Inflammation, Proteolysis and IL-1 Beta Receptor Inhibition in Chronic Hemodialysis Patients
Condition: End Stage Renal Disease
MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Inflammation
Study type: Interventional

Summary: 
      Chronic hemodialysis (CHD) patients display multiple metabolic abnormalities related to
      advanced uremia. Despite vigorous attempts to prevent these abnormalities and their
      consequences, most CHD patients suffer from a unique form of nutritional derangement, which
      can be termed as "uremic wasting". Several studies have demonstrated that the presence of
      uremic wasting, especially the degree of loss of muscle mass, sharply increases mortality and
      hospitalization rate in CHD patients.

      Several factors have been thought to be associated with uremic wasting, including hormonal
      derangement, anorexia, physical inactivity, and concurrent illnesses. Chronic inflammation,
      also highly prevalent in these patients, causes muscle catabolism in animal models and
      certain clinical conditions. Epidemiological studies show an association between chronic
      inflammation and uremic wasting in hemodialysis patients indicating a possible causal
      relationship.

      The cause for the activated inflammatory state in CHD patients is believed to be
      multi-factorial. Nevertheless, it is certainly important for the host to limit its biological
      activity by eliciting a stronger anti-inflammatory response, for example through the
      production of naturally occurring receptor antagonist. Interleukin 1 beta, one of the major
      pro-inflammatory cytokines has been shown to be associated with protein catabolism in several
      chronic disease states, including advanced uremia. A balance between interleukin 1 beta
      (agonist) and its naturally occurring receptor antagonist IL-1ra may play a pivotal role in
      controlling the inflammatory response and its consequences in this population.

      The overall goal of this particular grant application is to examine the short-term effects of
      the administration of the recombinant form of IL-1ra on 1) chronic inflammatory state and 2)
      protein homeostasis in chronically inflamed CHD patients.

      We have updated our protocol to perform an interim analysis. The interim analysis will be
      performed after half of the planned study sample has been enrolled (14 subjects; 7 in each
      arm). The interim analysis has been approved by the Data Safety Monitoring Board.
    


Intervention name(s): kineret; placebo
Intervention type(s): Drug; Drug
Intervention description(s): 100 mg administered subcutaneously every other day (3 days a week during hemodialysis) for 4 weeks; 100 mg administered subcutaneously every other day (3 days a week during hemodialysis) for 4 weeks
Other intervention name(s): Anakinra
Intervention MeSH terms: Interleukin 1 Receptor Antagonist Protein
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: inflammation; end stage renal disease