Urinary pigment epithelium-derived factor as a marker of diabetic nephropathy.
BACKGROUND
Pigment epithelium-derived factor (PEDF), a serine protease inhibitor, regulates extracellular matrix production in the kidney. We sought the association between urinary PEDF (uPEDF) and development of nephropathy among patients with type 2 diabetes (T2DM).


METHODS
Two human studies were performed in which uPEDF was determined by ELISA. These studies included (1) a cross-sectional study of T2DM (n = 228) and healthy controls (n = 46) [corrected] and (2) a longitudinal study of hypertensive T2DM with microalbuminuria (MA; n = 42) treated with irbesartan for 6 months. An animal study was performed in which PEDF was measured in the kidney and urine samples of control rats, rats rendered diabetic with streptozotocin that were also fed a high-fat diet, and diabetic rats treated with irbesartan for 3 months.


RESULTS
Cross-sectional study: compared to controls, uPEDF was significantly higher in patients with diabetic nephropathy. uPEDF independently correlated with MA. In the MA group, uPEDF in patients with diabetic retinopathy was significantly higher than that in patients without diabetic retinopathy. Longitudinal study: irbesartan significantly decreased uPEDF in T2DM with MA. Animal study: in diabetic rats, increased PEDF was observed in both the urine and kidney samples. uPEDF showed a significant correlation with the expression of PEDF in the kidney. Irbesartan could significantly decrease the PEDF expression in the kidneys of diabetic rats as well as uPEDF.


CONCLUSIONS
uPEDF may serve as a novel marker for screening for nephropathy among patients with T2DM and monitoring the response to therapy.
Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.
Haibing
H
Chen
Zhi
Z
Zheng
Rongxia
R
Li
Junxi
J
Lu
Yuqian
Y
Bao
Xiafang
X
Ying
Rong
R
Zeng
Weiping
W
Jia
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000175:diagnosis / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D003921:Diabetes Mellitus, Experimental / Q000175:diagnosis / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000652:urine; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000652:urine*; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000652:urine; D005136:Eye Proteins / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015843:Serpins / Q000652:urine*; D000099174:Pigment Epithelium-Derived Factor
D015415:Biomarkers; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor