Urinary Cyclophilin A as a New Marker for Diabetic Nephropathy: A Cross-Sectional Analysis of Diabetes Mellitus.
Type 2 diabetes mellitus (DM) is the most common single cause of end-stage renal disease. Albuminuria is the most commonly used marker to predict onset of diabetic nephropathy (DN) without enough sensitivity and specificity to detect early DN. This is the first study to identify urinary cyclophilin A (CypA) as a new biomarker for early DN.We recruited DM outpatients and healthy control subjects from January 2014 to December 2014. In this cross-sectional study, patients' urine samples were collected to determine the expression of urinary CypA. We also treated mesangial (MES-13) and tubular (HK-2) cells with glucose or free radicals to observe the expression of secreted CypA in Western blot analysis.A total of 100 DN patients and 20 healthy control subjects were enrolled. All variables were matched. In univariate analysis, the concentration of urinary CypA correlated well with the progression of renal function. A significant increase in urinary CypA was noted in stage 2 DN and persisted in later stages. We could diagnose stage 2 DN using urinary CypA with a sensitivity of 90.0% and specificity of 72.7%. The area under curve was up to 0.85, indicating a good discriminatory power. In cellular models, MES-13 and HK-2 cells can both release CypA.Urinary CypA is a good biomarker for early DN detection in humans and it can be released from either mesangial or tubular cells. The underlying molecular mechanisms still need further clarification in cellular and animal studies.
From the Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital (S-FT, M-JW, C-HC); School of Medicine, China Medical University (S-FT, C-HC); Department of Life Science, Tunghai University (S-FT, C-WS, C-HC, MH); School of Medicine, Chung Shan Medical University (M-JW, C-HC); Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taichung (C-PF); Vascular and Genomic Research Center, Changhua Christian Hospital, Changhua (C-SL); and Life Science Research Center, Tunghai University, Taichung, Taiwan R.O.C. (MH).
Shang-Feng
SF
Tsai
Chien-Wei
CW
Su
Ming-Ju
MJ
Wu
Cheng-Hsu
CH
Chen
Chia-Po
CP
Fu
Chin-San
CS
Liu
Mingli
M
Hsieh
D000328:Adult; D015415:Biomarkers / Q000652:urine; D003430:Cross-Sectional Studies; D021984:Cyclophilin A / Q000652:urine*; D003928:Diabetic Nephropathies / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D021984:Cyclophilin A