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

• DOI: 10.2337/dc20-0630
• Publication Date: 2020-09-05T00:26:46Z
• Authors: Katsuhito Ihara; Jan Skupien; Hiroki Kobayashi; Zaipul I. Md Dom; Jonathan M. Wilson; Kristina O’Neil; Hannah S. Badger; Lenden M. Bowsman; Eiichiro Satake; Matthew D. Breyer; Kevin L. Duffin; Andrzej S. Krolewski
• Keywords: Albuminuria

OBJECTIVE The role of fibrosis in early progressive renal decline 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 fibrosis. This study examined an association circulating levels these proteins with decline. RESEARCH DESIGN AND METHODS Individuals enrolled the Joslin Kidney Study estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 were monitored for 6–12 years ascertain fast decline, defined as eGFR loss ≥5 m2/year. RESULTS A total 1,181 individuals studied: 681 without 500 albuminuria. Median albumin-to-creatinine ratio (ACR) at baseline 97 24 mg/g, respectively. During follow-up, 152 experienced decline: 6.9% those normoalbuminuria 21% In both subgroups, risk increased increasing (P < 0.0001) MMP-7 0.0001). After adjustment relevant clinical characteristics known biomarkers, increase by one quartile index (combination MMP-7) was associated higher (odds 1.63; 95% CI 1.30–2.04). similar statistically significant among patients CONCLUSIONS Elevation profibrotic development diabetes. independent from albuminuria status points importance fibrotic process