Nadja Sparding1,2, Daniel Guldager Kring Rasmussen1, Federica Genovese1, Morten Asser Karsdal1, Mads Hornum3,4, Bo Feldt-Rasmussen3,4, Rebecca Packington5, Nicholas M Selby5,6. 1. Nordic Bioscience, Herlev, Denmark. 2. Biomedical Sciences, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark. 3. Department of Nephrology, Rigshospitalet, Copenhagen, Denmark. 4. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 5. Centre for Kidney Research and Innovation, Academic Unit for Translational Medical Sciences, University of Nottingham, Nottingham, United Kingdom. 6. Department of Renal Medicine, University Hospitals of Derby and Burton, Derby, United Kingdom.
Abstract
Background: AKI involves a rapid decrease in kidney function that may be associated with structural damage. Early markers predicting AKI are emerging, but tools to assess patients' long-term health risks after AKI are still lacking. Endotrophin (ETP) is a bioactive molecule released during the formation of collagen type VI. We evaluated the potential of circulating ETP as a prognostic biomarker of adverse outcomes after AKI. Methods: We measured ETP in plasma samples collected 1 year after an episode of AKI, using the PRO-C6 ELISA in 801 patients (393 patients with AKI and 408 controls) from the prospective AKI Risk in Derby (ARID) study (ISRCTN25405995), who were then followed until year 3. Kidney disease progression was defined as ≥25% decline in eGFR combined with a decline in CKD stage. Results: ETP levels were significantly higher in the AKI group compared with controls (P<0.001). In the AKI group, ETP could discriminate patients with kidney disease progression at year 3 (AUC=0.67, P<0.01), whereas eGFR could not (AUC=0.51, P=0.57). In logistic regression including common risk factors, ETP was independently associated with kidney disease progression in patients with AKI (OR=1.10, P<0.01). ETP could discriminate survivors from nonsurvivors at year 3 (AUC=0.64, P<0.01). In a Cox proportional hazards regression for mortality after AKI that included common risk factors, only ETP (HR=1.05; P<0.001) and age (HR=1.06, P<0.01) were retained in the final model. Conclusions: Patients in the AKI group had higher levels of plasma ETP at year 1 as compared with those who had not had AKI. In the AKI group, ETP levels predict kidney disease progression and mortality. Because ETP is a profibrotic molecule, our findings may indicate that ETP identifies patients with active fibrogenesis after AKI, suggestive of long-term renal remodeling, which is associated with patient outcome.
Background: AKI involves a rapid decrease in kidney function that may be associated with structural damage. Early markers predicting AKI are emerging, but tools to assess patients' long-term health risks after AKI are still lacking. Endotrophin (ETP) is a bioactive molecule released during the formation of collagen type VI. We evaluated the potential of circulating ETP as a prognostic biomarker of adverse outcomes after AKI. Methods: We measured ETP in plasma samples collected 1 year after an episode of AKI, using the PRO-C6 ELISA in 801 patients (393 patients with AKI and 408 controls) from the prospective AKI Risk in Derby (ARID) study (ISRCTN25405995), who were then followed until year 3. Kidney disease progression was defined as ≥25% decline in eGFR combined with a decline in CKD stage. Results: ETP levels were significantly higher in the AKI group compared with controls (P<0.001). In the AKI group, ETP could discriminate patients with kidney disease progression at year 3 (AUC=0.67, P<0.01), whereas eGFR could not (AUC=0.51, P=0.57). In logistic regression including common risk factors, ETP was independently associated with kidney disease progression in patients with AKI (OR=1.10, P<0.01). ETP could discriminate survivors from nonsurvivors at year 3 (AUC=0.64, P<0.01). In a Cox proportional hazards regression for mortality after AKI that included common risk factors, only ETP (HR=1.05; P<0.001) and age (HR=1.06, P<0.01) were retained in the final model. Conclusions: Patients in the AKI group had higher levels of plasma ETP at year 1 as compared with those who had not had AKI. In the AKI group, ETP levels predict kidney disease progression and mortality. Because ETP is a profibrotic molecule, our findings may indicate that ETP identifies patients with active fibrogenesis after AKI, suggestive of long-term renal remodeling, which is associated with patient outcome.
Authors: David P Basile; Joseph V Bonventre; Ravindra Mehta; Masaomi Nangaku; Robert Unwin; Mitchell H Rosner; John A Kellum; Claudio Ronco Journal: J Am Soc Nephrol Date: 2015-10-30 Impact factor: 10.121
Authors: Kerry L Horne; Rebecca Packington; John Monaghan; Timothy Reilly; Christopher W McIntyre; Nicholas M Selby Journal: Nephron Clin Pract Date: 2014-11-28
Authors: Marlies Ostermann; Alexander Zarbock; Stuart Goldstein; Kianoush Kashani; Etienne Macedo; Raghavan Murugan; Max Bell; Lui Forni; Louis Guzzi; Michael Joannidis; Sandra L Kane-Gill; Mathieu Legrand; Ravindra Mehta; Patrick T Murray; Peter Pickkers; Mario Plebani; John Prowle; Zaccaria Ricci; Thomas Rimmelé; Mitchell Rosner; Andrew D Shaw; John A Kellum; Claudio Ronco Journal: JAMA Netw Open Date: 2020-10-01
Authors: Daniel G K Rasmussen; Tine W Hansen; Bernt J von Scholten; Signe H Nielsen; Henrik Reinhard; Hans-Henrik Parving; Martin Tepel; Morten A Karsdal; Peter K Jacobsen; Federica Genovese; Peter Rossing Journal: Diabetes Care Date: 2018-04-11 Impact factor: 19.112
Authors: Shu Sun; Kim Henriksen; Morten A Karsdal; Inger Byrjalsen; Jörn Rittweger; Gabriele Armbrecht; Daniel L Belavy; Dieter Felsenberg; Anders F Nedergaard Journal: PLoS One Date: 2015-12-07 Impact factor: 3.240