Serum endotrophin, a type VI collagen cleavage product, is associated with increased mortality in chronic kidney disease

Abstract

Background Patients with chronic kidney disease (CKD) are at increased risk of end-stage renal disease (ESRD) and early mortality. The underlying pathophysiological processes are not entirely understood but may include dysregulation of extracellular matrix formation with accelerated systemic and renal fibrosis. We assessed the relationship between endotrophin (ETP), a marker of collagen type VI formation, and adverse outcomes in a cohort of patients with CKD. Methods We measured serum ETP levels in 500 patients from the Renal Impairment in Secondary Care (RIISC) study, a prospective observational study of patients with high-risk CKD. Patients were followed up until death or progression to ESRD. Cox regression analysis was used to assess the relationship between ETP and risk of adverse outcomes. Results During a median follow-up time of 37 months, 104 participants progressed to ESRD and 66 died. ETP level was significantly associated with progression to ESRD (HR 1.79 [95% CI 1.59±2.02] per 10 ng/mL increase; HR 11.05 [4.98±24.52] for highest vs lowest quartile; both P<0.0001). ETP level was also significantly associated with mortality (HR 1.60 [1.35± 1.89] per 10 ng/mL increase; HR 12.14 [4.26±34.54] for highest vs lowest quartile; both P<0.0001). After adjustment for confounding variables, ETP was no longer significantly associated with progression to ESRD but remained independently associated with mortality (HR 1.51 [1.07±2.12] per 10 ng/mL increase, P = 0.019). Conclusions Serum ETP level is independently associated with mortality in CKD. This study provides the basis for further exploratory work to establish whether collagen type VI formation is mechanistically involved in the increased mortality risk associated with CKD.