Volume 16, Issue 3, Pages 208-211 (July 2006
Proteolytic Mechanisms, Not Malnutrition, Cause Loss of Muscle Mass in Kidney Failure
William E. Mitch, MD
Hypoalbuminemia and muscle atrophy are frequently found in patients with chronic kidney disease (CKD) and patients being treated by dialysis. These abnormalities are usually attributed to malnutrition, meaning that they are caused by an inadequate diet. However, the evidence indicates that malnutrition is rarely the mechanism causing loss of protein stores. Instead, low values of serum albumin are closely related to the presence of inflammation and loss of muscle mass is attributable to activation of specific proteases. In uremic rodents and patients, the initial step in the loss of muscle protein is an activation of caspase-3. This cleaves the complex structure of muscle, and its action can be detected by the presence of a characteristic 14-kDa actin fragment in the insoluble fraction of muscle. The second step in uremia-induced loss of muscle protein is an activation of the ubiquitin-proteasome system, which rapidly degrades proteins released by caspase-3 cleavage of muscle proteins. Activation of both caspase-3 and the ubiquitin-proteasome system occur when there is suppression of the cellular signaling pathway activated by insulin/insulinlike growth factor 1, the phosphatidylinositol 3-kinase/Akt pathway. A potential therapeutic target for preventing loss of muscle protein is to stimulate activity of this signaling pathway.
Volume 16, Issue 3, Pages 237-240 (July 2006)
Nutritional Status in Hemodialysis Patients: Options for On-Line Convective Treatment
Vincenzo Savica, MD⁎†, Francesco Ciolino, MD†, Paolo Monardo, MD†, Agostino Mallamace, MD⁎, Rodolfo Savica, MD⁎, Domenico Santoro, MD⁎‡, Guido Bellinghieri, MD⁎‡
Although hemodialysis (HD) has improved the life expectancy of patients with end-stage renal disease (ESRD), uremic patients continue to experience high morbidity and mortality. Two of the most important risk factors for morbidity and mortality are protein-energy malnutrition (PEM) and inflammation. The causes for PEM in ESRD are numerous. The use of materials for dialysis, especially of the dialyzer membrane, is reported as one of the recognized causes for chronic inflammation in hemodialysis. We performed a 6-month prospective study examining the influence of on-line predilution hemodiafiltration on the inflammatory and nutritional status in a population of male hemodialysis patients using ultrapure dialysis fluid and polyamide dialyzers. We evaluated serum C-reactive protein, albumin, and transferrin and some nutritional parameters such as body mass index (BMI), phase angle (φ), fatty mass (FM), and free fatty mass (FFM) using bioelectrical impedance (BIA). Results showed significant amelioration of BMI and the re-equilibrium of the acute phase protein after on-line predilution hemodiafiltration. These results support the hypothesis that on-line predilution hemodiafiltration, as convective extracorporeal treatment, may be used to treat malnourished hemodialysis patients and to prevent malnutrition in the ESRD patient at risk for malnutrition.