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Pediatric Nephrology (Berlin, Germany) Mar 2020In children with chronic kidney disease (CKD), optimal control of bone and mineral homeostasis is essential, not only for the prevention of debilitating skeletal...
The dietary management of calcium and phosphate in children with CKD stages 2-5 and on dialysis-clinical practice recommendation from the Pediatric Renal Nutrition Taskforce.
In children with chronic kidney disease (CKD), optimal control of bone and mineral homeostasis is essential, not only for the prevention of debilitating skeletal complications and achieving adequate growth but also for preventing vascular calcification and cardiovascular disease. Complications of mineral bone disease (MBD) are common and contribute to the high morbidity and mortality seen in children with CKD. Although several studies describe the prevalence of abnormal calcium, phosphate, parathyroid hormone, and vitamin D levels as well as associated clinical and radiological complications and their medical management, little is known about the dietary requirements and management of calcium (Ca) and phosphate (P) in children with CKD. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists, who develop clinical practice recommendations (CPRs) for the nutritional management of various aspects of renal disease management in children. We present CPRs for the dietary intake of Ca and P in children with CKD stages 2-5 and on dialysis (CKD2-5D), describing the common Ca- and P-containing foods, the assessment of dietary Ca and P intake, requirements for Ca and P in healthy children and necessary modifications for children with CKD2-5D, and dietary management of hypo- and hypercalcemia and hyperphosphatemia. The statements have been graded, and statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs based on the clinical judgment of the treating physician and dietitian. These CPRs will be regularly audited and updated by the PRNT.
Topics: Advisory Committees; Calcium, Dietary; Child; Child Nutritional Physiological Phenomena; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Hypercalcemia; Hyperphosphatemia; Hypocalcemia; Kidney Failure, Chronic; Nutritional Requirements; Pediatrics; Phosphates; Renal Dialysis
PubMed: 31667620
DOI: 10.1007/s00467-019-04370-z -
Nephrology, Dialysis, Transplantation :... Jan 2024Phosphorus is an essential mineral that is, in the form of inorganic phosphate (Pi), required for building cell membranes, DNA and RNA molecules, energy metabolism,... (Review)
Review
Phosphorus is an essential mineral that is, in the form of inorganic phosphate (Pi), required for building cell membranes, DNA and RNA molecules, energy metabolism, signal transduction and pH buffering. In bone, Pi is essential for bone stability in the form of apatite. Intestinal absorption of dietary Pi depends on its bioavailability and has two distinct modes of active transcellular and passive paracellular absorption. Active transport is transporter mediated and partly regulated, while passive absorption depends mostly on bioavailability. Renal excretion controls systemic Pi levels, depends on transporters in the proximal tubule and is highly regulated. Deposition and release of Pi into and from soft tissues and bone has to be tightly controlled. The endocrine network coordinating intestinal absorption, renal excretion and bone turnover integrates dietary intake and metabolic requirements with renal excretion and is critical for bone stability and cardiovascular health during states of hypophosphataemia or hyperphosphataemia as evident from inborn or acquired diseases. This review provides an integrated overview of the biology of phosphate and Pi in mammals.
Topics: Animals; Humans; Phosphates; Phosphorus; Intestinal Absorption; Hyperphosphatemia; Minerals; Mammals
PubMed: 37660247
DOI: 10.1093/ndt/gfad188 -
Renal Failure Dec 2023This study was designed to examine the relative safety and efficacy of sevelamer in the treatment of chronic kidney disease (CKD) patients in comparison to placebo,... (Meta-Analysis)
Meta-Analysis Review
This study was designed to examine the relative safety and efficacy of sevelamer in the treatment of chronic kidney disease (CKD) patients in comparison to placebo, calcium carbonate (CC), or lanthanum carbonate (LC). The PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were searched for articles published through 18 June 2022. The quality of relevant studies was independently analyzed by two investigators who also extracted data from these manuscripts as per Cochrane Collaboration Handbook 5.3. The safety and efficacy of sevelamer as a treatment for hyperphosphatemia in CKD patients were then examined through a meta-analysis, with the primary patient-level outcomes of interest in this analysis being all-cause mortality and the incidence of gastrointestinal adverse effects. Vascular calcification score was also examined as an intermediate outcome, while serum biochemical parameters including levels of phosphate (P), calcium (Ca), intact parathyroid hormone (iPTH), lipids, C-reactive protein (CRP), or fibroblast growth factor-23 (FGF-23) were additionally assessed. In total, this meta-analysis incorporated data from 34 randomized controlled trials (RCTs) enrolling 2802 patients. Sevelamer was associated with reduced all-cause mortality (RR 0.28, CI 0.19 - 0.41, ) and Vessel calcification score (RR -0.58, CI -1.11 to -0.04, ) and induced less hypercalcemia (MD -0.28, CI 0.40 to -0.16, ) and hyperphosphatemia (MD -0.22, CI -0.32 to -0.13, ) when compared with Ca-based binders in CKD5D individuals. No significant differences in gastrointestinal adverse events (GAEs) incidence were observed. These data suggest that sevelamer may represent a beneficial means of protecting CKD patients against death and vessel calcification when used to treat hyperphosphatemia, while we found no clinically important benefits in decreasing gastrointestinal adverse effects.
Topics: Humans; Sevelamer; Hyperphosphatemia; Chelating Agents; Phosphates; Renal Insufficiency, Chronic; Renal Dialysis
PubMed: 37272189
DOI: 10.1080/0886022X.2023.2210230 -
Biochemical Society Transactions Feb 2022Hyperphosphatemia results from an imbalance in phosphate (Pi) homeostasis. In patients with and without reduced kidney function, hyperphosphatemia is associated with... (Review)
Review
Hyperphosphatemia results from an imbalance in phosphate (Pi) homeostasis. In patients with and without reduced kidney function, hyperphosphatemia is associated with cardiovascular complications. The current mainstays in the management of hyperphosphatemia are oral Pi binder and dietary Pi restriction. Although these options are employed in patients with chronic kidney disease (CKD), they seem inadequate to correct elevated plasma Pi levels. In addition, a paradoxical increase in expression of intestinal Pi transporter and uptake may occur. Recently, studies in rodents targeting the renal Na+/Pi cotransporter 2a (Npt2a), responsible for ∼70% of Pi reabsorption, have been proposed as a potential treatment option. Two compounds (PF-06869206 and BAY-767) have been developed which are selective for Npt2a. These Npt2a inhibitors significantly increased urinary Pi excretion consequently lowering plasma Pi and PTH levels. Additionally, increases in urinary excretions of Na+, Cl- and Ca2+ have been observed. Some of these results are also seen in models of reduced kidney function. Responses of FGF23, a phosphaturic hormone that has been linked to the development of left ventricular hypertrophy in CKD, are ambiguous. In this review, we discuss the recent advances on the role of Npt2a inhibition on Pi homeostasis as well as other pleiotropic effects observed with Npt2a inhibition.
Topics: Animals; Female; Humans; Hyperphosphatemia; Male; Mice; Mice, Knockout; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic; Sodium-Phosphate Cotransporter Proteins, Type IIa
PubMed: 34994388
DOI: 10.1042/BST20211005 -
Scientific Reports Nov 2023Phosphate binders (PBs) generally have a high pill burden. Tenapanor selectively inhibits sodium/hydrogen exchanger isoform 3, reducing intestinal phosphate absorption....
Phosphate binders (PBs) generally have a high pill burden. Tenapanor selectively inhibits sodium/hydrogen exchanger isoform 3, reducing intestinal phosphate absorption. Tenapanor is a novel drug administered as a small tablet, twice daily. This multicenter, open-label, single-arm, phase 3 study aimed to evaluate the long-term safety of tenapanor and its efficacy in decreasing PB pill burden. Tenapanor 5 mg twice daily was administered to hemodialysis patients with serum phosphorus level 3.5-7.0 mg/dl at baseline; the dose could be increased up to 30 mg twice daily. Patients could also switch from PBs. The primary endpoint was safety during 52-week administration. The key secondary endpoint was a ≥ 30% reduction in the total pill number of daily PBs and tenapanor from baseline. Of 212 patients starting treatment, 154 completed the study. Diarrhea was the most frequent adverse event, occurring in 135 patients (63.7%); most events were classified as mild (74.8%). No clinically significant changes occurred other than serum phosphorus level. At Week 52/discontinuation, 158/204 patients (77.5%) achieved the key secondary endpoint. Complete switching from PBs to tenapanor was achieved in 50-76 patients (26.7%-41.5%), and 80 patients (51.9%) at Week 8-12 and Week 50, respectively. Serum phosphorus remained generally stable within the target range (3.5-6.0 mg/dl). These findings suggest the long-term safety and tolerability of tenapanor. Tenapanor could reduce or eliminate PB pill burden while controlling serum phosphorus levels.Trial registration: NCT04771780.
Topics: Humans; Hyperphosphatemia; Phosphates; Phosphorus; Renal Dialysis; Sodium-Hydrogen Exchanger 3
PubMed: 37925471
DOI: 10.1038/s41598-023-45080-9 -
Clinical Journal of the American... Dec 2020
Topics: Adult; Diet; Humans; Hyperphosphatemia; Phosphates; Renal Dialysis
PubMed: 33380472
DOI: 10.2215/CJN.18171120 -
Cleveland Clinic Journal of Medicine Aug 2018In caring for patients with chronic kidney disease, it is important to prevent and treat hyperphosphatemia with a combination of dietary restrictions and phosphorus... (Review)
Review
In caring for patients with chronic kidney disease, it is important to prevent and treat hyperphosphatemia with a combination of dietary restrictions and phosphorus binders. This review describes the pathophysiology and control of hyperphosphatemia and the different classes of phosphorus binders with respect to their availability, cost, side effects, and scenarios in which one class of binder may be more beneficial than another.
Topics: Chelating Agents; Humans; Hyperphosphatemia; Phosphorus; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 30102593
DOI: 10.3949/ccjm.85a.17054 -
Current Opinion in Nephrology and... Sep 2022Targeting sodium phosphate cotransporter 2a (Npt2a) offers a novel strategy for treating hyperphosphatemia in chronic kidney disease (CKD). Here we review recent studies... (Review)
Review
PURPOSE OF REVIEW
Targeting sodium phosphate cotransporter 2a (Npt2a) offers a novel strategy for treating hyperphosphatemia in chronic kidney disease (CKD). Here we review recent studies on the efficacy of Npt2a inhibition, its plasma phosphate (Pi)-lowering effects, as well as potential "off-target" beneficial effects on cardiovascular consequences.
RECENT FINDINGS
Two novel Npt2a-selective inhibitors (PF-06869206 and BAY-767) have been developed. Pharmacological Npt2a inhibition shows a significant phosphaturic effect and consequently lowers plasma Pi and parathyroid hormone (PTH) levels regardless of CKD. However, plasma fibroblast growth factor 23 (FGF23), a master regulator of Pi homeostasis, shows inconsistent responses between these two inhibitors (no effect by PF-06869206 vs. reduction by BAY-767). In addition to the effects on Pi homeostasis, Npt2a inhibition also enhances urinary excretions of Na+, Cl-, and Ca2+, which is recapitulated in animal models with reduced kidney function. The effect of Npt2a inhibition by BAY-767 on vascular calcification has been studied, with positive results showing that oral treatment with BAY-767 (10 mg kg-1) attenuated the increases in plasma Pi and Ca2+ content in the aorta under the setting of vascular calcification induced by a pan-FGF receptor inhibitor. Together, Npt2a inhibition offers a promising therapeutic approach for treating hyperphosphatemia and reducing cardiovascular complications in CKD.
SUMMARY
Npt2a inhibition significantly increases urinary Pi excretion and lowers plasma Pi and PTH levels; moreover, it exerts pleiotropic "off-target" effects, providing a novel treatment for hyperphosphatemia and exhibiting beneficial potential for cardiovascular complications in CKD.
Topics: Animals; Calcium; Fibroblast Growth Factors; Humans; Hyperphosphatemia; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic; Sodium-Phosphate Cotransporter Proteins, Type IIa; Vascular Calcification
PubMed: 35894284
DOI: 10.1097/MNH.0000000000000828 -
International Journal of Infectious... Sep 2022Nonrespiratory manifestations of COVID-19 include endocrine disorders, among which are calcium-magnesium-phosphate homeostasis abnormalities, which seem to influence the...
OBJECTIVES
Nonrespiratory manifestations of COVID-19 include endocrine disorders, among which are calcium-magnesium-phosphate homeostasis abnormalities, which seem to influence the disease severity and patient outcome. The aim of this study was to evaluate the prevalence and impact of calcium-magnesium-phosphate and vitamin D3 disorders on survival in patients hospitalized for COVID-19 depending on the severity of the disease and kidney function.
DESIGN OR METHODS
The study was conducted between April 2020 and May 2021 at Central Clinical Hospital in Warsaw, Poland. A total of 146 patients who had tested concentration of at least one of the studied elements, estimated glomerular filtration ratio, creatinine levels, and blood saturation, and were diagnosed with COVID-19 disease were included in the analysis.
RESULTS
We found that hypermagnesemia was common and associated with a 1.5-fold increased risk of death in the whole cohort. Hyperphosphatemia also increased the risk of death, exactly 2.4-fold. Furthermore, we found a statistically significant association between increased mortality in the whole cohort and hypovitaminosis D3 (P <0.05). Serum creatinine concentration and estimated glomerular filtration ratio significantly correlated with serum magnesium and phosphate levels.
CONCLUSION
Hypermagnesemia, hyperphosphatemia, and hypovitaminosis D but not hypocalcemia influence the mortality of patients with COVID-19. These parameters should be monitored routinely in this group of patients, especially in those with decreased kidney function.
Topics: COVID-19; Calcium; Humans; Hyperphosphatemia; Magnesium; Metabolic Diseases; Phosphates
PubMed: 35803468
DOI: 10.1016/j.ijid.2022.06.057 -
Kidney International May 2009Hyperphosphatemia is an inevitable consequence of end-stage chronic kidney disease and is present in the majority of dialysis patients. Hyperphosphatemia is... (Review)
Review
Hyperphosphatemia is an inevitable consequence of end-stage chronic kidney disease and is present in the majority of dialysis patients. Hyperphosphatemia is observationally and statistically associated with increased cardiovascular mortality among dialysis patients. Dietary restriction of phosphate and current dialysis modalities are not sufficiently effective to maintain serum phosphate levels within the recommended range, so the majority of dialysis patients require oral phosphate binders. However, the benefits of achieving the recommended range have yet to be shown prospectively. Unfortunately, conventional phosphate binders are not reliably effective and are associated with a range of limitations and side effects. Aluminum-containing agents are highly efficient but no longer widely used because of proven toxicity. Calcium-based salts are inexpensive, effective, and most widely used, but there is now concern about their association with hypercalcemia and vascular calcification. Sevelamer hydrochloride is associated with fewer adverse effects, but a large pill burden and high cost are limiting factors to its wider use. Lanthanum carbonate is another non-aluminum, calcium-free phosphate binder. Preclinical and clinical studies have shown a good safety profile, and it appears to be well tolerated and effective in reducing phosphate levels in dialysis patients; however, it is similarly expensive. Data on its safety profile over 6 years of treatment are now published. Achievement of opinion-based guidelines appears to have become an end in itself. Dialysis patient outcomes are worse than outcomes for many types of cancer, yet prospective, outcome-based randomized controlled trials are not being undertaken for reasons that are difficult to explain.
Topics: Chelating Agents; Humans; Hyperphosphatemia; Lanthanum; Phosphates; Polyamines; Renal Dialysis; Sevelamer
PubMed: 19279554
DOI: 10.1038/ki.2009.60