Lipid Lowering Agents to Limit Lipid Oxidation and Activation of Clotting System in Nephrotic Syndrome
Condition: Nephrotic Syndrome; Hyperlipidemia
MeSH terms: Nephrotic Syndrome; Nephrosis; Hyperlipidemias; Hyperlipoproteinemias; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this research study is to learn if using statin in patients with nephrotic
      syndrome could lower the risk of blood clots. Nephrotic syndrome is a collection of signs and
      symptoms that occur when the glomeruli -the tiny filters that work in the kidney- leak
      protein in the urine.

      One of the symptoms associated with nephrotic syndrome is hyperlipidemia: too much bad
      cholesterol (LDL). This bad cholesterol could be linked to the increased risk of blood clots
      in patients with nephrotic syndrome. The study doctors would like to see if taking a statin
      drug to reduce the amount of bad cholesterol could reduce the risk of blood clots.
    

Detailed description: 
      Venous thromboembolic (VTE) events are common in the nephrotic syndrome (NS) occurring in up
      to 30% of patients when systematically screened. The investigator proposes to explore a novel
      mechanism for the increased clot formation in NS. To date, the only consistently identified
      underlying risk factor for VTEs is severe hypoalbuminemia related to the NS. The underlying
      pathophysiology related to VTE in NS remains poorly understood and has previously been
      ascribed to dysregulation of pro- and anticoagulant clotting factors due to urinary protein
      losses and reflected by the low serum albumin. However, the direct evidence for this
      mechanism is inconsistent and relatively poor. Another feature of NS is that of severe
      hyperlipidemia which also correlates with hypoalbuminemia. In other severely hyperlipidemic
      states (e.g. Familial Hypercholesterolemia), the level of oxidized low-density lipoprotein
      (oxLDL) is markedly elevated. Forms of oxidized LDL interact with monocytes and macrophages
      leading to expression of Tissue Factor (TF), a procoagulant molecule. Furthermore, monocytes
      and macrophages activated in this fashion also release microparticles, small cell-membrane
      derived vesicles, that also express TF and participate in initiating intravascular clot
      formation. the investigator hypothesizes that the hyperlipidemia of the nephrotic syndrome
      leads to elevations in oxidized LDL and in turn, elevations in microparticle Tissue Factor
      (MP-TF) and its activity. The investigator also hypothesizes that serum albumin levels will
      inversely correlate with hyperlipidemia as well as oxLDL levels and MP-TF activity. Here, the
      investigator will study the effect of treatment with HMGCoA reductase inhibitors (statins) on
      ox LDL and MP-TF activity patients with NS.
    

Intervention name(s): Pravastatin
Intervention type(s): Drug
Intervention description(s): After collecting baseline plasma samples, participants will receive pravastatin 20mg daily. After 6 weeks, we will collect samples and safety data. Subsequent statin therapy will be at the discretion of the treating physician.
Other intervention name(s): Pravachol
Intervention MeSH terms: Pravastatin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: nephrotic; hyperlipidemia; oxLDL; kidney