TY - JOUR
T1 - The kidney specific protein myo -inositol oxygenase, a potential biomarker for diabetic nephropathy
AU - Gao, Peng
AU - Xu, Bo
AU - Song, Panai
AU - Zhu, Xuejing
AU - Yuan, Shuguang
AU - Kanwar, Yashipal S.
AU - Sun, Lin
N1 - Funding Information:
This work was supported by grants from the National Natural Sciences Foundation of China ( 稃猃礃?爃爃猃稂I, National Basic Research Program of China ( 球爃猃砀ᰀFC 猃甃爃眃眃爃猀 and 球爃猃稀ᰀFC 猃甃猃瘃爃爃琂I. We would like to acknowledge the help and support of the Department of Nephology, Second Xiangya Hospital, Central South University, Changsha, the China and Departments of Pathology &?edicine, Northwestern University, Chicago, USA. We also thank Dr. Kanwar, for his helpful advice on the manuscript.
Publisher Copyright:
© 2018 The Author(s). Published by S. Karger AG, Basel.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Background/Aims: Renal tubular injury plays an important role in the progression of diabetic nephropathy (DN). However, there is a lack of specific biomarkers for tubular damage in incipient DN. We have evaluated the role of myo-inositol oxygenase (MIOX) in the tubular injury of DN, but whether it could serve as a new biomarker for the early diagnosis of DN is unclear. Methods: Ninety patients with type 2 diabetes mellitus (T2DM) were divided into normoalbuminuria, microalbuminuria and macroalbuminuria groups. Fifteen patients from the last group were pathologically diagnosed as type 2 DN (T2DN), and fifteen patients with minimal change disease served as a control group. The expression of MIOX and silent information regulator 1 (Sirt1) in renal biopsies was determined by immunohistochemistry (IHC), and serum/urine MIOX, Sirt1, KIM-1 and NGAL were measured using enzyme-linked immunosorbent assays (ELISAs). Spearman's correlation and multiple regression analyses were carried out for statistical analyses. Results: Compared with the controls, MIOX expression was significantly increased in the renal tissues of T2DN patients, and was positively correlated with tubulointerstitial lesions and renal ROS production but inversely correlated with Sirt1 expression. In addition, the serum and urine MIOX were significantly increased and gradually elevated with the increasing of UACR. Interestingly, elevated MIOX levels in serum and urine were found in diabetic patients without early signs of glomerular damage (normoalbuminuric group). Further multivariate regression analysis showed that sMIOX and uMIOX correlated significantly with HbA1c, serum creatinine and logUACR, respectively. Conclusion: These data indicate that increased MIOX expression in the kidney contributes to tubular damage in DN. The concentration of MIOX in the serum and urine may serve as a new biomarker for the early diagnosis of DN.
AB - Background/Aims: Renal tubular injury plays an important role in the progression of diabetic nephropathy (DN). However, there is a lack of specific biomarkers for tubular damage in incipient DN. We have evaluated the role of myo-inositol oxygenase (MIOX) in the tubular injury of DN, but whether it could serve as a new biomarker for the early diagnosis of DN is unclear. Methods: Ninety patients with type 2 diabetes mellitus (T2DM) were divided into normoalbuminuria, microalbuminuria and macroalbuminuria groups. Fifteen patients from the last group were pathologically diagnosed as type 2 DN (T2DN), and fifteen patients with minimal change disease served as a control group. The expression of MIOX and silent information regulator 1 (Sirt1) in renal biopsies was determined by immunohistochemistry (IHC), and serum/urine MIOX, Sirt1, KIM-1 and NGAL were measured using enzyme-linked immunosorbent assays (ELISAs). Spearman's correlation and multiple regression analyses were carried out for statistical analyses. Results: Compared with the controls, MIOX expression was significantly increased in the renal tissues of T2DN patients, and was positively correlated with tubulointerstitial lesions and renal ROS production but inversely correlated with Sirt1 expression. In addition, the serum and urine MIOX were significantly increased and gradually elevated with the increasing of UACR. Interestingly, elevated MIOX levels in serum and urine were found in diabetic patients without early signs of glomerular damage (normoalbuminuric group). Further multivariate regression analysis showed that sMIOX and uMIOX correlated significantly with HbA1c, serum creatinine and logUACR, respectively. Conclusion: These data indicate that increased MIOX expression in the kidney contributes to tubular damage in DN. The concentration of MIOX in the serum and urine may serve as a new biomarker for the early diagnosis of DN.
KW - Biomarker
KW - Diabetic nephropathy
KW - Tubular damage
KW - myo-inositol oxygenase
UR - http://www.scopus.com/inward/record.url?scp=85058141962&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058141962&partnerID=8YFLogxK
U2 - 10.1159/000495635
DO - 10.1159/000495635
M3 - Article
C2 - 30504713
AN - SCOPUS:85058141962
SN - 1420-4096
VL - 43
SP - 1772
EP - 1785
JO - Kidney and Blood Pressure Research
JF - Kidney and Blood Pressure Research
IS - 6
ER -
