title: The association between endostatin and kidney disease and mortality in patients with type 2 diabetes.
abstract: OBJECTIVE
  Circulating endostatin, a biologically active derivate of collagen XVIII, is considered to be a marker of kidney disease and a risk factor for its related mortality. However, less is known of the role of endostatin in diabetes and the development of diabetic nephropathy. For this reason, our study investigated the associations between circulating endostatin and the prevalence and progression of kidney disease, and its mortality risk in patients with type 2 diabetes (T2D).
  
  
  METHODS
  This was a cohort study of 607 patients with T2D (mean age: 61 years, 44% women). Estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was used to assess the patients' kidney function decline and mortality.
  
  
  RESULTS
  Of the total study cohort, 20 patients declined by ≥20% in eGFR over 4 years, and 44 died during the follow-up (mean duration: 6.7 years). At baseline, participants with diabetic nephropathy (defined as eGFR<60mL/min/1.73m2) and/or microalbuminuria [defined as a urinary albumin-to-creatinine ratio (ACR)>3g/mol] had higher median levels of endostatin than those without nephropathy (62.7μg/L vs 57.4μg/L, respectively; P=0.031). In longitudinal analyses adjusted for age, gender, baseline eGFR and ACR, higher endostatin levels were associated with a higher risk of decline (≥20% in eGFR, OR per 1 SD increase: 1.73, 95% CI: 1.13-2.65) and a higher risk of mortality (HR per 1 SD increase: 1.57, 95% CI: 1.19-2.07).
  
  
  CONCLUSIONS
  In patients with T2D, circulating endostatin levels can predict the progression of kidney disease and mortality independently of established kidney disease markers. The clinical usefulness of endostatin as a risk marker in such patients merits further studies.
authors.affiliation: Division of Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden. Electronic address: axelcefam@hotmail.com.
authors.forename: A C
authors.initials: AC
authors.lastname: Carlsson
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: C J
authors.initials: CJ
authors.lastname: Östgren
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Länne
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: F H
authors.initials: FH
authors.lastname: Nystrom
authors.affiliation: Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Ärnlöv
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000401:mortality; D043169:Endostatins / Q000097:blood*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000401:mortality
chemical_list: D043169:Endostatins
keywords: Albumin-to-creatinine ratio; Angiogenesis; Chronic kidney disease; Community; Extracellular matrix remodeling; NIDDM