Phosphate concentrations and modifying factors in healthy children from 12 to 24 months of age

Context Phosphate homeostasis and its modifiers in early childhood are inadequately characterized. Objective To determine physiological plasma phosphate concentration and modifying factors in healthy infants at 12 to 24 months of age. Design This study included 525 healthy infants (53% girls), who participated in a randomized vitamin D intervention (VIDI) trial and received daily vitamin D3 supplementation of either 10 or 30 μg from age two weeks to 24 months. Biochemical parameters were measured at 12 and 24 months. Dietary phosphate intake was determined at 12 months. Main Outcome Measures Plasma phosphate concentrations at 12 and 24 months of age. Results Mean (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, 25OHD, intact and C-terminal FGF23, 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 to 0.009 and 0.002 to 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 to 0.011, p<0.001). Conclusion Plasma 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.

Relationships between phosphatemia/phosphaturia and EEG/HRV parameters in patients with chronic pyelonephritis

Background. As part of the project "Relationships between parameters of electrolytes exchange and EEG&HRV in people without kidney disease and patients with chronic pyelonephritis" we have previously shown that parameters of calcium exchange and EEG/HRV are closely related. In this study, we analyzed the relationships between parameters of phosphate exchange and EEG/HRV in the same cohort of patients. Material and methods. The object of observation were 48 males and 15 females 24-76 years old, who came to the spa Truskavets’ (Ukraine) for the treatment of chronic pyelonephritis in remission. We recorded simultaneosly EEG (“NeuroCom Standard”) and electrocardiogram ("CardioLab+HRV") in II lead to assess the parameters of HRV. Phosphate concentration was determined in blood plasma and daily urine. Results. It was stated normal or moderately reduced plasma phosphate levels in combination with a very wide range of phosphate urinary excretion. A very strong canonical correlation was found between phosphatemia and EEG/HRV parameters (R=0,982). The correlations with the parameters of the beta and theta rhythms of the EEG and the HRV are positive, while with the parameters of the delta rhythm of the EEG are negative. The canonical correlation between phosphaturia and EEG parameters is also very strong (R=0,879). Conclusion. Parameters of phosphate exchange and EEG/HRV are closely related, however the question of the causal nature of correlations remains open.

SGLT2 inhibition versus sulfonylurea treatment effects on electrolyte and acid–base balance: secondary analysis of a clinical trial reaching glycemic equipoise: Tubular effects of SGLT2 inhibition in Type 2 diabetes

Sodium–glucose transporter (SGLT)2 inhibitors increase plasma magnesium and plasma phosphate and may cause ketoacidosis, but the contribution of improved glycemic control to these observations as well as effects on other electrolytes and acid–base parameters remain unknown. Therefore, our objective was to compare the effects of SGLT2 inhibitors dapagliflozin and sulfonylurea gliclazide on plasma electrolytes, urinary electrolyte excretion, and acid–base balance in people with Type 2 diabetes (T2D). We assessed the effects of dapagliflozin and gliclazide treatment on plasma electrolytes and bicarbonate, 24-hour urinary pH and excretions of electrolytes, ammonium, citrate, and sulfate in 44 metformin-treated people with T2D and preserved kidney function. Compared with gliclazide, dapagliflozin increased plasma chloride by 1.4 mmol/l (95% CI 0.4–2.4), plasma magnesium by 0.03 mmol/l (95% CI 0.01–0.06), and plasma sulfate by 0.02 mmol/l (95% CI 0.01–0.04). Compared with baseline, dapagliflozin also significantly increased plasma phosphate, but the same trend was observed with gliclazide. From baseline to week 12, dapagliflozin increased the urinary excretion of citrate by 0.93 ± 1.72 mmol/day, acetoacetate by 48 μmol/day (IQR 17–138), and β-hydroxybutyrate by 59 μmol/day (IQR 0–336), without disturbing acid–base balance. In conclusion, dapagliflozin increases plasma magnesium, chloride, and sulfate compared with gliclazide, while reaching similar glucose-lowering in people with T2D. Dapagliflozin also increases urinary ketone excretion without changing acid–base balance. Therefore, the increase in urinary citrate excretion by dapagliflozin may reflect an effect on cellular metabolism including the tricarboxylic acid cycle. This potentially contributes to kidney protection.

Renal Phosphate Handling in Antiretroviral-naïve HIV-infected Patients

Background: Human immunodeficiency virus (HIV) infection impairs renal function, thereby affecting renal phosphate metabolism. Objectives: We prospectively estimated the prevalence of phosphate abnormalities (mild, moderate to life-threatening hypophosphataemia, and hyperphosphataemia) before initiating antiretroviral therapy (ART). Methods: A cross-sectional analysis was performed on 170 consecutive newly diagnosed ART-naïve, HIV-infected patients attending our HIV/AIDS clinics over a period of one year. Fifty (50) screened HIV-negative blood donors were used for comparison (controls). Blood and urine were collected simultaneously for phosphate and creatinine assay to estimate fractional phosphate excretion (FEPi %) and glomerular filtration rate (eGFR). Results: eGFR showed significant difference between patients’ and controls’ medians (47.89ml/min/1.73m2 versus 60ml/min/1.73m2, p <0.001); which denotes a moderate chronic kidney disease in the patients. Of the 170 patients, 78 (45.9%) had normal plasma phosphate (0.6-1.4 mmol/L); 85 (50%) had hyperphosphataemia. Grades 1, 2 and 3 hypophosphataemia was observed in 3 (1.8%), 3 (1.8%), and 1(0.5%) patient(s) respectively. None had grade 4 hypophosphataemia. Overall, the patients had significantly higher median of plasma phosphate than the controls, 1.4 mmol/L (IQR: 1.0 – 2.2) versus 1.1 mmol/L (IQR: 0.3 – 1.6), p <0.001, implying hyperphosphataemia in the patients; significantly lower median urine phosphate than the controls, 1.5 mmol/L (IQR: 0.7 -2.1) versus 8.4 mmol/L (IQR: 3.4 – 16), p <0.001), justifying the hyperphosphataemia is from phosphate retention; but a non-significantly lower median FEPi% than the controls, 0.96 % (IQR: 0.3 -2.2) versus 1.4% (IQR: 1.2 -1.6), p > 0.05. Predictors of FEPi% were age (Odds ratio, OR 0.9, p = 0.009); weight (OR 2.0, p < 0.001); CD4+ cells count predicted urine phosphate among males (p = 0.029). Conclusion: HIV infection likely induces renal insufficiency with reduced renal phosphate clearance. Thus, hyperphosphataemia is highly prevalent, and there is mild to moderate hypophosphataemia but its life-threatening form (grade 4) is rare among ART-naïve HIV patients.

Effects of Potassium or Sodium Supplementation on Mineral Homeostasis: A Controlled Dietary Intervention Study

Context Although dietary potassium and sodium intake may influence calcium-phosphate metabolism and bone health, the effects on bone mineral parameters, including fibroblast growth factor 23 (FGF23), are unclear. Objective Here, we investigated the effects of potassium or sodium supplementation on bone mineral parameters. Design, setting, participants We performed a post hoc analysis of a dietary controlled randomized, blinded, placebo-controlled crossover trial. Prehypertensive individuals not using antihypertensive medication (n = 36) received capsules containing potassium chloride (3 g/d), sodium chloride (3 g/d), or placebo. Linear mixed-effect models were used to estimate treatment effects. Results Potassium supplementation increased plasma phosphate (from 1.10 ± 0.19 to 1.15 ± 0.19 mmol/L, P = 0.004), in line with an increase in tubular maximum of phosphate reabsorption (from 0.93 ± 0.21 to 1.01 ± 0.20 mmol/L, P &lt; 0.001). FGF23 decreased (114.3 [96.8-135.0] to 108.5 [93.5-125.9] RU/mL, P = 0.01), without change in parathyroid hormone and 25-hydroxy vitamin D3. Fractional calcium excretion decreased (from 1.25 ± 0.50 to 1.11 ± 0.46 %, P = 0.03) without change in plasma calcium. Sodium supplementation decreased both plasma phosphate (from 1.10 ± 0.19 to 1.06 ± 0.21 mmol/L, P = 0.03) and FGF23 (from 114.3 [96.8-135.0] to 108.7 [92.3-128.1] RU/mL, P = 0.02). Urinary and fractional calcium excretion increased (from 4.28 ± 1.91 to 5.45 ± 2.51 mmol/24 hours, P &lt; 0.001, and from 1.25 ± 0.50 to 1.44 ± 0.54 %, P = 0.004, respectively). Conclusions Potassium supplementation led to a decrease in FGF23, which was accompanied by increase in plasma phosphate and decreased calcium excretion. Sodium supplementation reduced FGF23, but this was accompanied by decrease in phosphate and increase in fractional calcium excretion. Our results indicate distinct effects of potassium and sodium intake on bone mineral parameters, including FGF23. Clinical Trial Registration number NCT01575041

Fetal Hemoglobin, Serum Total Cholesterol, Plasma Phosphate and Serum Calcium Levels in Patients with Leukemia and Lymphoma

In this study, fetal hemoglobin (HbF), blood total cholesterol, phosphate and calcium levels of leukemia and lymphoma cases in Mandalay were determined. It was a cross-sectional, comparative study. Thirty adult cases of leukemia and lymphoma and equal number of control subjects of comparable age (14 to 80 yrs) and sex were studied. Mean HbF of leukemia group (n=9), acute myeloid leukemia (AML) subgroup (n=6) and controls (n=30) were 2.72±0.47%, 3.17±0.69% and 1.39±0.25% of total Hb, respectively. The HbF levels of leukemia group and AML were significantly higher than that of controls (p<0.02). Mean serum total cholesterol levels of leukemia group, AML subgroup and controls were found to be 126.5±17.38 mg%, 137.96±24.66 mg% and 177.18±7.68 mg%, respectively. Cholesterol levels of leukemia group and AML were lower than that of controls. Mean plasma phosphate levels of leukemia and lymphoma cases (n=30), leukemia group (n=9) and lymphoma group (n=21) were 1.21±0.07 mmol/l, 1.33±0.17 mmol/l and 1.15±0.06 mmol/l, respectively. Mean phosphate level of controls was 0.94 mmol/l. Plasma phosphate levels of the whole cases and individual case groups were significantly higher than that of controls (p<0.001). Mean serum calcium levels of the whole cases, leukemia group and lymphoma group were 10.16±0.36 mg%, 10.03±0.75 mg% and 10.21±0.45 mg%, respectively. Mean serum calcium level of controls was 8.55±0.14 mg%. Serum calcium levels of the whole cases and individual case groups were found to be significantly higher than that of controls (p<0.01). The study showed that not only raised HbF but also hypocholesterolaemia might be the diagnostic clues in leukemia cases. Recognition of blood phosphate and calcium changes leads to appropriate therapy and a reduction of morbidity.

Parathyroid Hormone and Plasma Phosphate Are Predictors of Soluble α-Klotho Levels in Adults of European Descent

Context α-klotho is an integral membrane protein that serves as a coreceptor for fibroblast growth factor 23 (FGF23) in conjunction with cognate fibroblast growth factor receptors. Proteolytic cleavage sheds the ectodomain of α-klotho (soluble α-klotho) as an endocrine substance into blood, urine, and cerebrospinal fluid. Objective To study the relationship of soluble α-klotho to mineral metabolism in the general population with mainly preserved kidney function. Design Cross-sectional analysis of the associations between soluble α-klotho with laboratory markers of markers of mineral metabolism in a population-based cohort. Setting Three centers in Switzerland including 1128 participants. Measures Soluble full-length α-klotho levels by a specific immunoassay and markers of mineral metabolism. Results The median serum level of soluble α-klotho was 15.0 pmol/L. Multivariable analyses using α-klotho as the outcome variable revealed a sex-by-PTH interaction: In men, PTH was positively associated with α-klotho levels, whereas this association was negative in women. Plasma phosphate associated with soluble α-klotho levels in an age-dependent manner, changing from a positive association in young adults gradually to a negative association in the elderly. The decline of 1,25 (OH)2 vitamin D3 levels in parallel to the gradual impairment of kidney function was greatly attenuated in the setting of high circulating soluble α-klotho levels. Conclusions Soluble α-klotho level is associated with plasma phosphate in an age-dependent manner and with PTH in a sex-dependent manner. Furthermore, our data reveal soluble α-klotho as a modulator of 1,25 (OH)2 vitamin D3 levels in individuals with preserved renal function.