Recent Advances in the Role of Diet in Bone and Mineral Disorders in Chronic Kidney Disease.

PURPOSE OF REVIEW: Chronic kidney disease mineral and bone disease (CKD-MBD) is a common complication of kidney disease and is strongly influenced by diet. The purpose of this manuscript is to review recent advances in the role of diet in CKD-MBD over the last 5 years. RECENT FINDINGS: Many of the recent studies examining the role of diet in CKD-MBD have focused on the adverse effects of high phosphorus consumption on bone health and metabolism. In general, the studies have shown that high phosphorus consumption worsens markers of bone and mineral metabolism but that eating a diet with a calcium to phosphorus ratio closer to 1:1 can attenuate some of these effects. Recent studies also showed that dietary counseling is efficacious for improving markers of CKD-MBD. High consumption of phosphorus aggravates CKD-MBD. Dietary counseling may ameliorate these effects, for example, by consuming diets with higher calcium to phosphorus ratios.

The Influence of Dietary Interventions on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).

Chronic kidney disease is a health problem whose prevalence is increasing worldwide. The kidney plays an important role in the metabolism of minerals and bone health and therefore, even at the early stages of CKD, disturbances in bone metabolism are observed. In the course of CKD, various bone turnover or mineralization disturbances can develop including adynamic hyperparathyroid, mixed renal bone disease, osteomalacia. The increased risk of fragility fractures is present at any age in these patients. Nutritional treatment of patients with advanced stages of CKD is aiming at prevention or correction of signs, symptoms of renal failure, avoidance of protein-energy wasting (PEW), delaying or prevention of the occurrence of mineral/bone disturbances, and delaying the start of dialysis. The results of studies suggest that progressive protein restriction is beneficial with the progression of renal insufficiency; however, other aspects of dietary management of CKD patients, including changes in sodium, phosphorus, and energy intake, as well as the source of protein and lipids (animal or plant origin) should also be considered carefully. Energy intake must cover patients' energy requirement, in order to enable correct metabolic adaptation in the course of protein-restricted regimens and prevent negative nitrogen balance and protein-energy wasting.

Use of a Phosphorus Points Education Program to Maintain Normal Serum Phosphorus in Pediatric Chronic Kidney Disease: A Case Report.

A 14-year-old male, with chronic kidney disease stage 4 (glomerular filtration rate 20 mL/min/1.73 m2) secondary to reflux nephropathy required dietary modification with evidence of renal osteodystrophy, presented with elevated serum phosphorus and parathyroid hormone. He was educated using a novel phosphorus point system where 1 point is equivalent to ∼50 mg of phosphorus. Dietary counseling was provided by a pediatric renal dietitian on phosphorus content of foods the patient typically consumed and converted to point system for daily tracking. The family reported limiting daily phosphorus points to less than 20 points daily for 15 months. The family completed a 3-day food record and provided points assigned to each food item. A Spearman's correlation of 0.7 (P < .001) was found between the family's and the dietitian's assignment of phosphorus points. The patient's recorded phosphorus intake remained below 1000 mg each day and met estimated calorie and protein needs. The patient also continued with age-appropriate weight gain and linear growth. Laboratory values showed phosphorus and intact parathyroid hormone remained within desired range. A phosphorus point system tool can be used to maintain normal serum phosphorus levels and subsequently prevent secondary hyperparathyroidism in patients with pediatric chronic kidney disease.

Dietary Protein Intake and Bone Across Stages of Chronic Kidney Disease.

PURPOSE OF REVIEW: This review aims to summarize the current evidence on the effect of very-low-, low-, and high-protein diets on outcomes related to chronic kidney disease-mineral and bone disorder (CKD-MBD) and bone health in patients with CKD. RECENT FINDINGS: Dietary protein restriction in the form of low- and very-low-protein diets have been used to slow down the progression of CKD. These diets can be supplemented with alpha-keto acid (KA) analogues of amino acids. Observational and randomized controlled trials have shown improvements in biochemical markers of CKD-MBD, including reductions in phosphorus, parathyroid hormone, and fibroblast growth factor-23. However, few studies have assessed changes in bone quantity and quality. Furthermore, studies assessing the effects of high-protein diets on CKD-MBD are scarce. Importantly, very-low- and low-protein diets supplemented with KA provide supplemental calcium in amounts that surpass current dietary recommendations, but to date there are no studies on calcium balance with KA. Current evidence suggests that dietary protein restriction in CKD may slow disease progression, which may subsequently benefit CKD-MBD and bone health outcomes. However, prospective randomized controlled trials assessing the effects of modulating dietary protein and supplementing with KA on all aspects of CKD-MBD and particularly bone health are needed.

Effects of Flaxseed Oil on Serum Bone Turnover Markers in Hemodialysis Patients: a Randomized Controlled Trial.

INTRODUCTION: Chronic kidney disease-mineral and bone disorder is a common complication in hemodialysis patients. The present study was designed to investigate the effects of flaxseed oil, a rich source of plant omega-3 fatty acid alpha-linolenic acid, on serum markers of bone formation and resorption in hemodialysis patients. MATERIALS AND METHODS: In this randomized controlled trial, 34 hemodialysis patients were randomly assigned to either the flaxseed oil or the control group. The patients in the flaxseed oil group received 6 g/d of flaxseed oil for 8 weeks, whereas the control group received 6 g/d of medium chain triglycerides oil. At baseline and the end of the 8th week, 7 mL of blood was obtained from each patient after a 12- to 14-hour fast and serum concentrations of osteocalcin, osteoprotegerin, N-telopeptide, and receptor activator of nuclear factor kappa B ligand were measured. RESULTS: Serum N-telopeptide concentration decreased significantly up to 17% in the flaxseed oil group at the end of week 8, as compared to baseline (P < .01), and the reduction was significant in comparison with the control group. There were no significant differences between the two groups in the mean changes of serum osteocalcin, osteoprotegerin, or receptor activator of nuclear factor kappa B ligand. CONCLUSIONS: This study indicates that daily consumption of 6 g/d of flaxseed oil may reduce bone resorption in hemodialysis patients.

PA21, a novel phosphate binder, improves renal osteodystrophy in rats with chronic renal failure.

The effects of PA21, a novel iron-based and non-calcium-based phosphate binder, on hyperphosphatemia and its accompanying bone abnormality in chronic kidney disease-mineral and bone disorder (CKD-MBD) were evaluated. Rats with adenine-induced chronic renal failure (CRF) were prepared by feeding them an adenine-containing diet for four weeks. They were also freely fed a diet that contained PA21 (0.5, 1.5, and 5%), sevelamer hydrochloride (0.6 and 2%) or lanthanum carbonate hydrate (0.6 and 2%) for four weeks. Blood biochemical parameters were measured and bone histomorphometry was performed for femurs, which were isolated after drug treatment. Serum phosphorus and parathyroid hormone (PTH) levels were higher in the CRF rats. Administration of phosphate binders for four weeks decreased serum phosphorus and PTH levels in a dose-dependent manner and there were significant decreases in the AUC0-28 day of these parameters in 5% PA21, 2% sevelamer hydrochloride, and 2% lanthanum carbonate hydrate groups compared with that in the CRF control group. Moreover, osteoid volume improved significantly in 5% of the PA21 group, and fibrosis volume and cortical porosity were ameliorated in 5% PA21, 2% sevelamer hydrochloride, and 2% lanthanum carbonate hydrate groups. These results suggest that PA21 is effective against hyperphosphatemia, secondary hyperparathyroidism, and bone abnormalities in CKD-MBD as sevelamer hydrochloride and lanthanum carbonate hydrate are, and that PA21 is a new potential alternative to phosphate binders.

Cost-effectiveness of dedicated dietitians for hyperphosphatemia management among hemodialysis patients in Lebanon: results from the Nutrition Education for Management of Osteodystrophy trial.

AIM: To assess the cost-effectiveness of nutrition education by dedicated dietitians (DD) for hyperphosphatemia management among hemodialysis patients. MATERIALS AND METHODS: This was a trial-based economic evaluation in 12 Lebanese hospital-based units. In total, 545 prevalent patients were cluster randomized to DD, trained hospital dietitian (THD), and existing practice (EP) groups. During Phase I (6 months), DD (n = 116) received intensive education by DD trained on renal nutrition, THD (n = 299) received care from trained hospital dietitians, and EP (n = 130) received usual care from untrained hospital dietitians. Patients were followed-up during Phase II (6 months). RESULTS: At baseline, EP had the lowest weekly hemodialysis time, and DD had the highest serum phosphorus and malnutrition-inflammation score. The additional costs of the intervention were low compared with the societal costs (DD: $76.7, $21,007.7; EP: $4.6, $18,675.4; THD: $17.4, $20,078.6, respectively). Between Phases I and II, DD showed the greatest decline in services use and societal costs (DD: -$2,364.0; EP: -$1,727.7; THD: -$1,105.7). At endline, DD experienced the highest decrease in adjusted serum phosphorus (DD: -0.32; EP: +0.16; THD: +0.04 mg/dL), no difference in quality-adjusted life-years (QALY), and the highest societal costs. DD had a cost-effectiveness ratio of $7,853.6 per 1 mg decrease in phosphorus, compared with EP; and was dominated by THD. Regarding QALY, DD was dominated by EP and THD. The results were sensitive to changes in key parameters. LIMITATIONS: The analysis depended on numerous assumptions. Interpreting the results is limited by the significant baseline differences in key parameters, suggestive of higher baseline societal costs in DD. CONCLUSIONS: DD yielded the greatest effectiveness and decrease in societal costs, but did not affect QALY. Regarding serum phosphorus, DD was likely to be cost-effective compared with EP, but had a low cost-effectiveness probability compared with THD. Regarding QALY, DD was not likely to be cost-effective. Assessing the long-term cost-effectiveness of DD, on similar groups, is recommended.

Management of phosphorus load in CKD patients.

Disturbances in mineral and bone metabolism play a critical role in the pathogenesis of cardiovascular complications in patients with chronic kidney disease (CKD). The term "renal osteodystrophy" has recently been replaced with "CKD-mineral and bone disorder (CKD-MBD)", which includes vascular calcification as well as bone abnormalities. In Japan, proportions of the aged and long-term dialysis patients are increasing which makes management of vascular calcification and parathyroid function increasingly more important. There are three main strategies to manage phosphate load: phosphorus dietary restriction, administration of phosphate binder and to ensure in the CKD 5D setting, an adequate dialysis.

Diets for patients with chronic kidney disease, should we reconsider?

Here we revisit how dietary factors could affect the treatment of patients with complications of chronic kidney disease (CKD), bringing to the attention of the reader the most recent developments in the field. We will briefly discuss five CKD-induced complications that are substantially improved by dietary manipulation: 1) metabolic acidosis and the progression of CKD; 2) improving the diet to take advantage of the benefits of angiotensin converting enzyme inhibitors (ACEi) on slowing the progression of CKD; 3) the diet and mineral bone disorders in CKD; 4) the safety of nutritional methods utilizing dietary protein restriction; and 5) evidence that new strategies can treat the loss of lean body mass that is commonly present in patients with CKD.

Nutritional education for the management of osteodystrophy (nemo) in patients on haemodialysis: a randomised controlled trial.

OBJECTIVE: To examine the effect of self-management dietary counselling (SMDC) on adherence to dietary management of hyperphosphatemia among haemodialysis patients. DESIGN: An eight-week cluster based randomised control trial. PARTICIPANTS: 122 stable adult patients were recruited from an HD unit in Sidon, Lebanon. Study groups were: full intervention (A) (n = 41), partial intervention (B) (n = 41) and control (C) (n = 40). INTERVENTION: Group (A) received SMDC, Group (B) received educational games only and Group (C) did not receive any research intervention. MAIN OUTCOME MEASURES: Serum phosphorus (P), Calcium Phosphate product (Ca × P) and two questionnaires: patient knowledge (PK) and dietary non-adherence (PDnA) to P reduced diet. RESULTS: Group A experienced a significant improvement in mean (± SD) P (6.54 ± 2.05 - 5.4 ± 1.97 mg/dl), Ca × P (58 ± 17 - 49 ± 12), PK scores (50 ± 17 - 69 ± 25%) and PDnA scores (21.4 ± 4.0 - 18.3 ± 2.0). Group B experienced a significant improvement in Ca × P (52 ± 14-45 ± 16). Group C did not experience any significant change post intervention. CONCLUSION: Our findings demonstrate the importance of patient-tailored counselling on serum P management.

The influence of medical and nonmedical factors to the progression of renal osteodystrophy.

We report a 13-year-old boy hospitalized for the first time at the age of 17 months with clinical and laboratory signs of chronic kidney disease (CKD) and renal osteodystrophy caused by severe obstructive uropathy of the single kidney. Prevention and treatment of renal osteodystrophy has been target for aggressive therapy and the great challenge for pediatric nephrologists. The outcome of the therapy of renal osteodystrophy is influenced by medical and non-medical factors. It was concluded that the place of living (in our example a small village distant from primary care physicians, far from the social care professionals and far from the hospital), inferior social and economical status with inadequate nutrition present negative factors that contributed to the outcome and development of CKD and its complications as is renal osteodystrohy. The coordination of medical and non-medical professionals is necessary on the primary and secondary level to achieve positive results of therapy in patients with CKD.

Vitamin D retains an important role in the pathogenesis and management of secondary hyperparathyroidism in chronic renal failure.

Chronic kidney disease (CKD) causes alterations in mineral metabolism inducing the development of secondary hyperparathyroidism (HPT) and renal osteodystrophy. Recently, it has been suggested that these alterations play an important role in determining extraskeletal calcification and thus cardiovascular morbidity and mortality among CKD patients. An impaired 1 alfa -hydroxylation of 25-hydroxycholecalciferol (25(OH)D3) to 1,25-dihydroxycholecalciferol (1,25(OH)2 D3) with decreased circulating 1,25(OH)2 D3 levels is commonly observed in patients with creatinine clearance below 70 ml/min. The reduction in 1,25(OH)2 D3 production triggers the up-regulation of parathyroid hormone (PTH) synthesis, through a decreased suppression on PTH gene transcription and a decreased intestinal calcium absorption. A reduced expression of vitamin D receptor (VDR) and a less efficient binding of the complex 1,25(OH)2 D3 -VDR to specific DNA segments account for the resistance to 1,25(OH)2 D3 in target cells. Thus, absolute and relative 1,25(OH)2 D3 deficiency is one of the causes of secondary HPT in patients with CKD, together with phosphate retention and skeletal resistance to PTH. Consistently with these pathophysiological mechanisms, the therapeutic use of 1,25(OH)2 D3 still represents a milestone for the treatment of secondary HPT and renal osteodystrophy, even though hypercalcemia and hyperphosphatemia are common adverse events and may increase the risk of cardiovascular calcifications. To reduce the impact of such adverse effects while retaining anti-PTH activity, 1,25(OH)2 D3 analogues with lower calcemic effects have been synthesized and are now available for clinical use.

[Role of diet in the management of osteodystrophy during progressive renal insufficiency]. / Papel de la dieta en el manejo de la osteodistrofia en la insuficiencia renal progresiva.

Secondary hyperparathyrodism (SH) is an early manifestation of chronic renal failure (CRF), which has serious complications. Moreover, treating SH is not a risk-free process. Once in its advanced state, it is extremely difficult to reverse and therefore it is critical an early intervention and prevention. An excess of phosphorus and a deficit of calcium and calcitriol are key factors in the evolution of SH. Despite the fact that plasma phosphorus levels remain normal until an extremely advanced stage of CRF, and even apparent hyperphosphatemia in mild CRF, it has been shown that restricting dietary levels of protein and phosphorus impedes the progression of SH. A decrease of protein in the diet also decreases the amount of calcium, thus the calcium levels must be supplemented in order to prevent their deficit. In addition to that slightly diminished levels of calcitriol can be observed in the early stages of CRF, thus it is logical to provide this hormone. However, administering calcitriol may induce hypercalcemia and hyperphosphatemia, which in turn risks the onset of cardiovascular calcifications and complications. Therefore, the calcitriol dosage should be small and then adjusted according to the degree of SH. Neither the PTH levels nor alterations in the phospho-calcium metabolism follow a linear increase appropriate to the decrease in renal function, therefore we propose a treatment strategy which adapts to the different degrees of renal failure.

Papel de la dieta en el manejo de la osteodistrofia en la insuficiencia renal progresiva / Role of the diet in the management of renal osteodystrophy progressive renal failure

El hiperparatiroidismo secundario (HPT 2º) se desarrolla desde fases iniciales de la insuficiencia renal crónica. Las complicaciones del HPT 2º son graves. El tratamiento del HPT 2º no está exento de riesgo. Cuando esta patología está evolucionada es muy difícil lograr su regresión, por todo ello, es imprescindible prevenirla. El tratamiento preventivo debe instaurarse lo antes posible, desde el comienzo de la enfermedad renal. La sobrecarga de fósforo y el déficit de calcio y calcitriol son los factores que favorecen su evolución. Aunque los niveles de fósforo plasmático permanecen normales hasta fases muy avanzadas de la IRC, e incluso puede observarse hipofosfatemia en la IRC leve, se demuestra que la restricción dietética de proteínas y fósforo tiene un efecto inhibidor en la progresión del HPT 2º. La restricción proteica, conlleva también una restricción en el aporte dietético de calcio, por ello es necesario asegurar un aporte correcto de calcio para que el efecto beneficioso de la dieta no se vea contrarrestado por un déficit de calcio. En la IRC se observan, de forma precoz, niveles discretamente disminuidos de calcitriol, por tanto parece coherente aportar suplementos de dicha hormona. Esto puede condicionar efectos negativos como hiperfosfatemia e ipercalcemia con riesgo de calcificaciones y complicaciones vasculares, por lo que es importante iniciar el tratamiento con dosis bajas, realizando ajustes según evolucionen los parámetros bioquímicos del HPT 2º. Los niveles de PTH no siguen un curso lineal a lo largo de la insuficiencia renal, tampoco lo hacen las alteraciones en el metabolismo fosfo-cálcico, por ello proponemos un esquema de tratamiento adaptado a los diferentes grados de insuficiencia renal (AU)

Secondary hyperparathyroidism (SH) is an early manifestation of chronic renal failure (CRF), which has serious complications. Moreover, treating SH is not a riskfree process. Once in its advanced state, it is extremely difficult to reverse and therefore it is critical an early intervention and prevention. An excess of phosphorus and a deficit of calcium and calcitriol are key factors in the evolution of SH. Despite the fact that plasma phosphorus levels remain normal until an extremely advanced stage of CRF, and even apparent hyperphosphatemia in mild CRF, it has been shown that restricting dietary levels of protein and phosphorus impedes the progression of SH. A decrease of protein in the diet also decreases the amount of calcium, thus the calcium levels must be supplemented in order to prevent their deficit. In addition to that slightly diminished levels of calcitriol can be observed in the early stages of CRF, thus it is logical to provide this hormone. However, administering calcitriol may induce hypercalcemia and hyperphosphatemia, which in turn risks the onset of cardiovascular calcifications and complications. Therefore, the calcitriol dosage should be small and then adjusted according to the degree of SH. Neither the PTH levels nor alterations in the phospho-calcium metabolism follow a linear increase appropiate to the decrease in renal function, therefore we propose a treatment strategy which adapts to the different degrees of renal failure (AU)

[Effects of vitamin D on protein turnover in children with renal osteopathy]. / Vliianie vitamina D na pokazateli belkovogo obmena u detei s renal'nymi osteopatiiami.

Amino acid analysis and investigation of nitrogen balance were done in 2 groups of the patients with renal failure and osteodystrophy on the diet and vitamin D treatment. The results of the investigations confirm vitamin D influence on free amino acid turnover. We observed significant elevations of plasma amino acids in patients treated with the diet and vitamin D in comparison with the patients without vitamin D supplementation. Vitamin D didn't influence on the retention, urinary and fecal excretion of endogenous nitrogen in patients with renal failure

Dietary and pharmacotherapeutic considerations in the management of renal osteodystrophy.

Renal osteodystrophy is an early complication of renal failure associated with significant morbidity. An understanding of dietary management and pharmacotherapeutic prevention and treatment of this condition is essential for members of the nephrology interdisciplinary team. The purpose of this article is to summarize the practical considerations of dietary and pharmacological management in renal osteodystrophy. Experientially based information from a 300-patient dialysis center is provided within specific guidelines, including sample diets and a pharmacotherapeutic algorithm. Treatment-outcome goals for serum phosphorus, serum calcium, and parathyroid hormone are discussed. Patient-specific factors are also discussed, including phosphorus load, calcium load, vitamin D supplementation, and dialysis treatment parameters.

Therapeutic effect of keto acids on renal osteodystrophy. A prospective controlled study.

The therapeutical effect of keto acids on bone histology was investigated in a prospective randomized controlled study of 40 patients. A marked improvement in osteofibrotic as well as in osteomalacic changes was found in bone biopsies after 12 months of treatment with keto acids.