Lipid Lowering Agents to Limit Lipid Oxidation and Activation of Clotting System in Nephrotic Syndrome

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.

Inclusion criteria

• Prevalent or incident patients of either sex, ages 18-70, with Membranous Nephropathy (MN) , Focal Segmental GlomeruloSclerosis (FSGS), or Minimal Change Disease (MCD).

• Proteinuria ≥ 3.0 g/day by 24hr urine collection or urine protein/creatinine ratio ≥ 2.
• Hyperlipidemia as defined by fasting or direct LDL ≥ 150 mg/dl. -

Exclusion criteria

Inability or unwillingness to comply with the study protocol and follow-up visits.

Patients unable to provide written consent will be excluded.

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