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

Recruiting

• Conditions: Nephrotic Syndrome; Hyperlipidemias

• Registration Number: NCT06373913
• Lead Sponsor: Kolding Sygehus

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.

Study Timeline

• Study Start: 2023-06-01
• Study First Submitted: 2023-10-10
• Status Verified: 2024-02
• Study First Submitted QC: 2024-04-15
• Last Update Submitted: 2024-04-15
• Study First Posted: 2024-04-18
• Last Update Posted: 2024-04-18
• Primary Completion: 2027-07-30
• Study Completion: 2028-07-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 75

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Kolding Sygehus, Lillebælt Hospital; 🇩🇰 Kolding, Denmark