Ying Fan1, Yang Fei1, Li Zheng2, Jiemin Wang2, Wenzhen Xiao3, Jiejun Wen1, Yanping Xu2, Yiyun Wang1, Li He1, Jian Guan4, Jia Wei2, John Cijiang He3,5, Niansong Wang1. 1. Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. 2. Portfolio & Project management, Asia & Emerging Market iMED, AstraZeneca R&D, Shanghai, China. 3. Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 4. Department of Otolaryngology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. 5. Renal Section, James J Peter Veterans Administration Medical Center, New York, New York, USA.
Abstract
BACKGROUND/AIMS: Glomerular endothelial cell injury plays a crucial role in the development of diabetic nephropathy (DN). CD146, an endothelial marker, was shown to increase in chronic kidney disease (CKD), but its role in DN remains unknown. We aim to assess whether CD146 could be used to evaluate disease severity and predict renal outcomes in DN at early stages. METHODS: 159 non-dialysis type 2-DN patients from 2008 to 2015 were enrolled to measure the plasma concentration of soluble CD146 (sCD146). 94 type 2 diabetes mellitus patients without DN and 100 healthy subjects were used as controls. The patients with CKD stage 1-3 were referred as early stage patients. Another independent cohort of 48 patients with biopsy-proved DN was used for the immunohistochemistry study of CD146. Renal outcomes were defined as doubling of serum creatinine, initiation of renal replacement therapy or death. RESULTS: We found that plasma level of sCD146 was upregulated and associated with renal function in DN patients. sCD146 was proved to be a more optimal marker than urine albumin creatinine ratio to evaluate disease severity in these DN patients. The kidney expression of CD146 was co-localized with endothelial marker CD31 and increased in DN. CD146 staining in kidney was correlated with the severity of pathological changes in DN patients. Survival analysis suggested that both plasma and biopsy expression of CD146 were correlated with renal outcomes. CONCLUSIONS: CD146 is associated with kidney injury and could be a good marker to predict renal outcomes in patients with early stages of DN.
BACKGROUND/AIMS: Glomerular endothelial cell injury plays a crucial role in the development of diabetic nephropathy (DN). CD146, an endothelial marker, was shown to increase in chronic kidney disease (CKD), but its role in DN remains unknown. We aim to assess whether CD146 could be used to evaluate disease severity and predict renal outcomes in DN at early stages. METHODS: 159 non-dialysis type 2-DN patients from 2008 to 2015 were enrolled to measure the plasma concentration of soluble CD146 (sCD146). 94 type 2 diabetes mellituspatients without DN and 100 healthy subjects were used as controls. The patients with CKD stage 1-3 were referred as early stage patients. Another independent cohort of 48 patients with biopsy-proved DN was used for the immunohistochemistry study of CD146. Renal outcomes were defined as doubling of serum creatinine, initiation of renal replacement therapy or death. RESULTS: We found that plasma level of sCD146 was upregulated and associated with renal function in DN patients. sCD146 was proved to be a more optimal marker than urine albumin creatinine ratio to evaluate disease severity in these DN patients. The kidney expression of CD146 was co-localized with endothelial marker CD31 and increased in DN. CD146 staining in kidney was correlated with the severity of pathological changes in DN patients. Survival analysis suggested that both plasma and biopsy expression of CD146 were correlated with renal outcomes. CONCLUSIONS:CD146 is associated with kidney injury and could be a good marker to predict renal outcomes in patients with early stages of DN.
Authors: Virginie Royal; Jarcy Zee; Qian Liu; Carmen Avila-Casado; Abigail R Smith; Gang Liu; Laura H Mariani; Stephen Hewitt; Lawrence B Holzman; Brenda W Gillespie; Jeffrey B Hodgin; Laura Barisoni Journal: J Am Soc Nephrol Date: 2020-02-21 Impact factor: 10.121
Authors: Amena Keshawarz; Shih-Jen Hwang; Gha Young Lee; Zhi Yu; Chen Yao; Anna Köttgen; Daniel Levy Journal: PLoS One Date: 2022-05-11 Impact factor: 3.752