Current epigenetic aspects the clinical kidney researcher should embrace

Chronic kidney disease (CKD), affecting 10-12% of the world's adult population, is associated with a considerably elevated risk of serious comorbidities, in particular, premature vascular disease and death. Although a wide spectrum of causative factors has been identified and/or suggested, there is still a large gap of knowledge regarding the underlying mechanisms and the complexity of the CKD phenotype. Epigenetic factors, which calibrate the genetic code, are emerging as important players in the CKD-associated pathophysiology. In this article, we review some of the current knowledge on epigenetic modifications and aspects on their role in the perturbed uraemic milieu, as well as the prospect of applying epigenotype-based diagnostics and preventive and therapeutic tools of clinical relevance to CKD patients. The practical realization of such a paradigm will require that researchers apply a holistic approach, including the full spectrum of the epigenetic landscape as well as the variability between and within tissues in the uraemic milieu

Associations between the measures of physical function, risk of falls and the quality of life in haemodialysis patients : a cross-sectional study

Background Impaired physical function due to muscle weakness and exercise intolerance reduces the ability to perform activities of daily living in patients with end-stage kidney disease, and by consequence, Health-Related Quality of Life (HRQoL). Furthermore, the risk of falls is an aggregate of physical function and, therefore, could be associated with HRQoL as well. The present study examined the associations between objective and subjective measures of physical function, risk of falls and HRQoL in haemodialysis patients. Methods This cross-sectional multicentre study included patients on maintenance haemodialysis. Physical function (quadriceps force, handgrip force, Sit-to-Stand, and six-minute walking test), the risk of falls (Tinetti, FICSIT-4, and dialysis fall index) and HRQoL (PROMIS-29 and EQ-5D-3 L) were measured and analysed descriptively, by general linear models and logistic regression. Results Of the 113 haemodialysis patients (mean age 67.5 +/- 16.1, 57.5% male) enrolled, a majority had impaired quadriceps force (86.7%) and six-minute walking test (92%), and an increased risk of falls (73.5%). Whereas muscle strength and exercise capacity were associated with global HRQoL (R-2 = 0.32) and the risk of falls, the risk of falls itself was related to psycho-social domains (R-2 = 0.11) such as depression and social participation, rather than to the physical domains of HRQoL. Objective measures of physical function were not associated with subjective fatigue, nor with subjective appreciation of health status. Conclusions More than muscle strength, lack of coordination and balance as witnessed by the risk of falls contribute to social isolation and HRQoL of haemodialysis patients. Mental fatigue was less common than expected, whereas, subjective and objective physical function were decreased

Composite uremic load and physical performance in hemodialysis patients : a cross-sectional study

Impaired physical performance is common in patients on hemodialysis (HD) and is associated with poor prognosis. A patient relevant marker of adequacy of dialysis is lacking. Previous studies evaluated uremic toxicity by assessing the impact of different uremic toxins separately. However, such an approach is most likely not reflective of true uremic toxicity. Therefore, this cross-sectional study aimed to examine if the uremic syndrome, estimated as one composite of different uremic toxins (facilitated by ridge regression method) to reflect the kinetic behavior during dialysis, is associated with physical performance in patients on HD. Levels of p-cresyl glucuronide and sulfate, indole-acetic acid, indoxyl sulfate, uric acid, hippuric acid, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid were assessed and associated by ridge regression to muscle strength, functional exercise capacity, and measures of balance and coordination. 75 HD patients were included (mean age 68 years, 57% male). The composite of different uremic toxins (i.e., uremic load) explained 22% of the variance in handgrip strength. Although there was an association between full body muscle strength and the composite uremic load independent of nutritional status, age and gender, the predictive power of composite uremic load for muscle weakness is limited. Single uremic toxins as well as composite uremic load were not associated with exercise capacity, coordination, and balance, indicating that the degree of uremia does not predict physical performance in patients on HD

MicroRNAs in AKI and kidney transplantation

MicroRNAs are epigenetic regulators of gene expression at the posttranscriptional level. They are involved in intercellular communication and crosstalk between different organs. As key regulators of homeostasis, their dysregulation underlies several morbidities including kidney disease. Moreover, their remarkable stability in plasma and urine makes them attractive biomarkers. Beyond biomarker studies, clinical microRNA research in nephrology in recent decades has focused on the discovery of specific microRNA signatures and the identification of novel targets for therapy and/or disease prevention. However, much of this research has produced equivocal results and there is a need for standardization and confirmation in prospective trials. This review aims to provide an overview of general concepts and available clinical evidence in both the pathophysiology and biomarker fields for the role of microRNA in AKI and kidney transplantation

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

The Causes of Kidney Allograft Failure: More Than Alloimmunity. A Viewpoint Article

Kidney allograft failure is a serious condition as it implies the need for re-initiation of dialysis with associated morbidity and mortality, reduced quality of life and higher economic cost. Despite improvements in short-term survival of kidney allografts, this progress was not matched in long-term graft survival. In this viewpoint paper, we summarize the available literature on the causes of kidney allograft failure, both early and late, both nonimmune and allo-immune, to gain better insight in the causes of graft failure. Such insight is necessary to better target therapies or take preventative measures, that improve long-term outcome after kidney transplantation.status: publishe

The importance of physical performance in the assessment of patients on haemodialysis: A survival analysis.

BackgroundPhysical performance is an important determinant of quality of life in patients on haemodialysis. An association between physical performance and survival could further enhance the importance of physical performance. We aimed to assess the association between different measures of physical performance and survival in dialysis patients.Methods117 patients on haemodialysis were included from December 2016 and followed up to September 2020. Muscle strength (quadriceps, handgrip strength, and sit-to-stand), exercise capacity (six-minute walking test, 6MWT) and the risk of falls (Dialysis Fall Index, Tinetti, and Frailty and Injuries: Cooperative Studies of Intervention Techniques) were measured at the time of inclusion. Hospitalisation, morbidity (Davies Stoke index) and death were recorded. Data were analysed by least squares linear regression models and competing risks survival hazard models.ResultsDuring the observation period (median 33, min 30 max 45 months), 45 patients died (= 38.5%), resulting in a mortality rate of 15% per year. Cardiovascular disease (42.9%) was the most common cause of death. All domains of physical performance were associated with mortality, with the highest hazards for an increased risk of falls (Hazard Ratio (HR) = 20.4, p = 0.003) and poor exercise capacity (HR = 7.4, pConclusionsThe 6MWT is associated with mortality in patients on haemodialysis and can be considered as a valid assessment tool to identify high-risk patients