to control for confounding changes in FA crystallization when using the model for investigating early and prophylactic AKI therapeutic interventions.NEW & NOTEWORTHY Here, we describe a novel method for the visualization and quantification of renal folic acid (FA) crystals in the rodent FA-induced acute kidney injury (FA-AKI) model. The protocol involves a straightforward histological approach followed by fully automated imaging and quantification steps. Applicability was confirmed by showing that the FA-AKI model is sex-dependent. The method can serve as a tool to aid in characterizing FA-AKI and to control for studies investigating prophylactic therapeutic avenues using FA-AKI.

O117 Burosumab in the management of X-linked hypophosphataemia: a retrospective cohort study reviewing anthropometric and biochemical markers

Abstract Introduction Rickets is a bone disease caused by a defect in mineralization. When left untreated, it has lifelong Orthopaedic sequelae. Burosumab, an anti-fibroblast growth factor 23 monoclonal antibody, improves rickets severity, symptoms, and growth in children with X-linked hypophosphataemia (XLH) followed to 64 weeks in clinical trials. International dosing guidance recommends targeting normal serum phosphate concentration. However, some children may not achieve this despite maximal dosing. This study compares clinical outcomes in children with XLH on long-term burosumab treatment who achieved normal phosphate, vs those who did not. Methods Single-centre retrospective review of a large paediatric cohort with XLH treated with burosumab. We evaluated growth and biochemical markers of bone health in those who did compared to those who did not achieve normal plasma phosphate concentration. Results Fifty-five children with XLH with median age 11.7 [6.8–15.5] years were included. 27 (49%) had low plasma phosphate concentration, and 27 (49%) normal phosphate after a median burosumab treatment duration of 3.3 [IQR 2.6–3.7] years. 1 (2%) did not have a recent phosphate level recorded. No difference in growth was found between normal and abnormal phosphate groups (p = 0.9). A trend of superior growth in those with normal compared with abnormal alkaline phosphatase level was observed. Conclusion Young children with XLH experience sustained growth on long-term burosumab treatment, albeit without normal plasma phosphate concentration in many. Consideration should be made to changing burosumab dosing recommendations to target the normalisation of alkaline phosphatase instead of plasma phosphate concentration.

Clinical and Functional Assessment of Digenicity in Renal Phosphate Wasting

Apart from increased fluid intake, patients with kidney stone disease (KSD) due to renal phosphate wasting require specific metaphylaxis. NaPi2a, NaPi2c, and NHERF1 regulate plasma phosphate concentration by reabsorbing phosphate in proximal kidney tubules and have been found altered in monogenic hypophosphatemia with a risk of KSD. In this study, we aimed at assessing the combined genetic alterations impacting NaPi2a, NaPi2c, and NHERF1. Therefore, we screened our hereditary KSD registry for cases of oligo- and digenicity, conducted reverse phenotyping, and undertook functional studies. As a result, we identified three patients from two families with digenic alterations in NaPi2a, NaPi2c, and NHERF1. In family 1, the index patient, who presented with severe renal calcifications and a bone mineralization disorder, carried digenic alterations affecting both NaPi transporter 2a and 2c. Functional analysis confirmed an additive genetic effect. In family 2, the index patient presented with kidney function decline, distinct musculature-related symptoms, and intracellular ATP depletion. Genetically, this individual was found to harbor variants in both NaPi2c and NHERF1 pointing towards genetic interaction. In summary, digenicity and gene dosage are likely to impact the severity of renal phosphate wasting and should be taken into account in terms of metaphylaxis through phosphate substitution.

Burosumab in management of X-linked hypophosphataemia: a retrospective cohort study of growth and serum phosphate levels

BackgroundBurosumab, an antifibroblast growth factor 23 monoclonal antibody, improves rickets severity, symptoms and growth in children with X-linked hypophosphataemia (XLH) followed up to 64 weeks in clinical trials. International dosing...

Effects of feeding fodder beet or kale in winter to dams and their heifer offspring on the heifer growth and production

Context Fodder beet (FB) is a widely used winter feed in New Zealand’s southern regions due to its high yield, consistent quality, and environmental benefits. However, FB is low in crude protein, phosphorus and fibre, and a survey showed that many dairy farmers were concerned that feeding FB may have negative impacts on lifetime performance. Aim To determine whether winter feeding FB or kale (Ka) to dairy cows, and then their heifer offspring at 1 and 2 years old, affects the heifer performance from birth until the end of their first lactation. Methods In June–August 2017, pregnant dairy cows were fed FB or kale over winter and then 140 of the resultant heifer offspring were divided into four treatment groups at 9–11 months old according to their dam’s winter diet and offered either FB or kale, with pasture baleage. The groups were as follows (dam crop–heifer crop): FB–FB, FB–Ka, Ka–FB, Ka–Ka. The heifers’ subsequent performance (growth, stature, milk production, and reproduction) was measured to the end of their first lactation (May 2020), and blood mineral status was monitored from May 2018 to May 2019. This observational study has its limitations, but is useful for generating hypotheses to test in more controlled research. Key results Heifers grazing FB in winter (June–August) 2018 had lower blood plasma urea and phosphate concentrations than did heifers grazing kale, despite similar dietary crude protein contents. Treatments had no effect on milk production. However, the heifer liveweights were affected and there was an indication of poorer reproductive performance. The FB–FB heifer treatment group had a lower average liveweight than the FB–Ka heifers from 1 to 2.8 years old. Conclusions Although no impact on milk production for the first lactation was observed, the key results suggest possible negative impacts of feeding heifers FB during winter, particularly if their dam also wintered on FB. Implications The combined effects of FB dam and heifer winter diets on lifetime productivity warrant further investigation to help develop sustainable FB feeding systems. When feeding FB, we recommend that farmers test their crops and supplements to ensure that sufficient nutrition, in particular protein and phosphorus are provided.

A potential new biomarker to monitor the phosphorus balance in dry dairy cows

The present study aimed at comparing different candidate blood biomarkers in their suitability to determine activation of regulatory mechanisms responding to phosphorus (P) deprivation in dry dairy cows on deficient dietary P supply. Fifteen multiparous dairy cows in late pregnancy were assigned to either a diet with low (1.6 g/kg DM) or adequate P content (3.5 g/kg DM) during the last 4 weeks of gestation. Blood samples were obtained immediately prior to initiating the experimental feeding period (T-bl), after 2 weeks of experimental feeding (T-1) and 4 days before calving, which was equivalent to at least 3 weeks of experimental feeding (T-2). Studied parameters were the plasma concentrations of phosphate (Pi), calcium (Ca), CrossLaps (CTX), a biomarker for bone mobilization, 1,25-(OH)2-Vitamin D (1,25-(OH)2D) and the activity of alkaline phosphatase (AlP). Treatment and time effects were studied with repeated measures ANOVA, and the different parameters were correlated to the dietary P intake in the days before sampling. Treatment effects were only identified for the individual increase in the plasma concentration of CTX related to baseline values (ΔCTX) and to a lesser extent for the Ca:Pi ratio in plasma. ΔCTX was the only parameter correlated to P intake at T-1 and with the strongest association with P intake at T-2. The results of this study provide first indications for the suitability of ΔCTX to determine the level of dietary P supply at which counter regulatory mechanism to negative P balance are triggered during the dry period. This parameter that is easily applicable in a field setting can assist the validation of current recommendations for the dietary P supply in dry cows.

Hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of FGF23-FGFR4 signaling.

Elevations in plasma phosphate concentrations (hyperphosphatemia) occur in chronic kidney disease (CKD), in certain genetic disorders, and following the intake of a phosphate-rich diet. Whether hyperphosphatemia and/or associated changes in metabolic regulators, including elevations of fibroblast growth factor 23 (FGF23) directly contribute to specific complications of CKD is uncertain. Here, we report that similar to patients with CKD, mice with adenine-induced CKD develop inflammation, anemia, and skeletal muscle wasting. These complications are also observed in mice fed high phosphate diet even without CKD. Ablation of pathologic FGF23-FGFR4 signaling did not protect mice on an increased phosphate diet or mice with adenine-induced CKD from these sequelae. However, low phosphate diet ameliorated anemia and skeletal muscle wasting in a genetic mouse model of CKD. Our mechanistic in vitro studies indicate that phosphate elevations induce inflammatory signaling and increase hepcidin expression in hepatocytes, a potential causative link between hyperphosphatemia, anemia, and skeletal muscle dysfunction. Our study suggests that high phosphate intake, as caused by the consumption of processed food, may have harmful effects irrespective of pre-existing kidney injury, supporting not only the clinical utility of treating hyperphosphatemia in CKD patients but also arguing for limiting phosphate intake in healthy individuals.

Risk factors and implications associated with renal mineralization in chronic kidney disease in cats.

BackgroundNephrocalcinosis is a pathological feature of chronic kidney disease (CKD). Its pathophysiological implications for cats with CKD are unexplored.ObjectivesIdentify nephrocalcinosis risk factors and evaluate its influence on CKD progression and all‐cause mortality.AnimalsFifty‐one euthyroid client‐owned cats with International Renal Interest Society (IRIS) stages 2‐3 azotemic CKD.MethodsRetrospective cohort study. Histopathological kidney sections were assessed for nephrocalcinosis (von Kossa stain). Nephrocalcinosis severity was determined by image analysis (ImageJ). Ordinal logistic regressions were performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression and mortality risk were assessed using linear mixed model and Cox regression, respectively. Cats were categorized by their owner‐reported time‐averaged phosphate‐restricted diet (PRD) intake, where PRD comprised ≥50%, 10‐50%, or none of food intake.ResultsNephrocalcinosis was rated as mild‐to‐severe in 78.4% and absent‐to‐minimal in 21.6% of cases. Higher baseline plasma total calcium concentration (tCa; odds ratio [OR] = 3.07 per 1 mg/dL; P = .02) and eating a PRD (10%‐50%: OR = 8.35; P = .01; ≥50%: OR = 5.47; P = .01) were independent nephrocalcinosis risk factors. Cats with absent‐to‐minimal nephrocalcinosis had increasing plasma creatinine (0.250 ± 0.074 mg/dL/month; P = .002), urea (5.06 ± 1.82 mg/dL/month; P = .01), and phosphate (0.233 ± 0.115 mg/dL/month; P = .05) concentrations over a 1‐year period, and had shorter median survival times than cats with mild‐to‐severe nephrocalcinosis.Conclusion and Clinical ImportanceHigher plasma tCa at CKD diagnosis and PRD intake are independently associated with nephrocalcinosis. However, nephrocalcinosis is not associated with rapid CKD progression in cats.

Effects of dietary phosphorus concentration during the transition period on plasma calcium concentrations, feed intake, and milk production in dairy cows

Our aim was to evaluate the effects of a low or high dietary phosphorus (P) concentration during the dry period, followed by either a high or low dietary P concentration during the first 8 wk of lactation, on plasma Ca concentrations, feed intake, and lactational performance of dairy cattle. Sixty pregnant multiparous Holstein Friesian dairy cows were assigned to a randomized block design with repeated measurements and dietary treatments arranged in a 2 × 2 factorial fashion. The experimental diets contained 3.6 (Dry-HP) or 2.2 (Dry-LP) g of P/kg of dry matter (DM) during the dry period, and 3.8 (Lac-HP) or 2.9 (Lac-LP) g of P/kg of DM during 56 d after calving period. In dry cows, plasma Ca concentrations were 3.3% greater when cows were fed 2.2 instead of 3.6 g of P/kg of DM. The proportion of cows being hypocalcemic (plasma Ca concentrations <2 mM) in the first week after calving was lowest with the low-P diets both during the dry period and lactation. Plasma Ca concentrations in wk 1 to 8 after calving were affected by dietary P level in the dry period and in the lactation period, but no interaction between both was present. Feeding Dry-LP instead of Dry-HP diets resulted in 4.1% greater plasma Ca values, and feeding Lac-LP instead of Lac-HP diets resulted in 4.0% greater plasma Ca values. After calving, plasma inorganic phosphate (Pi) concentrations were affected by a 3-way interaction between sampling day after calving, and dietary P levels during the dry period and lactation. From d 1 to d 7 postpartum, cows fed Lac-HP had increased plasma Pi concentrations, and the rate appeared to be greater in cows fed Dry-LP versus Dry-HP. In contrast, plasma Pi concentrations decreased from d 1 to d 7 postpartum in cows fed Lac-LP, and this decrease was at a higher rate for cows fed Dry-HP versus Dry-LP. After d 7, plasma Pi concentrations remained rather constant at 1.5 to 1.6 mM when cows received Lac-HP, whereas with Lac-LP plasma Pi concentrations reached stable levels (i.e., 1.3-1.4 mM) at d 28 after calving. Milk production, DM intake, and milk concentrations of P, Ca, fat, protein, and lactose were not affected by any interaction nor the levels of dietary P. It is concluded that the feeding of diets containing 2.2 g of P/kg of DM during the last 6 wk of the dry period and 2.9 g of P/kg of DM during early lactation increased plasma Ca levels when compared with greater dietary P levels. These low-P diets may be instrumental in preventing hypocalcemia in periparturient cows and do not compromise DM intake and milk production. Current results suggest that P requirements in dairy cows during dry period and early lactation can be fine-tuned toward lower values than recommended by both the National Research Council and the Dutch Central Bureau for Livestock Feeding. Caution however is warranted to extrapolate current findings to entire lactations because long-term effects of feeding low-P diets containing 2.9 of g/kg of DM on production and health needs further investigation.

Phosphate Concentrations and Modifying Factors in Healthy Children From 12 to 24 Months of Age.

ContextPhosphate homeostasis and its modifiers in early childhood are inadequately characterized.ObjectiveTo determine physiological plasma phosphate concentration and modifying factors in healthy infants at 12 to 24 months of age.DesignThis study included 525 healthy infants (53% girls), who participated in a randomized vitamin D intervention trial and received daily vitamin D3 supplementation of either 10 or 30 μg from age 2 weeks to 24 months. Biochemical parameters were measured at 12 and 24 months. Dietary phosphate intake was determined at 12 months.Main Outcome MeasuresPlasma phosphate concentrations at 12 and 24 months of age.ResultsMean (SD) phosphate concentration decreased from 12 months (1.9 ± 0.15 mmol/L) to 24 months (1.6 ± 0.17 mmol/L) of age (P < 0.001 for repeated measurements). When adjusted by covariates, such as body size, creatinine, serum 25-hydroxyvitamin D, intact and C-terminal fibroblast growth factor 23, mean plasma phosphate was higher in boys than girls during follow-up (P = 0.019). Phosphate concentrations were similar in the vitamin D intervention groups (P > 0.472 for all). Plasma iron was associated positively with plasma phosphate at both time points (B, 0.006 and 0.005; 95% CI, 0.004-0.009 and 0.002-0.008; P < 0.001 at both time points, respectively). At 24 months of age, the main modifier of phosphate concentration was plasma creatinine (B, 0.007; 95% CI 0.003-0.011, P < 0.001).ConclusionPlasma phosphate concentration decreased from age 12 to 24 months. In infants and toddlers, the strongest plasma phosphate modifiers were sex, iron, and creatinine, whereas vitamin D supplementation did not modify phosphate concentrations.

The effect of attenuating dietary phosphate restriction on blood ionized calcium concentrations in cats with chronic kidney disease and ionized hypercalcemia.

BackgroundHypercalcemia is commonly observed in cats with azotemic chronic kidney disease (CKD). Dietary phosphate restriction is considered standard of care but may contribute to the development of hypercalcemia. The optimal dietary management strategy for these cats is unclear.ObjectivesTo describe the effect of feeding a moderately phosphate‐restricted diet (MP; 1.5 g/Mcal phosphorus; Ca : P ratio, 1.3) to cats with concurrent azotemic CKD and ionized hypercalcemia.AnimalsClient‐owned cats with ionized hypercalcemia (ionized calcium [iCa] concentration >1.4 mmol/L) at diagnosis of CKD (n = 11; baseline hypercalcemics) or after CKD diagnosis while eating a phosphate‐restricted clinical renal diet (0.8 g/Mcal phosphorus; Ca : P ratio, 1.9; n = 10; RD hypercalcemics).MethodsChanges in variables over time, after starting MP at visit 1, were assessed using linear mixed model analysis within each group of cats. Data are reporte as median [25th, 75th percentiles].ResultsAt visit 1, iCa was 1.47 [1.42, 1.55] mmol/L for baseline hypercalcemics and 1.53 [1.5, 1.67] mmol/L for RD hypercalcemics. Blood iCa decreased (P < .001) when RD hypercalcemics were fed MP, with iCa <1.4 mmol/L in 8/10 cats after 2.2 [1.8, 3.7] months. Plasma phosphate concentrations did not change. In contrast, the baseline hypercalcemic group overall showed no change in iCa but a decrease in plasma phosphate concentration during 8.8 [5.5, 10.6] months on the MP diet, although 4/11 individual cats achieved iCa <1.4 mmol/L by 3.4 [1.0, 6.2] months.Conclusions and Clinical ImportanceAttenuation of dietary phosphate restriction could result in normalization of iCa in cats that develop hypercalcemia while eating a clinical renal diet.

Regulation of Plasma Phosphate Concentration and Diurnal Rhythm

Regulation of Plasma Phosphate Concentration and Diurnal Rhythm

Risk factors associated with disturbances of calcium homeostasis after initiation of a phosphate-restricted diet in cats with chronic kidney disease.

BackgroundDietary phosphate restriction improves survival in cats with chronic kidney disease (CKD). However, feeding a phosphate‐restricted diet may disrupt calcium homeostasis leading to hypercalcemia in some cats.ObjectivesTo identify risk factors associated with increasing plasma total calcium (tCa) concentration after transition to a phosphate‐restricted diet and to explore its role in CKD‐mineral and bone disorder (CKD‐MBD) in cats.AnimalsSeventy‐one geriatric (≥9 years) euthyroid client‐owned cats with International Renal Interest Society (IRIS) stage 2 to 3 azotemic CKD.MethodsRetrospective cross‐sectional cohort study. Changes in plasma tCa concentration in the first 200 days of diet transition were assessed using linear regression. Binary logistic regressions were performed to identify risk factors for increasing calcium concentration. Changes in clinicopathological variables associated with CKD‐MBD over time were explored using linear mixed model and generalized linear mixed model analyses.ResultsLower baseline plasma potassium (odds ratio [OR] = 1.19 per 0.1 mmol/L decrease; P = .003) and phosphate (OR = 1.15 per 0.1 mmol/L decrease; P = .01) concentrations remained independent risk factors for increasing plasma tCa concentration. Plasma creatinine (β = .069 ± .029 mg/dL; P = .02), symmetric dimethylarginine (β = .64 ± .29 μg/dL; P = .03), phosphate (β = .129 ± .062 mg/dL; P = .04), and ln[FGF23] (β = .103 ± .035 pg/mL; P = .004) concentrations had significantly increased rates of change in cats with increasing plasma tCa concentration over time.Conclusion and Clinical ImportanceLower plasma potassium or phosphate concentrations or both at the time of transition of cats with CKD to a phosphate‐restricted diet are independently associated with increased risk of an increase in plasma tCa concentration. Increasing plasma tCa concentration is associated with progression of CKD.

Pharmacokinetics interaction of calcium on the treatment of sputum positive pulmonary tuberculosis patients

Tuberculosis (TB) in children is a neglected aspect of the TB epidemic despite it constituting 20% or more of all TB cases in many countries with high TB incidence. Tuberculosis constitutes a serious global health problem with nearly 10 million new cases of tuberculosis (2011) and 1.4 million deaths every year. In pharmacokinetic studies, co-administration of various inhibitors of this enzyme (e.g., erythromycin, antifungal substances, protease inhibitors, and grapefruit juice) raised plasma phosphate concentrations by up to 500%. Materials and Methods: The study was conducted in Chennai tuberculosis hospital from January 2012 through July 2015 in seven target groups, with consecutive recruitment. The first group consisted of otherwise deselected patients who are presented with suspected tuberculosis to the tuberculosis hospital in Chennai. Blood samples were collected from the subjects of tuberculosis Hospital at Chennai. To non-treatment and treatment variations, fasting blood samples were collected from 8 AM - 9 AM. Experiments were carried out as soon as possible. Whenever there was a delay in experiments, samples were stored at -10° to -15°C for a maximum of 1 day. Blood samples thus collected using standard sampling techniques were centrifuged to get the serum that was analysed phosphorus levels by Phosphomolybdate method. The study protocol was approved by the Institutional ethics committee and was carried out in accordance with the principle of the declaration of Helsinki. Results: In the study, mean serum phosphorus level in newly diagnosed patients was 13 ± 3.30 mg/dl, after first month treatment to sixth month treatment the level was 13 ± 3.60mg/dl, 11 ± 3.30 mg/dl, 10.50 ± 3.30 mg/dl, 11 ± 3.30 mg/dl, 11.20 ± 2.80 mg/dl and 10.20 ± 2.80 mg/dl respectively. Six-month treatment 20 patients were get the hyperphosphatemia for include female 9 patients. One study suggests that Estrogen may act directly to suppress sodium-dependent phosphate absorption in the renal proximal tubules inducing phosphaturia and decreased serum phosphate; women who are post-menopausal and Estrogen deficient would be at increased risk for hyperphosphatemia Low serum phosphate levels are associated with reduced cardiac output and also with risk for arrhythmia. Conclusion: Our findings offer the possibility that early intervention will help achieve calcium and phosphorus conversion and ultimately a successful treatment outcome. In order for us to update guidelines and optimize patient care, some gaps in the evidence base need to be addressed. Although available data demonstrate the association between hyperphosphatemia and increased risk of mortality, it remains a challenge in the clinic to achieve and maintain recommended serum phosphorus concentrations. Keywords: Hyperphosphatemia, Phosphomolybdate Method, Pulmonary Tuberculosis