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 ...
Purpose: Renal tubulointerstitial fibrosis is strongly linked to the progressive decline of renal function seen in chronic kidney disease. State-of-the-art noninvasive diagnostic modalities are currently unable to detect the earliest changes associated with the onset of fibrosis. This study was unde...
May 25, 2020
Journal:
Magn Reson Med
Author:
Nielsen PM, Mariager CØ, Mølmer M, Sparding N, Genovese F, Karsdal MA, Nørregaard R, Bertelsen LB, Laustsen C
Diabetic kidney disease is a worldwide epidemic, and therapies are incomplete. Clinical data suggest that improved renal outcomes by Na+-glucose cotransporter 2 inhibitor (SGLT2i) are partly beyond their antihyperglycemic effects; however, the mechanisms are still elusive. Here, we investigated the ...
April 1, 2020
Journal:
AM J Physiol Renal Physiol
Author:
Hodrea J, Balogh DB, Hosszu A, Lenart L, Besztercei B, Koszeqi S, Sparding N, Genovese F, Wagner LJ, Szabo AJ, Fekete A
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, Ferro C, Fenton A, Cockwell P, Karsdal MA
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:
Rasmussen DG, Boesby L, Nielsen SH, Teepel M, Birot S, Karsdal MA, Kamper Al, Genovese F
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, Rasmussen DG, Hansen TW, Tofte N, Winther SA, Holm Nielsen S, Theilade S, Karsdal MA, Genovese F, Rossing P
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:
Rasmussen DG, Nielsen PM, Kasab-Oglo ôY, Nielsen SH, Kerulf-Lassen C, Karsdal MA, Genovese F, Nørregaard R
BACKGROUND AIMS: Remodelling of extracellular matrix is crucial in progressive liver fibrosis. Collagen type III desposition has been shown in acute decompensation. Extratracellular matrix is compiled of deposition of various components. The role of basement membrane collagen type IV in advanced cir...
February 9, 2019
Journal:
Liver Int
Author:
Lehmann J, Praktiknjo M, Nielsen MJ, Schierwagen R, Meyer C, Thomas D, Violi F, Strassburg CP, Bendtsen F, Møller S, Krag A, Leeming DJ, Trebicka J, Karsdal MA
KEY POINTS: Increased activation of the renin-angiotensin-aldosterone system (RAAS) and elevated growth factor production are of crucial importance in the development of renal fibrosis leading to diabetic kidney disease. The aim of this study was to provide evidence for the antifibrotic potential of...
January 17, 2019
Journal:
Am J Physiol Endocrinol Metab
Author:
koszegi S, Molnar A, Lenart L, Hodrea J, Balogh DB, Lakat T, Szkibinszjik J, Hoszu A, Sparding N, Genovese F, Wagner L, Vannay A, Szabo AJ, Fekete A
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, guldager Kring Rasmussen D, Brix S, Jesky M, Fenton A, Ferro CJ, Karsdal MA, Genovese F, Cockwell P
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:
Rasmussen DG, Fenton A, Jesky M, Ferro C, Boor P, Tepel M, Karsdal MA, Genovese F, Cockwell P
Cerebral non-oxidative carbohydrate consumption may be driven by a β2-adrenergic mechanism. This study tested whether the 46G \u003e A (G16R) single nucleotide polymorphism of the β2-adrenergic receptor gene (ADRB2) influences the metabolic and cerebrovascular responses to administration of adrenali...
September 5, 2017
Journal:
Front Physiol
Author:
Rokamp KZ, Staalsø JM, Zaar M, Rasmussen P, Petersen LG, Nielsen RV, Secher NH, Olsen NV, Nielsen HB
BACKGROUND: In patients with cardiovascular disease, guidelines for administration of red blood cells (RBC) are mainly based on studies outside the vascular surgical setting with the recommendation to use a haemoglobin (hb) trigger-level lower than by guidelines from The European Society for Vascula...
September 1, 2017
Journal:
Acta Anaesthesiol Scand
Author:
Shahidi S, Hellemann D, Pedersen OB, Wetterslev J, Nielsen HB, Møller A
ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates ...
July 26, 2017
Journal:
PLoS One
Author:
Dower K, Zhao S, Schlerman FJ, Savary L, Campanholle G, Johnson BG, Xi L, Nguyen V, Zhan Y, Lech MP, Wang J, Nie Q, Karsdal MA, Genovese F, Boucher G, Brown TP, Zhang B, Homer BL, Martinez RV
Kidney allograft failure due to chronic injury/rejection remains the main cause of graft loss in renal transplant recipients (RTR). Here, we investigated whether specific biomarkers of extracellular matrix (ECM) turnover are associated with allograft function and chronic kidney disease (CKD) stage i...
April 21, 2017
Journal:
PLoS One
Author:
Stribos EGD, Nielsen SH, Brix S, Karsdal MA, Seelen MA, van Goor H, Bakker SJL, Olinga P, Mutsaers HAM, Genovese F
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...
April 12, 2017
Journal:
PLoS One
Author:
Genovese F, Cockwell P, Karsdal MA, Sørensen J, Ferro CJ, Jesky MD, Fenton A
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, Rasmussen DG, Yazdani S, Navis G, van Goor H, Karsdal MA, Genovese F, van den Born J
The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) su...
During chronic kidney disease (CKD) there is a dysregulation of extracellular matrix (ECM) homeostasis leading to renal fibrosis. Lysosomal proteases such as cathepsins (Cts) regulate this process in other organs, however, their role in CKD is still unknown. Here we describe a novel role for catheps...
February 1, 2016
Journal:
Sci Rep
Author:
Fox C, Cocchiaro P, Oakley F, Howarth R, Callaghan K, Leslie J, Luli S, Wood KM, Sheerin NS, Genovese F, Moles A
Background and aims: Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human ...
July 3, 2015
Journal:
Dig Dis Sci
Author:
Nielsen MJ, Lehmann J, Leeming DJ, Schierwagen R, Klein S, Jansen C, Strassburg CP, Bendtsen F, Møller S, Sauerbruch T, Karsdal MA, Krag A, Trebicka J
Background: The extent of renal fibrosis in chronic kidney disease (CKD) is the best predictor for progression of most renal diseases. To date, no established biomarkers of renal fibrosis exist. Methods: We measured circulating and urinary-specific matrix metalloproteinase (MMP)-generated collagen ...
July 1, 2015
Journal:
Nephrol Dial Transplant
Author:
Papasotiriou M, Genovese F, Klinkhammer BM, Kunter U, Nielsen SH, Karsdal MA, Floege J, Boor P
Abstract Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation w...
July 1, 2015
Journal:
J Exp Biol
Author:
McGee-Lawrence M, Buckendahl P, Carpenter C, Henriksen K, Vaughan M, Donahue S
Background: Renal fibrosis is the hallmark of progression to end-stage kidney disease. Non-invasive biomarkers of renal fibrosis could serve as specific end points in clinical trials and improve monitoring and stratification of patients with chronic kidney disease (CKD). To address this, we measured...
April 26, 2015
Journal:
Nephrol Dial Transplant
Author:
Genovese F, Boor P, Papasotiriou M, Leeming DJ, Karsdal MA, Floege J
Objective: Cardiovascular diseases are among the most common causes of mortality in renal failure patients undergoing haemodialysis. A high turnover rate of the proteoglycan versican, represented by the increased presence of its fragmentation products in plasma, has previously been associated with c...
October 29, 2014
Journal:
PLoS One
Author:
Federica Genovese 20, Karsdal MA, Leeming DJ, Scholze A, Tepel M
Interstitial fibrosis is the common endpoint of end-stage chronic kidney disease (CKD) leading to kidney failure. The clinical course of many renal diseases, and thereby of CKD, is highly variable. One of the major challenges in deciding which treatment approach is best suited for a patient but also...
March 28, 2014
Journal:
Fibrogenesis Tissue Repair
Author:
Genovese F, Manresa AA, Leeming DJ, Karsdal MA, Boor P
Objective: The 7S domain of collagen type IV (P4NP_7S) assessed in plasma represents systemic collagen type IV formation. The objective of the study was to investigate the association of systemic collagen type IV formation with survival among patients undergoing hemodialysis. Methods: We performed ...
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