Protein-energy wasting (PEW), a term proposed by the International Society of Renal Nutrition and Metabolism (ISRNM), refers to the multiple nutritional and catabolic alterations that occur in chronic kidney disease (CKD) and associate with morbidity and mortality. To increase awareness, identify research needs, and provide the basis for future work to understand therapies and consequences of PEW, ISRNM provides this consensus statement of current knowledge on the etiology of PEW syndrome in CKD. Although insufficient food intake (true undernutrition) due to poor appetite and dietary restrictions contribute, other highly prevalent factors are required for the full syndrome to develop. These include uremia-induced alterations such as increased energy expenditure, persistent inflammation, acidosis, and multiple endocrine disorders that render a state of hypermetabolism leading to excess catabolism of muscle and fat. In addition, comorbid conditions associated with CKD, poor physical activity, frailty, and the dialysis procedure per se further contribute to PEW.

Premature cardiovascular disease (CVD), including stroke, peripheral vascular disease, sudden death, coronary artery disease, and congestive heart failure, is a notorious problem in patients with chronic kidney disease (CKD). Because the presence of CVD is independently associated with kidney function decline, it appears that the relationship between CKD and CVD is reciprocal or bidirectional, and that it is this association that leads to the vicious circle contributing to premature death. As randomized, placebo-controlled trials have so far been disappointing and unable to show a survival benefit of various treatment strategies, such a lipid-lowering, increased dialysis dose and normalization of hemoglobin, the risk factor profile seems to be different in CKD compared with the general population. Indeed, seemingly paradoxical associations between traditional risk factors and cardiovascular outcome in patients with advanced CKD have complicated our efforts to identify the real cardiovascular culprits. This review focuses on the many new pieces that need to be fit into the complicated puzzle of uremic vascular disease, including persistent inflammation, endothelial dysfunction, oxidative stress, and vascular ossification. Each of these is not only highly prevalent in CKD but also more strongly linked to CVD in these patients than in the general population. However, a causal relationship between these new markers and CVD in CKD patients remains to be established. Finally, two novel disciplines, proteomics and epigenetics, will be discussed, because these tools may be helpful in the understanding of the discussed vascular risk factors.

Background and objectives Reduced muscle mass and strength are prevalent conditions in dialysis patients. However, muscle strength and muscle mass are not congruent; muscle strength can diminish even though muscle mass is maintained or increased. This study addresses phenotype and mortality associations of these muscle dysfunction entities alone or in combination (i.e., concurrent loss of muscle mass and strength/mobility, here defined as sarcopenia).Design, setting, participants, & measurements This study included 330 incident dialysis patients (203 men, mean age 53613 years, and mean GFR 762 ml/min per 1.73 m 2 ) recruited between 1994 and 2010 and followed prospectively for up to 5 years. Low muscle mass (by dual-energy x-ray absorptiometry appendicular mass index) and low muscle strength (by handgrip) were defined against young reference populations according to the European Working Group on Sarcopenia in Older People.Results Whereas 20% of patients had sarcopenia, low muscle mass and low muscle strength alone were observed in a further 24% and 15% of patients, respectively. Old age, comorbidities, protein-energy wasting, physical inactivity, low albumin, and inflammation associated with low muscle strength, but not with low muscle mass (multivariate ANOVA interactions). During follow-up, 95 patients (29%) died and both conditions associated with mortality as separate entities. When combined, individuals with low muscle mass alone were not at increased risk of mortality (adjusted hazard ratio [HR], 1.23; 95% confidence interval [95% CI], 0.56 to 2.67). Individuals with low muscle strength were at increased risk, irrespective of their muscle stores being appropriate (HR, 1.98; 95% CI, 1.01 to 3.87) or low (HR, 1.93; 95% CI, 1.01 to 3.71).Conclusions Low muscle strength was more strongly associated with aging, protein-energy wasting, physical inactivity, inflammation, and mortality than low muscle mass. Assessment of muscle functionality may provide additional diagnostic and prognostic information to muscle-mass evaluation.

The first reports connecting uremic inflammation with a wasted and atherogenic phenotype and poor outcome initiated in the late 1990s. Since then, about 3500 publications appear on Medline, reflecting the exponential interest that this topic has evoked in nephrology. What was described as a "novel" risk factor 10 years ago has now evolved into an established finding in patients with end-stage renal disease (ESRD). The purpose of this review is to summarize the main advances contributing to our current understanding of the complex inflammatory processes present in ESRD. Causes and consequences of inflammation, genetic heritability of the inflammatory response, implications on outcome prognostication, and contemporary therapeutic evidence are some of the various topics discussed.

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Skeletal muscle mass and muscle function are negatively affected by a variety of conditions inherent to chronic kidney disease (CKD) and to dialysis treatment. Skeletal muscle mass and function serve as indicators of the nutritional and clinical state of CKD patients, and low values or derangements over time are strong predictors of poor patient outcomes. However, muscle size and function can be affected by different factors, may decline at different rates, and may have different patient implications. Therefore, operational definitions of frailty and sarcopenia have emerged to encompass these 2 dimensions of muscle health, i.e., size and functionality. The aim of this review is to appraise available methods for assessment of muscle mass and functionality, with an emphasis on their accuracy in the setting of CKD patients. We then discuss the selection of reference cutoffs for defining conditions of muscle wasting and dysfunction. Finally, we review definitions applied in studies addressing sarcopenia and frailty in CKD patients and discuss their applicability for diagnosis and monitoring.

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