Hyperlipidemias, Nephrotic Syndrome
Conditions
Brief summary
Nephrotic syndrome (NS) is characterized by gross proteinuria (\>3.5 g/day), hypoalbuminaemia, edema and often hyperlipidemia. Hyperlipidemia is correlated with increased morbidity and mortality. The study aim is to investigate the role of the protein convertase subtilisin/kexin type 9 (PCSK9) in hyperlipidemia of NS, which has been suggested to play an important role. This is done by testing the following hypotheses: 1. PCSK9 is increased in patients with NS and hyperlipidemia compared to kidney-healthy controls 2. The level of PCSK9 in plasma correlates to the degree of proteinuria. 3. PCSK9 i increased in the kidney tissue of patients with NS The study will compare plasma levels of PCSK9 in correlation with degree of protein in the urine between test persons with NS and kidney healthy controls. Furthermore the investigators will study the the degree of PCSK9 in the kidney in biopsies obtained from test persons with nephrotic syndrome and test persons without proteinuria.
Detailed description
Hyperlipidemia in kidney disease is associated with a substantially increase of risk in development of atherosclerotic cardiovascular disease (CVD) (European Atherosclerosis Society 2011). Furthermore animal studies have suggested that hyperlipidemia escalates progression of glomerular injury. Nephrotic syndrome (NS) - the feature of many primary and secondary glomerulopathies - is characterized by gross proteinuria (\>3.5 g/day), hypoalbuminaemia, edema and often hyperlipidemia. The protein Convertase subtilisin/kexin 9 (PCSK9) is over expressed in NS and has been suggested to play an important role in developing of hyperlipidemia. PCSK9 increases the LDL receptor degradation by preventing it from recycling to the cell membrane, resulting in increased plasma LDL cholesterol. PCSK9 is produced primarily in the liver, but to a lesser extent in the brain, intestine and kidney. A recent study found that the expression of renal PCSK9 is increased in mice with experimental NS compared to controls. The investigators want to further explore this. The overall aim is to decrease morbidity and mortality associated with NS and hyperlipidemia, by testing the following hypotheses: 1. PCSK9 is increased in patients with NS and hyperlipidemia compared to kidney-healthy controls 2. The level of PCSK9 in plasma correlates to the degree of proteinuria. 3. PCSK9 i increased in the kidney tissue of patients with NS The study want to compare plasma levels of PCSK9 in correlation with degree of protein in the urine between test persons with NS and kidney healthy controls. Furthermore the investigators will study the the degree of PCSK9 in the kidney in biopsies obtained from test persons with nephrotic syndrome and test persons without proteinuria in a subgroup of the test persons assigned to kidney biopsy regardless of the project.
Interventions
None listed
Sponsors
Odense University Hospital
Vejle Hospital
Kolding Sygehus
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years old * Patients admitted to the Medical Department and/or the Medical Emergency Department, Kolding Sygehus.
Exclusion criteria
* Refusal to give informed consent * Treatment with PCSK9 inhibitors * Any acute or chronic condition that would limit the ability of the patient to participate in the study * Control group: proteinuria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma PCSK9 correlated to the degree of protein in the urine | Measured at inclusion and for the nephrotic group after remission, if this is accomplished within a year | PCSK9 in plasma measured by ELISA, correlated to protein in 24hour urine |
| Degree of PCSK9 in kidney tissue | Measured at inclusion in test person group, if this is performed within in the study period (before august 2028). | Immunohistochemistry; degree of staining a in test persons, who are subjected to kidney biopsy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Localization of PCSK9 in kidney tissue | Measured at inclusion in test person group, if this is performed within in the study period (before august 2028). | Immunohistochemistry; localization of staining a in test persons, who are subjected to kidney biopsy. |
Countries
Denmark
Contacts
Primary ContactRikke Z Langkilde, MD, phd
Backup ContactAnne D Thuesen, MD, phd
Outcome results
None listed