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

NCT06373913 | Recruiting DMC

• 1 other identifier: MASP2NSRZL
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

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. 1.PCSK9 is increased in patients with NS and hyperlipidemia compared to kidney-healthy controls
2. 2.The level of PCSK9 in plasma correlates to the degree of proteinuria.
3. 3.PCSK9 i increased in the kidney tissue of patients with NS

Conditions

Hyperlipidemias; Nephrotic Syndrome

Outcome Measures

Primary Outcomes (2)

• Plasma PCSK9 correlated to the degree of protein in the urine

  PCSK9 in plasma measured by ELISA, correlated to protein in 24hour urine

  Measured at inclusion and for the nephrotic group after remission, if this is accomplished within a year

• Degree of PCSK9 in kidney tissue

  Immunohistochemistry; degree of staining a in test persons, who are subjected to kidney biopsy.

  Measured at inclusion in test person group, if this is performed within in the study period (before august 2028).

Secondary Outcomes (1)

• 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).

Study Arms (3)

Nephrotic syndrome

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

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient with \>3.5 g/day of proteinuria will be included in the nephrotic syndrome group. Control test subjects will be excluded if proteinuria occur.

You may qualify if:

• years old
• Patients admitted to the Medical Department and/or the Medical Emergency Department, Kolding Sygehus.

You may not qualify if:

• 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

Sponsors & Collaborators

• Kolding Sygehus: lead
• Odense University Hospital: collaborator
• Vejle Hospital: collaborator

Study Sites (1)

Kolding Sygehus, Lillebælt Hospital

Kolding, 6000, Denmark

RECRUITING

Related Publications (3)

• Liu S, Vaziri ND. Role of PCSK9 and IDOL in the pathogenesis of acquired LDL receptor deficiency and hypercholesterolemia in nephrotic syndrome. Nephrol Dial Transplant. 2014 Mar;29(3):538-43. doi: 10.1093/ndt/gft439. Epub 2013 Oct 28.

  PMID: 24166456 BACKGROUND

• Molina-Jijon E, Gambut S, Mace C, Avila-Casado C, Clement LC. Secretion of the epithelial sodium channel chaperone PCSK9 from the cortical collecting duct links sodium retention with hypercholesterolemia in nephrotic syndrome. Kidney Int. 2020 Dec;98(6):1449-1460. doi: 10.1016/j.kint.2020.06.045. Epub 2020 Aug 1.

  PMID: 32750454 BACKGROUND

• Haas ME, Levenson AE, Sun X, Liao WH, Rutkowski JM, de Ferranti SD, Schumacher VA, Scherer PE, Salant DJ, Biddinger SB. The Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Nephrotic Syndrome-Associated Hypercholesterolemia. Circulation. 2016 Jul 5;134(1):61-72. doi: 10.1161/CIRCULATIONAHA.115.020912.

  PMID: 27358438 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Urine, blood samples, kidney biopsy tissue

MeSH Terms

Conditions

Hyperlipidemias; Nephrotic Syndrome

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Central Study Contacts

Rikke Z Langkilde, MD, phd

CONTACT

004576362554; rikke.zachar.langkilde@rsyd.dk

Anne D Thuesen, MD, phd

CONTACT

004576360555; Anne.Daugaard.Thuesen2@rsyd.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2023
• First Posted: April 18, 2024
• Study Start: June 1, 2023
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2028
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)