Chronic Kidney Di Ea E Mineral And Bone Di Order Pdf
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- Chronic Kidney Disease – Mineral and Bone Disorder: pathophysiology and treatment
- Low-protein diets for chronic kidney disease patients: the Italian experience
- Parathyroid Hormone Measurement in Chronic Kidney Disease: From Basics to Clinical Implications
- Low-protein diets for chronic kidney disease patients: the Italian experience
The Journal publishes articles on basic or clinical research relating to nephrology, arterial hypertension, dialysis and kidney transplants. It is governed by the peer review system and all original papers are subject to internal assessment and external reviews. The journal accepts submissions of articles in English and in Spanish languages.
Chronic Kidney Disease – Mineral and Bone Disorder: pathophysiology and treatment
Magnesium is an essential mineral and a cofactor for hundreds of enzymes. Magnesium is involved in many physiologic pathways, including energy production, nucleic acid and protein synthesis , ion transport, cell signaling , and also has structural functions. More information. Severe magnesium deficiency can impede vitamin D and calcium homeostasis.
Certain individuals are more susceptible to magnesium deficiency, especially those with gastrointestinal or renal disorders, those suffering from chronic alcoholism, and older people. Preliminary studies have shown that magnesium improved insulin sensitivity in individuals at risk for type 2 diabetes mellitus.
Randomized controlled trials have also investigated the role of magnesium supplementation in the prevention of complications following stroke or heart surgery. Magnesium sulfate is used in obstetric care for the prevention of seizures in pregnant women with preeclampsia or eclampsia.
Observational studies and randomized controlled trials also support a role for magnesium in preventing brain damage in premature infants. The use of magnesium supplementation is currently being explored in the management of various conditions, including hypertension, cardiovascular disease, type 2 diabetes mellitus, asthma and pain. About half of the US adult population may have insufficient magnesium intakes to support nutritional adequacy. Dietary sources rich in magnesium include green leafy vegetables, unrefined grains, legumes , beans, and nuts.
Excessive intake of supplemental magnesium can result in adverse effects, especially in individuals with impaired kidney functions.
Magnesium plays important roles in the structure and the function of the human body. The adult human body contains about 25 grams g of magnesium. Magnesium is the second most abundant intracellular cation after potassium. Protein -bound and chelated magnesium serve to buffer the pool of free, ionized magnesium 1. Magnesium is involved in more than essential metabolic reactions, some of which are discussed below 2.
The metabolism of carbohydrates and fats to produce energy requires numerous magnesium-dependent chemical reactions. Magnesium is required by the adenosine triphosphate ATP -synthesizing protein in mitochondria. ATP, the molecule that provides energy for almost all metabolic processes, exists primarily as a complex with magnesium MgATP 3.
Magnesium is required for a number of steps during synthesis of deoxyribonucleic acid DNA , ribonucleic acid RNA , and proteins. Several enzymes participating in the synthesis of carbohydrates and lipids require magnesium for their activity. Glutathione , an important antioxidant , requires magnesium for its synthesis 3. Magnesium plays a structural role in bone, cell membranes , and chromosomes 3.
Magnesium is required for the active transport of ions like potassium and calcium across cell membranes. Through its role in ion transport systems, magnesium affects the conduction of nerve impulses , muscle contraction, and normal heart rhythm 3.
Cell signaling requires MgATP for the phosphorylation of proteins and the formation of the cell-signaling molecule, cyclic adenosine monophosphate cAMP.
Calcium and magnesium concentrations in the fluid surrounding cells affect the migration of a number of different cell types. Such effects on cell migration may be important in wound healing 3. High doses of zinc in supplemental form apparently interfere with the absorption of magnesium. Large increases in the intake of dietary fiber have been found to decrease magnesium utilization in experimental studies.
However, the extent to which dietary fiber affects magnesium nutritional status in individuals with a varied diet outside the laboratory is not clear 2, 3. Dietary protein intake may affect magnesium absorption. The active form of vitamin D calcitriol may slightly increase intestinal absorption of magnesium 6. However, it is not clear whether magnesium absorption is calcitriol-dependent as is the absorption of calcium and phosphate. High calcium intake has not been found to affect magnesium balance in most studies.
Inadequate blood magnesium concentrations are known to result in low blood calcium concentrations, resistance to parathyroid hormone PTH action, and resistance to some of the effects of vitamin D 2, 3. Magnesium deficiency in healthy individuals who are consuming a balanced diet is quite rare because magnesium is abundant in both plant and animal foods and because the kidneys are able to limit urinary excretion of magnesium when intake is low.
The following conditions increase the risk of magnesium deficiency 7 :. Poor dietary intake, gastrointestinal problems, and increased urinary loss of magnesium may all contribute to magnesium depletion in people suffering from alcoholism.
Older adults have relatively low dietary intakes of magnesium 8, 9. Intestinal magnesium absorption tends to decrease with age, and urinary magnesium excretion tends to increase with age; thus, suboptimal dietary magnesium intake may increase the risk of magnesium depletion in the elderly 2. Although severe magnesium deficiency is uncommon, it has been induced experimentally.
When magnesium deficiency was induced in humans, the earliest sign was a decrease in serum magnesium concentration. Hypomagnesemia usually describes serum magnesium concentrations less than 0.
Over time, serum calcium concentration also began to decrease hypocalcemia despite adequate dietary calcium. Hypocalcemia persisted despite increased secretion of parathyroid hormone PTH , which regulates calcium homeostasis.
Usually, increased PTH secretion quickly results in the mobilization of calcium from bone and normalization of blood calcium concentration. As the magnesium depletion progressed, PTH secretion diminished to low concentrations. In addition to hypomagnesemia, signs of severe magnesium deficiency included hypocalcemia, low serum potassium concentrations hypokalemia , retention of sodium , low circulating PTH concentrations, neurological and muscular symptoms tremor , muscle spasms, tetany , loss of appetite, nausea, vomiting, and personality changes 3.
While mild magnesium deficiency may not elicit clinical symptoms, it may be associated with an increased risk of developing chronic diseases see Disease Prevention 1. There is currently no reliable indicator of magnesium status.
The magnesium tolerance test, which basically determines magnesium retention using h urine collection following the intravenous administration of magnesium, is considered to be the gold standard 1.
If this method is a good indicator of hypomagnesemia in adults, it appears to be poorly sensitive to changes in magnesium status in healthy people. Moreover, the method is invasive and cumbersome, and thus difficult to use routinely Another method to assess magnesium status is through measurements of plasma ionized magnesium, which represents the physiologically active form of magnesium.
However, it is unknown whether plasma ionized magnesium reflect body stores However, each of these indicators has limitations. Although predominantly used in epidemiological studies and the sole indicator available to clinicians, serum magnesium concentration has been found to poorly respond to magnesium supplementation.
Finally, a state of magnesium deficiency has not been associated to a clear cutoff concentration of magnesium in the urine. Urinary magnesium concentration fluctuates rapidly with dietary intakes, but measurements of hour urinary magnesium can be used in addition to other indicators to assess population status. In , the Food and Nutrition Board of the Institute of Medicine increased the Recommended Dietary Allowance RDA for magnesium, based on the results of tightly controlled balance studies that utilized more accurate methods of measuring magnesium Table 1 2.
Balance studies are useful for determining the amount of a nutrient that will prevent deficiency; however, such studies provide little information regarding the amount of a nutrient required for chronic disease prevention or optimal health.
Metabolic syndrome refers to the concomitant presentation of several metabolic disorders in an individual, including dyslipidemia, hypertension , insulin resistance , and obesity People with metabolic syndrome are at greater risk of developing type 2 diabetes mellitus , cardiovascular disease , and some types of cancer Several meta-analyses of primarily cross-sectional studies have also reported an inverse association between dietary magnesium intake and risk of metabolic syndrome Moreover, lower serum magnesium concentrations have been reported in individuals with metabolic syndrome compared to controls 18, At present, additional evidence is needed from prospectively designed studies to inform the potential relationship between dietary and circulating magnesium and the risk of metabolic syndrome.
This might constitute a potential mechanism through which magnesium could play a role in the prevention of metabolic disorders. Large prospective cohort studies have examined the relationship between magnesium and blood pressure.
However, the fact that foods high in magnesium fruit, vegetables, whole grains are frequently high in potassium and dietary fiber has made it difficult to evaluate the independent effect of magnesium on blood pressure.
In one of these studies, data from 5, men and women followed for a median period of 7. There was also no evidence of an association between circulating magnesium concentrations and the risk of hypertension in a meta-analysis of three prospective cohort studies The relationship between magnesium intake and risk of hypertension suggests that improving diet quality or using magnesium supplements might play a role in the prevention of hypertension in those with inadequate dietary intakes.
The calcification of atherosclerotic plaques that occurs with the progression of atherosclerosis has been associated with a three- to four-fold increase in the risk of cardiovascular events and mortality Individuals with chronic kidney disease CKD : Abnormalities in mineral and bone metabolism are not uncommon in individuals with impaired kidney function and have been associated with an increased risk of cardiovascular disease and mortality 29, In particular, elevated blood phosphorus concentration and increased deposition of calcium phosphate within the vasculature are thought to promote vascular calcification.
Since magnesium can function as a calcium antagonist , it has been suggested that it could be utilized to slow down or reverse the calcification of vessels observed in patients with CKD.
In a cross-sectional study in patients with pre-dialysis CKD, higher serum magnesium concentrations were associated with lower coronary artery calcification density scores in those in the higher end of normal serum phosphorus concentrations i.
One small randomized , placebo -controlled trial in participants with pre-dialysis CKD examined the effect of oral, slow-release magnesium hydroxide on the calcification propensity of serum by measuring the time needed for primary calciprotein particles containing amorphous calcium phosphate to transform into secondary calciprotein particles containing crystalline hydroxyapatite Increased serum calcification propensity has been associated with greater risk of mortality in patients with impaired kidney function 33, A larger randomized controlled trial in patients with pre-dialysis CKD is underway to examine further the effect of oral magnesium on markers of vascular calcification, markers of mineral and bone metabolism, incidence of cardiovascular events, and deterioration of kidney function Serum magnesium concentration was also found to be inversely associated with vascular calcification in recent population-based cross-sectional studies No research has yet examined whether improving magnesium status of generally healthy people could play a role in atherosclerosis prevention.
A more recent meta-analysis by Fang et al. Only two prospective studies have examined the risk of heart failure in relation to magnesium intakes. However, in the recent meta-analysis of eight studies by Fang et al.
It is important to note that while these prospective cohort studies assessed the association between dietary magnesium and cardiovascular disease, they did not account for the use of supplemental magnesium by a significant fraction of participants. Serum magnesium concentrations: One large prospective study almost 14, men and women associated higher serum magnesium concentrations with a lower risk of CHD in women but not in men This study was included in a meta-analysis of four studies that showed no evidence of a reduced risk of CHD with increasing serum magnesium concentrations In contrast, a 0.
In the recently published British Regional Heart Study that followed 3, men for a mean 15 years, there was no association between serum magnesium concentration and incidental CHD events, yet serum magnesium concentration was inversely associated with the risk of heart failure A number of early studies found lower cardiovascular -related mortality in populations who routinely consume "hard" water.
Hard alkaline water is generally high in magnesium but may also contain more calcium and fluoride than "soft" water, making the cardioprotective effects of hard water difficult to attribute to magnesium alone Additionally, meta-analyses of prospective studies have found no associations between magnesium intake and cardiovascular 50 or all-cause mortality Occurrence of hypomagnesemia has been reported in patients who suffered from a subarachnoid hemorrhage a type of stroke caused by the rupture of a cerebral aneurysm Poor neurologic outcomes following an aneurysmal subarachnoid hemorrhage aSAH have been linked to inappropriate calcium -dependent contraction of arteries known as cerebral arterial vasospasm , leading to delayed cerebral ischemia Because magnesium is a calcium antagonist and potent vasodilator , several randomized controlled trials have examined whether intravenous magnesium sulfate infusions could reduce the incidence of vasospasm after aSAH.
Low-protein diets for chronic kidney disease patients: the Italian experience
Due to the variability of PTH assays, preanalytical sample errors, and the phenomenon of end-organ PTH hyporesponsiveness, current CKD-MBD guidelines recommend a wide range for serum PTH targets 2—9 the upper normal limit of the intact PTH assay in dialysis patients to diminish the risk of developing adynamic bone disease. Nevertheless, a sizeable proportion of CKD patients still experience renal osteodystrophy despite having serum PTH levels within the recommended range. Therefore, a new mass spectrometry-based assay, which is capable of specifically measuring the whole spectra of PTH fragments, can potentially improve diagnostic accuracy for renal osteodystrophy. However, the effects of different PTH fragments on bone metabolism, vascular calcification, and mortality in CKD patients warrant further research. The complex pathophysiology of CKD-MBD involves a number of feedback loops between the kidney, parathyroid glands, bone, intestine, and vasculature, and usually commences early in the course of CKD prior to the onset of clinically detectable abnormalities in serum calcium, phosphate, PTH, and vitamin D levels [ 3 — 6 ].
Parathyroid Hormone Measurement in Chronic Kidney Disease: From Basics to Clinical Implications
Metrics details. Nutritional treatment has always represented a major feature of CKD management. Over the decades, the use of nutritional treatment in CKD patients has been marked by several goals. The first of these include the attainment of metabolic and fluid control together with the prevention and correction of signs, symptoms and complications of advanced CKD. The aim of this first stage is the prevention of malnutrition and a delay in the commencement of dialysis.
Within each recommendation, the strength of recommendation is indicated as Level 1 , Level 2 , or not graded , and the quality of the supporting evidence is shown as A , B , C , or D. This Clinical Practice Guideline Update is based upon systematic literature searches last conducted in September supplemented with additional evidence through February It is designed to assist decision making.
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.
Low-protein diets for chronic kidney disease patients: the Italian experience
The Kidney Disease: Improving Global Outcomes KDIGO Clinical Practice Guideline document was based on the best information available at that time and was designed not only to provide information but also to assist in decision-making. In addition to the international KDIGO Work Group, which included worldwide experts, an independent Evidence Review Team was assembled to ensure rigorous review and grading of the existing evidence. Based on the evidence from new clinical trials, an updated Clinical Practice Guideline was published in The KDIGO Clinical Practice Guideline document was based on the best information available at that time and was designed not only to provide information but also to assist in decision-making [ 2 ]. Not only did the international KDIGO Work Group include worldwide experts but in addition, an independent Evidence Review Team was assembled to ensure a rigorous review and appraisal of the existing evidence. Briefly, the process included refining questions, developing the literature search strategy, extracting data and critically appraising the literature, summarizing the evidence, revising the recommendation statements, and grading evidence quality and the strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation GRADE approach [ 2 , 6 ].
Emphasis is now placed on the need to start therapy early in the course of CKD. This article will outline the main mechanisms involved in CKD-MBD and the therapeutic interventions that aim to control this complication. In normal bone, the remodelling process is tightly controlled. Osteoblasts produce a bone matrix from collagen and ground substances that become mineralised. Osteoclasts degrade bone to initiate normal bone remodelling and mediate bone loss in pathologic conditions by increasing their resorptive activity.
Magnesium is an essential mineral and a cofactor for hundreds of enzymes. Magnesium is involved in many physiologic pathways, including energy production, nucleic acid and protein synthesis , ion transport, cell signaling , and also has structural functions. More information. Severe magnesium deficiency can impede vitamin D and calcium homeostasis. Certain individuals are more susceptible to magnesium deficiency, especially those with gastrointestinal or renal disorders, those suffering from chronic alcoholism, and older people. Preliminary studies have shown that magnesium improved insulin sensitivity in individuals at risk for type 2 diabetes mellitus.
PDF | Children with chronic kidney disease (CKD) are at high risk of Disorders of Bone Mineral Metabolism in Chronic Kidney Disease and children with CKD and on dialysis (;) emphasize the lack of pediatric information and (61) Disthabanchong S, Martin KJ, McConkey CL, Gonzalez EA.
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