TY - JOUR

T1 - Circulating Levels of Endotrophin Are Prognostic for Long-Term Mortality after AKI

AU - Sparding, Nadja

AU - Rasmussen, Daniel Guldager Kring

AU - Genovese, Federica

AU - Karsda, Morten Asser

AU - Hornum, Mads

AU - Feldt-Rasmussen, Bo

AU - Packington, Rebecca

AU - Selby, Nicholas M.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - acute kidney injury and ICU nephrology

KW - AKI

KW - basic science

KW - biomarker

KW - collagen type VI

KW - endotrophin

KW - fibrosis

KW - peptide fragments

KW - prognosis

KW - ACUTE KIDNEY INJURY

KW - VI

U2 - 10.34067/KID.0000422021

DO - 10.34067/KID.0000422021

M3 - Journal article

C2 - 36128492

VL - 3

SP - 809

EP - 817

JO - Kidney360

JF - Kidney360

SN - 2641-7650

IS - 5

ER -