Isoflavones and Acute-phase Response in Chronic Renal Failure
Condition: Kidney Failure, Chronic
MeSH terms: Renal Insufficiency; Kidney Failure, Chronic; Acute-Phase Reaction
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a randomized, double-blinded dietary intervention in hemodialysis patients to
      determine the clinical and metabolic effects of soy isoflavones on disease activity,
      including improvement of blood markers of acute-phase response, and decreased blood levels of
      markers of metabolic bone disease.
    

Detailed description: 
      Up to 40 percent of end stage renal disease (ESRD) patients suffer from a chronic
      inflammatory process which is not currently amenable to specific treatment and is associated
      with high morbidity and mortality. High circulating levels and production of pro-inflammatory
      cytokines are an essential part of this ongoing acute-phase response and they are believed to
      exacerbate many of the clinical manifestations of ESRD, including renal osteodystrophy. Like
      in all other inflammatory processes that have undergone more extensive investigation, the
      nuclear factor, Nuclear Factor Kappa-B (NFKB) promises to be a critical cellular intermediate
      of this acute-phase response and to be both mediator and target of inflammatory cytokine
      effects. In the current search for agents that may be able to negate the ongoing acute-phase
      response of ESRD, the soy isoflavones genistein and daidzein have emerged as potentially
      useful. These isoflavones are present in many soyfoods, are available as over-the-counter
      nutritional supplements and have received growing attention due to their biological
      properties and potential as therapeutic agents. Inhibitory effects of the isoflavones on
      tyrosine kinase and NFKB activity, on inflammatory cytokine production and on oxidative
      stress have been demonstrated by this group and by many other investigators and they may be
      highly relevant to the renal failure population. Additionally, we have found recently that
      intake of soy food by ESRD patients results in very high blood levels of isoflavones and it
      is well tolerated.

      It is our working hypothesis that in chronic renal failure a variety of endogenous and
      exogenous factors trigger acute-phase response with activation of NFKB and production of
      pro-inflammatory cytokines, and that intervention with soy isoflavones inhibits NFKB
      activation and cytokines production, thus blocking the ongoing acute-phase response and
      affecting positively clinically relevant parameters of disease activity in ESRD.

      The specific objective of this proposal is to conduct a randomized, double-blinded dietary
      intervention trial in hemodialysis patients to determine whether:

        1. Dietary intake of the soy isoflavones by ESRD patients with clinical signs of ongoing
           acute-phase response decreases the production of the proinflammatory cytokines
           TNF-alpha, IL-1 and IL-6 in peripheral blood, thus changing the balance between these
           cytokines and their antagonists sTNF RI, sTNF RII, and IL-1ra.

        2. Suppression of inflammatory cytokine production by soy isoflavones is associated with
           improvement of clinically relevant parameters of disease activity, including improvement
           of blood markers of acute-phase response, and decreased blood levels of markers of
           metabolic bone disease.

        3. Intake of soy isoflavones suppresses NF-KB activity in peripheral blood monocytic cells
           of ESRD patients, in a manner consistent with change of cytokine levels and of clinical
           parameters of disease.
    

Intervention name(s): soy isoflavones
Intervention type(s): Drug
Allocation: Randomized
Masking: Double
Primary purpose: Treatment