Loss of
protein stores, presenting as clinical wasting, is reported to have a prevalence of 30-60% and is an important risk factor for mortality in
chronic kidney disease (CKD) patients. There is debate as to whether the clinical wasting in CKD patients represents
malnutrition or
cachexia.
Malnutrition results from inadequate intake of nutrients, despite a good appetite, and manifests as
weight loss associated with adaptive metabolic responses such as decreased basic metabolic rate and preservation of lean body mass at the expense of fat mass. Furthermore, the abnormalities in
malnutrition can usually be overcome simply by supplying more food or altering the composition of the diet. In contrast,
cachexia is characterized by maladaptive responses such as
anorexia, elevated basic metabolic rate, wasting of lean body tissue, and underutilization of fat tissue for energy. Diet supplementation and intradialytic
parenteral nutrition have not been successful in reversing
cachexia in CKD. The etiology of
cachexia in CKD is complex and multifactorial. Two major factors causing muscle wasting in
uremia are
acidosis and decreased
insulin responses.
Inflammation secondary to
cytokines may also play a significant role. The
hypoalbuminemia of CKD patients is principally associated with
inflammation and not changes in food intake. There is also recent evidence that hypothalamic
neuropeptides may be important in the downstream signaling of
cytokines in the pathogenesis of
cachexia in CKD. Elevated circulating levels of
cytokines, such as
leptin, may be an important cause of
uremia-associated
cachexia via signaling through the central
melanocortin system. Further research into the molecular pathways leading to
cachexia may lead to novel therapeutic
therapy for this devastating and potentially fatal complication of CKD.