Elevated Serum Phosphorus Levels Research Articles

THU457 Variable Presentations Of Hypophosphatasia In Two Patients In The Outpatient Setting

Abstract Disclosure: A. Elmaaz: None. S. Batool: None. P. Dandona: None. Introduction: Hypophosphatasia is a rare disorder characterized by defective mineralization of bone and teeth which is caused by an autosomal inherited mutation in the tissue nonspecific alkaline phosphatase (ALP) encoding genes. Here we present two cases of multiple dental and bony defects secondary to low ALP enzyme activity due to hypophosphatasia. Case 1: A 27-year-old female with history of mitochondrial disease, gastroparesis, malabsorption syndrome, and autonomic dysfunction was referred to Endocrinology clinic because of persistently low serum ALP levels associated with recurrent muscle, joint, and bone pain since the age of 13. She had history of multiple tooth extractions because of dental developmental abnormalities and fractures. She also reported history of fractures of three of her fingers in both hands during her childhood and teenage years. The patient was adopted and was unaware of any biological family history. Physical examination was remarkable for short-statured female, 4'8". Notably, the middle phalanges in little fingers bilaterally were shorter than the other fingers. Workup showed vitamin D level of 21 (30-80) ng/ml, despite being on 50,000 IU twice a week for 6 months with normal PTH and ionized calcium levels. The repeated serum level of ALP was 24 (31-125) U/L with bone and liver isoenzymes levels of 42% and 58 % respectively. Vitamin B6 level was 13.2 (2.1-21.7) ng/ml. Bone mineral density was unremarkable. Case 2: A 53-year-old female with history of congenital left hip dysplasia, hypertension, and dyslipidemia was seen by Endocrinology service for evaluation of decreased ALP levels. She denied any history of falls or fractures. However, she reported chronic bone pain, especially in bilateral hip joints with history of multiple surgeries in her left hip joint. She had required teeth braces and multiple dental surgeries during her childhood due to dental maldevelopment. Her height was 4'8". Laboratory workup was remarkable for low serum ALP level of 30 U/L with bone isoenzyme of 24 %. Vitamin B6 level was 206.7 (2.1-21.7) ng/ml. She had elevated serum phosphorus levels with normal calcium, PTH, and vitamin D levels. Pyridoxal-5- Phosphate level was high. Bone mineral density revealed osteopenia. Conclusion: Hypophosphatasia is a rare disease, hence it could be easily missed due to high variability in clinical presentations and severity of symptoms. Low serum levels of ALP with history of bone pain, recurrent fractures, premature loss of deciduous teeth, or loss of adult dentition should raise the suspicion of hypophosphatasia. Resistance to vitamin D supplementation is another clue to the diagnosis. A multidisciplinary approach is required for appropriate management. Presentation: Thursday, June 15, 2023

The association between serum phosphorus and common carotid artery intima-media thickness in ischemic stroke patients.

An elevated concentration of phosphorus is associated with an increased risk of atherosclerosis and cardiovascular diseases. Common carotid artery intima-media thickness (cIMT) is an imaging marker of atherosclerosis. However, data on the relationship between phosphorus and cIMT in ischemic stroke are scarce. We aimed to evaluate the association between serum phosphorus levels and cIMT in patients who had experienced ischemic stroke. A total of 1,450 ischemic stroke patients were enrolled. Participants were divided into four groups (quartiles) according to baseline serum phosphorus level. Carotid atherosclerosis was identified by measurement of cIMT; abnormal cIMT was defined as a maximum cIMT or mean cIMT ≥ 1 mm. Multivariable logistic regression models were used to assess the association between serum phosphorus level and the presence of abnormal cIMT. In the multivariable adjusted analysis, falling into the highest quartile for serum phosphorus (Q4) was associated with a 2.00-fold increased risk of having abnormal maximum cIMT [adjusted odds ratio (OR) 2.00; 95% confidence interval (CI) 1.44-2.79] and a 1.76-fold increased risk of having abnormal mean cIMT (adjusted OR 1.76; 95% CI 1.22-2.53) in comparison to Q1. Furthermore, the association between serum phosphorus and abnormal cIMT was confirmed in analyses treating serum phosphorus as a continuous variable and in subgroup analyses. In acute ischemic stroke patients, baseline elevated serum phosphorus level was found to be independently associated with carotid atherosclerosis, as measured by cIMT.

Optimal Administration of Phosphorus Adsorbents When Using Medical Nutritional Supplements for Tube-fed Patients.

All medical enteral nutrition products contain phosphorus and when administered to patients with chronic kidney disease (CKD) and on dialysis, they lead to the risk of elevated serum phosphorus levels. Thus, serum phosphorus levels should be monitored, and phosphorus adsorbents should be used in cases of high serum phosphorus levels. In this study, we investigated the effect of phosphorus adsorbents on enteral nutrition, using Ensure Liquid®, a medical nutritional formula, for patients with CKD and those on dialysis. Additionally, we compared the effects of the simple suspension method, in which various phosphorus-adsorbing agents are suspended and mixed directly with the nutritional formula for tube administration (hereafter referred to as the "pre-mix method"), and the conventional method, in which only the phosphorus-adsorbing agents are administered separately from the nutritional formula for tube administration (hereafter referred to as the "normal administration method"). The administration of various phosphorus adsorbents using the pre-mix technique resulted in a phosphorus removal rate of 8-15% (approximately 12% on average). Therefore, through the pre-mix method, maintaining the phosphorus content of Ensure Liquid® below the daily phosphorus intake standard was possible for patients on dialysis. The pre-mix method via the simple suspension method of administering phosphorus adsorbent with Ensure Liquid® resulted in less drug adsorption to the injector and tube and a higher phosphorus removal rate than the normal administration method.

Potential role of Niacin as Adjuvant to Sevelamer on Serum levels of Inorganic phosphorus, Calcium and Calcium-phosphorus product in Hemodialysis patients with Hyperphosphatemia

Hyperphosphatemia is a serious biochemical abnormality that affected almost patients undergoing maintenance hemodialysis and has independent association with high risk of mortality due to cardiovascular diseases. The mechanism linking hyperphosphatemia to cardiovascular mortality is vascular calcification that it is promoted by elevated serum phosphorus level. The control of hyperphosphatemia remains a major challenge. All currently phosphate binders have requirement for dosing with each meals that contributed to high pill burden and reduce patient compliance. Calcium-based binders preferred to be avoided due to their high risk of vascular classification, while the expensiveness of non-calcium based binder represent their major drawbacks. Niacin; a naturally occurring water-soluble vitamin and the first used antidyslipidemic drug, has been demonstrated to show therapeutic potential for hyperphosphatemia treatment in hemodialysis patients. It decreases phosphorus absorption in the GIT, thereby lowering serum phosphorus level. This study is designed to evaluate the efficacy of niacin as adjuvant therapy to sevelamer carbonate (as a phosphate binder) in hemodialysis patients. This prospective, randomized clinical trial was conducted among patients with hyperphosphatemia. Seventy nine patients were enrolled in this study; only 39 patients completed the study. Thirty nine patients were assigned randomly into two groups; group (1) 19 patients treated with sevelamer alone (2400mg/day), group (2) 20 patients treated with a combination of sevelamer (2400mg/day) and niacin (1000 mg/day) for 2 months . Clinical outcomes (Pi, Ca, Ca x P product) serum levels were evaluated at time of enrolment, after 1 month and after 2 month of treatment. Results of this study showed that the patients who administered orally niacin as adjuvant to sevelamer had the superiority over using sevelamer alone in the reduction of both serum phosphorus level and (Ca x P) product level (-30% and -37%) respectively after 2 months of treatment in respect to baseline levels. Meanwhile, there was no statistically significant difference observed in serum calcium level. Administration of niacin for hemodialysis patients is an effective strategy for reducing the serum levels of inorganic phosphorus and calcium-phosphorus product which subsequently reduce risks of cardiovascular diseases associated with hyperphosphatemia.

Factors associated with aortic valve stenosis in Japanese patients with end-stage kidney disease

BackgroundAortic valve stenosis (AS) has a high prevalence and poor prognosis in patients who receive maintenance dialysis. However, few large-scale observational studies in Japan have investigated patients with AS who underwent dialysis. In this study, we investigated the prevalence and factors associated with AS in Japanese patients who underwent dialysis.MethodsIn this cross-sectional analysis, we enrolled patients who underwent dialysis and transthoracic echocardiography between July 1, 2017 and June 30, 2018. Patients with a maximum aortic jet velocity (Vmax) ≥ 2.0 m/s, pressure gradient (PG) between the left ventricle and ascending aorta (mean PG) ≥ 20 mmHg, or aortic valve area (AVA) ≤ 1.0 cm2 were categorized into the AS group (G1). Patients with Vmax ≥ 3.0 m/s, mean PG ≥ 20 mmHg, or AVA ≤ 1.0 cm2 were categorized into the moderate and severe AS groups (G2). We performed multivariate logistic regression analysis and compared G1 and G2 with the non-AS group to determine the risk factors for AS. We also investigated the risk factors for aortic valve calcification, which is a pre-stage for AS.ResultsOf the 2,786 patients investigated, 555 (20.0%) and 193 (6.9%) were categorized into G1 and G2, respectively. Multivariate logistic regression analysis revealed that age, long-term dialysis, and elevated serum phosphorus levels were associated with AS in both the groups (p < 0.05). These factors were converted into ordinal categories, and a multivariate logistic regression analysis was performed. Patients with serum phosphorus levels measuring 5.0–5.9 mg/dL and > 6.0 mg/dL showed a higher risk of AS than those with serum phosphorus levels measuring < 4.0 mg/dL (odds ratio 2.24, p = 0.01 and odds ratio 2.66, p = 0.005, respectively). Aortic valve calcification was associated with age, long-term dialysis, diabetes mellitus, administration of vitamin D receptor activators, elevated serum calcium levels, and anemia (p < 0.05 for all).ConclusionsPatients on dialysis showed a high prevalence of AS, which was associated with age, long-term dialysis, and elevated serum phosphorus levels.Trial registrationUMIN000026756, registered on March 29, 2017.

COVID‑19 induced hypoparathyroidism: A case report

Low levels of serum calcium, elevated levels of serum phosphorus and absent or abnormally low levels of serum parathyroid hormone characterize hypoparathyroidism, a rare endocrine deficiency illness. Hypoparathyroidism is caused by injury to the parathyroid gland as a result of surgery or autoimmune disease. In addition, hypoparathyroidism may develop due to genetic causes or infiltrative diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by multi-organ involvement, including the dysfunction of endocrine glands. Previous studies have demonstrated that SARS-CoV-2 infection induces endocrine tissue damage via various mechanisms, including direct cell damage from viral entry to the glands by binding to the angiotensin converting enzyme 2 receptors and replication, vasculitis, arterial and venous thrombosis, hypoxic cell damage, immune response and the cytokine storm. The effects of the new coronavirus, coronavirus disease 2019 (COVID-19) on the parathyroid glands have received limited attention. Hypoparathyroidism has been observed in a small number of individuals as a result of SARS-CoV-2 infection. The present study describes the case of a patient with primary hypoparathyroidism induced by COVID-19. Clinicians should also keep in mind that, despite the fact that SARS-CoV-2 has no known tropism for the parathyroid glands, it can result in primary hypoparathyroidism and decompensation of old primary hypoparathyroidism.

European hemodialysis patient satisfaction with phosphate binders is associated with serum phosphorus levels: the Dialysis Outcomes and Practice Patterns Study.

BackgroundHemodialysis (HD) patients are commonly prescribed phosphate binders (PBs) to manage serum phosphorus levels, as hyperphosphatemia is strongly associated with poorer survival. Nonadherence with the PB prescription is associated with elevated serum phosphorus levels. We studied associations between patient satisfaction with their PB and serum phosphorus levels and mortality rates.MethodsAdult HD patients in Germany, Italy, Spain and the UK in the Dialysis Outcomes and Practice Patterns Study were administered a survey instrument in late 2017. Patients were asked about their satisfaction with their PBs, as measured through three questions (difficulty, inconvenience and dissatisfaction) on a 5-point Likert scale, with each dichotomized into average worst versus good responses. These were used as predictors in linear regression models of continuous serum phosphorus levels and in Cox proportional hazards models of mortality, with adjustments for demographics, comorbidities and laboratory values.ResultsPatients having greater difficulty, inconvenience and dissatisfaction with their PB had higher serum phosphorus levels in adjusted models {+0.21 mg/dL [95% confidence interval (CI) ±0.23], +0.30 (±0.21) and 0.36 (±0.22), respectively}, and higher odds of having serum phosphorus levels ≥6.0 mg/dL. Measures of dissatisfaction were also associated with an elevated risk of mortality, with adjusted hazard ratios of 2.2 (95% CI 1.3–3.6), 1.6 (1.0–2.6) and 1.7 (1.1–2.7), respectively; this association was not strongly affected by adjustment for baseline serum phosphorous level.ConclusionsSelf-reported difficulty, inconvenience and dissatisfaction in taking one’s prescribed PBs were associated with elevated serum phosphorus levels and serum phosphorus levels above clinically meaningful thresholds. While the mechanism for the association with mortality is unclear, patient-reported satisfaction should be considered when attempting to manage patient serum phosphorus levels.

Greater consumption of noodle is associated with higher serum phosphorus levels: a cross-sectional study on healthy participants

Higher serum phosphorus levels are associated with mortality and cardiovascular events, both in healthy individuals and those with chronic kidney disease. Owing to the increasing westernization of eating habits, a decrease in rice consumption and an increase in the intake of bread and noodle products were observed in Japan. This cross-sectional study investigated the influence of staple food (rice, bread, and noodle) consumption patterns on the serum levels of phosphorus and phosphate-regulating factors in 103 healthy young participants. Fasting blood and 24-h urine samples were collected; data about dietary habits were collected using a brief-type self-administered diet history questionnaire. Cluster analysis was conducted to assess subgroups classified according to staple food consumption patterns. Serum levels of phosphorus and phosphate-regulating factors did not significantly differ between subgroups classified based on the frequency of rice or bread consumption. However, the serum levels of phosphorus and fibroblast growth factor 23 were more significantly elevated in the higher than in the lower noodle consumption frequency subgroup. Cluster analysis defined three clusters, and the serum phosphorus levels in the high-noodle cluster were significantly higher than that in the high-bread and high-rice clusters. A high consumption of noodles was associated with elevated serum phosphorus levels. The trial was registered in the University Hospital Medical Information Network (UMIN) Center system (The name of the trial register: Hidekazu Arai, and UMIN accession number: UMIN000034352).

PDB12 EFFICACY AND SAFETY OF ETELCALCETIDE IN THE TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN ADULT PATIENTS WITH CHRONIC KIDNEY DISEASE UNDERGOING DIALYSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Chronic kidney disease (CKD) is a condition with an irreversible reduction in the number of functioning nephrons, which results in progressive and permanent deterioration in kidney function. There were numerous complications associated with CKD which include secondary hyperparathyroidism. Controlling elevated serum phosphorus levels and directly targeting suppression of intact parathyroid hormone (iPTH) production remain targets. This study aimed to evaluate the efficacy and safety of etelcalcetide in the treatment of secondary hyperparathyroidism in adult patients with CKD undergoing dialysis

Sucroferric Oxyhydroxide in Maintenance Hemodialysis: A Retrospective, Comparative Cohort Study

Rationale & ObjectiveHigh pill burden associates with reduced phosphate-binder adherence among dialysis patients, contributing to elevated serum phosphorus levels. We compared the real-world effectiveness of sucroferric oxyhydroxide (SO) versus other phosphate binders in hemodialysis patients over 2 years.Study DesignRetrospective cohort study.Setting & ParticipantsAdult in-center hemodialysis patients prescribed 2 years of uninterrupted SO therapy (maintenance SO; n = 222) compared with patients who discontinued SO therapy (discontinued SO; n = 596) within 90 days of first prescription and switched to other phosphate binder(s) for 2 years.ExposuresPhosphate binders.OutcomesAchievement of serum phosphorus levels ≤ 5.5 mg/dL, pill burden, and hospitalizations.Analytical ApproachComparisons were made quarterly (Q1-Q8) between maintenance SO and discontinued SO using Poisson and mixed-effects linear regression.ResultsPatients achieving serum phosphorus levels ≤ 5.5 mg/dL increased from baseline in maintenance SO (46 [20.7%] to a maximum of 104 [46.8%; P < 0.001]) and discontinued SO (96 [16.1%] to a maximum of 201 [33.7%]; P < 0.001). 100 (45%) maintenance SO patients achieved target serum phosphorus levels at Q8 with 3.1 fewer pills per day from baseline (7.5 to 4.4 pills per day; P < 0.001), and 190 (31.9%) discontinued SO patients achieved serum phosphorus levels ≤ 5.5 mg/dL at Q8 with pill burden unchanged (9.1 to 9.3 pills per day; P = 0.3). Among all patients during 2 years, mean serum phosphorus levels decreased by −0.66 mg/dL and −0.45 mg/dL (maintenance SO vs discontinued SO; P = 0.014), and mean pill burden decreased in maintenance SO (8.5 to 5.1 pills per day; P < 0.001), but not in discontinued SO (11.6 to 10.9 pills per day; P = 0.2). The serum phosphorus level decrease with SO was confirmed in a sensitivity analysis including patients with SO therapy for 2 or fewer years. Compared with discontinued SO, maintenance SO patients had 35.6 fewer hospitalizations per 100 patient-years (incidence rate ratio, 0.75 [95% CI, 0.58-0.96]).LimitationsNo data for treatment indication, tolerance, or adherence.ConclusionsPatients maintained on SO therapy were more likely to achieve target serum phosphorus levels, use 50% fewer phosphate-binder pills per day, and have fewer hospital admissions than patients switched to treatment with other binders.

Higher serum phosphorus predicts residual renal function loss in male but not female incident peritoneal dialysis patients.

Elevated serum phosphorus level is a risk factor for progression of chronic kidney disease in non-dialysis patients. However, the association of serum phosphorus level with residual renal function (RRF) loss among incident continuous ambulatory peritoneal dialysis (CAPD) patients remains unclear. We performed a retrospective analysis of prospectively collected cohort of 1245 incident CAPD patients from January 2006 to December 2015 and followed up until December 2017. Patients were stratified into tertiles according to baseline serum phosphorus levels. RRF loss was defined as residual glomerular filtration rate (mL/min/1.73m2) reaching zero or estimated urine output less than 200mL/day on two successive clinic visits. Propensity-score matched Cox's proportional hazards and competing risk models were performed to examine the association of serum phosphorus with RRF loss. A total of 421 (33.82%) patients had loss of RRF over a median follow-up of 26.23months. In the entire cohort, elevated serum phosphorus was associated with increased risk for RRF loss after adjustment. In the propensity-score matched cohort, patients in the 3rd tertile of serum phosphorus had a 51% higher risk of RRF loss than those in the combination of the 1st and 2nd tertiles. Furthermore, the association of serum phosphorus level with RRF loss differed by sex (interaction P = 0.018). The adjusted HRs per 1mg/dL increase in serum phosphorus level of RRF loss were 1.32 (95% CI 1.15-1.50, P < 0.001) for male and 1.03 (95% CI 0.87-1.21, P = 0.750) for female, respectively. These findings persisted in competing risk analysis. Higher serum phosphorus levels independently predicts RRF loss in men treated with CAPD.

Association between Serum Indoxyl Sulfate Levels and Endothelial Function in Non-Dialysis Chronic Kidney Disease.

Indoxyl sulfate (IS), a product metabolized from tryptophan, is negatively correlated with renal function and cardiovascular diseases in patients with chronic kidney disease (CKD). We investigated the association between serum IS levels and endothelial function in patients with CKD. Fasting blood samples were obtained from 110 patients with stages 3–5 CKD. The endothelial function, represented by vascular reactivity index (VRI), was measured non-invasively using digital thermal monitoring. Serum IS levels were determined using liquid chromatography–mass spectrometry. Twenty-one (19.1%), 36 (32.7%), and 53 (48.2%) patients had poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0) vascular reactivity. By univariate linear regression analysis, a higher prevalence of smoking, advanced age, higher systolic, and diastolic blood pressure (DBP), elevated levels of serum phosphorus, blood urea nitrogen, creatinine, and IS were negatively correlated with VRI values, but estimated glomerular filtration rate negatively associated with VRI values. After being adjusted by using multivariate stepwise linear regression analysis, DBP and IS levels were significantly negatively associated with VRI values in CKD patients. We concluded that IS level associated inversely with VRI values and had a modulating role in endothelial function in patients with stages 3–5 CKD.

The relation between serum phosphorus levels and long-term mortality in Chinese patients with ST-segment elevation myocardial infarction.

BackgroundElevated serum phosphorus levels may be associated with adverse outcomes in cardiovascular disease. This study aimed to investigate the relation between serum phosphorus levels and risk of all-cause mortality in Chinese patients with ST-segment elevation myocardial infarction (STEMI) who had preserved renal function at baseline.MethodsWe enrolled patients with STEMI who had preserved renal function at baseline in Xuanwu Hospital from January 2011 to December 2016. Those patients were divided into four groups based on serum phosphorus levels. All-cause mortality rates were compared between groups. Mean duration of follow up was 54.6 months. We used Cox proportional-hazards models to examine the relation between serum phosphorus levels and all-cause mortality after adjustment for potential confounders.Results1989 patients were involved and 211 patients (10.6%) died during follow-up. Based on serum phosphorus levels, patients were categorized into the following groups: < 2.50 mg/dL (n = 89), 2.51–3.50 mg/dL (n = 1066), 3.51–4.50 mg/dL (n = 672) and > 4.50 mg/dL (n = 162), respectively. The lowest mortality occurred in patients with serum phosphorus levels between 2.51–3.50 mg/dL, with a multivariable-adjusted hazard ratio of 1.19 (95% CI: 0.64–1.54), 1.37 (95% CI: 1.22–1.74), and 1.46 (95% CI: 1.35–1.83) in patients with serum phosphorus levels of < 2.50 mg/dL, 3.51–4.50 mg/dL and > 4.50 mg/dL, respectively.ConclusionsElevated serum phosphorus levels were associated with all-cause mortality in Chinese patients with STEMI who had preserved renal function at baseline.

Habitual confectionery intake is associated with serum phosphorus levels : A cross-sectional study on healthy subjects.

Hyperphosphatemia is associated with an increased risk of developing cardiovascular disease. Recently, it has been shown that high serum phosphorus levels are associated with increased cardiovascular events in healthy subjects, but the dietary factors determining serum phosphorus level have not been fully investigated. The study investigated the influence of habitual dietary factors on serum phosphorus levels in healthy young participants. This cross-sectional study conducted fasting blood sampling in 109 healthy young people and used a brief-type self-administered diet history questionnaire to evaluate the subject's habitual meals. Since the bioavailability of dietary phosphorus depends on the food sources, habitual phosphorus intakes from different food groups and intake frequency (times/month) of processed foods were calculated. The mean serum phosphorus level was 3.9 0.5 mg/dl ; 10.1% of the subjects had serum phosphorus levels that exceeded the reference levels of 4.5 mg/dl. Total phosphorus intake and phosphorus intake from animal-based food did not differ between serum phosphorus quartiles. Higher intake of confectionery was associated with increased serum phosphorus levels. This study showed that frequent consumption of confectionery was associated with elevated serum phosphorus levels. Additional studies are needed to determine whether this is a causal relationship. J. Med. Invest. 66 : 134-140, February, 2019.

Evaluation of promising biochemical markers of nutritional osteodystrophy in goats

Fibrous osteodystrophy (FO), a metabolic bone disorder, has been reported in different animal species with variable susceptibility. Albeit, it is commonly reported in horses, the clinical disease is also recorded globally in goats. Diagnosis of fibrous osteodystrophy is mainly based on various clinical examination methods including biochemical alterations which can be adopted as routine diagnostic method. Therefore, the present study was aimed to investigate calcium: phosphorus (Ca:P) ratio and alkaline phosphatase (ALP) activity as biochemical diagnostic markers in goats diagnosed for fibrous osteodystrophy by clinical and radiological examinations. Blood samples were obtained from 11 goats diagnosed to have clinical fibrous osteodystrophy and 10 healthy goats, and used for harvesting serum. Goats with fibrous osteodystrophy revealed markedly elevated serum phosphorus level and ALP activity, and lowered calcium level in comparison to healthy goats. Remarkably lower serum Ca:P ratio was also observed in diseased goats. Radiological examination of skull of diseased goats revealed radio-lucent areas on the mandible as well as the upper jaw. In conclusion, marked reduction in Ca:P ratio and elevation in ALP activity could be promising biochemical diagnostic marker of fibrous osteodystrophy in goats.

Impact of Serum Phosphorus Levels on Outcomes After Implantation of Drug-Eluting Stents in Patients on Hemodialysis.

Elevated serum phosphorus level is an important risk factor for cardiovascular death in general patients on hemodialysis (HD). However, the effect of serum phosphorus levels on outcomes after drug-eluting stent (DES) implantation in HD patients is unknown.Methods and Results:This was a post-hoc study of the OUCH study series, a series of prospective multicenter registries of HD patients who underwent DES implantation comprising 359 patients from 31 centers in Japan. Patients were categorized into 3 groups according to their preprocedural serum phosphorus levels. The 1-year clinical outcomes of the 336 patients treated for de novo lesions were evaluated. Compared with patients with high (>5.5 mg/dL; n=65) or normal (3.5-5.5 mg/dL; n=219) serum phosphorus levels, those with low serum phosphorus levels (<3.5 mg/dL; n=52) had significantly fewer target lesion revascularization events (13.9% vs. 16.9% vs. 1.9%; P=0.0090) and major adverse cardiac and cerebrovascular events (29.2% vs. 31.1% vs. 13.5%; P=0.032). Multivariate logistic regression analysis revealed that low serum phosphorus level was an independent negative predictor for major adverse cardiac and cerebrovascular events (adjusted odds ratio, 0.31; 95% confidence interval, 0.12-0.70; P=0.0036). Lowering of serum phosphorus levels beyond the current recommended range may be considered in HD patients who undergo DES implantation.

Effects of serum phosphorus on vascular calcification in a healthy, adult population: A systematic review

Cardiovascular disease has been associated with elevated serum phosphorus levels, which have been associated with cardiovascular mortality. This is commonly seen in the chronic kidney disease (CKD) population where studies have shown that high phosphorus levels cause coronary artery calcification. Although studies have independently associated vascular stiffness and serum phosphorus in those with and without CKD, there are fewer data in individuals without CKD. Therefore, the aim of this systematic review was to analyze whether serum phosphorus levels are associated with cardiovascular calcification in healthy individuals. A systematic review of the literature that was conducted revealed10 articles, all cross-sectional studies, that met eligibility criteria. These criteria were peer-reviewed studies on a healthy, adult population written in the English language. Studies lacking data on serum phosphorus and measured to assess its association with vascular calcification were excluded. Studies on subjects with CKD, other chronic diseases,or on children were also excluded. Of the 10 studies located, 8 indicated an association between serum phosphorus and vascular calcification. One study did not indicate an association. One study indicated a statistically significant association between serum phosphorus and vascular calcification prevalence, but not incidence. Studies were limited since no randomized controlled trials were available. This systematic review generates gaps in research. Dueto considerable amounts of phosphorus additives in the food supply, there may be a connection to dietary phosphorusand vascular calcification. Additionally, phosphorus binders may assist in the prevention of vascular calcificationbut have not been studied in a healthy population. Further study on both dietary phosphorus restriction and phosphorus binders is needed. While 8 out of 10 cross-sectional studies found an association in this systematic review,the topic of vascular calcification and serum phosphorus needs further study if a cause and effect relationship is to be detected.

Cinacalcet ameliorates aortic calcification in uremic rats via suppression of endothelial-to-mesenchymal transition.

Experimental studies found that cinacalcet (CINA) markedly attenuated vascular calcification in uremic rats, but its underlying mechanisms are still largely unknown. Recent evidence have demonstrated that endothelial cells (ECs) participate in ectopic calcification in part by mediating endothelial-to-mesenchymal transition (EndMT). In this study, we investigated whether CINA ameliorated aortic calcification in uremic rats via suppression of EndMT. Uremia was induced in rats by feeding rats a 0.75% adenine diet for 4 weeks. After adenine withdrawal, the rats were maintained on a 1.03% phosphorus diet for next 8 weeks. At initiation of the adenine diet, rats were orally administered CINA (10mg/kg one day) for 12 weeks. The aortic expression of EndMT- and chondrocyte- markers was examined. The effect of elevated PTH on EndMT was also studied in aortic ECs. In uremic rats, CINA treatment significantly decreased the serum PTH concentrations, but did not affect the elevated levels of serum calcium (Ca), phosphorus (P) and Ca×P product. Besides, CINA significantly attenuated aortic calcification, and inhibited the expression of chondrocyte markers (SOX9 and COL2A1) and chondrocyte proteoglycan in uremic aortas. Moreover, CINA treatment largely abolished the up-regulation of mesenchymal markers (FSP1 and α-SMA) and down-regulation of the endothelial marker (CD31), which accompanied aortic calcification in uremic aorta samples. In vitro, PTH increased the expression of EndMT-markers in a concentration- and time-dependent manner. These findings suggest that strategies aiming at reducing serum PTH might prevent uremic aortic calcification by abrogating EndMT.

Psychosocial Factors That Create Barriers to Managing Serum Phosphorus Levels in Pediatric Dialysis Patients: A Retrospective Analysis

Abnormal phosphorus homeostasis is among the medley of metabolic disturbances commonly associated with chronic kidney disease. We sought to determine the psychosocial factors that create barriers to controlling serum phosphorus levels in children on dialysis and to evaluate the perceptions of children and caregivers on the ease or difficulty of following a dietary phosphorus restriction and taking phosphorus binder medications. Single center cross-sectional study. Pediatric dialysis unit at a children's hospital. Forty-eight patients on chronic hemodialysis or peritoneal dialysis (mean age: 11.03±6.88years; 69% male). Serum phosphorus levels were recorded from electronic health records and converted to a mean phosphorus standard deviation score (SDS) for each individual. Mean phosphorus SDS values were compared to each independent categorical variable using an analysis of variance test, continuous variables were analyzed using linear regression, and logistic regression was used to determine odds ratios. There was a significant relationship between age and phosphorus SDS (P<.001), with patients over 13years of age having the highest prevalence of hyperphosphatemia (88%). Patients and caregivers who identified phosphorus levels as "controlled" had lower phosphorus SDS values compared to the other subjects (P=.003). However, of the patients and caregivers who reported that serum phosphorus levels were "controlled," 46% were hyperphosphatemic. Furthermore, 73% and 87% of patients and caregivers reported that following a phosphorus-restricted diet and taking phosphorus binders were "easy"; yet, 40% and 49% of these patients were hyperphosphatemic, respectively. In the present study, elevated serum phosphorus levels were most common in adolescent dialysis patients. There also appears to be a disconnect between the perceived ease of following a phosphorus-restricted diet and taking phosphorus binders and the achievement of normal serum phosphorus levels. These data further emphasize the importance of ongoing education regarding dietary and medical management requirements.

An optical method for serum calcium and phosphorus level assessment during hemodialysis.

Survival among hemodialysis patients is disturbingly low, partly because vascular calcification (VC) and cardiovascular disease are highly prevalent. Elevated serum phosphorus (P) and calcium (Ca) levels play an essential role in the formation of VC events. The purpose of the current study was to reveal optical monitoring possibilities of serum P and Ca values during dialysis. Twenty-eight patients from Tallinn (Estonia) and Linköping (Sweden) were included in the study. The serum levels of Ca and P on the basis of optical information, i.e., absorbance and fluorescence of the spent dialysate (optical method) were assessed. Obtained levels were compared in means and SD. The mean serum level of Ca was 2.54 ± 0.21 and 2.53 ± 0.19 mmol/L; P levels varied between 1.08 ± 0.51 and 1.08 ± 0.48 mmol/L, measured in the laboratory and estimated by the optical method respectively. The levels achieved were not significantly different (p = 0.5). The Bland-Altman 95% limits of agreement between the two methods varied from −0.19 to 0.19 for Ca and from −0.37 to 0.37 in the case of P. In conclusion, optical monitoring of the spent dialysate for assessing the serum levels of Ca and P during dialysis seems to be feasible and could offer valuable and continuous information to medical staff.