Phosphate in Cardiovascular Disease: From New Insights Into Molecular Mechanisms to Clinical Implications.

Hyperphosphatemia is a common feature in patients with impaired kidney function and is associated with increased risk of cardiovascular disease. This phenomenon extends to the general population, whereby elevations of serum phosphate within the normal range increase risk; however, the mechanism by which this occurs is multifaceted, and many aspects are poorly understood. Less than 1% of total body phosphate is found in the circulation and extracellular space, and its regulation involves multiple organ cross talk and hormones to coordinate absorption from the small intestine and excretion by the kidneys. For phosphate to be regulated, it must be sensed. While mostly enigmatic, various phosphate sensors have been elucidated in recent years. Phosphate in the circulation can be buffered, either through regulated exchange between extracellular and cellular spaces or through chelation by circulating proteins (ie, fetuin-A) to form calciprotein particles, which in themselves serve a function for bulk mineral transport and signaling. Either through direct signaling or through mediators like hormones, calciprotein particles, or calcifying extracellular vesicles, phosphate can induce various cardiovascular disease pathologies: most notably, ectopic cardiovascular calcification but also left ventricular hypertrophy, as well as bone and kidney diseases, which then propagate phosphate dysregulation further. Therapies targeting phosphate have mostly focused on intestinal binding, of which appreciation and understanding of paracellular transport has greatly advanced the field. However, pharmacotherapies that target cardiovascular consequences of phosphate directly, such as vascular calcification, are still an area of great unmet medical need.

Tenapanor: A Phosphate Absorption Inhibitor for the Management of Hyperphosphatemia in Patients with Kidney Failure.

Because of increased risks of cardiovascular disease and death, patients with hyperphosphatemia receiving maintenance dialysis are advised to limit phosphorus consumption and are prescribed phosphate binders in an effort to better control serum phosphate concentrations. Because of large pill size, pill burden, and tolerability issues, phosphate binder adherence is relatively poor. On ingestion, phosphate is absorbed from the intestine via transcellular or paracellular transport. Data show that inhibiting sodium-hydrogen exchanger 3 modulates paracellular phosphate absorption (the predominant pathway in humans). Tenapanor is a first-in-class, minimally absorbed, phosphate absorption inhibitor that selectively inhibits sodium-hydrogen exchanger 3, with a mechanism distinct from, and complementary to, that of phosphate binders. In phase 3 and postregistrational studies, tenapanor conferred statistically significant and clinically meaningful reductions in serum phosphate in patients receiving maintenance dialysis with hyperphosphatemia. Here, we review the available preclinical and clinical data on the effects of tenapanor on controlling intestinal phosphate absorption.

Gut Microbiota and Uremic Retention Solutes in Adults With Moderate CKD: A 6-Day Controlled Feeding Study.

OBJECTIVE: To determine serum and urine concentrations of the uremic retention solutes (URSs), indoxyl sulfate (IS), p-cresol sulfate (PCS), and trimethylamine N-oxide (TMAO), and gut microbiota composition in individuals with moderate chronic kidney disease (CKD) compared with matched adults without CKD in a 6-day controlled feeding study. DESIGN AND METHODS: This study was a secondary analysis in which 8 adults with moderate CKD were matched for age, sex, and race with 8 adults without CKD in a parallel-arm, 6-day controlled feeding study. IS, PCS, and TMAO were quantified using liquid chromatography-mass spectrometry in fecal samples, fasting serum, and fasting spot urine samples collected at the end of the feeding period. RESULTS: Fasting serum URS concentrations were 2.8 to 4.9x higher in CKD compared to controls (all P < .05). No differences were found in the composition of the gut microbiota between patients with and without CKD when analyzing samples for α-diversity, ß-diversity, and only minor abundance differences across taxa were apparent. Estimated glomerular filtration rate (eGFR) was inversely related to each serum URS in the whole cohort (all P < .01). However, within groups the relationships between eGFR and serum URS remained strong for CKD patients for IS and TMAO (both P < .05) but weakened for PCS (P = .10). eGFR was only correlated with urine PCS in the whole cohort (P = .03); within groups, no correlation for eGFR with any urine URS was observed. Only urine TMAO was higher in CKD compared to controls (P < .05). CONCLUSION: Serum URS concentrations are elevated in adults with CKD compared to matched non-CKD adults without differences in gut microbiota composition after consuming the same controlled study diet for 6 days. Future studies are needed to determine if specific dietary components may differentially alter the microbiota and URS.

Effects of Plant-Based Protein Consumption on Kidney Function and Mineral Bone Disorder Outcomes in Adults With Stage 3-5 Chronic Kidney Disease: A Systematic Review.

INTRODUCTION: Plant-based protein is of growing interest for dietary management of chronic kidney disease (CKD) and is hypothesized to preserve kidney function and reduce CKD-mineral bone disorder (MBD) complications, among other benefits. This systematic review aimed to summarize the available clinical trial evidence for the effect of plant-based protein on kidney function and CKD-MBD outcomes in adults with stage 3-5 CKD not on dialysis. METHODS: Searches of Medline, Embase, Agricola, CAB abstracts, Web of Science, Scopus, and hand searching were performed. Clinical trials with ≥8 participants ≥18 years of age with an estimated glomerular filtration rate <60 mL/min/1.73 m2 but not on dialysis were included. Additionally, only clinical trials with ≥1-week interventions with ≥50% dietary protein from plant-based sources and reported at least one outcome for both kidney function and CKD-MBD outcomes were included. Of the 10,962 identified abstracts, 32 met inclusion criteria and were assessed for risk of bias. RESULTS: Results for kidney function and CKD-MBD outcomes were heterogenous, with most studies having suboptimal methodological quality. In most of the studies (27/32), protein source was altered only secondarily to low-protein diet interventions. Thus, data synthesis and interpretation were focused on a subset of five studies that investigated a change in protein source only (i.e., animal vs. plant). Of this subset, four studies reported no change in kidney function, while one study reported a decrease. Three studies reported no change in serum phosphorus, and one study reported lower serum phosphorus following a vegetarian diet. Further, limited data and inconclusive results were observed for phosphaturic hormones, parathyroid hormone, and fibroblast growth factor-23. CONCLUSION: Current clinical trial evidence on plant-based protein interventions for preserving kidney function and preventing CKD-MBD is limited to inform clinical guidelines at this time. This systematic review emphasizes the ongoing need to research the effects of plant-based protein on kidney function and CKD-MBD outcomes.

'Phos'tering a Clear Message: The Evolution of Dietary Phosphorus Management in Chronic Kidney Disease.

Phosphorus is a vital nutrient, but disturbances in phosphorus homeostasis are central to chronic kidney disease-mineral and bone disorder. To minimize disturbances, traditional dietary guidance focused on a numerical phosphorus target leading to the exclusion of many healthy foods and implementation challenges. Contemporary phosphorus guidance focuses on dietary source, avoiding additives, and emphasizing low-phosphorus bioaccessibility foods, leading to a more liberal approach. Additional work is needed to demonstrate the efficacy of these contemporary approaches and understand the influence of specific foods, processing, and cooking methods. Unfortunately, patient education using traditional and contemporary strategies may give mixed messages, particularly related to plant-based foods. Thus, greater clarity on the effects of specific foods and dietary patterns may improve phosphorus education. This review aims to discuss the evolution of dietary phosphorus management while highlighting areas for future research that can help move the field toward stronger evidence-based guidance to prevent and treat hyperphosphatemia.

Natural stable calcium isotope ratios: a new gold standard for bone balance?

Bone calcium balance is the net gain, loss, or equilibrium of calcium moving to and from bone, which reflects bone balance. There are currently no clinically available tools for measuring real-time bone balance. In this issue, Shroff et al. demonstrate the use of natural stable calcium isotope ratios as a novel biomarker of bone balance in children with chronic kidney disease on dialysis that is highly repeatable and associated with radiological and biochemical markers of bone metabolism.

Blueberry Polyphenols do not Improve Bone Mineral Density or Mechanical Properties in Ovariectomized Rats.

Osteoporosis-related bone fragility fractures are a major public health concern. Given the potential for adverse side effects of pharmacological treatment, many have sought alternative treatments, including dietary changes. Based on recent evidence that polyphenol-rich foods, like blueberries, increase calcium absorption and bone mineral density (BMD), we hypothesized that blueberry polyphenols would improve bone biomechanical properties. To test this, 5-month-old ovariectomized Sprague-Dawley rats (n = 10/gp) were orally gavaged for 90 days with either a purified extract of blueberry polyphenols (0-1000 mg total polyphenols/kg bw/day) or lyophilized blueberries (50 mg total polyphenols/kg bw/day). Upon completion of the dosing regimen, right femur, right tibia, and L1-L4 vertebrae were harvested and assessed for bone mineral density (BMD), with femurs being further analyzed for biomechanical properties via three-point bending. There were no differences in BMD at any of the sites analyzed. For bone mechanical properties, the only statistically significant difference was the high dose group having greater ultimate stress than the medium dose, although in the absence of differences in other measures of bone mechanical properties, we concluded that this result, while statistically significant, had little biological significance. Our results indicate that blueberry polyphenols had little impact on BMD or bone mechanical properties in an animal model of estrogen deficiency-induced bone loss.

A Systematic Review and Qualitative Analysis of Existing Dietary Mobile Applications for People With Chronic Kidney Disease.

OBJECTIVE: The goal of this study was to systematically evaluate the quality of electronic applications (apps) available for chronic kidney disease (CKD) dietary management. METHODS: The review consisted of (1) a systematic search for all mobile CKD diet apps available on the App Store and Google Play Store, (2) an evaluation to determine how well existing apps met criteria for an ideal app, and (3) a systematic literature review of publications found through Google Scholar, Mendeley, and PubMed that reviewed specific CKD diet apps and the broader field. RESULTS: After applying systematic search criteria, 10 unique apps were identified. Ten of 14 criteria considered necessary in an ideal CKD diet app were applied to the 13 apps. Important criteria such as tailoring recommendations to CKD stage or individual dietary needs, tracking nutrient intake, allowing data to be accessible to clinicians, availability on different app platforms, and including CKD-friendly recipes were not consistently available in the apps. None of the apps used the most contemporary nutrition guidelines on which to base their recommendations. While the literature suggests there is demand for CKD diet apps, common shortcomings of available apps including barriers to usability, inclusion of erroneous information, the requirement of a high e-literacy level, user costs, lack of privacy, security, and interactive features, and the inability of caregivers or family members to use apps to assist in patient care. CONCLUSIONS: The few CKD dietary apps currently on the market for people with CKD have notable limitations in terms of content and software design. Opportunities therefore exist for improving on available CKD diet apps and thereby fulfilling an important unmet need for patients with CKD.

Intestinal Phosphorus Absorption in Moderate CKD and Healthy Adults Determined Using a Radioisotopic Tracer.

BACKGROUND: Reducing intestinal phosphorus absorption is a cornerstone in CKD-MBD management. Yet, knowledge gaps include how CKD pathophysiology affects intestinal phosphorus absorption. In vivo rodent studies suggest that intestinal phosphorus absorption remains inappropriately normal in early-moderate CKD, despite declining 1,25-dihydroxyvitamin D (1,25D). We measured intestinal phosphorus absorption in patients with moderate CKD versus healthy adults using a direct radiotracer method. METHODS: Patients with CKD and healthy adults matched for age, sex, and race were enrolled in this 8-day controlled diet study: the first 6 days outpatient and the final 2 days inpatient. Oral and intravenous doses of 33P and serial blood and urine sampling determined intestinal phosphorus absorption during the final 2 days. Secondary outcomes included fasting biochemistries and 24-hour urine phosphorus (uP). RESULTS: In total, n=8 patients with CKD (eGFR=29-55 ml/min per 1.73 m2) and n=8 matched healthy controls completed the study. On a controlled diet, no difference in fractional intestinal phosphorus absorption was detected between patients with CKD and healthy adults (0.69 versus 0.62, respectively; P=0.52), and this was similar for 24-hour uP (884 versus 935 mg/d, respectively; P=0.70). Fractional intestinal phosphorus absorption was not significantly related to 24-hour uP. Patients with CKD had higher serum intact PTH and intact FGF23 and lower 1,25D. The relationship between 1,25D and fractional intestinal phosphorus absorption was not statistically significant. CONCLUSIONS: Intestinal phosphorus absorption with typical dietary intake did not differ in patients with moderate CKD compared with controls, despite lower serum 1,25D levels. In this setting, a relationship between 24-hour uP and fractional or absolute intestinal absorption was not evident. Further investigation is needed to determine what factors influence intestinal phosphorus absorption in CKD and the apparent lack of compensation by the intestine to limit phosphorus absorption in the face of declining kidney function and reduced 1,25D. Whether this is evident across a range of dietary phosphorus intakes, as well as CKD severity, also needs to be determined. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Phosphorus Absorption in Healthy Adults and in Patients with Moderate Chronic Kidney Disease, NCT03108222.

EOS789, a broad-spectrum inhibitor of phosphate transport, is safe with an indication of efficacy in a phase 1b randomized crossover trial in hemodialysis patients.

The treatment of hyperphosphatemia remains challenging in patients receiving hemodialysis. This phase 1b study assessed safety and efficacy of EOS789, a novel pan-inhibitor of phosphate transport (NaPi-2b, PiT-1, PiT-2) on intestinal phosphate absorption in patients receiving intermittent hemodialysis therapy. Two cross-over, randomized order studies of identical design (ten patients each) compared daily EOS789 50 mg to placebo with meals and daily EOS789 100 mg vs EOS789 100 mg plus 1600 mg sevelamer with meals. Patients ate a controlled diet of 900 mg phosphate daily for two weeks and began EOS789 on day four. On day ten, a phosphate absorption testing protocol was performed during the intradialytic period. Intestinal fractional phosphate absorption was determined by kinetic modeling of serum data following oral and intravenous doses of 33Phosphate (33P). The results demonstrated no study drug related serious adverse events. Fractional phosphate absorption was 0.53 (95% confidence interval: 0.39,0.67) for placebo vs. 0.49 (0.35,0.63) for 50 mg EOS789; and 0.40 (0.29,0.50) for 100 mg EOS789 vs. 0.36 (0.26,0.47) for 100 mg EOS789 plus 1600 mg sevelamer (all not significantly different). The fractional phosphate absorption trended lower in six patients who completed both studies with EOS789 100 mg compared with placebo. Thus, in this phase 1b study, EOS789 was safe and well tolerated. Importantly, the use of 33P as a sensitive and direct measure of intestinal phosphate absorption allows specific testing of drug efficacy. The effectiveness of EOS789 needs to be evaluated in future phase 2 and phase 3 studies.

Intestinal phosphorus absorption: recent findings in translational and clinical research.

PURPOSE OF REVIEW: The purpose of this review is to discuss recent findings in intestinal phosphorus absorption pathways, particularly the contributions of paracellular versus transcellular absorption, and the differential findings from studies using in vitro versus in vivo techniques of assessing phosphorus absorption in experimental animal studies. RECENT FINDINGS: Experimental animal studies show that in vivo effects of low phosphorus diets, 1,25D, and chronic kidney disease on intestinal phosphorus absorption efficiency contradict effects previously established ex vivo/in vitro. Recent in vivo studies also suggest that the paracellular pathway accounts for the majority of phosphorus absorption in animals across very low to high luminal phosphate concentrations. The data from experimental animal studies correspond to recent human studies showing the effectiveness of targeted inhibition of paracellular phosphate absorption. Additionally, recent human studies have demonstrated that NaPi-2b inhibition alone does not appear to be effective in lowering serum phosphate levels in patients with chronic kidney disease. Pursuit of other transcellular phosphate transporter inhibitors may still hold promise. SUMMARY: In vivo animal and human studies have added to our understanding of intestinal phosphorus absorption pathways, regulation, and mechanisms. This is beneficial for developing effective new strategies for phosphate management in patients with chronic kidney disease.

Spot Urine Samples to Estimate Na and K Intake in Patients With Chronic Kidney Disease and Healthy Adults: A Secondary Analysis From a Controlled Feeding Study.

OBJECTIVE: The objective of this study was to assess the agreement between estimated 24-hour urinary sodium excretion (e24hUNa) and estimated 24-hour urinary potassium excretion (e24hUK), calculated from a spot urine sample using several available equations and actual sodium and potassium intake from a controlled diet in both healthy participants and those with chronic kidney disease (CKD). DESIGN AND METHODS: This study is a secondary analysis of a controlled feeding study in CKD patients matched to healthy controls. Participants (n = 16) consumed the controlled diet, which provided ∼2400 mg Na/day and ∼3000 mg K/day, for 8 days. On days 7 and 8, participants consumed all meals and collected all urine in an inpatient research setting, and they were discharged on day 9. The day 7 morning spot urine sample was used to calculate e24hUNa and e24hUK, which was compared with known sodium and potassium intake, respectively. RESULTS: Average e24hUNa from the INTERSALT and Tanaka-Na equations were higher than actual sodium intake by 373 mg and 559 mg, respectively, though the differences were not significant. e24hUNa from the Nerbass-SALTED equation in CKD participants was significantly higher than actual sodium intake by ∼2000 mg (P < .001), though e24hUNa from the Nerbass-RRID equation was not different from intake. e24hUK from the Tanaka-K equation was significantly lower than actual potassium intake (P < .001). For both e24hUNa and e24hUK for all participants, agreement with actual intake was poor, and e24hUNa and e24hUK were not correlated with actual sodium or potassium intake, respectively. CONCLUSION: e24hUNa and e24hUK are poor indicators of true sodium and potassium intake, respectively, in both healthy and CKD participants. Findings should be confirmed in larger sample sizes with varying levels of dietary sodium and potassium.

Plant-Based Diets, the Gut Microbiota, and Trimethylamine N-Oxide Production in Chronic Kidney Disease: Therapeutic Potential and Methodological Considerations.

High circulating trimethylamine-N-oxide (TMAO) is associated with an increased risk of cardiovascular disease and mortality in people with chronic kidney disease (CKD). In individuals with CKD, reduced kidney function leads to decreased excretion of TMAO, which results in accumulation in the circulation. Higher circulating TMAO has been linked to higher intake of animal-based foods in omnivorous diets. Thus, plant-based diets have been suggested as an intervention to slow the progression of CKD and reduce cardiovascular risk, perhaps explained in part by reduced TMAO production. This article reviews the current evidence on plant-based diets as a dietary intervention to decrease gut-derived TMAO production in patients with CKD, while highlighting methodological issues that present challenges to advancing research and subsequent translation of this approach. Overall, we find that plant-based diets are promising for reducing gut-derived TMAO production in patients with CKD but that further interventional studies are warranted.

Adverse Effects of Autoclaved Diets on the Progression of Chronic Kidney Disease and Chronic Kidney Disease-Mineral Bone Disorder in Rats.

BACKGROUND: Autoclaving rodent diets is common in laboratory animals, but autoclaving increases the formation of dietary advanced glycation end-products (AGE). We studied the effect of autoclaved (AC) diet alone or in combination with a diet high in bioavailable phosphorus on biochemistries of chronic kidney disease-mineral and bone disorder (CKD-MBD), intestinal gene expression, and oxidative stress. METHODS: Male CKD rats (Cy/+) and normal littermates were fed 1 of 3 diets: AC 0.7% phosphorus grain-based diet for 28 weeks (AC); AC diet for 17 weeks followed by non-autoclaved (Non-AC) 0.7% phosphorus casein diet until 28 weeks (AC + Casein); or Non-AC diet for 16 weeks followed by a Non-AC purified diet until 30 weeks (Non-AC + Casein). RESULTS: AC diets contained ~3× higher AGEs and levels varied depending on the location within the autoclave. Rats fed the AC and AC + Casein diets had higher total AGEs and oxidative stress, irrespective of kidney function. Kidney function was more severely compromised in CKD rats fed AC or AC + Casein compared to Non-AC + Casein. There was a disease-by-diet interaction for plasma phosphorus, parathyroid hormone, and c-terminal fibroblast growth factor-23, driven by high values in the CKD rats fed the AC + Casein diet. Compared to Non-AC + Casein, AC and AC + Casein-fed groups had increased expression of receptor of AGEs and intestinal NADPH oxidase dual oxidase-2, independent of kidney function. CONCLUSIONS: Autoclaving rodent diets impacts the progression of CKD and CKD-MBD, highlighting the critical importance of standardizing diets in experiments.

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.

Phosphate Binders and Nonphosphate Effects in the Gastrointestinal Tract.

Phosphate binders are commonly prescribed in patients with end-stage kidney disease to prevent and treat hyperphosphatemia. These binders are usually associated with gastrointestinal distress, may bind molecules other than phosphate, and may alter the gut microbiota, altogether having systemic effects unrelated to phosphate control. Sevelamer is the most studied of the available binders for nonphosphate-related effects including binding to bile acids, endotoxins, gut microbiota-derived metabolites, and advanced glycation end products. Other binders (calcium- and noncalcium-based binders) may bind vitamins, such as vitamin K and folic acid. Moreover, the relatively new iron-based phosphate binders may alter the gut microbiota, as some of the iron or organic ligands may be used by the gastrointestinal bacteria. The objective of this narrative review is to provide the current evidence for the nonphosphate effects of phosphate binders on gastrointestinal function, nutrient and molecule binding, and the gut microbiome.

Pilot Study of the Effects of High-Protein Meals During Hemodialysis on Intradialytic Hypotension in Patients Undergoing Maintenance Hemodialysis.

OBJECTIVE: Patients undergoing hemodialysis (HD) have high protein and energy requirements, and protein-energy wasting is common and associated with poor outcomes. Eating during dialysis may improve nutritional status by counteracting the catabolic effects of HD treatment; but eating during HD may be discouraged because of concerns of postprandial hypotension. However, little data are available to support this practice. In this study, we hypothesized that high-protein meals during HD do not lead to symptomatic intradialytic hypotension events. DESIGN: A 9-week, nonrandomized, parallel-arm study. SETTING: A single in-center HD clinic. SUBJECTS: Eighteen patients undergoing HD from 2 shifts completed the study. Patients were aged 62 ± 16 years with dialysis vintage of 3.4 ± 2.6 years. INTERVENTION: Patients in the intervention group (n = 9) undergoing HD received meals of ∼30 g protein and ∼1/3 daily recommended intakes of sodium, potassium, phosphorus, and fluid during dialysis for 25 consecutive HD sessions. The control group (n = 9) completed all aspects of the study including a visit by study personnel but were not given meals. The 25 consecutive sessions before the start of the intervention/control phase were used as a baseline comparison for each patient. MAIN OUTCOME MEASURE: Symptomatic hypotension event frequency. RESULTS: In the intervention arm, there were 19 symptomatic hypotension events in 5 patients prestudy and 18 events in 6 patients during the study. In the control arm, there were 16 events in 7 patients prestudy and 13 events in 7 patients during the study. Change in the frequency of symptomatic hypotension events from prestudy to during study was not different between groups (P = .71). There was no effect of meals on nutritional status, but patients reported positive attitudes toward receiving meals during dialysis. CONCLUSION: High-protein meals during HD did not increase symptomatic hypotension events. Larger, longer term studies are needed to confirm these results and evaluate whether high-protein meals on dialysis benefit nutritional status and clinical outcomes.

Diet and Diabetic Kidney Disease: Plant Versus Animal Protein.

PURPOSE OF REVIEW: The goal of this review is to present an overview of the evidence on the effectiveness of plant-based diets in delaying progression of diabetic kidney disease (DKD). RECENT FINDINGS: The ideal quantity of dietary protein has been a controversial topic for patients with DKD. Smaller studies have focused on protein source, plant versus animal, for preventing progression. Limited evidence suggests that dietary patterns that focus on plant-based foods, those that are lower in processed foods, or those that are lower in advanced glycation end products (AGE) may be useful in prevention of DKD progression. Increasing plant-based foods, incorporating diet patterns that limit processed foods, or potentially lowering AGE contents in diets may be beneficial for dietary management of DKD. However, dietary studies specifically targeted at DKD treatment are sparse. Further, large trials powered to assess outcomes including changes in kidney function, end-stage kidney disease, and mortality are needed to provide more substantial evidence for these diets.

Calcium Balance in Chronic Kidney Disease.

PURPOSE OF REVIEW: The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. RECENT FINDINGS: Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

Effects of Excessive Dietary Phosphorus Intake on Bone Health.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of dietary phosphorus, its sources, recommended intakes, and its absorption and metabolism in health and in chronic kidney disease and to discuss recent findings in this area with a focus on the effects of inorganic phosphate additives in bone health. RECENT FINDINGS: Recent findings show that increasing dietary phosphorus through inorganic phosphate additives has detrimental effects on bone and mineral metabolism in humans and animals. There is new data supporting an educational intervention to limit phosphate additives in patients with chronic kidney disease to control serum phosphate. The average intake of phosphorus in the USA is well above the recommended dietary allowance. Inorganic phosphate additives, which are absorbed at a high rate, account for a substantial and likely underestimated portion of this excessive intake. These additives have negative effects on bone metabolism and present a prime opportunity to lower total phosphorus intake in the USA. Further evidence is needed to confirm whether lowering dietary phosphorus intake would have beneficial effects to improve fracture risk.