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| Name | Class |
|---|---|
| Odense University Hospital | OTHER |
| Vejle Hospital | OTHER |
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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:
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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Localization of PCSK9 in kidney tissue | Immunohistochemistry; localization 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). |
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Inclusion Criteria:
Exclusion Criteria:
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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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rikke Z Langkilde, MD, phd | Contact | 004576362554 | rikke.zachar.langkilde@rsyd.dk | |
| Anne D Thuesen, MD, phd | Contact | 004576360555 | Anne.Daugaard.Thuesen2@rsyd.dk |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kolding Sygehus, Lillebælt Hospital | Recruiting | Kolding | 6000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24166456 | Background | 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. | |
| 32750454 | 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. |
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| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D009404 | Nephrotic Syndrome |
| ID | Term |
|---|---|
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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Urine, blood samples, kidney biopsy tissue
| 27358438 | 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. |
| D009401 | Nephrosis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |