Admission Lower Serum Phosphate Ion Levels Predict Acute Hydrocephalus of Aneurysmal Subarachnoid Hemorrhage

Introduction: The relationship between serum phosphate ion (sPi) and the occurrence of acute hydrocephalus (aHCP) in aneurysmal subarachnoid hemorrhage (aSAH) remains largely unknown and controversial. The primary aim of this study was to investigate the association between sPi on admission and aHCP following aSAH.Methods: The study included 635 patients over the age of 19 years diagnosed with aSAH in our institution from September 2012 to June 2018. Data on clinical characteristics, laboratory parameters, treatments, and outcomes were collected and analyzed. The association between lower sPi levels and aHCP was assessed in univariate and multivariate analyses. Propensity-score matching (PSM) analysis was performed to reduce significant differences in baseline characteristics between the aHCP group and non-HCP group.Results: The overall incidence of aHCP following aSAH was 19.37% (123/512). Lower sPi levels were detected in patients with aHCP compared with those without [0.86 (0.67–1.06) vs. 1.04 (0.84–1.21) mmol/L] in the univariate analysis. In the multivariate analysis, lower sPi level, high modified Fisher (mFisher) grade, and high Hunt-Hess grade were associated with aHCP [odds ratios (OR) 1.729, 95% confidence interval (CI) 1.139–2.623, p = 0.01; mFisher OR 0.097,95% CI 0.055–0.172, p < 0.001; Hunt-Hess, OR 0.555, 95% CI 0.320–0.961, P = 0.036]. After PSM, the matched aHCP group had a significantly lower sPi level than the matched non-aHCP group [0.86 (0.67–1.06) vs. 0.94 (0.76–1.12) mmol/L, p = 0.044]. The area under the curve (AUC) of the sPi level and the logistic regression model based on these predictors (sPi, Hunt-Hess grade, and mFisher grade) was 0.667 and 0.840 (sensitivity of 88.6% and specificity of 68.4%) for predicting aHCP, respectively.Conclusions: Lower sPi levels predict the occurrence of aHCP, and the model constructed by sPi levels, Hunt-Hess grade, and mFisher grade markedly enhances the prediction of aHCP after aSAH.

The Effectiveness and Safety of Calcium Carbonate Use in Chronic Kidney Disease Patients with Normophosphatemia

Background: Patients with early and moderate stages of chronic kidney disease (CKD) have normal serum phosphate levels. Increased fibroblast growth factor-23 (FGF23) levels in these patients are responsible for maintaining normophosphatemia status by increasing the excretion of phosphate through urine. However, an increased serum FGF23 level is related to cardiomegaly, vascular calcification, CKD progression, and mortality. This study aimed to examine the effectiveness and safety of calcium carbonate use in stage 3 or 4 CKD patients with normophosphatemia. Methods: This double-blind randomized controlled trial (ClinicalTrials.gov identifier NCT03550534) included stage 3 or 4 CKD patients with normophosphatemia who visited the nephrology or endocrinology clinic at Dr. Cipto Mangunkusumo Hospital. Forty-six subjects were randomized to receive either calcium carbonate or placebo over a 12-weeks period. Urine phosphate, serum phosphate, serum calcium, and serum intact FGF23 levels were measured before and after the intervention. Results: The baseline characteristics of the two groups were similar, except for the higher prevalence of dyslipidemia in the placebo group. The CaCO3 group had shown reduced levels of FGF23 compared to the placebo group, -8.03 vs. 0.15 pg/ml respectively (p = 0.019). The median level of FGF23 showed a significant decrease only in the CaCO3 group. An increase in eGFR and a slightly decrease in urine phosphate were observed in the CaCO3 group; however, the data was found to be statistically not significant. No significant changes were noted in the serum calcium levels in both groups. Conclusion: The administration of calcium carbonate has been shown to be effective and safe for moderate CKD patients with normophosphatemia due to its effect in lowering FGF23 levels without escalating the serum calcium level.

A standard enteral formula versus an iso-caloric lower carbohydrate/high fat enteral formula in the hospital management of adolescent and young adults admitted with anorexia nervosa: a randomised controlled trial

Background The nutritional rehabilitation of malnourished patients hospitalised with anorexia nervosa is essential. The provision of adequate nutrition must occur, while simultaneously, minimising the risk of refeeding complications, such as electrolyte, metabolic, and organ dysfunction. The aim of this study was to compare the efficacy and safety of an iso-caloric lower carbohydrate/high fat enteral formula (28% carbohydrate, 56% fat) against a standard enteral formula (54% carbohydrate, 29% fat). Methods Patients (aged 15–25 years) hospitalised with anorexia nervosa were recruited into this double blinded randomised controlled trial. An interim analysis was completed at midpoint, when 24 participants, mean age 17.5 years (± 1.1), had been randomly allocated to lower carbohydrate/high fat (n = 14) or standard (n = 10) feeds. Results At baseline, there was no significant difference in degree of malnutrition, medical instability, history of purging or serum phosphate levels between the two treatment arms. A significantly lower rate of hypophosphatemia developed in patients who received the lower carbohydrate/high fat formula compared to standard formula (5/14 vs 9/10, p = 0.013). The serum phosphate level decreased in both feeds, however it decreased to a larger extent in the standard feed compared to the lower carbohydrate/high fat feed (standard feed 1.11 ± 0.13 mmol/L at baseline vs 0.88 ± 0.12 mmol/L at week 1; lower carbohydrate/high fat feed 1.18 ± 0.19 mmol/L at baseline vs 1.06 ± 0.15 mmol/L at week 1). Overall, serum phosphate levels were significantly higher in the lower carbohydrate/high fat feed compared with standard feed treatment arm at Week 1 (1.06 ± 0.15 mmol/L vs 0.88 ± 0.12 mmol/L, p < 0.001). There was no significant difference in weight gain, number of days to reach medical stability, incidence of hypoglycaemia, or hospital length of stay. Conclusions The results of this study indicate that enteral nutrition provided to hospitalised malnourished young people with anorexia nervosa using a lower carbohydrate/high fat formula (28% carbohydrate, 56% fat) seems to provide protection from hypophosphatemia in the first week compared to when using a standard enteral formula. Further research may be required to confirm this finding in other malnourished populations. Trial Registration: ANZCTR, ACTRN12617000342314. Registered 3 March 2017, http://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000342314

Higher one-year achievement rate of serum phosphate associated with lower cardiovascular mortality in hemodialysis patients

Background Estimation of phosphate load in hemodialysis patients is always controversial in clinical practice. The aim of this study was to verify individual achievement rate of serum phosphate as the evaluation of phosphate load through investigating its impact on cardiovascular mortality in hemodialysis patients. Methods This was a single-center, retrospective cohort study. A total of 251 maintenance hemodialysis patients were enrolled. The individual achievement rate of serum phosphate was defined as the times of tests within the target range divided by total times of tests over a period of time. Cox regression model was used to examine the relationship between individual achievement rate of serum phosphate and cardiovascular mortality. Results The mean age of the study population was 61 ± 13 years old. A total of 44 (17.5%) patients died from cardiovascular disease (CVD) during a median follow-up of 65 months. Multivariable Cox analysis showed that one-year serum phosphate achievement rate of 0% (HR = 4.117, P = 0.016) and 25% (HR = 3.343, P = 0.023) increased the risk of cardiovascular mortality while the achievement rate of 50% (HR = 2.129, P = 0.162) and 75% (HR = 1.080, P = 0.902) did not, compared to the rate of 100%. Urea reduction ratio (URR) was positively, while serum intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), normalized protein catabolic rate (nPCR), and total phosphate-binding capacity of drug were negatively associated with achievement in target of serum phosphate. Conclusions Keeping one-year achievement rate of serum phosphate higher than 50% provides significant clinical benefits in reducing cardiovascular mortality.

Hypercalcaemia associated with disseminated cryptococcosis

We report an elderly man who presented with giddiness and right-sided weakness, constipation and constitutional symptoms for 6 months duration. Blood investigations indicated hypercalcaemia with normal serum phosphate and acute kidney injury. Serum intact parathyroid hormone was suppressed. CT revealed bilateral tiny lung nodules with right upper lobe tree in bud appearance and incidental findings of bilateral adrenal lesion. Tuberculosis was ruled out. CT adrenal showed multiseptated hypodense rim enhancement adrenal lesion bilaterally. Adrenal function tests were normal except for low dehydroepiandrosterone (DHEA). Right-sided cervical lymph node biopsy confirmed fungal infection with the presence of intracellular and extracellular fungal yeast. Serum cryptococcus antigen titre was positive. Our final diagnosis was disseminated cryptococcosis with lungs, bilateral adrenal gland and lymph nodes involvement. The patient was then treated with antifungal treatment. Serum calcium was normalised after 1 month with marked clinical improvement.

Phosphate Metabolism and Pathophysiology in Parathyroid Disorders and Endocrine Tumors

The advent of new insights into phosphate metabolism must urge the endocrinologist to rethink the pathophysiology of widespread disorders, such as primary hyperparathyroidism, and also of rarer endocrine metabolic bone diseases, such as hypoparathyroidism and tumor-induced hypophosphatemia. These rare diseases of mineral metabolism have been and will be a precious source of new information about phosphate and other minerals in the coming years. The parathyroid glands, the kidneys, and the intestine are the main organs affecting phosphate levels in the blood and urine. Parathyroid disorders, renal tubule defects, or phosphatonin-producing tumors might be unveiled from alterations of such a simple and inexpensive mineral as serum phosphate. This review will present all these disorders from a ‘phosphate perspective’.

Association Between Admission Serum Phosphate and Risk of Acute Kidney Injury in Critically Ill Patients with Rhabdomyolysis: A Retrospective Study Based on MIMIC-III

Background The incidence of acute kidney injury(AKI) is high in critically ill patients with rhabdomyolysis. Limited evidence was proved of the association between serum phosphate levels at intensive care unit(ICU) admission and the subsequent risk of AKI. Our study aims to assess if serum phosphate level at admission was independently associated with AKI risk in these patients. Methods This study extracted and analyzed data from Medical Information Mart for Intensive Care-Ⅲ(MIMIC-Ⅲ,version1.4). Rhabdomyolysis was defined as a peak creatine kinase(CK) level higher than 1000 U/L. Serum phosphate was measured within the first day into the ICU and was categorized to 4 groups(<2.6, 2.6-3.4, 3.5-4.5, >4.5mg/dl). AKI was defined according to the Kidney Disease Improving Global Outcome (KDIGO) guidelines. Adjusted smoothing spline plots and multivariate logistic regressions were carried out to explode the association between serum phosphate and risk of AKI. Subgroup analyse was applied to verify the consistency of the association.Results Three hundred and twenty-one patients(67.8% male) diagnosed as rhabdomyolysis were eligible for this analysis. AKI occurred in 204(63.6%) patients of total. Incidence of AKI with admission serum phosphate groups<2.6, 2.6-3.4, 3.5-4.5 and>4.5mg/dl were 52.6%, 56.8%, 68.4% and 75.9%, respectively. Smoothing spline curve showed that there was a positive curve between the elevated phosphate values and increasing risk of AKI, and there was no threshold saturation effect. In multivariate logistic regression, OR was 1.3(95%CI 1.1-1.6, P=0.012, P trend=0.034) after adjusting confounders. Subgroup analyses proved the consistency of the relationship in these patients except in the strata of creatine kinase.Conclusion In rhabdomyolysis patients admitted to ICU, serum phosphate level at admission was independently associated with an increased risk of AKI. As phosphate levels rise, the risk of AKI increased.

The effect of dietary phosphorus load and food matrix on postprandial serum phosphate in hemodialysis patients: a pilot study

Background: Potential dietary strategies for controlling hyperphosphataemia include the use of protein sources with lower phosphorus bioavailability such as pulses and nuts, focus on phosphorus to protein ratios and the avoidance of all phosphate additives. Methods: We conducted a controlled crossover feeding study in 8 haemodialysis (HD) patients to investigate the acute postprandial effect of a modified versus standard low phosphorus diet for one day on serum phosphate, potassium and intact parathyroid levels in prevalent HD patients. Each participant consumed the modified diet on one day and the standard diet on a second day one week apart. The modified diet included beef and less dairy, with a lower phosphorus to protein ratio, as well as plant-based protein, whole grains, pulses and nuts containing phytates which reduces phosphorus bioavailability. Both diets were tailored for each participant to provide 1.1g protein/kg ideal body weight. Participants provided fasting bloods before breakfast, a pre-prandial sample before the lunch time main meal and samples at one-hour intervals for the four hours after the lunch time main meal, for analysis of phosphate, potassium and intact parathyroid hormone (iPTH). Results: At four hours post the lunch time main meal on each study day, individuals on the modified diet had serum phosphate readings 0.30 mmol/l lower than when on the standard diet (p-value = 0.015, 95% confidence interval [CI] -0.57, -0.04). The corresponding change in serum potassium at four hours was a decrease of 0.675 mmol/l (p-value = 0.011, CI -1.25, -0.10). Conclusions: Decreases in both serum phosphate and serum potassium readings on a modified low phosphorus diet encourage further larger studies to explore the possibility of greater food choice and healthier plant-based diets in HD patients. ClinicalTrials.gov registration: NCT04845724 (15/04/2021)