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C-terminal agrin fragment

Zhiguo Li, Minshu Li, Kristofer Wood, Steffan Hettwer, Suraj A Muley, Fu-Dong Shi, Qiang Liu, Shafeeq S Ladha
INTRODUCTION: Agrin is essential for the formation and maintenance of neuromuscular junctions (NMJs). NT-1654 is a C-terminal fragment of mouse neural agrin. In this study, we determined the effects of NT-1654 on the severity of experimental autoimmune myasthenia gravis (EAMG). METHODS: EAMG was induced in female Lewis rats by immunization with the Torpedo acetylcholine receptor (tAChR) and complete Freund's adjuvant (CFA). NT-1654 was dissolved in phosphate-buffered saline (PBS) and injected daily subcutaneously into tAChR immunized rats during the first 10 days after immunization, and then every other day for the following 20 days...
November 28, 2017: Muscle & Nerve
T Gagliano-Jucá, T W Storer, K M Pencina, T G Travison, Z Li, G Huang, S Hettwer, P Dahinden, S Bhasin, S Basaria
In a subset of men, sarcopenia and physical dysfunction occur due to destabilization of the neuromuscular junction (NMJ), which is manifested by elevated serum concentrations of C-terminal agrin fragment (CAF). Testosterone administration improves physical function in some studies; however, its effects on serum circulating CAF concentrations remain unknown. Here we evaluate the effects of testosterone administration on circulating CAF levels in mobility-limited men with low testosterone aged 65 or older participating in the Testosterone in Older Men with Mobility Limitations (TOM) Trial...
January 2018: Andrology
Spyridon Arampatzis, Georgios Chalikias, Vasilios Devetzis, Stavros Konstantinides, Uyen Huynh-Do, Dimitrios Tziakas
BACKGROUND: Patients with acute myocardial infarction are at high risk for acute kidney injury. Novel biomarkers that can predict acute kidney injury in AMI may allow timely interventions. C-terminal fragment of agrin (CAF), a proteoglycan of the glomerular and tubular basement membrane, have been recently associated with rapid renal function deterioration and proximal tubular dysfunction. It is unknown whether elevated CAF levels may serve as a novel AKI biomarker in patients presenting with AMI...
June 24, 2017: BMC Nephrology
Dan Yu, Hai-Xia Li, Yi Liu, Ze-Wei Ying, Jing-Jing Guo, Chen-Ying Cao, Jia Wang, Yuan-Fang Li, Hui-Rong Yang
BACKGROUND: C-terminal agrin fragment (CAF) has been shown to be a promising new biomarker for kidney function. The aim of this study was to verify the reference intervals for CAF in Chinese healthy adults and to assess the efficiency of CAF for monitoring renal function after transplantation. METHODS: Serum samples were collected from 200 healthy adult subjects and 60 living donor kidney recipients before and on day 1, day 2 and at 6 months after transplantation...
May 2017: Journal of Clinical Laboratory Analysis
Arezoo Daryadel, Monika Haubitz, Marta Figueiredo, Dominik Steubl, Marcel Roos, Armin Mäder, Stefan Hettwer, Carsten A Wagner
Agrin, a multidomain proteoglycan and neurotrypsin, a neuronal serine protease, are important for forming (neuromuscular) synapses. Proteolytical activity of neurotrypsin produces a C-terminal fragment of agrin, termed CAF, of approximately 22 kDA molecular size which also circulates in blood. The presence of CAF in urine suggests either glomerular filtration or secretion into urine. Blood levels of CAF have been identified as a potential novel marker of kidney function. Here we describe that several nephron segments in the mouse kidney express agrin and neutrotrypsin in addition to the localization of both protein in the glomerulum...
2016: PloS One
Nadja Scherbakov, Michael Knops, Nicole Ebner, Miroslava Valentova, Anja Sandek, Ulrike Grittner, Pius Dahinden, Stefan Hettwer, Jörg C Schefold, Stephan von Haehling, Stefan D Anker, Michael Joebges, Wolfram Doehner
BACKGROUND: C-terminal Agrin Fragment (CAF) has been proposed as a novel biomarker for sarcopenia originating from the degeneration of the neuromuscular junctions. In patients with stroke muscle wasting is a common observation that predicts functional outcome. We aimed to evaluate agrin sub-fragment CAF22 as a marker of decreased muscle mass and physical performance in the early phase after acute stroke. METHODS: Patients with acute ischaemic or haemorrhagic stroke (n = 123, mean age 70 ± 11 y, body mass index BMI 27...
March 2016: Journal of Cachexia, Sarcopenia and Muscle
Francesco Landi, Riccardo Calvani, Maria Lorenzi, Anna Maria Martone, Matteo Tosato, Michael Drey, Emanuela D'Angelo, Ettore Capoluongo, Andrea Russo, Roberto Bernabei, Graziano Onder, Emanuele Marzetti
BACKGROUND: The C-terminal agrin fragment (CAF), a circulating byproduct of neuromuscular junction disassembly, has been proposed as a possible biomarker for sarcopenia. However, its validity in "real-world", multimorbid older persons is currently unknown. The present study was undertaken to verify if serum CAF levels were associated with sarcopenia in a population of old and very old persons living in the community. METHODS: Data were from the ilSIRENTE Aging and Longevity Study, a prospective cohort study conducted in all persons aged 80years and older residing in the Sirente geographic area (Italy; n=332)...
June 15, 2016: Experimental Gerontology
Dominik Steubl, Marcel Roos, Stefan Hettwer, Susanne Angermann, Ming Wen, Christoph Schmaderer, Peter Luppa, Uwe Heemann, Lutz Renders
BACKGROUND/AIMS: This study compares the peritoneal elimination of the low-molecular-weight-protein (LMWP) C-terminal agrin fragment (tCAF, size 22 kDa), a promising biomarker for kidney function, in continuous cycling peritoneal dialysis (CCPD) and continuous ambulatory peritoneal dialysis (CAPD). METHODS: 103 sets of serum, 24h-urine and dialysate samples were obtained in 15 CCPD (63 sets) and 11 CAPD (40 sets) patients. Total, renal and peritoneal substrate removals/clearances were measured/calculated for tCAF, creatinine, blood-urea-nitrogen (BUN), cystatin C and albumin and correlated with the peritoneal transport type...
2016: Kidney & Blood Pressure Research
Dominik Steubl, Marcel Roos, Stefan Hettwer, Robin Satanovskij, Susanne Tholen, Ming Wen, Christoph Schmaderer, Anna-Lena Hasenau, Peter Luppa, Lynne Stecher, Uwe Heemann, Lutz Renders
BACKGROUND: Total C-terminal agrin fragment (tCAF) is a new biomarker that was previously correlated with kidney function. This article studies the validity of tCAF as a biomarker for kidney function in chronic kidney disease (CKD). METHODS: Plasma tCAF, serum creatinine (Cr), cystatin C (CyC), blood urea-nitrogen (BUN) concentrations and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals [71 without CKD (CKD 0°) and 355 CKD patients]...
September 1, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
Vasilios Devetzis, Arezoo Daryadel, Stefanos Roumeliotis, Marios Theodoridis, Carsten A Wagner, Stefan Hettwer, Uyen Huynh-Do, Passadakis Ploumis, Spyridon Arampatzis
BACKGROUND: Diabetes is the leading cause of CKD in the developed world. C-terminal fragment of agrin (CAF) is a novel kidney function and injury biomarker. We investigated whether serum CAF predicts progression of kidney disease in type 2 diabetics. METHODS: Serum CAF levels were measured in 71 elderly patients with diabetic nephropathy using a newly developed commercial ELISA kit (Neurotune®). Estimated glomerular filtration rate (eGFR) and proteinuria in spot urine were assessed at baseline and after 12 months follow up...
2015: PloS One
I Bondoc, S K Cochrane, T S Church, P Dahinden, S Hettwer, F-C Hsu, R S Stafford, M Pahor, T W Buford
OBJECTIVES: C-terminal Agrin Fragment (CAF) has been proposed as a potential circulating biomarker for predicting changes in physical function among older adults. To determine the effect of a one-year PA intervention on changes in CAF concentrations and to evaluate baseline and longitudinal associations between CAF concentrations and indices of physical function. DESIGN: Ancillary study to the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P), a multi-site randomized clinical trial designed to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability...
November 2015: Journal of Nutrition, Health & Aging
Lisa Steinbeck, Nicole Ebner, Miroslava Valentova, Tarek Bekfani, Sebastian Elsner, Pius Dahinden, Stefan Hettwer, Nadja Scherbakov, Jörg C Schefold, Anja Sandek, Jochen Springer, Wolfram Doehner, Stefan D Anker, Stephan von Haehling
AIMS: Skeletal muscle wasting affects 20% of patients with chronic heart failure and has serious implications for their activities of daily living. Assessment of muscle wasting is technically challenging. C-terminal agrin-fragment (CAF), a breakdown product of the synaptically located protein agrin, has shown early promise as biomarker of muscle wasting. We sought to investigate the diagnostic properties of CAF in muscle wasting among patients with heart failure. METHODS AND RESULTS: We assessed serum CAF levels in 196 patients who participated in the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF)...
December 2015: European Journal of Heart Failure
Dominik Steubl, Anna Vogel, Stefan Hettwer, Susanne Tholen, Peter B Luppa, Ina-Christine Rondak, Lutz Renders, Uwe Heemann, Marcel Roos
BACKGROUND: C-terminal agrin fragment (CAF), cleavage product of agrin, was previously correlated with kidney function in renal transplant patients. This article studies the predictive value of CAF for long-term outcomes in renal transplant recipients. METHODS: In this observational cohort study, serum CAF, creatinine and blood-urea-nitrogen (BUN) concentrations and eGFR (CKD-EPI) were assessed 1-3 months after transplantation in 105 patients undergoing kidney transplantation...
January 2016: Clinical Chemistry and Laboratory Medicine: CCLM
Alexander Kalinkovich, Gregory Livshits
Sarcopenia, an age-related decline in skeletal muscle mass and function, dramatically affects the life quality of elder people. In view of increasing life expectancy, sarcopenia renders a heavy burden on the health care system. However, although there is a consensus that sarcopenia is a multifactorial syndrome, its etiology, underlying mechanisms, and even definition remain poorly delineated, thus, preventing development of a precise treatment strategy. The main aim of our review is to critically analyze potential sarcopenia biomarkers in light of the molecular mechanisms of their involvement in sarcopenia pathogenesis...
July 2015: Ageing Research Reviews
Michael Drey, Michael Behnes, Robert Kob, Dominic Lepiorz, Stefan Hettwer, Cornelius Bollheimer, Cornel C Sieber, Thomas Bertsch, Ursula Hoffmann
BACKGROUND: One of the main causes of acute kidney injury (AKI) in patients treated on an intensive care unit (ICU) is sepsis. The identification of new biomarkers indicating the early development and future course of AKI are of utmost medical interest. The C-terminal agrin fragment (CAF) is measurable in blood serum and might reflect kidney function. Therefore, this study evaluates CAF in patients presenting to an internal ICU with severe sepsis or septic shock. Serum levels of CAF are correlated with biomarkers of kidney function, markers of systemic inflammation, and the presence of AKI and renal replacement therapy (RRT)...
2015: Clinical Laboratory
Dominik Steubl, Stefan Hettwer, Pius Dahinden, Peter Luppa, Ina-Christine Rondak, Claudia Regenbogen, Konrad F Stock, Lutz Renders, Uwe Heemann, Marcel Roos
BACKGROUND: C-terminal agrin fragment (CAF, size 22 kDa) is a promising new biomarker for kidney function. This study evaluated the usefulness of CAF as a serum biomarker for residual renal function (RRF) in patients undergoing automated peritoneal dialysis (APD). PATIENTS AND METHODS: Serum, urine and dialysate samples were obtained in 12 end-stage renal disease patients undergoing APD. Total, renal and peritoneal clearances were calculated for CAF, creatinine, blood urea nitrogen (BUN) and cystatin c...
February 2015: International Urology and Nephrology
Emanuele Marzetti, Riccardo Calvani, Maria Lorenzi, Federico Marini, Emanuela D'Angelo, Anna Maria Martone, Michela Celi, Matteo Tosato, Roberto Bernabei, Francesco Landi
BACKGROUND: Serum concentrations of the C-terminal fragment of agrin (CAF), a component of the neuromuscular junction (NMJ), are elevated in older community-dwellers with sarcopenia. Whether CAF may be used as a marker for muscle wasting in the presence of NMJ mechanical damage is presently unknown. The present study was undertaken to verify if serum CAF levels were associated with sarcopenia in older hip fractured patients. METHODS: Analyses were conducted in older adults hospitalized for traumatic hip fracture...
December 2014: Experimental Gerontology
Jeffrey R Stout, Maren S Fragala, Jay R Hoffman, Edward H Robinson, William P Mccormack, Jeremy R Townsend, Adam R Jatjner, Nadia S Emerson, Leonardo P Oliveira, David H Fukuda
INTRODUCTION: The aim of this study was to examine the relationship between serum C-terminal agrin fragment (CAF) concentrations and neuromuscular fatigue in older adults. METHODS: Twenty-two healthy older men and women volunteered for this study. Resting fasted blood samples were collected and prepared for measurement of serum CAF concentration by a commercially available ELISA kit. The onset of neuromuscular fatigue was measured by monitoring electromyographic fatigue curves from the vastus lateralis muscle using the physical working capacity at fatigue threshold (PWCFT ) test...
January 2015: Muscle & Nerve
Dominik Steubl, Stefan Hettwer, Pius Dahinden, Petra Wolf, Peter Luppa, Carsten A Wagner, Claudius Küchle, Christoph Schmaderer, Lutz Renders, Uwe Heemann, Marcel Roos
C-terminal agrin fragment (CAF, 22 kDa) has been shown to be a promising new rapid biomarker for kidney function. This study evaluated the influence of hemodialysis (HD) and hemodiafiltration (HDF) treatment on serum CAF concentrations in patients with end-stage renal disease (ESRD). A total of 36 patients with ESRD undergoing chronic HD/HDF treatment were enrolled (21 high-flux-HD/Fx60 membrane, 7 high-flux-HD/Elisio19H membrane, and 8 HDF/Elisio19H membrane). On a midweek session, blood samples were obtained before, at halftime, and post-treatment...
November 2014: Translational Research: the Journal of Laboratory and Clinical Medicine
Dominik Steubl, Stefan Hettwer, Wim Vrijbloed, Pius Dahinden, Petra Wolf, Peter Luppa, Carsten A Wagner, Lutz Renders, Uwe Heemann, Marcel Roos
BACKGROUND: The C-terminal agrin fragment (CAF) is a cleavage product of agrin, the major proteoglycan of the glomerular basement membrane. This article studies if CAF could serve as a biomarker for renal function in renal transplant recipients. MATERIAL AND METHODS: We measured serum CAF and creatinine concentrations and calculated estimated glomerular filtration rate (eGFR) (MDRD) in 96 healthy individuals and in 110 end-stage renal disease patients undergoing kidney transplantation before and after transplantation...
2013: American Journal of Nephrology
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