Serum Phosphate Concentrations In Patients Research Articles

The Effect of Niacinamide Supplementation on Phosphate Concentrations in Dutch Dialysis Patients: a randomised, crossover trial

ObjectiveHyperphosphatemia is a common complication in patients with kidney failure, despite the use of phosphate binders (PBs). Vitamin B3, either in the form of niacin or niacinamide (NAM), shows potential as “add-on” treatment to reduce serum phosphate concentrations in this population. NAM seems to lack many of the side-effects that are observed with niacin. The aim of this study was to investigate whether NAM is an effective and acceptable treatment in reducing serum phosphate concentrations in patients with kidney failure. MethodsDiaNia was a double-blind placebo-controlled randomised crossover trial, comparing NAM (250-500 mg/day) to placebo as “add-on” treatment to an individual treatment with approved PBs for 12 weeks in patients receiving hemodialysis. The primary outcome was serum phosphate concentrations, and the secondary outcomes were platelet counts as well as drop-outs due to side-effects. Data was analysed using both per-protocol (PP) and intention-to-treat (ITT) analyses. ResultsMean age of the PP population (n=26) was 63.6 ± 17.2 years and 53.8% were men. NAM treatment significantly reduced serum phosphate with 0.59 mg/dL (p=0.03). Linear mixed models (LMMs) demonstrated superiority of 12 weeks NAM over 12 weeks placebo with a between-treatment difference of 0.77 mg/dL (95% CI 0.010, 1.43; p=0.03). Similar results, although not significant, were found in the ITT population. We found no between-treatment differences in platelet counts and during the NAM treatment we observed three drop-outs due to side effects (8.6%). ConclusionNAM is effective in reducing serum phosphate concentrations in patients with kidney failure receiving hemodialysis. In addition, NAM is well-tolerated and seems not to increase the risk of thrombocytopenia. Thus, NAM can be valuable as “add-on” treatment to combat hyperphosphatemia in patients with kidney failure. However, more research in larger populations is needed to confirm this.

P-17 Hypophosphatemia related to intravenous iron therapy: A case report

Abstract Introduction Intravenous iron supplementation is a good alternative to oral iron replacement in iron deficiency anaemia. Intravenous iron formulations such as ferric carboxymaltose allow administration of high doses of elemental iron and enable correction of total iron deficit in one or two infusions. An important complication of ferric carboxymaltose is hypophosphatemia caused by increased secretion of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). In this case, we aimed to present our patient with this rare side effect of intravenous iron replacement. Clinical Case A 40-year-old female patient who has no chronic systemic disease was admitted to our endocrinology service for fatigue and weakness. In the patient's history, it was learned that she had been treated with 2500 mg intravenous iron replacement (ferric carboxymaltose) for iron deficiency anaemia in the last month. In the laboratory tests; serum phosphorus 1.05 mg/dl (normal 2.5-4.5 mg/dl), corrected calcium 8.45 mg/dl (normal 8.4-10.2 mg/dl), 25-OH vitamin D 31.4 µg/L (normal >30 µg/L), parathormone 83.2 pg/ml (normal 15-65 ng/ml), alkaline phosphatase 63 U/L (normal 35-105 U/L). Fractional excretion of phosphate (FePO4) confirmed renal phosphate wasting (FePO4: 28.6%; normal <5%). Urinary protein and glucose were negative. FGF23 measured 71 pg/ml (normal <59 pg/mL). Intravenous iron-induced hypophosphataemia was suspected. After initiation of oral phosphate and 1,25-dihydroxyvitamin D3 supplementation, serum phosphate rose to reference range (Figure 1). The patient was taken to outpatient follow-up. Conclusion Physicians should be aware of hypophosphatemia as a common complication of intravenous iron therapy and monitor serum phosphate concentrations in patients receiving repeated doses.Figure 1.Patient phosphorus data during follow-up

Hypophosphatemia after intravenous iron therapy: Comprehensive review of clinical findings and recommendations for management.

Contemporary intravenous iron formulations allow administration of high doses of elemental iron and enable correction of total iron deficit in one or two infusions. An important but underappreciated complication of certain formulations is hypophosphatemia caused by increased secretion of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). The pathophysiology of FGF23-induced hypophosphatemia due to certain intravenous iron formulations has been recently investigated in prospective clinical trials. To reach the correct diagnosis, clinicians must recognize the typical clinical manifestations of intravenous iron-induced hypophosphatemia and identify a specific pattern of biochemical changes (hyperphosphaturic hypophosphatemia triggered by high FGF23 that causes low 1,25 (OH)2 vitamin D, hypocalcemia and secondary hyperparathyroidism). Physicians and patients should be aware of hypophosphatemia as a common complication of intravenous iron therapy and monitor serum phosphate concentrations in patients receiving repeated doses of specific intravenous iron formulations. Symptoms of hypophosphatemia are associated with severity and duration. Persistent hypophosphatemia can occur with iron therapy and can cause debilitating diseases including myopathy, osteomalacia and fractures. This review summarizes the current understanding of the iron-phosphate axis as well as complications of intravenous iron-induced hypophosphatemia.

The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD.

Niacin downregulates intestinal sodium-dependent phosphate transporter 2b expression and reduces intestinal phosphate transport. Short-term studies have suggested that niacin lowers serum phosphate concentrations in patients with CKD and ESRD. However, the long-term effects of niacin on serum phosphate and other mineral markers are unknown. The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Trial was a randomized, double-blind, placebo-controlled trial testing extended release niacin in persons with prevalent cardiovascular disease. We examined the effect of randomized treatment with niacin (1500 or 2000 mg) or placebo on temporal changes in markers of mineral metabolism in 352 participants with eGFR<60 ml/min per 1.73 m2 over 3 years. Changes in each marker were compared over time between the niacin and placebo arms using linear mixed effects models. Randomization to niacin led to 0.08 mg/dl lower plasma phosphate concentrations per year of treatment compared with placebo (P<0.01) and 0.25 mg/dl lower mean phosphate 3 years after baseline (3.32 versus 3.57 mg/dl; P=0.03). In contrast, randomization to niacin was not associated with statistically significant changes in plasma intact fibroblast growth factor 23, parathyroid hormone, calcium, or vitamin D metabolites over 3 years. The use of niacin over 3 years lowered serum phosphorous concentrations but did not affect other markers of mineral metabolism in participants with CKD.

Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis.

Hyperphosphatemia is common among patients with CKD stage 5D and is associated with morbidity and mortality. Current guidelines recommend lowering serum phosphate concentrations toward normal. Tenapanor is a minimally absorbed small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 that functions in the gut to reduce sodium and phosphate absorption. This randomized, double-blind, placebo-controlled trial assessed the effects of tenapanor on serum phosphate concentration in patients with hyperphosphatemia receiving hemodialysis. After a 1- to 3-week washout of phosphate binders, we randomly assigned 162 eligible patients (serum phosphate =6.0 to <10.0 mg/dl and a 1.5-mg/dl increase from before washout) to one of six tenapanor regimens (3 or 30 mg once daily or 1, 3, 10, or 30 mg twice daily) or placebo for 4 weeks. The primary efficacy end point was change in serum phosphate concentration from baseline (randomization) to end of treatment. In total, 115 patients (71%) completed the study. Mean serum phosphate concentrations at baseline (after washout) were 7.32-7.92 mg/dl for tenapanor groups and 7.87 mg/dl for the placebo group. Tenapanor provided dose-dependent reductions in serum phosphate level from baseline (least squares mean change: tenapanor =0.47-1.98 mg/dl; placebo =0.54 mg/dl; P=0.01). Diarrhea was the most common adverse event (tenapanor =18%-68%; placebo =12%) and frequent at the highest tenapanor doses. In conclusion, tenapanor treatment resulted in statistically significant, dose-dependent reductions in serum phosphate concentrations in patients with hyperphosphatemia receiving hemodialysis. Additional studies are required to clarify the optimal dosing of tenapanor in patients with CKD-related hyperphosphatemia.

Oral phosphate binders in CKD - is calcium the (only) answer?

All-cause mortality and cardiovascular- related mortality have both been linked to abnormal serum phosphate concentrations in chronic kidney disease (CKD). Aberrant serum phosphate concentration in patients with CKD has also been associated with adverse cardiac and renal outcomes. Early prevention or management of rising or high serum phosphate concentrations in patients with CKD is now considered to be an important intervention to prevent downstream complications resulting from the poor management of serum calcium and parathyroid hormone (PTH). It is widely considered that starting phosphate binder therapy early, with concurrent dietary management of serum phosphate, constitutes an effective course of interventions, although normalization of serum phosphate in dialysis patients remains atypical, unless specific dialytic measures are also undertaken. Calcium- based phosphate binders are often the first type of binders prescribed due to their low cost. Evidence shows that most phosphate binders are roughly equally effective in lowering serum phosphate concentrations in adults compared to placebo, with a small probability that sevelamer hydrochloride is better than calcium acetate or lanthanum carbonate. However, not all binders are created equal in regards to their safety profiles. The potential for accumulations and toxicities does exist with very long-term continuous exposure. We discuss these issues in the course of this review.

Increased serum phosphate concentrations in patients with advanced chronic kidney disease treated with diuretics.

Serum phosphate concentrations usually show great variability in patients with advanced chronic kidney disease (ACKD) not on dialysis. Diuretics treatment can have an influence over the severity of mineral-bone metabolism alterations related to ACKD, but their effect on serum phosphate levels is less known. This study aims to determine whether diuretics are independently associated with serum phosphate levels, and to investigate the mechanisms by which diuretics may affect phosphate metabolism. 429 Caucasian patients with CKD not on dialysis were included in this cross-sectional study. In addition to conventional serum biochemical measures, the following parameters of renal phosphate excretion were assessed: 24-hours urinary phosphate excretion, tubular maximum phosphate reabsorption (TmP), and fractional excretion of phosphate (FEP). 58% of patients were on treatment with diuretics. Patients on diuretics showed significantly higher mean serum phosphate concentration (4.78 ± 1.23 vs. 4.24 ± 1.04 mg/dl; P<.0001), and higher TmP per GFR (2.77 ± 0.72 vs. 2.43 ± 0.78 mg/dl; P<.0001) than those not treated with diuretics. By multivariate linear and logistic regression, significant associations between diuretics and serum phosphate concentrations or hyperphosphataemia remained after adjustment for potential confounding variables. In patients with the highest phosphate load adjusted to kidney function, those treated with diuretics showed significantly lower FEP than those untreated with diuretics. Treatment with diuretics is associated with increased serum phosphate concentrations in patients with ACKD. Diuretics may indirectly interfere with the maximum renal compensatory capacity to excrete phosphate. Diuretics should be considered in the studies linking the relationship between serum phosphate concentrations and cardiovascular alterations in patients with CKD.

維持血液透析患者における炭酸ランタンの剤形変更による血清リン濃度の変化

維持血液透析患者における炭酸ランタンの剤形変更による血清リン濃度の変化

Phosphate Additives in Food

Hyperphosphatemia has been identified in the past decade as a strong predictor of mortality in advanced chronic kidney disease (CKD). For example, a study of patients in stage CKD 5 (with an annual mortality of about 20%) revealed that 12% of all deaths in this group were attributable to an elevated serum phosphate concentration. Recently, a high-normal serum phosphate concentration has also been found to be an independent predictor of cardiovascular events and mortality in the general population. Therefore, phosphate additives in food are a matter of concern, and their potential impact on health may well have been underappreciated. We reviewed pertinent literature retrieved by a selective search of the PubMed and EU databases (www.zusatzstoffe-online.de, www.codexalimentarius.de), with the search terms "phosphate additives" and "hyperphosphatemia." There is no need to lower the content of natural phosphate, i.e. organic esters, in food, because this type of phosphate is incompletely absorbed; restricting its intake might even lead to protein malnutrition. On the other hand, inorganic phosphate in food additives is effectively absorbed and can measurably elevate the serum phosphate concentration in patients with advanced CKD. Foods with added phosphate tend to be eaten by persons at the lower end of the socioeconomic scale, who consume more processed and "fast" food. The main pathophysiological effect of phosphate is vascular damage, e.g. endothelial dysfunction and vascular calcification. Aside from the quality of phosphate in the diet (which also requires attention), the quantity of phosphate consumed by patients with advanced renal failure should not exceed 1000 mg per day, according to the guidelines. Prospective controlled trials are currently unavailable. In view of the high prevalence of CKD and the potential harm caused by phosphate additives to food, the public should be informed that added phosphate is damaging to health. Furthermore, calls for labeling the content of added phosphate in food are appropriate.

The secondary dyslipidemia and deranged serum phosphate concentration in thyroid disorders

Hyperlipidemia is a secondary disorder associated with many metabolic disorders including hypothyroidism. The occurrence of dyslipidemia in subclinical hypothyroidism is controversial. Hyperphosphatemia may accompany the dyslipidemia in some metabolic disorders. Both hyperlipidemia and hyperphosphatemia are considered to be risk factors for the coronary heart diseases. In the present study, we investigated the occurrence of dyslipidemia and altered serum phosphate concentrations in patients with thyroid disorders. The results indicated a significantly elevated serum cholesterol and triglyceride concentrations in the hypothyroid patients. The dyslipidemia was accompanied with significantly elevated serum phosphate level. On the other hand, no significant difference was evident in the serum lipid or phosphate concentrations of subclinical hypothyroid patients compared to euthyroid subjects. A significantly reduced serum phosphate level was shown in hyperthyroid patients with unaltered serum lipid levels. Significant correlations were evident between TSH and T 4 levels as independent parameters and the serum concentrations of triglyceride, cholesterol and phosphate. The results indicate in hypothyroidism that a secondary hyperphosphatemia may aggravate myocardial and arterial abnormalities induced by the secondary hyperlipidemia, which may need correction.

Ultradian variation in serum phosphate concentration in patients on haemodialysis

To study how much the serum phosphate concentration could vary on the day before scheduled dialysis we obtained 24-37 timed measurements during 24 h in nine patients on maintenance haemodialysis. During the observation there was an increase in serum phosphate concentration of 0.239 +/- 0.022, P < 0.01). Surprisingly six of the nine patients exhibited nine statistically and clinically significant nadirs with decrements of 0.21 +/- 0.04 mmol/l against an intra-assay standard deviation of about 0.05 mmol/l. Five of the nadirs occurred at 11.40-14.50, mean 12.59, and three at 19.00-21.30, mean 20.00. We found no coinciding changes in the serum calcium concentration. These findings indicate that serum phosphate concentrations do not always reflect phosphorus balance or intake.