Circulating markers of ageing and allostatic load: a slow train coming

Dealing with the growing burden of age-related morbidities is one of the greatest challenges facing modern society. How we age across the lifecourse and how psychosocial and lifestyle factors interplay with the biology of ageing remains to be fully elucidated. Sensitive and specific biomarkers with which to interrogate the biology of the ageing process are sparse. Recent evidence suggests that non-coding RNAs are key determinants of such processes and that these can be used as potential circulatory bio-markers of ageing. They may also provide a mechanism which mediates the spread of allostatic load across the body over time, ultimately reflecting the immunological health and physiological status of tissues and organs. The interplay between exosomal microRNAs and ageing processes is still relatively unexplored, although circulating microRNAs have been linked to the regulation of a range of physiological and pathological processes and offer insight into mechanistic determinants of healthspan

Fabry disease: a new model of premature aging?

No abstract available

Intradialytic Aerobic Exercise in the United Arab Emirates: a Descriptive Study

Aim: Intradialytic exercise (IDE) improves hyperphosphatemia management in hemodialysis (HD) patient in addition to other clinical outcomes. The aim of the study is to present the strategies needed to integrate such a protocol in an HD unit in UAE and patients’ baseline characteristics.Methods: The largest HD unit in Sharjah emirate was chosen. All eligible patients (n=57) in the unit were included. Patients were stable adults HD patients who served as their own controls. The intervention included an aerobic low intensity IDE of 45 minutes per HD session, tailored to each patient’s fitness scale (BORG scale) for 6 months. Patients were educated on the importance of exercise. Outcome measures were barriers to exercise, serum phosphorus (P), urea reduction ratio (URR), malnutrition inflammation score, quality of life (QOL using euroqol5) collected at baseline and post intervention.Results: A total of 41 patients completed the study, 61% were males; 90.2%, 53.7% and 14.6% suffered from hypertension, diabetes and cardiovascular disease respectively. Hypherphosphatemia was prevalent among 75% of the patients with a mean of 5.76 ± 1.66 mg/dl. Mean age was 48 ± 14.37 years, BMI 24.98 ± 6.09 kg/m2, URR 71.88 ± 8.52%, and Kt/v 1.32 ± 1.09. The main barrier to exercise was identified to be fatigue on HD days by 58.5% of patients, followed by fear of getting hurt (36.6%). Finally, 80.4% of patients were mildly malnourished and QOL scale was 65.02% ± 18.54. Conclusion: Our study highlighted the widespread of hyperphosphatemia and malnutrition in our sample. The IDE regimen, if proven effective in future studies, could be integrated in the routine practice and may improve patients’ outcomes. 

Attitudes and Barriers to Physical Activity in Hemodialysis Patients: Could Intradialytic Exercise Modify These Factors?

Introduction: This study pioneers in determining the impact of Intradialytic Exercise (IDE) on attitudes and barriers to Physical Activity (PA) in Hemodialysis (HD) patients in the United Arab Emirates, a non-western country with different cultural backgrounds. Subjects and Methods: Forty-one adult HD patients from Al-Qassimi Hospital were recruited for a quasi-experimental intervention with pre-post evaluation. IDE patients trained for 45 minutes per HD session, 2-3 times per week, for 6 months on a static bicycle. Exercise intensity was assessed using the Borg Scale. Participants were educated on the importance of exercise. Results: 30 patients completed the study. The percentage of patients exercising was higher post intervention, but dropped to baseline at the follow up period. At post intervention and follow-up, patient’s knowledge about the benefits and safety of exercise increased, with some patients facing no barrier to PA at the end of the study (p=0.05). There was a significant increase in patients endorsing the “too many medical problems” barrier, and a significant decrease in patients endorsing the “can’t afford to exercise” barrier. Nephrologists and nurses acknowledge the importance of exercise in HD patients, but the former do not prescribe it. Conclusions: Aerobic IDE and knowledge empowerment programs could help HD patients increase their knowledge about exercise benefits and safety and shed some barriers to exercise, although patients appear to easily fall back into their normal habits. Even after an IDE program was adopted in the unit, the medical team is still concerned about the risks of exercise in HD patients

Effects of intradialytic aerobic exercise on hemodialysis patients: a systematic review and meta-analysis

© 2019, The Author(s). Objective: Intradialytic exercise (IDE) is not yet a routine practice for hemodialysis patients, the lack of guidelines supporting it being a major reason. This systematic review and meta-analysis of aerobic IDE interventions examined the efficacy of IDE regarding quality of life (QOL), serum phosphorus, dialysis efficiency, inflammatory status, vitamin D3, parathyroid hormone, intake of phosphate binders, mortality and hospitalization rate. Methods: Pubmed, Medline (Ovid), Embase (Ovid), Cochrane, and Cinahl (EBSCO) databases were searched to retrieve studies up to June 12, 2018. A manual reference search was also performed. Studies were included if they evaluated (a) aerobic IDE effect on at least one of our study parameters, (b) adult hemodialysis patients, (c) patients for \u3e 1 month. Results: Twenty-two studies were retrieved (706 participants), of which 12 were eligible for meta-analysis. Aerobic IDE had a significant positive effect on the QOL physical component score (QOL-PSC) and on mental component score (QOL-MCS) of SF36, but not on serum phosphorus or Kt/V. Conclusions: IDE incorporation into clinical practice has a significant positive effect on QOL-PSC and QOL-MCS. In the reviewed studies, IDE did not result in any health hazard in hemodialysis patients. Nevertheless, future research should assess the long-term effectiveness and safety of IDE. The limitations of this review include the lack of quality analysis of the studies, the limited number of studies that could be included in the meta-analysis, the diversity in the exercise intensity, duration and modality, and the limited data for several outcomes. Prospero registration ID: CRD42016052062

Effect of intradialytic exercise on hyperphosphatemia and malnutrition

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Intradialytic exercise (IDE) is not routinely prescribed in hemodialysis (HD) units despite its potential benefits on patients’ outcomes. This study was the first in the United Arab Emirates to examine the effect of aerobic IDE on hyperphosphatemia, malnutrition, and other health outcomes among HD patients. Participants were chosen from the largest HD unit in Sharjah Emirate for a quasi-experimental intervention with pre and post evaluation. The study lasted for 12 months. Study parameters were collected at baseline, post intervention, and follow-up. The intervention included a moderate-intensity aerobic IDE of 45 min per HD session; intensity was assessed using the Borg Scale. Patients were educated on the importance of exercise. Study outcomes were serum phosphorus (P), malnutrition inflammation score (MIS), quality of life (QOL), and pertinent blood tests. Forty-one eligible consenting HD patients were included in the study. Results at follow-up showed a non-significant reduction in P (p = 0.06) in patients who were hyperphosphatemic at baseline, but not in the sample as whole. MIS did not deteriorate throughout the study (p = 0.97). IDE resulted in a non-significant increase in the QOL visual analogue scale (p = 0.34). To conclude, aerobic IDE for 45 min is safe and could be beneficial, especially for hyperphosphatemic patients

Inflammation and premature aging in advanced chronic kidney disease

Systemic inflammation in end-stage renal disease (ESRD) is an established risk factor for mortality and a catalyst for other complications which are related to a premature aging phenotype, including muscle wasting, vascular calcification and other forms of premature vascular disease, depression, osteoporosis and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have direct effect on cellular and tissue function. In addition to uremia-specific causes such as abnormalities in the phosphate- Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect are abnormal or misplaced protein structures as well as abnormalities in tissue homeostasis, which evoke danger signals through damage associated molecular patters (DAMPS) as well as the senescence associated secretory phenotype (SASP). Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserve, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relation between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences are discussed

Protein-bound uremic toxin profiling as a tool to optimize hemodialysis

Aim : We studied various hemodialysis strategies for the removal of protein-bound solutes, which are associated with cardiovascular damage. Methods : This study included 10 patients on standard (3x4h/week) high-flux hemodialysis. Blood was collected at the dialyzer inlet and outlet at several time points during a midweek session. Total and free concentration of several protein-bound solutes was determined as well as urea concentration. Per solute, a two-compartment kinetic model was fitted to the measured concentrations, estimating plasmatic volume (V-1), total distribution volume (V-tot) and inter-compartment clearance (K-21). This calibrated model was then used to calculate which hemodialysis strategy offers optimal removal. Our own in vivo data, with the strategy variables entered into the mathematical simulations, was then validated against independent data from two other clinical studies. Results : Dialyzer clearance K, V-1 and V-tot correlated inversely with percentage of protein binding. All Ks were different from each other. Of all protein-bound solutes, K-21 was 2.7-5.3 times lower than that of urea. Longer and/or more frequent dialysis that processed the same amount of blood per week as standard 3x4h dialysis at 300mL/min blood flow showed no difference in removal of strongly bound solutes. However, longer and/or more frequent dialysis strategies that processed more blood per week than standard dialysis were markedly more adequate. These conclusions were successfully validated. Conclusion : When blood and dialysate flow per unit of time and type of hemodialyzer are kept the same, increasing the amount of processed blood per week by increasing frequency and/or duration of the sessions distinctly increases removal

Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results.

Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysis Outcomes (MONDO) database to evaluate the association between lipids and infection-related or CV mortality. The study began on the first day of lipid measurement and continued for up to 4 years. We applied Cox proportional models with time-varying covariates to study associations of LDL-C, HDL cholesterol (HDL-C), and triglycerides (TGs) with all-cause, CV, infectious, and other causes of death. Overall, 6,147 patients died (19.2% from CV, 13.2% from infection, and 67.6% from other causes). After multivariable adjustment, higher LDL-C, HDL-C, and TGs were independently associated with lower all-cause death risk. Neither LDL-C nor TGs were associated with CV death, and HDL-C was associated with lower CV risk. Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non-CV causes. LDL-C was associated with reduced all-cause and infectious, but not CV mortality, which resulted in the inverse association with all-cause mortality