Profibrotic Circulating Proteins and Risk of Early Progressive Renal Decline in Patients With Type 2 Diabetes With and Without Albuminuria.

Autor:	Ihara K; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA.; Department of Medicine, Harvard Medical School, Boston, MA.; Department of Nephrology, Tokyo Medical and Dental University, Tokyo, Japan., Skupien J; Department of Metabolic Diseases, Jagellonian University Medical College, Krakow, Poland jan.skupien@uj.edu.pl andrzej.krolewski@joslin.harvard.edu., Kobayashi H; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA.; Department of Medicine, Harvard Medical School, Boston, MA., Md Dom ZI; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA.; Department of Medicine, Harvard Medical School, Boston, MA., Wilson JM; Diabetes and Complication Department, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN., O'Neil K; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA., Badger HS; Diabetes and Complication Department, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN., Bowsman LM; Diabetes and Complication Department, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN., Satake E; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA.; Department of Medicine, Harvard Medical School, Boston, MA., Breyer MD; Diabetes and Complication Department, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN., Duffin KL; Diabetes and Complication Department, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN., Krolewski AS; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA jan.skupien@uj.edu.pl andrzej.krolewski@joslin.harvard.edu.; Department of Medicine, Harvard Medical School, Boston, MA.
Jazyk:	angličtina
Zdroj:	Diabetes care [Diabetes Care] 2020 Nov; Vol. 43 (11), pp. 2760-2767. Date of Electronic Publication: 2020 Sep 04.
DOI:	10.2337/dc20-0630
Abstrakt:	Objective: The role of fibrosis in early progressive renal decline in type 2 diabetes is unknown. Circulating WFDC2 (WAP four-disulfide core domain protein 2) and matrix metalloproteinase 7 (MMP-7; Matrilysin) are postulated to be biomarkers of renal fibrosis. This study examined an association of circulating levels of these proteins with early progressive renal decline. Research Design and Methods: Individuals with type 2 diabetes enrolled in the Joslin Kidney Study with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 were monitored for 6-12 years to ascertain fast early progressive renal decline, defined as eGFR loss ≥5 mL/min/1.73 m 2 /year. Results: A total of 1,181 individuals were studied: 681 without and 500 with albuminuria. Median eGFR and albumin-to-creatinine ratio (ACR) at baseline were 97 mL/min/1.73 m 2 and 24 mg/g, respectively. During follow-up, 152 individuals experienced fast early progressive renal decline: 6.9% in those with normoalbuminuria and 21% with albuminuria. In both subgroups, the risk of renal decline increased with increasing baseline levels of WFDC2 ( P < 0.0001) and MMP-7 ( P < 0.0001). After adjustment for relevant clinical characteristics and known biomarkers, an increase by one quartile in the fibrosis index (combination of levels of WFDC2 and MMP-7) was associated with higher risk of renal decline (odds ratio 1.63; 95% CI 1.30-2.04). The association was similar and statistically significant among patients with and without albuminuria. Conclusions: Elevation of circulating profibrotic proteins is associated with the development of early progressive renal decline in type 2 diabetes. This association is independent from albuminuria status and points to the importance of the fibrotic process in the development of early renal decline. (© 2020 by the American Diabetes Association.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu