Increased Phosphate Levels Research Articles

Effects on calcium phosphate homeostasis after sodium-glucose cotransporter 2 inhibitor in patients with advanced chronic kidney disease and type 2 diabetes mellitus

BackgroundThe effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on calcium phosphate homeostasis in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remain uncertain. MethodsA retrospective observational cohort study of patients with T2DM at CKD stage G3b-5ND who received SGLT2i as compared to control from 1 January 2015 through 31 December 2021 was recruited. Propensity score assignment at 1:3 ratio by logistic regression was done. All patients were followed for 12 months. Outcomes were changes in phosphate level. ResultsWe analyzed 1,450 SGLT2i users and 4,350 control subjects. At the 12th month, SGLT2i users had a slower increase in phosphate levels (absolute change: −0.01 ± 0.28 vs + 0.14 ± 0.34 mmol/L; percentage change: −0.74 % ± 25.56 vs + 10.88 ± 28.15 %, P for both < 0.001). The proportion of patients with high phosphate was lower with SGLT2i (8.2 % vs 24.6 % increase). In the generalized estimating equation, SGLT2i was linked to a longitudinal reduction in phosphate (B −0.039, P<0.001). ConclusionsSGLT2i can effectively slow down the progression of phosphate retention in advanced CKD with T2DM.

Description of Pre-Hemodialysis Serum Phosphate in Late-Stage Kidney Disease Patients of Productive Age (15-64 Years) at the Indonesian Christian University General Hospital

In Indonesia, end-stage kidney disease is still a health problem that needs attention. End-stage kidney disease or abbreviated as PGTA reflects the fifth stage of chronic kidney disease, at this stage, there is a buildup of toxins, fluids, electrolytes, and the remains of the body's metabolism. In stage 5 chronic kidney disease, the glomerular filtration rate decreases &lt; 15 ml/minute / 1.73 m2 and has occurred for 3 months or more. One of the clinical complications of end-stage renal disease is an increase in phosphate levels in the patient's blood serum (hyperphosphatemia), this occurs due to disruption of the kidney's phosphate excretion function. Hyperphosphatemia in PGTA patients can result in hyperparathyroidism, soft tissue, and cardiovascular calcification, and affect bone mineral disorders. In kidney disease patients with a glomerular filtration rate &lt; 30 ml/minute / 1.73m2, the prevalence of hyperphosphatemia complications increased to 23%. This study aims to determine the description of pre-hemodialysis inorganic phosphate levels in the serum of PGTA patients of productive age (15-64 years) undergoing hemodialysis at the Indonesian Christian University General Hospital for the period January 2022. The research conducted was a descriptive study, to determine the description of phosphate levels serum of PGTA patients. The data used in this study is primary data by directly taking the blood of 20 pre-hemodialysis patients with end-stage kidney disease and then examining it in the laboratory. In this study, the results showed that 10 PGTA patients (50%) experienced an increase in serum inorganic phosphate levels above normal (&gt;5 mg/dl). Meanwhile, 9 people (45%) had normal serum phosphate levels (2.5 - 5 mg/dl), and 1 other person had below normal serum phosphate levels (&lt;2.5 mg/dl). Keywords: Inorganic Phosphate, Hemodialysis, Hyperphosphatemia, End Stage Renal Disease

Serum phosphate levels and the development of sepsis associated acute kidney injury: evidence from two independent databases.

We aimed to investigate the association between serum phosphate levels and the risk for developing sepsis associated acute kidney injury (SAKI). Septic patients from the Medical Information Mart for Intensive Care IV (MIMIC IV) and the eICU Collaborative Research Database (eICU-CRD) were enrolled. Restricted cubic spline (RCS) was used to visualize the relationship between phosphate levels and the risk of SAKI. Patients were divided into four categories based on their serum phosphate levels. Logistic regression analysis, receiver operating characteristic (ROC) curve and subgroup analysis were performed to evaluate the predictive value of serum phosphate for SAKI. A total of 9,244 and 2,124 patients from the MIMIC IV and eICU-CRD database were included in the final analysis. RCS curve revealed a non-linear correlation between phosphate levels and the risk of SAKI (p for non-linearity <0.05). Each 1 mg/dL increase in phosphate levels was associated with a 1.51 to 1.64-fold increased risk of SAKI (OR 2.51-2.64, p < 0.001) in the MIMIC IV cohort and a 0.29 to 0.38-fold increased risk (OR 1.29-1.38, p < 0.001) in the eICU-CRD cohort. Compared to the normal-low category, hyperphosphatemia and normal-high category were independently associated with an increased risk of SAKI, while hypophosphatemia was independently associated with a decreased risk in the MIMIC IV cohort. A similar trend was observed in the eICU-CRD cohort, but statistical significance disappeared in the hypophosphatemia category and the adjusted model of normal high category. These finding was consistent in subgroup analysis. Elevated serum phosphate, even within the normal range, is an independent risk factor for developing SAKI in septic patients. Abnormal change in serum phosphate levels may be a novel biomarker for early prediction of SAKI occurrence.

Hydro-climatic consequences on zooplankton diversity and abundance in perennial Vavuniya reservoir and seasonal Thandikulam reservoir in Vavuniya, Sri Lanka

BackgroundZooplankton exhibit strong responses for minute changes in their habitat. Therefore, this study intended to investigate the impacts of hydro-climatic factors and related water quality variables on zooplankton abundance and diversity in the perennial Vavuniya reservoir (VR) and seasonal Thandikulam reservoir (TR), Vavuniya, Sri Lanka.ResultsZooplankton diversity and abundance showed some peculiarities between seasonal and perennial reservoirs under varying hydro-climatic factors and water quality parameters during wet and dry seasons (July 2018–February 2019). There were 14 Rotifera, 4 Cladocera and 5 Copepod species in VR, and in TR, 12 Rotifera, 2 Cladocera and 5 Copepod species were identified. Although these reservoirs are located at proximity (2.48 km), the responses via zooplankton community structure toward environmental factors have been shown uniqueness to some extent. Significant negative correlation was observed for increasing {text{NO}}_{{3}}^{ - } (p = 0.044) and {text{PO}}_{{4}}^{{{3} - }} (p = 0.010) concentrations with zooplankton diversity in perennial VR; however, only {text{PO}}_{{4}}^{{{3} - }} concentration showed a significantly (p = 0.042) negative correlation in seasonal TR. Interestingly, total zooplankton abundance showed significant negative correlations with {text{NO}}_{{3}}^{ - } (p = 0.013) and {text{PO}}_{{4}}^{3 - } (p = 0.038) in perennial VR; however, insignificant negative correlation was observed in seasonal TR. Copepods make up the majority of total zooplankton abundance in both reservoirs and were significantly affected by increased atmospheric temperature. Cladocera abundance in VR was highly sensitive (p = 0.032; r = − 0.856) to changes in water level. Increasing water level significantly favors the total zooplankton abundance in the seasonal reservoir but not in perennial.ConclusionsSensitivity of zooplankton community structure varies between seasonal and perennial reservoirs in different magnitudes. This is due to the increasing temperatures, increasing phosphate levels and decreasing water levels with the combination of other factors resulting in specific responses of zooplankton diversity and abundance. Therefore, it would not be surprised to use zooplankton community structure to sense the vibrant responses of different freshwater habitats.

Design Principles and Applications of Selective Lanthanide-Based Receptors for Inorganic Phosphate.

Phosphate is an anion of both environmental and medical significance. The increase in phosphate levels in surface waters due primarily to run-offs from fertilized agricultural fields causes widespread eutrophication and increasingly large dead-zones. Hyperphosphatemia, a condition in which blood phosphate levels are elevated, is a primary cause of increased mortality and morbidity in chronic or advanced kidney disease. Resolving both of these issues require, in part, new technology that could selectively sequester phosphate in water at neutral pH. The high hydration energy of phosphate, which prevents organic receptors from functioning in water with sufficient affinity, can be overcome via coordination to a hard metal ion. The hardness, oxophilicity and lability of lanthanide ions make them excellent candidates for the design of high affinity phosphate receptors. In this perspective, we discuss how the principles of lanthanide coordination chemistry can be exploited to design sensitive and selective receptors for phosphate. Unlike many supramolecular systems, these hosts do not recognize their anionic guests via directed electrostatic and hydrogen bonding interactions. Instead, the selectivity of our fluxional receptors is governed entirely by acid-base chemistry and electrostatic forces. Parameters that affect the affinity and selectivity of the receptors include the basicities of the coordinating ligand and of the targeted anion, the acidity of the lanthanide ion, and the geometry of the ligand. Uniquely, their affinity for phosphate can be readily tuned by orders of magnitude either by peripheral interactions or by the lanthanide ion itself without affecting their exquisite selectivity over competing anions such as bicarbonate and chloride.

Correlation between serum levels of Fibroblast Growth Factor-23 (FGF-23) and parathyroid hormone levels in predialysis Chronic Kidney Disease (CKD) patients at Sanglah General Hospital, Bali, Indonesia

Backgrounds: Chronic kidney disease (CKD) is an abnormality in the kidney that lasts for more than 3 months. Increased phosphate levels in the blood due to CKD will stimulate the secretion of Fibroblast Growth Factor 23 (FGF-23). Increased secretion of FGF-23 happens to maintain phosphate balance because the capacity of excretion of phosphorus in the kidneys decreases and leads to the incidence of secondary hyperparathyroidism due to Parathyroid Hormone (PTH). This study aims to evaluate the relationship between serum levels of FGF-23 and PTH in predialysis CKD patients.Methods: An analytical observational study with a cross-sectional approach has been conducted in this study from August until October 2020. Analysis of the relationship between serum levels of Fibroblast Growth Factor (FGF-23) and intact parathyroid hormone using the Spearman correlation test with a significance level of =0.05. Data were analyzed using SPSS version 17 for Windows.Results: A total of 75 people consisting of 49 male participants (65.3%) and 26 female participants (34.7%). The normality test showed that the data were not normally distributed (p&lt;0.05), so the Spearman correlation test was used to evaluate the relationship between FGF-23 and intact PTH. The statistical analysis results showed a low significant positive correlation (r=0.168; p=0.046) between serum levels of FGF-23 and serum levels of intact PTH.Conclusion: There was a low significant positive correlation between FGF-23 and PTH serum levels in predialysis CKD patients.

Circadian misalignment leads to changes in cortisol rhythms, blood biochemical variables and serum miRNA profiles

The circadian clock plays a critical role in synchronizing the inner molecular, metabolic and physiological processes to environmental cues that cycle with a period of 24 h. Non-24 h and shift schedules are commonly used in maritime operations, and both of which can disturb circadian rhythms. In this study, we first conducted an experiment in which the volunteers followed a 3-d rotary schedule with consecutive shift in sleep time (rotatory schedule), and analyzed the changes in salivary cortisol rhythms and blood variables. Next we conducted another experiment in which the volunteers followed an 8 h-on and 4-h off schedule (non-24-h schedule) to compare the changes in blood/serum variables. The rotatory schedule led to elevated levels of serum cortisol during the early stage, and the phase became delayed during the early and late stages. Interestingly, both of the schedules caused comprehensive changes in blood/serum biochemical variables and increased phosphate levels. Furthermore, transcriptomic analysis of the plasma miRNAs from the volunteers following the rotatory schedule identified a subset of serum miRNAs targeting genes involved in circadian rhythms, sleep homeostasis, phosphate transport and multiple important physiological processes. Overexpression of miRNAs targeting the phosphate transport associated genes, SLC20A1 and SLC20A2, showed altered expression due to rotary schedule resulted in attenuated cellular levels of phosphate, which might account for the changed levels in serum phosphate. These findings would further our understanding of the deleterious effects of shift schedules and help to optimize and enhance the performances and welfare of personnel working on similar schedules.

Efficacy and safety of sucroferric oxyhydroxide in the treatment of hyperphosphataemia in chronic kidney disease in Asturias. FOSFASTUR study

Alterations in bone and mineral metabolism are very common in chronic kidney disease (CKD). The increase in phosphate levels leads to bone disease, risk of calcification and greater mortality, so any strategy aimed at reducing them should be welcomed. The latest drug incorporated into the therapeutic arsenal to treat hyperphosphataemia in CKD is Sucroferric Oxyhydroxide (SFO). ObjectiveTo analyse the efficacy and safety of OSF in three cohorts of patients, one with advanced chronic kidney disease not on dialysis (CKD-NoD), another on peritoneal dialysis (PD) and the last on haemodialysis (HD), followed for six months. MethodsA prospective, observational, multicentre study in clinical practice. Clinical and epidemiological variables were analysed. The evolution of parameters relating to alterations in bone and mineral metabolism and anaemia was analysed. ResultsEighty-five patients were included in the study (62 ± 12 years, 64% male, 34% diabetic), 25 with CKD-NoD, 25 on PD and lastly, 35 on HD. In 66 patients (78%), SFO was the first phosphate binder; in the other 19, SFO replaced a previous phosphate binder due to poor tolerance or efficacy. The initial dose of SFO was 964 ± 323 mg/day. Overall, serum phosphate levels saw a significant reduction at three months of treatment (19.6%, P < 0.001). There were no differences in the efficacy of the drug when the different populations analysed were compared. Over the course of the study, there were no changes to levels of calcium, PTHi, ferritin, or the transferrin and haemoglobin saturation indices, although there was a tendency for the last two to increase. Twelve patients (14%) withdrew from follow-up, ten due to gastrointestinal adverse effects (primarily diarrhoea) and two were lost to follow-up (kidney transplant). The mean dose of the drug that the patients received increased over time, up to 1147 ± 371 mg/day. ConclusionsSFO is an effective option for the treatment of hyperphosphataemia in patients with CKD both in the advanced phases of the disease and on dialysis. We found similar efficacy across the three groups analysed. The higher their baseline phosphate level, the greater the reduction in the serum levels. A notable reduction in phosphate levels can be achieved with doses of around 1000 mg/day. Diarrhoea was the most common side effect, although it generally was not significant.

Phosphate Dosing in Drinking Water Distribution Systems Promotes Changes in Biofilm Structure and Functional Genetic Diversity.

Water utilities treat drinking water by adding phosphate to prevent metal dissolution from water pipe work systems and particularly lead poisoning. Phosphate can be a limiting nutrient for microbial biofilms in DWDS, yet its effects on these microbial consortia are not well understood. This research presents results from phosphate dosing experiments using a real scale chlorinated DWDS, comparing standard phosphate concentrations of United Kingdom drinking water (1 mgP/L) with a double dose (2 mgP/L) commonly used in plumbosolvency treatment. Biofilm development during phosphate treatment experiments was monitored using a holistic approach by combining metagenomics analysis, flow cytometry and SEM characterisation. The increase of phosphate levels in drinking water, reduced biofilm cell numbers and promoted the presence of poorly distributed biofilms on inner pipe surfaces. Metagenomics analysis using genetic markers (16S rRNA and ITS2) showed that phosphate influenced biofilm community structure, particularly fungal composition. Whole metagenome sequencing showed that phosphate enrichment favoured the presence of sequencing reads associated to ATPases, ion transporters and DNA-interacting proteins, whilst reads associated to nitrogen metabolism were predominant in control samples. This research brings new knowledge regarding the influence of phosphate treatment on the composition and structure of biofilms within DWDS, and the implications that this might have for the management of these systems.

Phosphate and methionine affect cadmium uptake in valerian (Valeriana officinalis L.)

This study investigated the effects of exogenous methionine (Met) and different phosphate (PO4) concentrations on Cd uptake and translocation in Valeriana officinalis L. Seedlings were grown in nutrient solutions with three different concentrations of phosphate (900, 1200, and 1500 μM) for two weeks, then exposed for 4 days to 10 μM Cd, either in presence or absence of 400 μM methionine. The Met treatment decreased root Cd accumulation by up to 40%, while it enhanced Cd uptake into the shoots by 50%. In absence of Met, shoot Cd uptake was not affected by the level of phosphate application, although root Cd contents increased. The latter effect was entirely due to increased apoplastic Cd binding. In presence of Met, the Cd accumulation of both plant parts showed trends to increase with increasing phosphate level. In contrast to the treatments without Met, however, the phosphate effect on root Cd was due to increased symplastic root Cd allocation. The results suggest that the effects of Met on Cd uptake were due to the formation of mobile Cd-Met complexes, reducing phosphate-promoted Cd-retention in the apoplast and enhancing Cd transfer into the root symplast. Irrespective of the treatment, shoot Cd accumulation showed a close linear relationship to shoot mass, suggesting that convective transport with the transpirational water stream was the rate-governing uptake process. The results indicate that methionine supplementation could reduce Cd accumulation in valerian roots, which are the parts of this plant harvested for medicinal purposes, in Cd-contaminated soil, while phosphate would enhance it.

Eficacia y seguridad de oxihidróxido sucroférrico en el tratamiento de la hiperfosforemia en la enfermedad renal crónica. Estudio FOSFASTUR

IntroductionAlterations in bone and mineral metabolism are very common in chronic kidney disease (CKD). The increase in phosphate levels leads to bone disease, risk of calcification and greater mortality, so any strategy aimed at reducing them should be welcomed. The latest drug incorporated into the therapeutic arsenal to treat hyperphosphataemia in CKD is sucroferric oxyhydroxide (SFO). ObjectiveTo analyse the efficacy and safety of SFO in 3 cohorts of patients, one with advanced CKD not on dialysis, another on peritoneal dialysis and the last on haemodialysis, followed for 6 months. MethodsA prospective, observational, multicentre study in clinical practice. Clinical and epidemiological variables were analysed. The evolution of parameters relating to alterations in bone and mineral metabolism and anaemia was analysed. ResultsEighty-five patients were included in the study (62±12 years, 64% male, 34% diabetic), 25 with advanced CKD not on dialysis, 25 on peritoneal dialysis and lastly, 35 on haemodialysis. In 66 patients (78%), SFO was the first phosphate binder; in the other 19, SFO replaced a previous phosphate binder due to poor tolerance or efficacy. The initial dose of SFO was 964±323mg/day. Overall, serum phosphate levels saw a significant reduction at 3 months of treatment (19.6%; P<.001). There were no differences in the efficacy of the drug when the different populations analysed were compared. Over the course of the study, there were no changes to levels of calcium, PTHi, ferritin, transferrin saturation index or haemoglobin, although there was a tendency for the last 2 to increase. Twelve patients (14%) withdrew from follow-up, 10 due to gastrointestinal adverse effects (primarily diarrhoea) and 2 were lost to follow-up (kidney transplant). The mean dose of the drug that the patients received increased over time, up to 1,147±371mg/day. ConclusionsSFO is an effective option for the treatment of hyperphosphataemia in patients with CKD both in the advanced phases of the disease and on dialysis. We found similar efficacy across the 3 groups analysed. The higher their baseline phosphate level, the greater the reduction in the serum levels. A notable reduction in phosphate levels can be achieved with doses of around 1,000mg/day. Diarrhoea was the most common side effect, although it generally was not significant.

Arsenite Oxidation by Dunaliella salina is Affected by External Phosphate Concentration.

Arsenic (As) contamination in terrestrial and aquatic environments is a well-known global environmental problem. The biooxidation of arsenite [As(III)] and subsequent arsenate [As(V)] removal have increasingly been used for remediation of As-polluted groundwater. However, little is known about As(III) oxidation by microalgae, especially those from saltwater environments. In this study, we investigated As(III) toxicity and oxidation in the marine microalga Dunaliella salina in the presence of different phosphate concentrations. The results of the As(III) toxicity experiments showed that D. salina was tolerant to As(III) (5.4 ± 0.31mg As L-1 at 72h of culture). The As(V) percentage in the P-enriched (11.2mg L-1) medium was 7.2-fold greater than in the P-deficient one after 24-h exposure, indicating As(III) oxidation by D. salina was more pronounced with increased phosphate levels. Treatment of As(III) with and without 2,4-dinitrophenol (DNP) on the algal cells showed that As(III) oxidation occurred mainly on the cell surface and in the cytoplasm of D. salina. The results of this study suggest that transformation of As(III) into As(V) may be an important pathway of detoxification in D. salina and that phosphate plays a key role in this oxidation process.

Competition between fulvic acid and phosphate-mediated surface properties and transport of titanium dioxide nanoparticles in sand porous media

Fulvic acid (FA) is a series of organic macromolecular compounds with many oxygen-containing functional groups and is easy to complex with nanoparticles (NPs) in the environment, thus affecting the stability and mobility of NPs in the water environment. Therefore, it is necessary to investigate the transport behavior of nano titanium dioxide (nTiO2) particles with FA in the presence of phosphate (P). A series of transport experiments were conducted by using nTiO2 suspended in phosphate background electrolyte with and without the addition of FA passing through water-saturated sand columns. The zeta potentials, hydrodynamic radii, and aggregation kinetics were measured, and the extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory and two-site kinetic attachment model (TSKAM) were employed to explain the underlying mechanism. The experimental results showed that the presence of FA compressed the transport of nTiO2 in phosphate electrolyte due to formation of larger complex via the adsorption of organic FA molecules onto nTiO2, which can strongly compete with phosphate adsorption, leading to reduced electrostatic repulsive forces between nTiO2 and sand. In the absence of FA at low pH (6.0), transport of individual nTiO2 was increased by low phosphate adsorption in response to increased phosphate levels, and then, transport was decreased with the increased number of cations (Na+) from the phosphate (P ≥ 1.0 mM) electrolyte due to the compressed electric double layer. From the goodness-of-fit of the modeling results, the TSKAM provided a good prediction for the retention and transport of nTiO2 in the copresence of FA and phosphate. The compressed transport of nTiO2 in the copresence of FA and phosphate was distinct from the synergistic transport in the copresence of humic acid.

A 300 μm Organotypic Bone Slice Culture Model for Temporal Investigation of Endochondral Osteogenesis.

Translational studies to elucidate the response of immature bone to biologic and physical stimuli have been held back by the lack of a viable long-term functional bone explant model. This study attempts to bridge this gap between cell culture and animal model studies. In this study, we describe a methodology to derive a 300 μm organotypic femur slice comprising physiological zones (epiphysis and meta-diaphysis) essential for endochondral bone development. The unique capability of slice culture model incorporating enhanced nutrient access to distinct bone tissue components associated with linear bone growth facilitates the investigation of the orchestrated cellular transition of chondrogenic and osteogenic cells involved in endochondral bone development in an ex vivo setup. Bone slices of 300 μm were prepared from 4-day-old postnatal rats and were viable in culture up to 21 days. On days 7 and 15, an increase in chondrogenic and osteogenic modulations was confirmed in epiphysis, metaphysis, and diaphysis. An increase in osteocytes, osteoblasts, and hypertrophic cells were found at these time points, as well as a noticeable increased expression of chondrogenic and osteogenic markers (collagen II, Runx2, and osteocalcin) confirmed endochondral progression. Osteoclast-mediated bone resorption was demonstrated on day 15 by tartrate-resistant acid phosphatase staining. Attenuated total reflection infrared spectroscopic analyses, furthermore, confirmed a time-dependent increase in phosphate levels, bone minerals, and hydroxyapatite for 15 days. Our establishment of a bone slice culture model closely mimicking the in vivo cellular transitions and endochondral microenvironment of a mineralizing bone provides a vital new tool for the elucidation of cellular and endochondral mechanisms of bone development, maturation, and growth plate modulations. The presented model has the potential to be utilized in implementation of preclinical, toxicological, and therapeutic investigations.

Development of a Cost-Effective Sensing Platform for Monitoring Phosphate in Natural Waters

A sensing platform for the in situ, real-time analysis of phosphate in natural waters has been realised using a combination of microfluidics, colorimetric reagent chemistries, low-cost LED-based optical detection and wireless communications. Prior to field deployment, the platform was tested over a period of 55 days in the laboratory during which a total of 2682 autonomous measurements were performed (854 each of sample, high standard and baseline, and 40 × 3 spiked solution measurements). The platform was subsequently field-deployed in a freshwater stream at Lough Rea, Co., Galway, Ireland, to track changes in phosphate over a five day period. During this deployment, 165 autonomous measurements (55 each of sample, high standard, and baseline) were performed and transmitted via general packet radio service (GPRS) to a web interface for remote access. Increases in phosphate levels at the sampling location coincident with rainfall events (min 1.45 µM to max 10.24 µM) were detected during the deployment. The response was found to be linear up to 50 µM PO43−, with a lower limit of detection (LOD) of 0.09 µM. Laboratory and field data suggest that despite the complexity of reagent-based analysers, they are reasonably reliable in remote operation, and offer the best opportunity to provide enhanced in situ chemical sensing capabilities. Modifications that could further improve the reliability and scalability of these platforms while simultaneously reducing the unit cost are discussed.

Serum phosphate levels are related to all-cause, cardiovascular and COPD mortality in men

Hyperphosphatemia has been associated with increased mortality in chronic kidney disease but the nature of such a relation in the general population is unclear. To investigate the association between phosphate (P) levels and all-cause and cause-specific mortality, we assessed two cohorts from the Rotterdam Study, with follow-up of 14.5 (RS-I) and 10.9 (RS-II) years until January 2012 with availability of fasting phosphate levels. Deaths were classified according to International Classification of Diseases into 7 groups: cardiovascular, cancer, infections, external, dementia, chronic lung diseases and other causes. Sex-stratified Weibull and competing-risks models were adjusted for age, BMI and smoking. Hazard ratios are expressed per 1 mg/dL increase in phosphate levels. The total number of participants included 3731 (RS-I, 2154 women) and 2494 (RS-II, 1361 women) subjects. The main outcome measures were all-cause and cause-specific mortality. A significant positive association was found between phosphate and all-cause mortality in men (pooled HR (95% CI): 1.46 (1.26–1.69)) but not in women (0.90 (0.77–1.05)). In men, higher phosphate increased the risk for cardiovascular mortality (1.66 (1.29–2.14)), other causes (1.67 (1.16–2.40)) and chronic lung disease mortality (1.94 (1.02–3.72)), the latter driven by mortality due to chronic obstructive pulmonary disease (COPD) (4.44 (2.08–9.49)). No relations were found for mortality due to infections, cancer, dementia or external causes. In conclusion, serum P is associated with increased all-cause, cardiovascular and COPD mortality in men but not women. The association with COPD mortality is novel and needs further research on underlying mechanisms.

Effect of Compost and Phosphate Applications on the Growth, Cadmium and Lead Uptake by Maize Plants Grown on Contaminated Soils

A pot experiment with maize (single cross-2030) was conducted to study the influence of phosphorus sources and levels and compost additions on growth, cadmium (Cd) and lead (Pb) contents of maize, as well as the availability of cadmium and lead in rhizosphere soil after the harvest of maize plants in three contaminated soils. It was observed in the three soils used in this study that compost addition increased significantly shoots and roots dry weight of maize plants and performed better than phosphate. With the three soils used in the study, results indicated that plants grown in soils amended with compost and supplied with rock phosphate (RP) at the high phosphate level, recorded the highest shoots & roots dry weight. Cadmium & lead contents of the both shoots & roots of maize plants were significantly reduced as a result of compost treatment. Rock phosphate addition significantly reduced Cd and Pb contents of both shoots and roots compared to single supper phosphate (SSP) for all soils examined. Increasing phosphate levels markedly reduced Cd and Pb contents of both shoots and roots with all soils studied. Also, the results revealed that plants grown in soils amended with compost and supplied with RP at high phosphate level recorded the lowest cadmium and lead contents of shoots and roots for the three soils used in this study. The availability of cadmium and lead in rhizosphere area after the harvest of maize plants were significantly decreased in all soils studied as a result of compost treatments. RP treatments significantly decreased the availability Cd and Pb in rhizosphere area of all soils studied compared to SSP addition. The available Cd and Pb in rhizosphere area were reduced as a result of increasing phosphate levels. The lowest value of available cadmium and lead in rhizosphere area of all studied soils were recorded for soils amended with compost and treated with RP at the high phosphate level.

Phosphate is a potential biomarker of disease severity and predicts adverse outcomes in acute kidney injury patients undergoing continuous renal replacement therapy.

Hyperphosphatemia is associated with mortality in patients with chronic kidney disease, and is common in critically ill patients with acute kidney injury (AKI); however, its clinical implication in these patients is unknown. We conducted an observational study in 1144 patients (mean age, 63.2 years; male, 705 [61.6%]) with AKI who received continuous renal replacement therapy (CRRT) between January 2009 and September 2016. Phosphate levels were measured before (0 h) and 24 h after CRRT initiation. We assessed disease severity using various clinical parameters. Phosphate at 0 h positively correlated with the Acute Physiology and Chronic Health Evaluation II (APACHE II; P < 0.001) and Sequential Organ Failure Assessment (SOFA; P < 0.001) scores, and inversely with mean arterial pressure (MAP; P = 0.02) and urine output (UO; P = 0.01). In a fully adjusted linear regression analysis for age, sex, Charlson comorbidity index (CCI), MAP, and estimated glomerular filtration rate (eGFR), higher 0 h phosphate level was significantly associated with high APACHE II (P < 0.001) and SOFA (P = 0.04) scores, suggesting that phosphate represents disease severity. A multivariable Cox model also showed that hyperphosphatemia was significantly associated with increased 28-day (HR 1.05, 95% CI 1.02–1.08, P = 0.001) and 90-day (HR 1.05, 95% CI 1.02–1.08, P = 0.001) mortality. Furthermore, patients with increased phosphate level during 24 h were at higher risk of death than those with stable or decreased phosphate levels. Finally, c-statistics significantly increased when phosphate was added to a model that included age, sex, CCI, body mass index, eGFR, MAP, hemoglobin, serum albumin, C-reactive protein, and APACHE II score. This study shows that phosphate is a potential biomarker that can reflect disease severity and predict mortality in critically ill patients receiving CRRT.

Hypoparathyroidism.

Hypoparathyroidism is a disease characterized by inadequately low circulating concentrations of parathyroid hormone (PTH) resulting in low calcium levels and increased phosphate levels in the blood. Symptoms of the disease result from increased neuromuscular irritability caused by hypocalcaemia and include tingling, muscle cramps and seizures. The most common cause of the disease is inadvertent removal of, or injury to, the parathyroid glands during neck surgery, followed by genetic, idiopathic and autoimmune aetiologies. Conventional treatment includes activated vitamin D and/or calcium supplements, but this treatment does not fully replace the functions of PTH and can lead to short-term problems (such as hypocalcaemia, hypercalcaemia and increased urinary calcium excretion) and long-term complications (which include nephrocalcinosis, kidney stones and brain calcifications). PTH replacement has emerged as a new treatment option. Clinical trials using human PTH(1-34) and PTH(1-84) showed that this treatment was safe and effective in studies lasting up to 6 years. Recombinant human PTH(1-84) has been approved in the United States and Europe for the management of hypoparathyroidism; however, its effect on long-term complications is still being evaluated. Clinical practice guidelines, which describe the consensus of experts in the field, have been published and recognize the need for more research to optimize care. In this Primer, we summarize current knowledge of the prevalence, pathophysiology, clinical presentation and management of hypoparathyroidism.

The biochemical and histological analysis of subcutaneous calcitonin and intramedullary methylprednisolone on bone repair after bone marrow ablation: an experimental comparative study in rats

BackgroundAlthough, glucocorticoid (GC) and calcitonin-induced changes in bone repair have been studied previously, the exact effects of these on fracture healing remain controversial. Hence, the purpose of this experimental study is to determine biochemical and histological effects of locally administrated GC and systemically administrated calcitonin on the kinetics of healing response after bone marrow ablation in rats.MethodsAfter having undergone marrow ablation, a steroid-treated group of rats (n = 24) received a single dose of intramedullary methylprednisolone (2 mg/kg), a calcitonin-treated group (n = 24) received intermittently administrated subcutaneous salmon calcitonin (16 IU/kg), and a control group (n = 24) received intramedullary saline (25 μl).ResultsBlood samples taken on days 1, 3, 7, 9, and 15 after ablation showed an increase in serum calcium, alkaline phosphatase (ALP), and phosphate levels in the Calcitonin and Control groups. Levels of calcium and ALP peaked on day 7 after ablation. However, an increase in phosphate levels indicated a biphasic reaction that peaked on the third and ninth day after ablation. Hypercalcemia was not observed in Steroid group because of the inhibition of osteoclastic bone resorption. In that group, the serum levels of ALP and phosphate were lower than baseline levels. The levels of urinary calcium excretion peaked 3 to 7 days after marrow ablation in the control group and 7 to 9 days after that procedure in the steroid group. Histologic evaluation showed that the rats in the control group demonstrated the expected healing period according to the histological grades and that a delay in healing occurred in the calcitonin group after day 9 because of the inhibition of osteoclastic bone resorption. All rats in the steroid group exhibited a decrease and delayed healing response.ConclusionTotal serum calcium, phosphate, and ALP levels increased after bilateral tibial bone marrow ablation and urine calcium and hydroxyproline excretion also increased as a factor of bone resorption. Subcutaneously administrated salmon calcitonin did not affect biochemical changes after marrow ablation. Single-dose intramedullary methylprednisolone inhibited extra-tibial bone resorption induced by cytokines after bone marrow ablation.