The association between serum endostatin, kidney disease progression and mortality in patients with chronic kidney disease in the Salford Kidney Study

Background: Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular morbidity. Circulating endostatin is associated with both cardiovascular morbidity and impaired kidney function in the general population, but the utility of endostatin as a prognostic marker for CKD progression and mortality in patients with CKD is not well studied. Aim: To study the association between serum endostatin and mortality as well as kidney function decline in a cohort of patients with CKD (Salford Kidney Study; SKS). Methods: Analyses were performed on baseline and annual follow-up samples from 970 adults in the SKS cohort with CKD stage 3-5. The association with mortality was studied using Cox proportional hazard models adjusted for age, gender, systolic and diastolic blood pressure, smoking status, diabetes mellitus, prior cardiovascular disease, creatinine-based estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (uPCR). Associations between endostatin and eGFR decline were studied with linear regression analyses. eGFR decline was defined as the percentage difference between baseline eGFR and follow-up eGFR (median follow-up, 6.2 years). Results: The median age of the cohort was 66 years, with a median eGFR of 30 mL/min/1.73 m2. Multivariate Cox regression models revealed an association between higher endostatin levels and mortality with adjustments for established cardiovascular risk factors (HR:1.14; CI:1.02-1.28; p=0.02), but it was attenuated and became non-significant after adjustments for baseline eGFR and uPCR. Baseline levels of endostatin were associated with eGFR decline but were non-significant after adjustments for baseline eGFR and uPCR. Changes of endostatin concentrations during the study were significantly associated with eGFR decline in all models (regression coefficient 0.0023 % decrease per month (95 % confidence intervals 0.0012-0.0034, p<0.001)). Conclusions: The clinical utility of plasma endostatin for risk prediction in CKD patients seems limited. Importantly, longitudinal changes of endostatin were significantly associated with eGFR decline. The clinical relevance of this warrants further studies.