How to cultivate sustainable physical health and wellness in transplant recipients: the emerging and enduring role of exercise scientists.

PURPOSE OF REVIEW: The aim of the current review is to highlight the importance of exercise training as an important section of transplant recipient rehabilitation process and explain the role of the exercise scientist in the development, implementation, and assessment of the exercise regime. RECENT FINDINGS: Transplant patients face a unique set of challenges in their recovery and rehabilitation process, often requiring a multifaceted approach to address the physical, emotional, and psychological aspects of their condition. Exercise training has emerged as a crucial component in the care of these patients, providing a means to improve functional capacity, enhance quality of life, and mitigate the adverse effects of transplant-related complications. Exercise scientists who are trained to assess patient's physical limitations, develop and deliver personalized exercise programs, and monitor their progress are uniquely positioned to play a crucial role in the treatment of patients with chronic conditions that require exercise training as a mean of improving and maintaining health and quality of life. SUMMARY: Exercise scientists are the appropriate professionals for providing transplant recipients with the recommended exercise training for maintaining and improving their health status as part of the overall plan of long-term care and support.

Exploring the impact of short daily haemodialysis on muscle strength and bone health in end-stage kidney disease patients.

BACKGROUND: Short-daily haemodialysis (SDH) has been strongly recommended over conventional haemodialysis (CHD) for end-stage kidney disease patients, though few studies have directly compared the effects of these two haemodialysis (HD) modalities on clinical variables related to patient's health. METHODS: We conducted a cross-sectional study in individuals undergoing HD, comparing epidemiological, clinical, metabolic, inflammatory, anthropometric, bone health/metabolism, and skeletal muscle function according to dialysis modality. One-hundred seventy-eight patients (20.8% females, 62 ± 2.5 years old), were analysed in this study, 86 (48%) of whom were undergoing CHD versus 92 (51%) who were undergoing SDH. RESULTS: SDH patients had significantly higher serum albumin levels (3.93 vs. 3.66 g/dL, P < 0.0001) and higher Kt/v (2.6 vs. 2.38, P < 0.0001). SDH group presented a significantly lower number of erythropoietin-stimulating agents compared with CHD group (percentage: 53.3 vs. 83.7%, P < 0.0001) and had lower levels of serum phosphate (4.9 vs. 5.3 mg/dL, P = 0.004) and parathyroid hormone (PTH) (398.4 vs. 480.4 pg/mL, P < 0.001) compared with CHD patients. In terms of bone health and metabolism, SDH patients had significantly higher total BMD, femur BMD, lumbar BMD, and femoral neck BMD compared with CHD patients (all P < 0.05). SDH patients also had lower anti-osteogenic and inflammatory biomarkers, including FGF23, sclerostin, TNF, IL-18, IL-17a, and C-reactive peptide (all P < 0.05). CHD modality was demonstrated to be a risk factor for low BMD (odds ratio: 4.02; 95% CI: 1.59-10.2, P = 0.003). In terms of skeletal muscle function, SDH patients had significantly higher 6-minute walking test (444.6 vs. 424.9 m, P = 0.04) and higher fat-free mass (52.3 vs. 51.68 kg, P = 0.02) compared with CHD patients. Higher fat-free mass and handgrip strength were associated with a 34% and 23% lower risk of low BMD, respectively. SDH patients had lower levels of the uremic toxin asymmetric dimethyl-l-arginine (ADMA) (1.8 vs. 2.07 µM, P = 0.002) and fasting blood glucose (132.6 vs. 141.7 mg/dL, P < 0.02) than CHD group. SDH patients also displayed higher levels of haemoglobin when compared with CHD group (11.9 vs. 10.2 g/dL, P < 0.0001). CONCLUSIONS: The present study improves our understanding of the relationship between dialysis modality and clinical variables that may influence HD patient's health. Grip strength and lean mass were positively correlated with bone mineral density in HD patients regardless of dialysis modality. SDH was associated with better bone mineral density, inflammatory profile, and skeletal muscle function when compared with CHD patients. These findings provide more evidence of the clinical benefits of SDH that should be explored in greater detail.

The effect of intradialytic exercise on calcium, phosphorus and parathyroid hormone: a randomized controlled trial.

BACKGROUND: Patients with kidney failure experience derangements of circulating markers of mineral metabolism and dysregulation of skeletal and cardiovascular physiology which results in high mortality rate in these patients. This study aimed to evaluate the effect of intradialytic exercise on regulation of these abnormalities in patients receiving chronic hemodialysis (HD). METHODS: In this randomized controlled trial conducted in an HD center in Iran, adult patients receiving chronic HD were randomized to intradialytic exercise (60 min) in the second hour of thrice weekly dialysis for 6 months (intervention) or no intradialytic exercise (control). The primary outcomes were serum calcium, serum phosphorous and parathyroid hormone levels. Secondary outcomes were serum alkaline phosphatase and calcium-phosphorous product. RESULTS: The study included 44 participants randomized to intervention (n = 22) or control (n = 22). During the 6-month intervention period, significant between-group changes were observed in all primary and secondary outcomes between the intervention and control groups. Statistical analyses reveal a significant increase in serum calcium (P < 0.05) as well as a significant decrease in serum phosphorous, parathyroid hormone, alkaline phosphatase and calcium-phosphorous product (P < 0.05). CONCLUSION: Intradialytic exercise performed for at least 60 min during thrice weekly dialysis sessions improves bone mineral metabolism in adult patients receiving HD. Further studies should focus on observing and comparing the effect of different types of exercise on bone mineral disorders and all-cause mortality in HD patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04916743, Registered on 08/06/2021. Registered trial name: The Effect of Intradialytic Exercise on Calcium, Phosphorous and Parathyroid Hormone: A Randomized Controlled Trial.

Exercise Rehabilitation for People With End-Stage Kidney Disease: Who Will Fill the Gaps?

Exercise rehabilitation is a well established therapy for reducing morbidity and mortality and improving quality of life and function across chronic conditions. People with dialysis-dependent kidney failure have a high burden of comorbidity and symptoms, commonly characterised as fatigue, dyspnoea, and the inability to complete daily activities. Despite more than 30 years of exercise research in people with kidney disease and its established benefit in other chronic diseases, exercise programs are rare in kidney care and are not incorporated into routine management at any stage. In this review, we describe the mechanisms contributing to exercise intolerance in those with end-stage kidney disease and outline the role of exercise rehabilitation in addressing the major challenges to kidney care: cardiovascular disease, symptom burden, and physical frailty. We also draw on existing models of exercise rehabilitation from other chronic conditions to inform the way forward and challenge the status quo of exercise rehabilitation in both practice and research.

Muscle Sodium Accumulation in Kidney Failure: Physiological Impact and Mitigation Strategies.

Skeletal muscle has recently been recognized as a nonosmotic sodium reservoir that buffers dietary sodium. The in-vivo quantification of muscle sodium is based on a novel technology, sodium magnetic resonance imaging. Studies using this technology have shown that muscle sodium accumulation may be a clinical complication of chronic kidney disease (CKD). This review aims to summarize existing evidence on muscle sodium accumulation in patients with CKD and to identify knowledge gaps and topics for further research. The literature examined in this review suggests that muscle sodium accumulation is associated with CKD progression and pathological conditions. However, the causalities between muscle sodium accumulation and its related pathological changes are still elusive mainly because it is still uncertain where and how sodium accumulates in the muscle. More research is needed to address these gaps and determine if muscle sodium is a new intervention target in CKD.

Advanced Glycation End Products and Inflammatory Cytokine Profiles in Maintenance Hemodialysis Patients After the Ingestion of a Protein-Dense Meal.

OBJECTIVE: The goal of this investigation was to evaluate circulating and skeletal muscle inflammatory biomarkers between maintenance hemodialysis (MHD) and demographic-matched control subjects (CON) before and after ingestion of a protein-rich meal. DESIGN AND METHODS: CON (n = 8; 50 ± 2 years; 31 ± 1 kg/m2) and MHD patients (n = 8; 56 ± 5 years; 32 ± 2 kg/m2) underwent a basal blood draw and muscle biopsy and serial blood draws after the ingestion of a mixed meal on a nondialysis day. Plasma advanced glycation end products (AGEs) and markers of oxidation were assessed via liquid chromatography-tandem mass spectrometry before and after the meal (+240 min). Circulating inflammatory cytokines and soluble receptors for AGE (sRAGE) isoforms (endogenous secretory RAGEs and cleaved RAGEs) were determined before and after the meal (+240 min). Basal muscle was probed for inflammatory cytokines and protein expression of related signaling components (RAGE, Toll-like receptor 4, oligosaccharyltransferase subunit 48, TIR-domain-containing adapter-inducing interferon-ß, total IκBα, and pIκBα). RESULTS: Basal circulating AGEs were 7- to 343-fold higher (P < .001) in MHD than those in CON, but only MG-H1 increased in CON after the meal (P < .001). There was a group effect (MHD > CON) for total sRAGEs (P = .02) and endogenous secretory RAGEs (P < .001) and a trend for cleaved RAGEs (P=.09), with no meal effect. In addition, there was a group effect (MHD < CON; P < .05) for circulating fractalkine, interleukin (IL)10, IL17A, and IL1ß and a trend (P < .10) for IL6 and macrophage inflammatory protein 1 alpha, whereas tumor necrosis factor alpha was higher in MHD (P < .001). In muscle, Toll-like receptor 4 (P = .03), TIR-domain-containing adapter-inducing interferon-ß (P = .002), and oligosaccharyltransferase subunit 48 (P = .02) expression was lower in MHD than that in CON, whereas IL6 was higher (P = .01) and IL8 (P = .08) tended to be higher in MHD. CONCLUSION: Overall, MHD exhibited an exaggerated, circulating, and skeletal muscle inflammatory biomarker environment, and the meal did not appreciably affect the inflammatory status.

How is exercise being prescribed for patients on hemodialysis? A scoping review.

BACKGROUND: Exercise is important for patients on hemodialysis, but details and descriptions on how it is prescribed are lacking. We reviewed the existing literature and described how exercise is being prescribed for patients on hemodialysis. METHODS: A scoping review according to the JBI and PRISMA-ScR guidelines was conducted. MEDLINE, EMBASE and other databases were searched from inception until December 2021. Websites, books, and guidelines were also searched. We included evidence from patients on hemodialysis, describing exercise protocols, in all settings and designs. RESULTS: Two hundred and eighty-five studies were included, yielding 327 exercise protocols. Aerobic (38.8%) and strength (21.4%) were the most prescribed exercise types. Exercise was mainly prescribed during dialysis (71.0%) and delivered within the first half of the session (94.6%). Although 33.3% of the exercise protocols did not report whether there was supervision or not, those that did were mostly delivered by physiotherapists (20.5%) and exercise physiologists (17.4%). The most followed exercise training principles were type (99.0%) and frequency (93.2%), whereas progression was adopted in 40.7% protocols. The most prescribed frequency and duration were three times/week (79.9%) and 30-60-min (69.2%) sessions, respectively. Exercise intensity was predominantly prescribed in moderate cut-offs (72.3%), mostly assessed by subjective methods (47.5%). CONCLUSIONS: Aerobic and strength were the most prescribed exercise types, mainly during dialysis. Interventions were mostly supervised by physiotherapists and exercise physiologists. Future exercise protocols for patients on hemodialysis should adopt recommended exercise principles, especially with systematic progression.

Subjective Thirst in Relation to Interdialytic Weight Gain: A Systematic Review of Observational Studies.

INTRODUCTION: Hemodialysis (HD) patients are often prescribed salt and fluid-restricted diets to reduce their interdialytic weight gain (IDWG) and prevent chronic volume overload and hypertension. However, adherence to fluid restrictions is poor, which may be due to HD patients' excessive thirst. The purpose of the review is to explore the association between HD patients' subjective thirst and IDWG, which may inform strategies to manage chronic volume overload. METHODS: We conducted the literature search in Web of Science, Cumulative Index to Nursing and Allied Health Literature, PubMed, and the Cochrane Library, until February 25, 2019. Studies performing statistical tests to assess the association between patients' subjective thirst and IDWG were included. RESULTS: A total of eighteen studies were included in the systematic review, which measured the relationship between patients' subjective thirst and IDWG. Among them, 14 studies found that different domains of thirst and different units of IDWG are positively associated. Therefore, there is a positive association between the patients' subjective thirst and IDWG. However, the findings should be interpreted cautiously as there was variability in thirst and IDWG measurement techniques, which might influence the estimated relationship in these studies. DISCUSSION/CONCLUSION: These data suggest that strategies are needed to reduce thirst to control IDWG in HD patients.

Home-delivered meals as an adjuvant to improve volume overload and clinical outcomes in hemodialysis.

Patients on chronic hemodialysis are counseled to reduce dietary sodium intake to limit their thirst and consequent interdialytic weight gain (IDWG), chronic volume overload and hypertension. Low-sodium dietary trials in hemodialysis are sparse and mostly indicate that dietary education and behavioral counseling are ineffective in reducing sodium intake and IDWG. Additional nutritional restrictions and numerous barriers further complicate dietary adherence. A low-sodium diet may also reduce tissue sodium, which is positively associated with hypertension and left ventricular hypertrophy. A potential alternative or complementary approach to dietary counseling is home delivery of low-sodium meals. Low-sodium meal delivery has demonstrated benefits in patients with hypertension and congestive heart failure but has not been explored or implemented in patients undergoing hemodialysis. The objective of this review is to summarize current strategies to improve volume overload and provide a rationale for low-sodium meal delivery as a novel method to reduce volume-dependent hypertension and tissue sodium accumulation while improving quality of life and other clinical outcomes in patients undergoing hemodialysis.

Exercise in Dialysis: Ready for Prime Time?

It is widely acknowledged that patients with end-stage kidney disease receiving maintenance hemodialysis (HD) may benefit from increasing their physical activity levels. Decades of exercise-related clinical trials have demonstrated improvements in various metrics related to dialysis patient's health and quality of life. Yet, the implementation of exercise programs in dialysis clinics today is scarce, and physical inactivity and dysfunction remain a hallmark of the disease. To address this issue, many groups worldwide are beginning to rethink how physical activity and exercise are prescribed in HD patients, as well as how to evaluate the efficacy of these programs. The vast majority of exercise interventions in HD patients have included intradialytic cycling as the predominant or only exercise prescription. Moreover, efficacy has most often been evaluated using standard measures of strength, physical function, and/or traditional cardiovascular disease risk factors (e.g., blood pressure, lipids, etc.). More recently, there has been a greater emphasis on novel intervention approaches that are focused on providing patients with a greater variety of options for exercise and enhanced motivational tools. The benefits of exercise on patient reported outcome measures (PROMs) and other clinically important outcomes are also becoming more prevalent. The purpose of this review was to: (1) critically review the data from several recently published large randomized clinical trials of exercise in HD patients, (2) discuss some of the novel approaches that groups across the world are taking to improve implementation and efficacy of exercise-related interventions in HD, and (3) discuss policy prescriptions that may be needed to continue improving exercise prescriptions for this critically ill patient population. While it may be too early to declare that exercise in dialysis is ready for prime time, exciting advances have been made in recent years, yet more work is needed to realize its full potential.

Effect of Intradialytic Oral Nutritional Supplementation with or without Exercise Improves Muscle Mass Quality and Physical Function in Hemodialysis Patients: A Pilot Study.

BACKGROUND: Oral nutritional supplementation (ONS) with or without exercise (EX) could improve muscle mass (MM) in chronic kidney disease. METHODS: Patients were randomized into two groups: (1) ONS and (2) ONS + EX. Thigh muscle area (cm2) and intramuscular lipid content via attenuation were evaluated at baseline and 6 months with computed tomography (CT) to measure MM quantity and quality. Physical function was measured by six-minute walk test (6 MWT), gait speed, handgrip strength (HGS), and Time Up and Go test (TUG) at baseline and 3 and 6 months. RESULTS: The ONS group (n= 14) showed statistically significant improvement in gait speed and HGS; ONS + EX group (n = 10) showed differences in gait speed, in 6 MWT, and HGS. In the ANOVA (3 times × 2 groups), no differences were observed between groups. Greater effect sizes in favor to ONS + EX group were observed in the 6 MWT (d = 1.02) and TUG test (d = 0.63). Muscle quality at six months revealed a significant trend in favor of the EX-group (p = 0.054). CONCLUSIONS: Both groups had improved physical function, and greater effect sizes were seen in the ONS + EX group for the 6 MWT and TUG test. Neither MM quantity or quality was improved in either group.

Conceptual Framework for Patient-Reported Outcome Measures in Clinical Trials of Skeletal Muscle Cramping Experienced in Dialysis: A Kidney Health Initiative Workgroup Report.

Skeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for innovative assessments or treatments. Research to prevent or treat skeletal muscle cramping in patients receiving dialysis is hindered by poorly understood pathophysiology, lack of an accepted definition, and the absence of a standardized measurement method. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a multidisciplinary workgroup to define a set of patient-reported outcome measures for use in clinical trials to test the effect of new dialysis devices, new KRTs, lifestyle/behavioral modifications, and medications on skeletal muscle cramping. Upon determining that foundational work was necessary, the workgroup undertook a multistep process to elicit concepts central to developing the basis for demonstrating content validity of candidate patient-reported outcome measures for skeletal muscle cramping in patients on dialysis. The workgroup sought to (1) create an accepted, patient-endorsed definition for skeletal muscle cramping that applies to all dialysis modalities, (2) construct a conceptual model for developing and evaluating a skeletal muscle cramping-specific patient-reported outcome measure, and (3) identify potential questions from existing patient-reported outcome measures that could be modified or adapted and subsequently tested in the dialysis population. We report the results of the workgroup's efforts, provide our recommendations, and issue a call to action to address the gaps in knowledge and research needs we identified. These action steps are urgently needed to quantify skeletal muscle cramping burden, assess the effect, and measure meaningful changes of new interventions to improve the experience of patients receiving dialysis and suffering from skeletal muscle cramping.

Global Policy Barriers and Enablers to Exercise and Physical Activity in Kidney Care.

OBJECTIVE: Impairment in physical function and physical performance leads to decreased independence and health-related quality of life in people living with chronic kidney disease and end-stage kidney disease. Physical activity and exercise in kidney care are not priorities in policy development. We aimed to identify global policy-related enablers, barriers, and strategies to increase exercise participation and physical activity behavior for people living with kidney disease. DESIGN AND METHODS: Guided by the Behavior Change Wheel theoretical framework, 50 global renal exercise experts developed policy barriers and enablers to exercise program implementation and physical activity promotion in kidney care. The consensus process consisted of developing themes from renal experts from North America, South America, Continental Europe, United Kingdom, Asia, and Oceania. Strategies to address enablers and barriers were identified by the group, and consensus was achieved. RESULTS: We found that policies addressing funding, service provision, legislation, regulations, guidelines, the environment, communication, and marketing are required to support people with kidney disease to be physically active, participate in exercise, and improve health-related quality of life. We provide a global perspective and highlight Japanese, Canadian, and other regional examples where policies have been developed to increase renal physical activity and rehabilitation. We present recommendations targeting multiple stakeholders including nephrologists, nurses, allied health clinicians, organizations providing renal care and education, and renal program funders. CONCLUSIONS: We strongly recommend the nephrology community and people living with kidney disease take action to change policy now, rather than idly waiting for indisputable clinical trial evidence that increasing physical activity, strength, fitness, and function improves the lives of people living with kidney disease.

Depressive Disorders Are Associated With Risk of Falls in People With Chronic Kidney Disease.

OBJECTIVES: People with chronic kidney disease (CKD) are at increased risk for falls and fall-related injuries. Depressive disorders (DEP) are common in individuals with CKD and may increase the risk of falls and fall-related injuries. However, not much is known about the relationship between DEP and falls in people with CKD. The purpose of this study was to determine the influence of DEP on the relationship between CKD, falls, and fall-related injuries. METHOD: Using the Behavioral Risk Factor Surveillance System, we identified 16,574 adults with CKD. Patients with CKD were stratified by history of self-reported DEP (SRDEP), and multivariate logistic regression was conducted to determine the odds for falls and fall-related injuries among those with and without SRDEP. RESULTS: In unadjusted regression analysis, falls (OR = 2.40, 95% CI = 2.08-2.76) and fall-related injuries (OR = 2.12, 95% CI = 1.72-2.59) were higher in individuals with CKD and history of SRDEP compared to those with CKD and no history of SRDEP. Adjustment for confounders had little effect on the relationship between a history of SRDEP and either falls (AOR = 1.87, 95% CI = 1.60-2.19) or fall-related injuries (AOR = 1.58, 95% CI = 1.26-1.97). CONCLUSIONS: People with CKD and DEP are at increased odds for falls and fall-related injuries even after adjustment for sociodemographic, lifestyle factors, and comorbidities. Prospective studies are warranted to further understand this relationship, but it may be prudent for clinicians, in particular nurses, to consider fall risk when treating DEP in patients with 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.

Physical Activity and Health in Chronic Kidney Disease.

Clinical Background and Epidemiology: Low physical activity is a common phenotype in individuals living with chronic kidney disease (CKD). It increases as renal function declines and is associated with adverse clinical outcomes and a poor quality of life (QOL). Both behavioral and disease-related factors contribute to the low physical activity levels in CKD. CKD has profound negative effects on skeletal muscle structure and function that are related to impairments in mitochondrial function, inflammation, oxidative stress, metabolic acidosis, and other uremia-related factors. These factors promote muscle protein catabolism and wasting, and impair strength, physical performance, and cardiorespiratory fitness. Moreover, the high burden of comorbid disease contributes to patient fatigue, fear of injury, and poor exercise self-efficacy. All of these factors reinforce patient's sedentary behavior, leading to a vicious cycle of disease and disability that further compromises their health and QOL. Data from both observational studies and exercise interventions indicate that increasing levels of physical activity may provide a range of benefits in CKD patients, including attenuating declines in renal function, and improving markers of physical function, cardiovascular disease risk, and QOL. Unfortunately, these results have not led to widespread implementation of exercise programs in CKD, and physical inactivity and poor physical function remain hallmarks of the disease worldwide. Challenges and Solutions: There are many frequently cited barriers to implementing exercise programs in CKD. These include: a lack of training and knowledge about physical activity/exercise prescriptions and interventions among health professionals; inadequate time to implement exercise programs due to other clinical responsibilities; a lack of specific funding and incentives to develop these programs; and a poor quality of the data demonstrating efficacy of exercise. Many CKD patients also are unmotivated to incorporate exercise into their daily lives due to time constraints, depression, and other comorbid diseases, and poor self-efficacy for exercise. Given these barriers, it is not surprising that physical activity/exercise programs have not become a component of standard of care for CKD patients. We discuss several potential solutions to address these barriers, including: (1) providing better education and training for healthcare professionals who provide exercise advise and counselling to individuals with CKD; (2) providing incentives to reimburse payers to develop and maintain exercise programs in CKD; and (3) providing more personalized approaches to exercise prescription and implementation of exercise programs that consider the unique circumstances of individual CKD patients. In summary, low physical activity levels in CKD patients result from a combination of many factors that adversely impact patient's health and QOL. Addressing this problem will require comprehensive intervention strategies that consider both the unique pathophysiology of CKD and the individual circumstances of those living with the disease.

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.

Association between physical activity and mortality in end-stage kidney disease: a systematic review of observational studies.

BACKGROUND: End-stage Kidney Disease patients have a high mortality and hospitalization risk. The association of these outcomes with physical activity is described in the general population and in other chronic diseases. However, few studies examining this association have been completed in end-stage Kidney Disease patients, raising the need to systematically review the evidence on the association of physical activity with mortality and hospitalization in this population. METHODS: Electronic databases (EBSCO, Scopus and Web of Science) and hand search were performed until March 2020 for observational studies reporting the association of physical activity with mortality or hospitalization in adult end-stage Kidney Disease patients on renal replacement therapy (hemodialysis, peritoneal dialysis and kidney transplant). Methodological quality of the included studies was assessed using the Quality in Prognosis Studies tool. The review protocol was registered in PROSPERO (CRD42020155591). RESULTS: Eleven studies were included: six in hemodialysis, three in kidney transplant, and two in hemodialysis and peritoneal dialysis patients. Physical activity was self-reported, except in one study that used accelerometers. All-cause mortality was addressed in all studies and cardiovascular mortality in three studies. Nine studies reported a significant reduction in all-cause mortality with increased levels of physical activity. Evidence of a dose-response relationship was found. For cardiovascular mortality, a significant reduction was observed in two of the three studies. Only one study investigated the association of physical activity with hospitalization. CONCLUSIONS: Higher physical activity was associated with reduced mortality in end-stage Kidney Disease patients. Future studies using objective physical activity measures could strengthen these findings. The association of physical activity with hospitalization should be explored in future investigations.