-
Advances in Nutrition (Bethesda, Md.) May 2019Calcium is the fifth most abundant element in the body with >99% residing in the skeleton as hydroxyapatite, a complex calcium phosphate molecule. This mineral supplies...
Calcium is the fifth most abundant element in the body with >99% residing in the skeleton as hydroxyapatite, a complex calcium phosphate molecule. This mineral supplies the strength to bones that support locomotion, but it also serves as a reservoir to maintain serum calcium concentrations. Calcium plays a central role in a wide range of essential functions. Its metabolism is regulated by 3 major transport systems: intestinal absorption, renal reabsorption, and bone turnover. Calcium transport in these tissues is regulated by a sophisticated homeostatic hormonal system that involves parathyroid hormone, and 1,25-dihydroxyvitamin D in response to decreased serum ionized calcium, detected by the calcium-sensing receptor (1).
Topics: Bone Remodeling; Calcium; Calcium, Dietary; Homeostasis; Humans; Intestinal Absorption; Parathyroid Hormone; Renal Reabsorption
PubMed: 30915443
DOI: 10.1093/advances/nmy086 -
Nutrients Jul 2016Potassium is an essential nutrient. It is the most abundant cation in intracellular fluid where it plays a key role in maintaining cell function. The gradient of... (Review)
Review
Potassium is an essential nutrient. It is the most abundant cation in intracellular fluid where it plays a key role in maintaining cell function. The gradient of potassium across the cell membrane determines cellular membrane potential, which is maintained in large part by the ubiquitous ion channel the sodium-potassium (Na+-K+) ATPase pump. Approximately 90% of potassium consumed (60-100 mEq) is lost in the urine, with the other 10% excreted in the stool, and a very small amount lost in sweat. Little is known about the bioavailability of potassium, especially from dietary sources. Less is understood on how bioavailability may affect health outcomes. Hypertension (HTN) is the leading cause of cardiovascular disease (CVD) and a major financial burden ($50.6 billion) to the US public health system, and has a significant impact on all-cause morbidity and mortality worldwide. The relationship between increased potassium supplementation and a decrease in HTN is relatively well understood, but the effect of increased potassium intake from dietary sources on blood pressure overall is less clear. In addition, treatment options for hypertensive individuals (e.g., thiazide diuretics) may further compound chronic disease risk via impairments in potassium utilization and glucose control. Understanding potassium bioavailability from various sources may help to reveal how specific compounds and tissues influence potassium movement, and further the understanding of its role in health.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Supplements; Evidence-Based Medicine; Global Health; Glucose Intolerance; Humans; Hypertension; Intestinal Absorption; Kidney; Models, Biological; Potassium; Potassium Deficiency; Potassium, Dietary; Renal Elimination; Renal Reabsorption
PubMed: 27455317
DOI: 10.3390/nu8070444 -
Cardiovascular Diabetology May 2022Type 2 diabetes mellitus (T2DM) is a chronic, complex metabolic disease characterized by chronic hyperglycemia causing from insufficient insulin signaling because of... (Review)
Review
Type 2 diabetes mellitus (T2DM) is a chronic, complex metabolic disease characterized by chronic hyperglycemia causing from insufficient insulin signaling because of insulin resistance or defective insulin secretion, and may induce severe complications and premature death. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are oral drugs used to reduce hyperglycemia in patients with T2DM, including empagliflozin, ertugliflozin, dapagliflozin and canagliflozin. The primary objective of this article is to examine the clinical benefit, safety, and tolerability of the four SGLT2 inhibitors approved by the US FDA. SGLT2 inhibitors increase urinary glucose excretion via inhibiting SGLT2 to decrease renal reabsorption of filtered glucose and reduce the renal threshold for glucose. Rather than stimulating insulin release, SGLT2 inhibitors improve β-cell function by improving glucotoxicity, as well as reduce insulin resistance and increase insulin sensitivity. Early clinical trials have confirmed the beneficial effects of SGLT2 in T2DM with acceptable safety and excellent tolerability. In recent years, SGLT2 inhibitors has been successively approved by the FDA to decrease cardiovascular death and decrease the risk of stroke and cardiac attack in T2DM adults who have been diagnosed with cardiovascular disease, treating heart failure (HF) with reduced ejection fraction and HF with preserved ejection fraction, and treat diabetic kidney disease (DKD), decrease the risk of hospitalization for HF in T2DM and DKD patients. SGLT2 inhibitors are expected to be an effective treatment for T2DM patients with non alcoholic fatty liver disease. SGLT2 inhibitors have a similar safety profile to placebo or other active control groups, with major adverse events such as Ketoacidosis or hypotension and genital or urinary tract infections.
Topics: Adult; Diabetes Mellitus, Type 2; Glucose; Humans; Hyperglycemia; Hypoglycemic Agents; Sodium; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35614469
DOI: 10.1186/s12933-022-01512-w -
Geriatrie Et Psychologie... Dec 2021Glucose and sodium tubular reabsorption inhibitors, or gliflozins, are a new therapeutic class. Their novel mechanism of action involves inhibition of a glucose and Na+...
Glucose and sodium tubular reabsorption inhibitors, or gliflozins, are a new therapeutic class. Their novel mechanism of action involves inhibition of a glucose and Na+ reabsorption co-transporter in the renal proximal tubule. They reduce blood glucose levels by reducing renal glucose reabsorption. They therefore cause glycosuria, which constitutes an energy loss and ultimately leads to a weight loss of around 2 to 3 kg. They reduce sodium load and lower blood pressure. This class improves HbA1c by about 0.7%. Empagliflozin has been shown to reduce all-cause mortality in type 2 diabetic patients at high cardiovascular risk and to reduce episodes of cardiac decompensation and is nephroprotective in diabetic and non-diabetic subjects. Empagliflozin, like other gliflozins, does not induce hypoglycaemia as it does not directly stimulate insulin secretion. Due to the high prevalence of type 2 diabetes, heart failure and renal failure in the elderly, gliflozins will become part of geriatric prescriptions. Their advantages and use must be known, especially as their role will be extended to numerous indications in the field of chronic diseases.
PubMed: 34933846
DOI: 10.1684/pnv.2021.0987 -
The Journal of Clinical Endocrinology... Feb 2022In X-linked hypophosphatemia (XLH), excess fibroblast growth factor-23 causes hypophosphatemia and low calcitriol, leading to musculoskeletal disease with clinical... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
In X-linked hypophosphatemia (XLH), excess fibroblast growth factor-23 causes hypophosphatemia and low calcitriol, leading to musculoskeletal disease with clinical consequences. XLH treatment options include conventional oral phosphate with active vitamin D, or monotherapy with burosumab, a monoclonal antibody approved to treat children and adults with XLH. We have previously reported outcomes up to 64 weeks, and here we report safety and efficacy follow-up results up to 160 weeks from an open-label, multicenter, randomized, dose-finding trial of burosumab for 5- to 12-year-old children with XLH.
METHODS
After 1 week of conventional therapy washout, patients were randomized 1:1 to burosumab every 2 weeks (Q2W) or every 4 weeks (Q4W) for 64 weeks, with dosing titrated based on fasting serum phosphorus levels between baseline and week 16. From week 66 to week 160, all patients received Q2W burosumab.
RESULTS
Twenty-six children were randomized initially into each Q2W and Q4W group and all completed treatment to week 160. In 41 children with open distal femoral and proximal tibial growth plates (from both treatment groups), total Rickets Severity Score significantly decreased by 0.9 ± 0.1 (least squares mean ± SE; P < 0.0001) from baseline to week 160. Fasting serum phosphorus increases were sustained by burosumab therapy throughout the study, with an overall population mean (SD) of 3.35 (0.39) mg/dL, within the pediatric normal range (3.2-6.1 mg/dL) at week 160 (mean change from baseline P < 0.0001). Most adverse events were mild to moderate in severity.
MAIN CONCLUSIONS
In children with XLH, burosumab administration for 160 weeks improved phosphate homeostasis and rickets and was well-tolerated. Long-term safety was consistent with the reported safety profile of burosumab.
CLINICALTRIALS.GOV
NCT02163577.
Topics: Antibodies, Monoclonal, Humanized; Child; Child, Preschool; Dose-Response Relationship, Drug; Familial Hypophosphatemic Rickets; Female; Fibroblast Growth Factor-23; Humans; Male; Phosphates; Renal Reabsorption; Severity of Illness Index
PubMed: 34636899
DOI: 10.1210/clinem/dgab729 -
Reviews of Physiology, Biochemistry and... 2021Phosphate is a multivalent ion critical for a variety of physiological functions including bone formation, which occurs rapidly in the developing infant. In order to... (Review)
Review
Phosphate is a multivalent ion critical for a variety of physiological functions including bone formation, which occurs rapidly in the developing infant. In order to ensure maximal bone mineralization, young animals must maintain a positive phosphate balance. To accomplish this, intestinal absorption and renal phosphate reabsorption are greater in suckling and young animals relative to adults. This review discusses the known intestinal and renal adaptations that occur in young animals in order to achieve a positive phosphate balance. Additionally, we discuss the ontogenic changes in phosphotropic endocrine signalling as it pertains to intestinal and renal phosphate handling, including several endocrine factors not always considered in the traditional dogma of phosphotropic endocrine signalling, such as growth hormone, triiodothyronine, and glucocorticoids. Finally, a proposed model of how these factors may contribute to achieving a positive phosphate balance during development is proposed.
Topics: Animals; Homeostasis; Humans; Infant; Intestinal Absorption; Kidney; Phosphates; Renal Reabsorption
PubMed: 33398502
DOI: 10.1007/112_2020_52 -
Journal of Clinical Pathology Nov 2019Phosphate in both inorganic and organic form is essential for several functions in the body. Plasma phosphate level is maintained by a complex interaction between... (Review)
Review
Phosphate in both inorganic and organic form is essential for several functions in the body. Plasma phosphate level is maintained by a complex interaction between intestinal absorption, renal tubular reabsorption, and the transcellular movement of phosphate between intracellular fluid and bone storage pools. This homeostasis is regulated by several hormones, principally the parathyroid hormone, 1,25-dihydroxyvitamin D and fibroblast growth factor 23. Abnormalities in phosphate regulation can lead to serious and fatal complications. In this review phosphate homeostasis and the aetiology, pathophysiology, clinical features, investigation and management of hypophosphataemia and hyperphosphataemia will be discussed.
Topics: Animals; Biomarkers; Bone and Bones; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Homeostasis; Humans; Hyperphosphatemia; Hypophosphatemia; Intestinal Absorption; Parathyroid Hormone; Phosphates; Renal Reabsorption; Vitamin D
PubMed: 31467040
DOI: 10.1136/jclinpath-2018-205130 -
Nutrients Oct 2019Folates are water-soluble B9 vitamins that serve as one-carbon donors in the de novo synthesis of thymidylate and purines, and in the conversion of homocysteine to... (Review)
Review
Folates are water-soluble B9 vitamins that serve as one-carbon donors in the de novo synthesis of thymidylate and purines, and in the conversion of homocysteine to methionine. Due to their key roles in nucleic acid synthesis and in DNA methylation, inhibiting the folate pathway is still one of the most efficient approaches for the treatment of several tumors. Methotrexate and pemetrexed are the most prescribed antifolates and are mainly used in the treatment of acute myeloid leukemia, osteosarcoma, and lung cancers. Normal levels of folates in the blood are maintained not only by proper dietary intake and intestinal absorption, but also by an efficient renal reabsorption that seems to be primarily mediated by the glycosylphosphatidylinositol- (GPI) anchored protein folate receptor α (FRα), which is highly expressed at the brush-border membrane of proximal tubule cells. Folate deficiency due to malnutrition, impaired intestinal absorption or increased urinary elimination is associated with severe hematological and neurological deficits. This review describes the role of the kidneys in folate homeostasis, the molecular basis of folate handling by the kidneys, and the use of high dose folic acid as a model of acute kidney injury. Finally, we provide an overview on the development of folate-based compounds and their possible therapeutic potential and toxicological ramifications.
Topics: Acute Kidney Injury; Animals; Antineoplastic Agents; Dietary Supplements; Folic Acid; Folic Acid Deficiency; Homeostasis; Humans; Kidney; Nutritional Status; Polycystic Kidney, Autosomal Dominant; Renal Insufficiency, Chronic; Renal Reabsorption; Risk Assessment; Risk Factors
PubMed: 31581752
DOI: 10.3390/nu11102353