Urinary afamin levels are associated with the progression of diabetic nephropathy

医学 糖尿病肾病 肌酐 肾功能 泌尿系统 糖尿病 肾脏疾病 尿 内科学 泌尿科 内分泌学 肾病 蛋白尿
作者
Yasushi Kaburagi,Eri Takahashi,Hiroshi Kajio,Satoshi Yamashita,Ritsuko Yamamoto‐Honda,Tomoko Shiga,Akinori Okumura,Atsushi Goto,Yuka Fukazawa,Norio Seki,Kazuyuki Tobe,Michihiro Matsumoto,Mitsuhiko Noda,Hiroyuki Unoki-Kubota
出处
期刊:Diabetes Research and Clinical Practice [Elsevier BV]
卷期号:147: 37-46 被引量:16
标识
DOI:10.1016/j.diabres.2018.02.034
摘要

Aims In this study, we applied quantitative proteomic analysis to identify urinary proteins associated with diabetic nephropathy (DN). Methods Two-dimensional image-converted analysis of liquid chromatography and mass spectrometry detected the proteins differentially excreted between normoalbuminuric and macroalbuminuric patients with type 2 diabetes mellitus (T2DM) (n = 6 each). Urinary levels of excreted proteins were measured by multiple reaction monitoring (MRM) analysis using an independent sample set (n = 77). Urinary afamin levels were measured by ELISA in T2DM and DN patients enrolled in this cohort study (n = 203). Results One-hundred-four proteins displayed significant alterations in excretion. Nine of these candidates were validated by MRM analysis. Among them, the levels of afamin, CD44 antigen, and lysosome-associated membrane glycoprotein 2, which have not previously been implicated in DN, were significantly associated with both the urinary albumin to creatinine ratio (ACR) and eGFR. We further measured afamin levels in urine collected from T2DM patients who did not yet have significant kidney disease (ACR < 300 mg/g or eGFR change rate ≤ 3.3%/year). The urinary afamin to creatinine ratio (Afa/Cre) was significantly higher in patients who progressed to a more severe DN stage or had early renal decline than in patients who did not. Conclusions Afa/Cre was significantly increased in T2DM patients who subsequently developed DN. Afa/Cre may be useful to predict patients with T2DM at high risk of nephropathy before the development of macroalbuminuria or reduced kidney function, although further validation studies in a larger population are needed.
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