Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

Date of acceptance: 01/07/2015 © 2015 Witham et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements UK NIHR HTA grant 10/71/01. We acknowledge the financial support of NHS Research Scotland in conducting this trial.Peer reviewedPublisher PD

Muscle wasting in chronic kidney disease: the role of the ubiquitin proteasome system and its clinical impact

Muscle wasting in chronic kidney disease (CKD) and other catabolic diseases (e.g. sepsis, diabetes, cancer) can occur despite adequate nutritional intake. It is now known that complications of these various disorders, including acidosis, insulin resistance, inflammation, and increased glucocorticoid and angiotensin II production, all activate the ubiquitin–proteasome system (UPS) to degrade muscle proteins. The initial step in this process is activation of caspase-3 to cleave the myofibril into its components (actin, myosin, troponin, and tropomyosin). Caspase-3 is required because the UPS minimally degrades the myofibril but rapidly degrades its component proteins. Caspase-3 activity is easily detected because it leaves a characteristic 14kD actin fragment in muscle samples. Preliminary evidence from several experimental models of catabolic diseases, as well as from studies in patients, indicates that this fragment could be a useful biomarker because it correlates well with the degree of muscle degradation in dialysis patients and in other catabolic conditions

Hypernatremia in the geriatric population

Maulin K Shah,1 Biruh Workeneh,1,2 George E Taffet1,3 1Department of Internal Medicine, 2Department of Nephrology, 3Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA Abstract: Hypernatremia in the geriatric population is a common disorder associated with significant morbidity and mortality. Older people are predisposed to developing hypernatremia because of age-related physiologic changes such as decreased thirst drive, impaired urinary concentrating ability, and reduced total body water. Medications may exacerbate this predisposition. Hypernatremia and dehydration occurring in nursing homes are considered indicators of neglect that warrant reporting, but there are other nonavoidable causes of hypernatremia, and consideration at time of presentation is essential to prevent delay in diagnosis and management. We describe a case illustrating the importance of the consideration of alternate explanations for hypernatremia in a nursing home resident, followed by a review of hypernatremia in the elderly population, to underscore that neglect is the etiology of exclusion after alternatives have been considered. Keywords: geriatric, hypernatremia, sodiu

Hyponatremia in the cancer patient.

Hyponatremia is a common electrolyte disorder observed in a wide variety of malignancies and is associated with substantial morbidity and mortality. Newer cancer therapies have improved patient outcomes while also contributing to new cases of hyponatremia. Patients should be monitored closely for the development of vasopressin and non-vasopressin mediated hyponatremia. Acute and symptomatic forms of hyponatremia require urgent intervention, and recent findings also support the correction of chronic asymptomatic hyponatremia. Optimizing hyponatremia may reduce medical costs, improve cancer survival, and quality of life. In this manuscript, we review the epidemiology, pathophysiology, etiology, diagnosis and treatment of hyponatremia in the cancer patient

Natural history of skeletal muscle mass changes in chronic kidney disease stage 4 and 5 patients: an observational study

Cross-sectional studies in dialysis demonstrate muscle wasting associated with loss of function, increased morbidity and mortality. The relative drivers are poorly understood. There is a paucity of data regarding interval change in muscle in pre-dialysis and dialysis-dependant patients. This study aimed to examine muscle and fat mass change and elucidate associations with muscle wasting in advanced CKD. 134 patients were studied (60 HD, 28 PD, 46 CKD 4–5) and followed up for two years. Groups were similar in age, sex and diabetes prevalence. Soft tissue cross-sectional area (CSA) was measured annually on 3 occasions by a standardised multi-slice CT thigh. Potential determinants of muscle and fat CSA were assessed. Functional ability was assessed by sit-to-stand testing. 88 patients completed follow-up (40 HD, 16 PD, 32 CKD). There was a significant difference in percentage change in muscle CSA (MCSA) over year 1, dependant on treatment modality (χ2 = 6.46; p = 0.039). Muscle loss was most pronounced in pre-dialysis patients. Muscle loss during year 1 was partially reversed in year 2 in 39%. Incident dialysis patients significantly lost MCSA during the year which they commenced dialysis, but not the subsequent year. Baseline MCSA, change in MCSA during year 1 and dialysis modality predicted year 2 change in MCSA (adjusted R2 = 0.77, p<0.001). There was no correlation between muscle or fat CSA change and any other factors. MCSA correlated with functional testing, although MCSA change correlated poorly with change in functional ability. These data demonstrate marked variability in MCSA over 2 years. Loss of MCSA in both pre-dialysis and established dialysis patients is reversible. Factors previously cross-sectionally shown to correlate with MCSA did not correlate with wasting progression. The higher rate of muscle loss in undialysed CKD patients, and its reversal after dialysis commencement, suggests that conventional indicators may not result in optimal timing of dialysis initiation

Effect of Progressive Resistance Training on Measures of Skeletal Muscle Hypertrophy, Muscular Strength and Health-Related Quality of Life in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis

First online: 03 April 2014Background and Objective: Skeletal muscle wasting resulting in reduced muscular strength and health-related quality of life (HR-QOL) is common in chronic kidney disease (CKD) and may be reversed with progressive resistance training (PRT). Therefore, we systematically assessed the effect of PRT on measures of skeletal muscle hypertrophy, muscular strength and HR-QOL in this cohort to inform clinical practice and guidelines. Design: We performed a systematic review and meta-analysis. Inclusion Criteria: We included randomised controlled trials (RCTs) that investigated the independent effect of PRT (>6 weeks) on measures of skeletal muscle hypertrophy [muscle mass or cross-sectional area (CSA)], muscular strength and/or HR-QOL in adults with CKD. Data Extraction and Analysis: The standardised mean difference (SMD) from each study was pooled to produce an overall estimate of effect and associated 95 % confidence interval (95 % CI) between treatment and control groups on primary outcomes. Results: Seven RCTs in 271 patients with Stage 3–5 CKD yielded seven studies on muscular strength (N = 249), six studies on total body muscle mass (N = 200) and six studies on HR-QOL (N = 223). PRT significantly improved standardised muscular strength [SMD 1.15 (95 % CI 0.80–1.49)] and HR-QOL [SMD 0.83 (95 % CI 0.51–1.16)], but not total body muscle mass [SMD 0.29 (95 % CI −0.27 to 0.86)] in our primary analysis. However, secondary analysis of six studies showed that PRT induced significant muscle hypertrophy of the lower extremities (leg mass, or mid-thigh or quadriceps CSA) [SMD 0.43 (95 % CI 0.11–0.76)], a pertinent analysis given that most studies implemented lower-body PRT only. Conclusions: Robust evidence from RCTs indicates that PRT can induce skeletal muscle hypertrophy and increase muscular strength and HR-QOL outcomes in men and women with CKD. Therefore, clinical practice guidelines should be updated to inform clinicians on the benefits of PRT in this cohort.Birinder S. Cheema, Danwin Chan, Paul Fahey, Evan Atlanti