Lipid Lowering Agents to Limit Lipid Oxidation and Activation of Clotting System in Nephrotic Syndrome
| Status: | Completed |
|---|---|
| Conditions: | High Cholesterol, Nephrology |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 8/31/2018 |
| Start Date: | May 2012 |
| End Date: | January 2017 |
Assessment of the Efficacy of Lipid-lowering Agents to Limit Lipid Oxidation and Activation of the Clotting System in Patients With the Nephrotic Syndrome: a Pilot Study.
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.
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.
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.
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.
We found this trial at
1
site
Chapel Hill, North Carolina 27510
Principal Investigator: Vimal K Derebail, MD
Phone: 919-966-2561
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