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

Abstract

Background: Acute kidney injury (AKI) is 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 formation of collagen type VI. We evaluated the potential of circulating ETP as a prognostic biomarker of adverse outcome following 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 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 to 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 non-survivors 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 to those who had not had AKI. In the AKI group, ETP levels predict kidney disease progression and mortality. Since endotrophin is a pro-fibrotic 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.

Roles of NAD+ in Acute and Chronic Kidney Diseases

“…Other studies revealed that adhesive glycoprotein fibronectin (FN) is also found [202][203][204]. Our group recently showed that circulating endotrophin, a collagen VI precursor, was involved in the pathogenesis and was a prognostic for mortality after AKI [205]; it was also involved in the development of fibrosis following IgA nephritis and ANCA vasculitis [206].…”

Outcome of use of a novel Modulator of Oxidative Phosphorylation on kidney function in patients with Chronic Kidney disease

“…NAD molecules and their activity in electron transfer in renal tissue has been shown to be low in CKD states. These cascade of oxidative in ammatory cells markers have been shown to contribute to renal brosis (19)(20)(21). Mitochondrial dysfunction has also been observed in CKD, and preventing mitochondrial damage reduces brogenesis in rat models (22).…”