Abstract
Protein-energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with an increased death risk from cardiovascular diseases. However, while even minor renal dysfunction is an independent predictor of adverse cardiovascular prognosis, PEW becomes clinically manifest at an advanced stage, early before or during the dialytic stage. Mechanisms causing loss of muscle protein and fat are complex and not always associated with anorexia, but are linked to several abnormalities that stimulate protein degradation and/or decrease protein synthesis. In addition, data from experimental CKD indicate that uremia specifically blunts the regenerative potential in skeletal muscle, by acting on muscle stem cells. In this discussion recent findings regarding the mechanisms responsible for malnutrition and the increase in cardiovascular risk in CKD patients are discussed. During the course of CKD, the loss of kidney excretory and metabolic functions proceed together with the activation of pathways of endothelial damage, inflammation, acidosis, alterations in insulin signaling and anorexia which are likely to orchestrate net protein catabolism and the PEW syndrome.
Highlights
Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, Azienda Ospedale UniversitàSan Martino, Genoa University, Viale Benedetto XV 6, Genoa, Italy; Department of Surgery, Azienda Ospedale UniversitàSan Martino, Genoa University, Tel.: +39-010-3538989; Fax: +39-010-3538899
We recently observed [96] that the Growth hormone (GH) acute anabolic response regarding two different GH receptor-downstream pathways is overall preserved in patients with advanced chronic kidney disease (CKD), while it is blunted in patients displaying evidence of microinflammation, suggesting a role for inflammatory changes in the regulation of skeletal muscle protein balance
Among men treated with hemodialysis, testosterone concentrations inversely correlate with all-cause and cardiovascular disease (CVD)-related mortality, as well as with markers of inflammation, which suggests that hypogonadism may be an additional treatable risk factor for patients with CKD [104,105]
Summary
Hypoalbuminemia is the most commonly used surrogate of PEW in dialysis patients and has a strong association with increased mortality [17 and morbidity [26. A confounding factor is that serum albumin and prealbumin are negative acute phase reactants and their serum levels are profoundly affected by the presence of an inflammatory response. It is already known from studies in 1940s (the “Minnesota Experiment”), that albumin levels are extraordinarily preserved, while fat an muscle mass is lost, when nutrient intake is curtailed [29. Hypoalbuminemia could be favoured by the loss of amino acids and/or protein during renal replacement therapy [32 It is not clear whether the negative clinical outcome in advanced CKD patients associated with hypoalbuminemia is a reflection of nutrition or of the inflammatory response or both. Reduced albumin binding of drugs and endogenous ligands is a feature of uremia [36
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