The Role of Proprotein-convertase-subtilisin/Kexin-type 9 in Kidney Damage in Nephrotic Syndrom (PCSK9)

Kolding Sygehus

Status: Enrolling

Conditions: Hyperlipidemias; Nephrotic Syndrome

Study type: Observational

Funder types: Other

Identifiers

NCT06373913

MASP2NSRZL

Details and patient eligibility

About

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.

Full 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.

Enrollment: 75 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

75 participants in 3 patient groups

Nephrotic syndrome

Description:

Patients with nephrotic syndrome (n=32). Blood samples and 24 hour urine samples will be obtained an all participants. Kidney biopsy will be used from 11 test persons, whos been subjected to kidney biopsy unrelated to the research project. 3

Kidney healthy controls

Description:

Patient with normal kidney function and no proteinuria (n=32). Blood samples and 24 hour urine samples will be obtained an all participants.

Kidney biopsy control

Description:

Patients without proteinuria who is subjected to kidney biopsy regardless of the research project.