The association between endostatin and kidney disease and mortality in patients with type 2 diabetes

• Published in: Diabetes & metabolism Vol. 42; no. 5; pp. 351 - 357
• Main Authors: Carlsson, A.C, Östgren, C.J, Länne, T, Larsson, A, Nystrom, F.H, Ärnlöv, J
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-11-2016
• Subjects: Albumin-to-creatinine ratio; Angiogenesis; Chronic kidney disease; Community; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - mortality; Endocrinology & Metabolism; Endostatins - blood; Extracellular matrix remodeling; Female; Health and Welfare; Humans; Hälsa och välfärd; Internal Medicine; Longitudinal Studies; Male; Medicin och hälsovetenskap; Middle Aged; NIDDM; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - epidemiology; Renal Insufficiency, Chronic - mortality; Angiogenesis; Chronic kidney disease; Extracellular matrix remodeling; Albumin-to-creatinine ratio; Community; NIDDM
• ISSN: 1262-3636; 1878-1780; 1878-1780
• DOI: 10.1016/j.diabet.2016.03.006

Abstract Aim 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 < 60 mL/min/1.73 m2 ) and/or microalbuminuria [defined as a urinary albumin-to-creatinine ratio (ACR) > 3 g/mol] had higher median levels of endostatin than those without nephropathy (62.7 μg/L vs 57.4 μg/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). Conclusion 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.