Objectives: There is a need for precision medicine and an unspoken promise of an optimal approach for identification of the right patients for value-based medicine based on big data. However, there may be a misconception that measurement of proteins is more valuable than measurement of fewer selecte...
August 26, 2021
Journal:
Clin Biochem
Author:
Karsdal MA, Rasmussen DGK, Bay-Jensen AC, Mortensen JH, Holm Nielsen S, Willumsen N, Jensen C, Manon-Jensen T, Jennings L, Reese-Petersen AL, Henriksen K, Leeming DJ, Bager CL, Genovese F, Bülow Sand JM
Background & aims: Progressive fibrosis has been identified as the major predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). Several biomarkers are currently being evaluated for their ability to substitute the liver biopsy as the reference standard. Recent clinical...
July 10, 2021
Journal:
JHEP Rep
Author:
Erhardtsen E, Rasmussen DGK, Frederiksen P, Leeming DJ, Gluud LL, Karsdal MA, Aithal GP, Shattenberg JM, Shevell DE
Background: Renal fibrosis is the hallmark of chronic kidney disease (CKD) and characterized by an imbalanced extracellular matrix remodeling. Endotrophin (ETP) is a signaling molecule released from collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels of CO...
April 29, 2021
Journal:
Nephrol Dial Transplant
Author:
Sparding N, Rasmussen DGK, Karsdal MA, Neprasova M, Maixnerova D, Satrapova V, Frausova D, Hornum M, Bartonova L, Honsova E, Kollar M, Koprivova H, Hruskova Z, Tesar V, Genovese F
Pulmonary fibrosis has been identified as a main factor leading to pulmonary dysfunction and poor quality of life in post-recovery Severe Acute Respiratory Syndrome (SARS) survivor's consequent to SARS-Cov-2 infection. Thus there is an urgent medical need for identification of readily available biom...
February 5, 2021
Journal:
Respir Res.
Author:
Leeming DJ, Rasmussen DGK, Christiansen C, Jenkins G, Mahrer TM, Vestbo J, Karsdal MA, Genovese F, Bülow Sand JM
he PRO-C6 assay, a reflection of collagen type VI synthesis, has been proposed as a non-invasive early biomarker of kidney fibrosis. We aimed to investigate cross-sectional and longitudinal associations between plasma and urine PRO-C6 and proven histological changes after kidney transplantation. The...
October 7, 2020
Journal:
J Clin Med
Author:
Yepes-Calderón M, Sotomayor CG, Rasmussen DGK, Hijmans RS, Te Velde-Keyzer CA, van Londen M, van Dijk M, Diepstra A, Berger SP, Karsdal MA, Bemelman FJ, de Fijter JW, Kers J, Florquin S, Genovese F, Bakker SJL, Sanders JS, Van Den Born J
Fibrosis is often heterogeneously distributed, and classical biopsies do not reflect this. Noninvasive methods for renal fibrosis have been developed to follow chronic kidney diseases (CKD) and to monitor anti-fibrotic therapy. In this study, we combined two approaches to assess fibrosis regression ...
August 14, 2020
Journal:
Pharmaceutics
Author:
Nielsen PM, Mariager CØ, Rasmussen DGK, Mølmer M, Karsdal MA, Laustsen C, Nørregaard R, Genovese F
There is an unmet need for high-quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non-alcoholic fatty liv...
April 9, 2020
Journal:
Liver Int
Author:
Karsdal MA, Daniels SJ, Nielsen SH, Bager CL, Rasmussen DGK, Loomba R, Surabattula R, Villesen IF, Luo Y, Gudmann NS, Nielsen MJ, George J, Christian R, Leeming DJ, Schuppan D, Shevell DE
Extracellular matrix (ECM) remodeling is a hallmark of the pathology of gastrointestinal disorders. Collagen type VI (COL6) is produced by fibroblasts, and the COL6 α3-chain has shown to be elevated in patients with ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC). Measuring...
April 3, 2020
Journal:
Sci Rep
Author:
Nielsen SH, Mortensen JH, Willumsen N, Mogensen DJ, Di Sabatino A, Mazza G, Jørgensen LN, Pinzani M, Klinge LG, Kjeldsen J, Leeming DJ, Karsdal MA, Genovese F, Rasmussen DGK, Giuffrida P
Background\r\nTubulointerstitial fibrosis is a major pathological feature in chronic kidney disease (CKD) and collagen type III (COL3) is a major component of the renal fibrotic scar. We hypothesized that a dysregulated turnover of COL3 is an important determinant of CKD progression. We assessed the...
January 14, 2020
Journal:
ERA-EDTA Clinical Kidney Journal
Author:
Genovese F, Rasmussen DGK, Jesky M, Fenton A, Cockwell P, Karsdal MA, Ferro CJ
Renal fibrosis is a hallmark of chronic kidney disease (CKD) caused by an imbalance between formation and degradation of extracellular matrix proteins. We investigated the collagen turnover profile of 81 non-dialysis CKD stage 2-5 patients by measuring peptides reflecting formation and degradation o...
November 5, 2019
Journal:
Sci Rep
Author:
Boesby L, Nielsen SH, Teepel M, Birot S, Karsdal MA, Kamper Al, Genovese F, Rasmussen DGK
OBJECTIVE: Patients with type 1 diabetes (T1D) have a higher risk of developing chronic kidney disease, cardiovascular events (CVEs), and mortality than the general population. We hypothesized that two previously published biomarkers, namely PRO-C6, a biomarker of collagen type VI formation, and C3M...
September 13, 2019
Journal:
Diabetes Care
Author:
Pilemann-Lyberg S, Hansen TW, Tofte N, Winther SA, Holm Nielsen S, Theilade S, Karsdal MA, Genovese F, Rossing P, Rasmussen DGK
BACKGROUND:Maintenance of kidney function in kidney allografts remains a challenge, as the allograft often progressively develops fibrosis after kidney transplantation. Fibrosis is caused by the accumulation of extracellular matrix proteins like type I and III collagen (COL I and III) that replace t...
August 1, 2019
Journal:
Nephrol Dial Transplant
Author:
Nielsen PM, Nielsen SH, Kerulf-Lassen C, Karsdal MA, Genovese F, Nørregaard R, Kasab-Oglo ÖY, Rasmussen DGK
BACKGROUND: Patients with chronic kidney disease (CKD) have increased risk of development of end-stage renal disease (ESRD) and early mortality. Fibrosis is the central pathogenic process in CKD and is caused by dysregulated extracellular matrix (ECM) remodeling. The laminin γ1 chain (LAMC1) is a co...
October 1, 2018
Journal:
PLoS One
Author:
Holm Nielsen S, Brix S, Jesky M, Fenton A, Ferro CJ, Karsdal MA, Genovese F, Cockwell P, Rasmussen DGK
OBJECTIVE: There is a need for non-invasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to anti-fibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be incl...
August 30, 2018
Journal:
Am J Physiol Gastrointest Liver Physiol
Author:
Karsdal MA, Hjuler ST, Luo Y, Nielsen MJ, Nielsen SH, Leeming DJ, Goodman ZD, Arch RH, Patel K, Schuppan D, Rasmussen DGK
OBJECTIVE: Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI for...
April 11, 2018
Journal:
Diabetes Care
Author:
Rasmussen DGK, Hansen TW, von Scholten BJ, Nielsen SH, Reinhard H, Parving HH, Tepel M, Karsdal MA, Jacobsen PK, Genovese F, Rossing P
Renal fibrosis is the central pathogenic process in progression of chronic kidney disease (CKD). Collagen type VI (COL VI) is upregulated in renal fibrosis. Endotrophin is released from COL VI and promotes pleiotropic pro-fibrotic effects. Kidney disease severity varies considerably and accurate inf...
December 1, 2017
Journal:
Scientific Reports, Nature
Author:
Fenton A, Jesky M, Boor P, Tepel M, Karsdal MA, Genovese F, Cockwell P, Ferro CJ, Rasmussen DGK
Background: Patients with chronic kidney disease (CKD) are at increased risk of end-stage renal disease (ESRD) and early mortality. The underlying pathophysiological processes are not entirely understood but may include dysregulation of extracellular matrix formation with accelerated systemic and re...
March 20, 2017
Journal:
J Transl Med.
Author:
Hijmans RS, Yazdani S, Navis G, van Goor H, Karsdal MA, Genovese F, van den Born J, Rasmussen DGK
A high level of extracellular matrix (ECM) turnover characterizes several lung diseases with fibrotic features. Type III collagen is one of the most abundant collagens in lung parenchyma, and cathepsins play a role in lung pathology, being responsible for tissue remodeling. In this study, we explore...
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