Circulating endotrophin (ETP) may be a prognostic biomarker of kidney disease progression and mortality following acute kidney injury (AKI), according to new study findings.

ETP is a bioactive molecule released during formation of collagen type VI, such as occurs during maladaptive repair processes in the kidney. “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,” Nadja Sparding, PhD, of Nordic Bioscience, Denmark, and colleagues wrote in Kidney360.

In the AKI Risk in Derby (ARID) study, the investigators matched 393 hospitalized patients with AKI and 408 without AKI (control group) by baseline estimated glomerular filtration rate (eGFR), age, and diabetes status. The measured ETP by PRO-C6 ELISA.

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Within 3 years, 7.7% of the AKI group and 4.6% of the control group had experienced kidney disease progression, defined as a 25% or more decline in eGFR along with an increase in chronic kidney disease (CKD) stage.

ETP measured at year 1 distinguished patients with kidney disease progression at year 3 in the AKI group (AUC=0.67) but not in the control group. In the AKI group, year 1 ETP was a significantly better discriminator than year 1 eGFR for progression, Dr Sparding and colleagues reported. In a multivariate model, ETP was independently associated with 1.1-fold increased odds of kidney disease progression in the AKI group.

Death occurred in 10.9% and 6.6% of the AKI and control group, respectively. Year 1 ETP levels were significantly lower among survivors than nonsurvivors with AKI at year 3 (median 10.68 vs 12.66 ng/mL), the investigators reported. Further, year 1 ETP significantly distinguished survivors from nonsurvivors in the AKI group (AUC=0.64) but not in the control group. Patients with the highest tertile of ETP (12.80-84.9 ng/mL) in the AKI group were significantly more likely to die compared with the control group. In adjusted Cox proportional hazards regression, year 1 ETP was independently associated with a 5% increased risk for mortality, whereas eGFR was not. According to Dr Sparding’s team, “This could indicate that ETP release is triggered by processes that follow the episode of AKI, whereas a change in eGFR might be the result of a range of processes.”

“Endotrophin, measured by PRO-C6, is a promising and novel post-AKI biomarker that needs to be validated in larger AKI cohorts, ideally with kidney biopsy available to confirm that the biomarker directly reflects fibrosis (although this may be challenging to achieve),” according to the investigators.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Sparding N, Guldager Kring Rasmussen D, Genovese F, et al. Circulating levels of endotrophin are prognostic for long-term mortality after acute kidney injury. Kidney360. Published online March 3, 2022. doi:10.34067/KID.0000422021