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There is increasing evidence showing the health benefits of physical activity, such as better survival and possibly even a slower decline in kidney function, in people with chronic kidney disease (CKD). There is convincing evidence that exercise training improves physical function measured as aerobic capacity, muscle endurance strength and balance at all ages and all stages of CKD. In fact, long-term adherence to well-designed and adequately monitored exercise training programmes is high. In general, patients express interest in exercise training and are motivated to improve their physical function and health. A growing number of nephrologists regard physical activity and exercise training as beneficial to patients with CKD. However, many feel that they do not have the knowledge to prescribe exercise training and suppose that patients are not interested. Patients state that support from healthcare professionals is crucial to motivate them to participate in exercise training programmes and overcome medical, physical and psychological barriers such as frailty, fatigue, anxiety and fear. Equally important is the provision of funding by healthcare providers to ensure adequate prescription and follow-up by trained exercise physiologists for this important non-pharmacological treatment.

Background Trimethylamine N-oxide (TMAO), a metabolite from red meat and fish consumption, plays a role in promoting cardiovascular events. However, data regarding TMAO and its impact on clinical outcomes are inconclusive, possibly due to its undetermined dietary source. Objective We hypothesized circulating TMAO derived from fish intake might cause less harm compared to red meat source by examining the concomitant level of 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), a known biomarker of fish intake, and investigated the association between TMAO, CMPF and outcomes. Design Patients were recruited from the European QUALity study on treatment in advanced CKD (EQUAL) among individuals ≥65 years whose eGFR had dropped for the first time to ≤20mL/min/1.73m2 during last 6 months. The association between TMAO, CMPF and outcomes including all-cause mortality and kidney replacement therapy (KRT) was assessed among 737 patients. Patients were further stratified by median cut-offs of TMAO and CMPF, suggesting high/low red meat and fish intake. Results During a median of 39 months’ follow-up, 232 patients died. Higher TMAO was independently associated with an increased risk of all-cause mortality (multivariable-hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.17, 1.83). Higher CMPF was associated with a reduced risk of both all-cause mortality (HR 0.79, 95%CI 0.71, 0.89) and KRT (HR 0.80, 95%CI 0.71, 0.90), independent of TMAO and other clinically relevant confounders. In comparison to patients with low TMAO and CMPF, patients with low TMAO and high CMPF had reduced risk of all-cause mortality (adjusted HR 0.49, 95% CI 0.31, 0.73), whereas those with high TMAO and high CMPF showed no association across adjusted models. Conclusions High CMPF conferred an independent role in health benefits and might even counteract the unfavorable association between TMAO and outcomes. Whether higher circulating CMPF are due to fish consumption, and/or CMPF is a protective factor remains to be verified.

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Background Patients with stage 4/5 chronic kidney disease (CKD) suffer from various symptoms. The retention of uremic solutes is thought to be associated with those symptoms. However, there are relatively few rigorous studies on the potential links between uremic toxins and symptoms in patients with CKD. Methods The EQUAL study is an ongoing observational cohort study of non-dialyzed patients with stage 4/5 CKD. EQUAL patients from Germany, Poland, Sweden, and the United Kingdom were included in the present study (n = 795). Data and symptoms self-report questionnaires were collected between April 2012 and September 2020. Baseline uric acid and parathyroid hormone and ten uremic toxins were quantified. We tested the association between uremic toxins and symptoms, and adjusted p-values for multiple testing. Results Symptoms were more frequent in women than in men with stage 4/5 CKD, while levels of various uremic toxins were higher in men. Only trimethylamine-N-oxide (positive association with fatigue), p-cresylsulfate with constipation, and 3 carboxy-4-methyl-5-propyl-2-furanpropionic acid (negative association with shortness of breath) demonstrated moderately strong associations with symptoms in adjusted analysis. The association of phenylacetylglutamine with shortness of breath was consistent in both sexes, although only reached statistical significance in the full population. By contrast, trimethylamine-N-oxide (fatigue) and p-cresyl sulfate and phenylacetylglutamine (constipation) were only associated with symptoms in men, who presented higher serum levels than women. Conclusion Only a limited number of toxins were associated with symptoms in persons with stage 4/5 CKD. Other uremic toxins, uremia related factors or psychosocial factors not yet explored might contribute to symptom burden.

Patients with chronic kidney disease (CKD) on hemodialysis (HD) experience treatment-related immobility and physical deconditioning, which is responsible for an increased risk of frailty and a high burden of multi-morbidity. Exercise has been shown to counteract this vicious cycle; however, its effectiveness has only been investigated in small cohorts. Therefore, the objective of the Dialysis Training Therapy (DiaTT) trial will be to assess the effects of a 12-month intradialytic exercise program on physical functioning, frailty and health economics in a large cohort of HD patients in a real-world setting. DiaTT will be a prospective, cluster-randomized (1:1), controlled, multi-center, interventional clinical trial across 28 dialysis units, aiming at the recruitment of >1100 CKD patients on HD. The intervention group will receive 12 months’ intradialytic exercise (combined aerobic and resistance training), whereas the usual care group will not receive intervention. The primary endpoint will be a change on the sit-to-stand test (STS60) result between baseline and 12 months. Secondary endpoints will include physical functioning, frailty, quality of life, 3-point MACE, hospitalizations, survival, quality of HD, health literacy and health care costs. By including almost as many patients as previously investigated in smaller trials, DiaTT will be the largest randomized, controlled trial assessing frailty, quality of life and mortality in the field of nephrology.

Introduction and Aims: Various programs of physical exercise have been shown to improve outcomes in hemodialysis (HD) patients. Increasing age and comorbidity, however, are perceived to limit options for therapeutic exercise on HD. An individually structured physical exercise program (SPEP), broadly applicable also for frail and elderly patients, was introduced in five units of a large non-profit provider. We compared outcomes in SPEP patients with propensity-score (PS) matched controls. Methods: Patients ( pts) were offered a supervised SPEP consisting of 30 mins. each of strength-and endurance training twice weekly. Data were collected prospectively from the electronic health records through a quality registry. Controls were selected based on a PS including age, sex, vascular access, albumin and 16 other variables. Outcomes assessed were survival and hospitalization rate. Results: 98 pts participated in the SPEP and were matched with 490 controls (mean age: 68.6 yrs (IQR 58-78), mean vintage 56.4 mo (SD 55.0), 45.4% female, 51.4% diabetic, 33.7% with PVD). 17.9% were > 80 years old, 10.5% had a baseline albumin of < 35g/l, 45.7% had > 4 co-morbidities, 78.4% had permanent contra-indications to transplantation. After one year of training, important outcome-associated parameters improved in SPEP pts. but not in controls. Hemoglobin increased 1.3 % (0.15 g/dl, p = n.s.), and serum anorganic phosphate decreased 1.8 % (0.03 mmol/l, p = 0.04). Survival at one year was higher in SPEP-pts than in controls ( p=n.s.), and hospitalizations were lower ( p=0.03). Conclusions: These results confirmed that improving strength and endurance by exercise while dialyzing was not only associated with improved surrogate markers but decreased hospitalizations and, possibly, mortality. Individualized training was feasible also in elderly and frail HD patients. This will likely translate into improved patients' well-being, care perception, and fall prevention. This SPEP, therefore, should be considered as a non-pharmaceutical and patient-centered routine part of hemodialysis treatment.

Background Patients with chronic kidney disease (CKD) are at a higher risk of major adverse cardiovascular events (MACE) compared to the general population, but gender differences in this risk, especially in older adults, are not fully known. We aim to identify gender differences in the risk of MACE in older European CKD patients, and explore factors which may explain these differences. Methods The European Quality study (EQUAL) is a prospective study on stage 4–5 CKD patients, ≥65 years old, not on dialysis, from Germany, Italy, the Netherlands, Poland, Sweden, and the UK. Cox regression and cumulative incidence competing risk curves were used to identify gender differences in MACE risks. Mediation analysis was used to identify variables which may explain risk differences between men and women. Results 417 men out of 1 134 (37%) and 185 women out of 602 women (31%) experienced at least one MACE, over a follow-up period of 5 years. Women had an 18% lower risk of first MACE compared to men (HR: 0.82; 95% CI: 0.69–0.97; p = 0.02), which was attenuated after adjusting for pre-existing cardiometabolic comorbidities and cardiovascular risk factors. There were no significant gender differences in the risk of recurrent MACE or fatal MACE. The risk difference in MACE by gender was larger in patients aged 65–75, compared to patients over 75. Conclusions In a cohort of older adults with advanced CKD, women had lower risks of MACE. These risk differences were partially explained by pre-existing cardiometabolic comorbidities and cardiovascular risk factors.