HyperlipidemiasPCSK9NCT06373913
The Role of Proprotein-convertase-subtilisin/Kexin-type 9 in Kidney Damage in Nephrotic Syndrom
An observational study of Hyperlipidemias and Nephrotic Syndrome, run by Kolding Sygehus at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperlipidemias, Nephrotic Syndrome
- How many people
- 75 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Jun 2023to 30 Jul 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 18 years old
- Patients admitted to the Medical Department and/or the Medical Emergency Department, Kolding Sygehus.
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Kolding Sygehus, Lillebælt Hospital
Kolding, 6000
Rikke Z Langkilde, md, phd, 004576362554
Anne D Thuesen, md, phd, 004576360555, Anne.Daugaard.Thuesen2@rsyd.dk
About this study
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:
Read more
- PCSK9 is increased in patients with NS and hyperlipidemia compared to kidney-healthy controls
- The level of PCSK9 in plasma correlates to the degree of proteinuria.
- 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.
Read the 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:
- PCSK9 is increased in patients with NS and hyperlipidemia compared to kidney-healthy controls
- The level of PCSK9 in plasma correlates to the degree of proteinuria.
- 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.
- Conditions
- Hyperlipidemias, Nephrotic Syndrome
- Medical subject headings
- Hyperlipidemias, Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma PCSK9 correlated to the degree of protein in the urine
PCSK9 in plasma measured by ELISA, correlated to protein in 24hour urine
Measured: 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: 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
Immunohistochemistry; localization of staining a in test persons, who are subjected to kidney biopsy.
Measured: Measured at inclusion in test person group, if this is performed within in the study period (before august 2028).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2024
- Study start1 Jun 2023
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HyperlipidemiasStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kolding Sygehus
- Sponsor type
- University, hospital or other
- Collaborators
- Odense University Hospital, Vejle Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06373913
- Sponsor's protocol ID
- MASP2NSRZL
- Acronym
- PCSK9
- Status last verified
- Sep 2025
- First submitted
- 10 Oct 2023
- Last updated
- 9 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24166456Molina-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.
PubMed 32750454Haas 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.
PubMed 27358438
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Proprotein-convertase-subtilisin/Kexin-type 9 in Kidney Damage in Nephrotic Syndrom
- ClinicalTrials.gov ID
- NCT06373913
- Acronym / sponsor ID
- PCSK9 / MASP2NSRZL
- Conditions
- Hyperlipidemias, Nephrotic Syndrome
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Kolding SygehusUniversity, hospital or other
- Collaborators
- Odense University Hospital, Vejle Hospital
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Jul 2028 (estimated)
- First posted
- 18 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- PCSK9 is increased in patients with NS and hyperlipidemia compared to kidney-healthy controls
- The level of PCSK9 in plasma correlates to the degree of proteinuria.
- 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:
- PCSK9 is increased in patients with NS and hyperlipidemia compared to kidney-healthy controls
- The level of PCSK9 in plasma correlates to the degree of proteinuria.
- 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- 18 years old
- Patients admitted to the Medical Department and/or the Medical Emergency Department, Kolding Sygehus.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Plasma PCSK9 correlated to the degree of protein in the urine
Time frame: 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
Time frame: 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.
1 secondary outcome
Localization of PCSK9 in kidney tissue
Time frame: Measured at inclusion in test person group, if this is performed within in the study period (before august 2028).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2025.
- Background: PubMed 24166456Liu 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.
- Background: PubMed 32750454Molina-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.
- Background: PubMed 27358438Haas 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.
- Individual participant dataSharing planned: No
Related trials for Hyperlipidemias
Not yet recruiting
Plasma Lipids-Dependent Vitamin E Metabolism During Dynamic Hyperlipidemia
Lipid Metabolism Disorders
Active, not recruiting
Developing a Learning COmmunity to Increase eNgagemeNt and Enrollment in Cardiovascular Clinical Trials (CONNECT)
Cardiovascular Diseases, Hypertension
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingObservational study
Causes and Natural History of Dyslipidemias
Hypercholesterolemia, Atherosclerosis
Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hyperlipidemias and Nephrotic Syndrome, run by Kolding Sygehus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rikke Z Langkilde, MD, phd (004576362554, rikke.zachar.langkilde@rsyd.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma PCSK9 correlated to the degree of protein in the urine (time frame: Measured at inclusion and for the nephrotic group after remission, if this is accomplished within a year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06373913, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2025.