Novel risk markers in the chronic kidney disease patient : new insights into the wasting-inflammation axis

• Patients with chronic kidney disease (CKD) have a risk of cardiovascular morbidity and mortality that is 20 ]30 fold higher than that of a similar person without CKD. While traditional (i.e Framingham) risk factors certainly contribute, they cannot by themselves explain this exacerbated mortality burden. Instead, novel factors such as inflammation and protein ]energy wasting (PEW; i.e. a newly proposed term for loss of body protein mass and fuel reserves), may play a far more important role for vascular disease than in the general population. This work tries to further characterize the inflammation ]PEW interplay as well as other possible consequences of uremic inflammation. Study I explores the major determinants and clinical consequences of anorexia in hemodialysis patients. We found that self ]reported poor appetite was associated with inflammation and poor outcome. The severity of symptoms associated to poor appetite was increased in men as compared to women. Study II explores the major determinants and clinical consequences of muscle atrophy in incident and prevalent dialysis patients. We found that visual signs of muscle atrophy are more common in female dialysis patients and progressively associated with inflammation, poor nutritional and anthropometric status and increased mortality. Study III investigates the prognostic impact of the novel biomarker soluble tumor necrosis factor ]like weak inducer of apoptosis (sTWEAK) on mortality in patients undergoing hemodialysis. We found that sTWEAK may be an additive, but not a primary marker, of the high mortality rate seen in hemodialysis patients with systemic inflammation. Study IV assesses the clinical and biochemical implications of low triiodothyronine levels in end ]stage renal disease patients with normal thyroid function. We found that low triiodothyronine levels in biochemically euthyroid CKD patients are independent predictors of all ]cause and cardiovascular ]related mortality, perhaps due to an intimate association with inflammation. Study V discerns the major determinants and plausible contribution of reduced telomere length on the mortality of dialysis patients. Age, male gender and systemic inflammation were important contributors to reduced telomere length in CKD patients, which may constitute a new mortality risk factor in this population.

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