Oh, My Gut! New insights on the role of the gastrointestinal tract and the gut microbiome in chronic kidney disease-mineral and bone disorder.

PURPOSE OF REVIEW: The aim of this review is to highlight recent evidence on the role of the gastrointestinal tract and gut microbiome on chronic kidney disease-mineral bone disorder (CKD-MBD) outcomes, including intestinal phosphorus absorption and sensing, and the effect of gut-oriented therapies. RECENT FINDINGS: Recent evidence has revealed a complex interplay among mineral metabolism and novel gut-related factors, including paracellular intestinal phosphate absorption, the gut microbiome, and the immune system, prompting a reevaluation of treatment approaches for CKD-MBD. The inhibition of NHE3 limits phosphate transport in the intestine and may lead to changes in the gut microbiome. A study in rats with CKD showed that the supplementation of the fermentable dietary inulin delayed CKD-MBD, lowering circulating phosphorus and parathyroid hormone, reducing bone remodeling and improving cortical parameters, and lowering cardiovascular calcifications. In non-CKD preclinical studies, probiotics and prebiotics improved bone formation mediated through the effect of butyrate facilitating the differentiation of T cells into Tregs, and Tregs stimulating the osteogenic Wnt10b, and butyrate was also necessary for the parathyroid hormone (PTH) bone effects. SUMMARY: Recent findings support multiple possible roles for gut-oriented therapies in addressing CKD-MBD prevention and management that should be further explored through clinical and translational studies.

Musculoskeletal Health Worsened from Carnitine Supplementation and Not Impacted by a Novel Individualized Treadmill Training Protocol.

INTRODUCTION: Chronic kidney disease (CKD) negatively affects musculoskeletal health, leading to reduced mobility, and quality of life. In healthy populations, carnitine supplementation and aerobic exercise have been reported to improve musculoskeletal health. However, there are inconclusive results regarding their effectiveness and safety in CKD. We hypothesized that carnitine supplementation and individualized treadmill exercise would improve musculoskeletal health in CKD. METHODS: We used a spontaneously progressive CKD rat model (Cy/+ rat) (n = 11-12/gr): (1) Cy/+ (CKD-Ctrl), (2) CKD-carnitine (CKD-Carn), and (3) CKD-treadmill (CKD-TM). Carnitine (250 mg/kg) was injected daily for 10 weeks. Rats in the treadmill group ran 4 days/week on a 5° incline for 10 weeks progressing from 30 min/day for week one to 40 min/day for week two to 50 min/day for the remaining 8 weeks. At 32 weeks of age, we assessed overall cardiopulmonary fitness, muscle function, bone histology and architecture, and kidney function. Data were analyzed by one-way ANOVA with Tukey's multiple comparisons tests. RESULTS: Moderate to severe CKD was confirmed by biochemistries for blood urea nitrogen (mean 43 ± 5 mg/dL CKD-Ctrl), phosphorus (mean 8 ± 1 mg/dL CKD-Ctrl), parathyroid hormone (PTH; mean 625 ± 185 pg/mL CKD-Ctrl), and serum creatinine (mean 1.1 ± 0.2 mg/mL CKD-Ctrl). Carnitine worsened phosphorous (mean 11 ± 3 mg/dL CKD-Carn; p < 0.0001), PTH (mean 1,738 ± 1,233 pg/mL CKD-Carn; p < 0.0001), creatinine (mean 1 ± 0.3 mg/dL CKD-Carn; p < 0.0001), cortical bone thickness (mean 0.5 ± 0.1 mm CKD-Ctrl, 0.4 ± 0.1 mm CKD-Carn; p < 0.05). Treadmill running significantly improves maximal aerobic capacity when compared to CKD-Ctrl (mean 14 ± 2 min CKD-TM, 10 ± 2 min CKD-Ctrl; p < 0.01). CONCLUSION: Carnitine supplementation worsened CKD progression, mineral metabolism biochemistries, and cortical porosity and did not have an impact on physical function. Individualized treadmill running improved maximal aerobic capacity but did not have an impact on CKD progression or bone properties. Future studies should seek to better understand carnitine doses in conditions of compromised renal function to prevent toxicity which may result from elevated carnitine levels and to optimize exercise prescriptions for musculoskeletal health.

A Systematic Review of Online Resources for the Dietary Management of Hyperphosphatemia in People With Chronic Kidney Disease.

OBJECTIVE: Internet search engines and social media websites are prominent and growing sources of dietary information for people with chronic kidney disease (CKD) and their healthcare providers. However, nutrition therapy for CKD is undergoing a paradigm shift, which may lead to inconsistent advice for managing hyperphosphatemia. The aim of this study was to summarize and evaluate online resources for phosphorus-specific nutrition therapy. DESIGN AND METHODS: Patient-facing resources were collected from Google, Yahoo, and Facebook in June-July 2021. Using nine independent search terms, the first 100 hits were reviewed. Dietary advice for food types, food groups, food subgroups, and individual food items was categorized as "restricted," "recommended," "mixed," and "not mentioned." Information on publication date, source, and author(s), phosphorus bioavailability, and demineralization were also collected. RESULTS: After removing duplicates, 199 resources from Google and Yahoo and 33 from Facebook were reviewed. Resources ranged from 2005 to 2021 and were primarily authored by registered dietitians and medical doctors (65% and 31%, respectively). Dietary advice mostly focuses on restricting high-phosphorus foods and phosphorus additive-based processed foods. Dietary restrictions were generally consistent with the traditional low-phosphorus diet, which targets whole grains, dairy, and plant-based protein foods, although major inconsistencies were noted. Phosphorus bioavailability and demineralization were rarely mentioned (16% and 8%, respectively). Similar findings were found on Facebook, but the limited number of resources limited meaningful comparisons. CONCLUSION: Results showed that online resources for phosphorus-specific nutrition therapy are highly restrictive of heart-healthy food items and contain significant inconsistencies. Given the widespread and increasing use of online resources by people with CKD and health care professionals to inform dietary choices, efforts are urgently needed to establish consensus for phosphorus-specific nutrition therapy. Until then, the findings of this study provide a basis for increasing awareness of the potential for confusion arising from online resources.

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.

Impact of diet on hydrogen sulfide production: implications for gut health.

PURPOSE OF REVIEW: Excessive hydrogen sulfide (H 2 S) production by the gut microbiota may contribute to the pathogenesis of multiple intestinal diseases, including colon cancer and ulcerative colitis. Therefore, understanding of dietary drivers of H 2 S production has potential implications for nutritional strategies to optimize gut health and treat intestinal diseases. RECENT FINDINGS: Recent studies support a positive relationship between dietary protein intake and H 2 S production. However, protein rarely exists in isolation in the diet, and dietary fiber intake could reduce H 2 S production in humans and animals, even with ∼30% of calories derived from protein. SUMMARY: These findings suggest that increased fiber intake may reduce H 2 S production irrespective of protein intake, enabling the ability to meet the metabolic demands of the illness while supporting gut health. Here we discuss two recent ulcerative colitis diet studies that illustrate this point.

Deconstructing Disease-Related Malnutrition: A New Assessment Framework for Clinical Practice.

Protein-energy wasting (PEW) is a key cause of functional impairment and poor health outcomes in people with chronic kidney disease. While PEW can be mitigated with nutrition therapy, it is a complex myriad of disorders with numerous interacting etiologies and corresponding presentations, which make it difficult to diagnose and manage in practice. A variety of scoring rubrics have been developed to facilitate malnutrition assessment. Although these tools have greatly benefited the recognition and treatment of PEW, the typical format of grading specified PEW indicators has the potential to overlook or overstate highly relevant individual-specific factors. This review presents a simple framework for malnutrition assessment that can be used to complement and evaluate conventional assessment tools. Unlike standard tools, which are designed to identify and rate malnutrition risk and severity, the malnutrition framework is conceptual model that organizes PEW assessment into three distinct, but interacting facets of PEW risk: nutrient balance, nutrition status, and malnutrition risk. The new framework encourages critical thinking about PEW risk that may help clinicians plan and interpret assessments to efficiently and effectively manage this condition.

Targeting the Gut Microbiota in Kidney Disease: The Future in Renal Nutrition and Metabolism.

There is increasing interest in the therapeutic potential of manipulating the gut microbiome of patients with chronic kidney disease (CKD). This is because there is a substantial deviation from a balanced gut microbiota profile in CKD, with many deleterious downstream effects. Nutritional interventions such as plant-based diets with reduced animal protein intake and the use of probiotics, prebiotics, and synbiotics may alter the microbiome. This article aims to briefly describe what is known about the gut microbiome in patients with CKD, factors contributing to gut dysbiosis, and outline important evidence gaps. Future potential therapies, including restoring the microbiota with food and microbiota-based and metabolomic-based therapies, are also discussed.

'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.

New Insights Into Dietary Approaches to Potassium Management in Chronic Kidney Disease.

Potassium disorders are one of the most common electrolyte abnormalities in patients with chronic kidney disease (CKD), contributing to poor clinical outcomes. Maintaining serum potassium levels within the physiologically normal range is critically important in these patients. Dietary potassium restriction has long been considered a core strategy for the management of chronic hyperkalemia in patients with CKD. However, this has been challenged by recent evidence suggesting a paradigm shift toward fostering more liberalized, plant-based dietary patterns. The advent of novel potassium binders and an improved understanding of gastrointestinal processes involved in potassium homeostasis (e.g., gastrointestinal potassium wasting) may facilitate a paradigm shift and incorporation of heart-healthy potassium-enriched food sources. Nevertheless, uncertainty regarding the risk-benefit of plant-based diets in the context of potassium management in CKD remains, requiring well-designed clinical trials to determine the efficacy of dietary potassium manipulation toward improvement of clinical outcomes in patients with CKD.

Nutritional and Dietary Management of Chronic Kidney Disease Under Conservative and Preservative Kidney Care Without Dialysis.

While dialysis has been the prevailing treatment paradigm for patients with advanced chronic kidney disease (CKD), emphasis on conservative and preservative management in which dietary interventions are a major cornerstone have emerged. Based on high-quality evidence, international guidelines support the utilization of low-protein diets as an intervention to reduce CKD progression and mortality risk, although the precise thresholds (if any) for dietary protein intake vary across recommendations. There is also increasing evidence demonstrating that plant-dominant low-protein diets reduce the risk of developing incident CKD, CKD progression, and its related complications including cardiometabolic disease, metabolic acidosis, mineral and bone disorders, and uremic toxin generation. In this review, we discuss the premise for conservative and preservative dietary interventions, specific dietary approaches used in conservative and preservative care, potential benefits of a plant-dominant low-protein diet, and practical implementation of these nutritional strategies without dialysis.

Effects of ferric citrate and intravenous iron sucrose on markers of mineral, bone, and iron homeostasis in a rat model of CKD-MBD.

BACKGROUND: Anemia and chronic kidney disease-mineral and bone disorder (CKD-MBD) are common and begin early in CKD. Limited studies have concurrently compared the effects of ferric citrate (FC) versus intravenous (IV) iron on CKD-MBD and iron homeostasis in moderate CKD. METHODS: We tested the effects of 10 weeks of 2% FC versus IV iron sucrose in rats with moderate CKD (Cy/+ male rat) and untreated normal (NL) littermates. Outcomes included a comprehensive assessment of CKD-MBD, iron homeostasis and oxidative stress. RESULTS: CKD rats had azotemia, elevated phosphorus, parathyroid hormone and fibroblast growth factor-23 (FGF23). Compared with untreated CKD rats, treatment with FC led to lower plasma phosphorus, intact FGF23 and a trend (P = 0.07) toward lower C-terminal FGF23. FC and IV iron equally reduced aorta and heart calcifications to levels similar to NL animals. Compared with NL animals, CKD animals had higher bone turnover, lower trabecular volume and no difference in mineralization; these were unaffected by either iron treatment. Rats treated with IV iron had cortical and bone mechanical properties similar to NL animals. FC increased the transferrin saturation rate compared with untreated CKD and NL rats. Neither iron treatment increased oxidative stress above that of untreated CKD. CONCLUSIONS: Oral FC improved phosphorus homeostasis, some iron-related parameters and the production and cleavage of FGF23. The intermittent effect of low-dose IV iron sucrose on cardiovascular calcification and bone should be further explored in moderate-advanced CKD.

A Comparison of Dietary Intake Between Individuals Undergoing Maintenance Hemodialysis in the United Kingdom and China.

OBJECTIVE: Protein-energy wasting is highly prevalent in people with end-stage kidney disease receiving regular hemodialysis. Currently, it is unclear what the optimal nutritional recommendations are, which is further complicated by differences in dietary patterns between countries. The aim of the study was to understand and compare dietary intake between individuals receiving hemodialysis in Leicester, UK and Nantong, China. METHODS: The study assessed 40 UK and 44 Chinese participants' dietary intake over a period of 14 days using 24-hour diet recall interviews. Nutritional blood parameters were obtained from medical records. Food consumed by participants in the UK and China was analyzed using the Nutritics and Nutrition calculator to quantify nutritional intake. RESULTS: Energy and protein intake were comparable between UK and Chinese participants, but with both below the recommended daily intake. Potassium intake was higher in UK participants compared to Chinese participants (2,115 [888] versus 1,159 [861] mg/d; P < .001), as was calcium (618 [257] versus 360 [312] mg/d; P < .001) and phosphate intake (927 [485] versus 697 [434] mg/d; P = .007). Vitamin C intake was lower in UK participants compared to their Chinese counterparts (39 [51] versus 64 [42] mg/d; P = .024). Data are reported here as median (interquartile range). CONCLUSION: Both UK and Chinese hemodialysis participants have insufficient protein and energy in their diet. New strategies are required to increase protein and energy intakes. All participants had inadequate daily intake of vitamins C and D; there may well be a role in the oral supplementation of these vitamins, and further studies are urgently needed.

Feeling gutted in chronic kidney disease (CKD): Gastrointestinal disorders and therapies to improve gastrointestinal health in individuals CKD, including those undergoing dialysis.

Chronic kidney disease (CKD) affects 9.1% of the population worldwide. CKD may lead to structural and functional gastrointestinal alterations, including impairment in the intestinal barrier, digestion and absorption of nutrients, motility, and changes to the gut microbiome. These changes can lead to increased gastrointestinal symptoms in people with CKD, even in early grades of kidney dysfunction. Gastrointestinal symptoms have been associated with lower quality of life and reduced nutritional status. Therefore, there has been considerable interest in improving gastrointestinal health in this clinical population. Gastrointestinal health can be influenced by lifestyle and medications, particularly in advanced grades of kidney dysfunction. Therapies focused on gastrointestinal health have been studied, including the use of probiotics, prebiotics, and synbiotics, yielding limited and conflicting results. This review summarizes the alterations in the gastrointestinal tract structure and function and provides an overview of potential nutritional interventions that kidney disease professionals can provide to improve gastrointestinal health in individuals with CKD.

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.

Effect of Dietary Inulin Supplementation on the Gut Microbiota Composition and Derived Metabolites of Individuals Undergoing Hemodialysis: A Pilot Study.

OBJECTIVE: The prebiotic fiber inulin has been studied in individuals undergoing hemodialysis (HD) due to its ability to reduce gut microbiota-derived uremic toxins. However, studies examining the effects of inulin on the gut microbiota and derived metabolites are limited in these patients. We aimed to assess the impact of a 4-week supplementation of inulin on the gut microbiota composition and microbial metabolites of patients on HD. DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled, crossover study, twelve HD patients (55 ± 10 y, 50% male, 58% Black American, BMI 31.6 ± 8.9 kg/m2, 33% diabetes mellitus) were randomized to consume inulin [10 g/d for females; 15 g/d for males] or maltodextrin [6 g/d for females; 9 g/d for males] for 4 weeks, with a 4-week washout period. We assessed the fecal microbiota composition, fecal metabolites (short-chain fatty acids (SCFA), phenols, and indoles), and plasma indoxyl sulfate and p-cresyl sulfate. RESULTS: At baseline, factors that explained the gut microbiota variability included BMI category and type of phosphate binder prescribed. Inulin increased the relative abundance of the phylum Verrucomicrobia and its genus Akkermansia (P interaction = 0.045). Inulin and maltodextrin resulted in an increased relative abundance of the phylum Bacteroidetes and its genus Bacteroides (P time = 0.04 and 0.03, respectively). Both treatments increased the fecal acetate and propionate (P time = 0.032 and 0.027, respectively), and there was a trend toward increased fecal butyrate (P time = 0.06). Inulin did not reduce fecal p-cresol or indoles, or plasma concentrations of p-cresyl sulfate or indoxyl sulfate. CONCLUSIONS: A 4-week supplementation of inulin did not lead to major shifts in the fecal microbiota and gut microbiota-derived metabolites. This may be due to high variability among participants and an unexpected increase in fecal excretion of SCFA with maltodextrin. Larger studies are needed to determine the effects of prebiotic fibers on the gut microbiota and clinical outcomes to justify their use in patients on HD.

The International Society of Renal Nutrition and Metabolism Commentary on the National Kidney Foundation and Academy of Nutrition and Dietetics KDOQI Clinical Practice Guideline for Nutrition in Chronic Kidney Disease.

The Academy of Nutrition and Dietetics and the National Kidney Foundation collaborated to provide an update to the Clinical Practice Guidelines (CPG) for nutrition in chronic kidney disease (CKD). These guidelines provide a valuable update to many aspects of the nutrition care process. They include changes in the recommendations for nutrition screening and assessment, macronutrients, and targets for electrolytes and minerals. The International Society of Renal Nutrition and Metabolism assembled a special review panel of experts and evaluated these recommendations prior to public review. As one of the highlights of the CPG, the recommended dietary protein intake range for patients with diabetic kidney disease is 0.6-0.8 g/kg/day, whereas for CKD patients without diabetes it is 0.55-0.6 g/kg/day. The International Society of Renal Nutrition and Metabolism endorses the CPG with the suggestion that clinicians may consider a more streamlined target of 0.6-0.8 g/kg/day, regardless of CKD etiology, while striving to achieve intakes closer to 0.6 g/kg/day. For implementation of these guidelines, it will be important that all stakeholders work to detect kidney disease early to ensure effective primary and secondary prevention. Once identified, patients should be referred to registered dietitians or the region-specific equivalent, for individualized medical nutrition therapy to slow the progression of CKD. As we turn our attention to the new CPG, we as the renal nutrition community should come together to strengthen the evidence base by standardizing outcomes, increasing collaboration, and funding well-designed observational studies and randomized controlled trials with nutritional and dietary interventions in patients with CKD.

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.

A Renal Clinician's Guide to the Gut Microbiota.

It is increasingly recognized that the gut microbiota plays a role in the progression of chronic diseases and that diet may confer health benefits by altering the gut microbiota composition. This is of particular relevance for chronic kidney disease (CKD), as the gut is a source of uremic retention solutes, which accumulate as a result of impaired kidney function and can exert nephrotoxic and other harmful effects. Kidney dysfunction is also associated with changes in the composition of the gut microbiota and the gastrointestinal tract. Diet modulates the gut microbiota, and there is much interest in the use of prebiotics, probiotics, and synbiotics as dietary therapies in CKD, as well as dietary patterns that beneficially alter the microbiota. This review provides an overview of the gut microbiota and its measurement, its relevance in the context of CKD, and the current state of knowledge regarding dietary manipulation of the microbiota.

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.