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Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival

      Highlights

      • Development of a cardiovascular event is very common in chronic kidney disease patients.
      • Plasma endostatin levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction.
      • Endostatin levels are independently associated with the development of cardiovascular events in chronic kidney disease patients.
      • Plasma endostatin levels may improve the prediction for cardiovascular event above that of traditionally used risk factors.

      Abstract

      Background and aims

      Endostatin, generated from collagen XVIII, and endorepellin, possess dual activity as modifiers of both angiogenesis and endothelial cell autophagy. Plasma endostatin levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. Few data on endostatins are available for patients with chronic kidney disease (CKD). We tested whether serum endostatin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population.

      Materials and method

      A total of 519 CKD pre-dialysis patients were included. Baseline plasma endostatin levels were measured in all patients. All included patients were followed-up (time-to-event analysis) until occurrence of death, fatal or nonfatal CVEs. Fatal and nonfatal CVE including death, stroke, and myocardial infarction were recorded prospectively

      Results

      The mean age of the patients was 52.2 ± 12.3 years. There were 241 (46.4%) males, 111 (21.4%) had diabetes, 229 (44.1%) were smokers and 103 (19.8%) had a previous CVE. After a median follow-up of 46 months, 46 patients died and 172 had a new CVE. In the univariable Cox survival analysis, higher endostatin levels were associated with a higher risk for both outcomes. However, after adjusting for traditional (age, gender, smoking status, diabetes, systolic blood pressure, HDL and total cholesterol) and renal-specific (eGFR, proteinuria and hsCRP) risk factors, endostatin levels remained associated only with the CVE outcome (HR = 1.88, 95% CI 1.37–2.41 for a 1 SD increase in log endostatin values).

      Conclusion

      Endostatin levels are independently associated with incident CVE in CKD patients, but show limited prediction abilities for all-cause mortality and CVE above traditional and renal-specific risk factors.

      Keywords

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