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Nephrol Dial Transplant. 2018 Oct 23. doi: 10.1093/ndt/gfy314. [Epub ahead of print]

Associations of urinary epidermal growth factor and monocyte chemotactic protein-1 with kidney involvement in patients with diabetic kidney disease.

Wu L1,2,3,4, Li XQ1,2,3,4, Chang DY1,2,3,4, Zhang H5, Li JJ5, Wu SL5, Zhang LX1,2,3,4,6, Chen M1,2,3,4, Zhao MH1,2,3,4.

Author information

1
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
2
Institute of Nephrology, Peking University, Beijing, China.
3
Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.
4
Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
5
Kailuan General Hospital Affiliated to North China University of Science and Technology, Tangshan, China.
6
Center for Data Science in Health and Medicine, Peking University, Beijing, China.

Abstract

Background:

In diabetic kidney disease (DKD), it is important to find biomarkers for predicting initiation and progression of the disease. Besides glomerular damage, kidney tubular injury and inflammation are also involved in the development of DKD. The current study investigated the associations of urinary epidermal growth factor (uEGF), monocyte chemotactic protein-1 (MCP-1) and the uEGF:MCP-1 ratio with kidney involvement in patients at early and advanced stages of DKD.

Methods:

The concentration of uEGF and uMCP-1 was measured in two Chinese population-based studies. The associations of uEGF, uMCP-1 and uEGF/MCP-1 with occurrence of DKD were studied in a cross-sectional study (n = 1811) of early stage DKD. Associations of baseline uEGF, uMCP-1 and uEGF/MCP-1 with kidney outcome were assessed in a longitudinal cohort (n = 208) of advanced-stage DKD.

Results:

In both studies, positive correlations were found between uEGF/urine creatinine (Cr) and estimated glomerular filtration rate (eGFR) at sampling and between uMCP-1/Cr and urinary albumin:creatinine ratio (uACR). In the cross-sectional study, uEGF/Cr and uEGF/MCP-1 were negatively associated with the occurrence of DKD {odds ratio (OR) 0.65 [95% confidence interval (CI) 0.54-0.79], P < 0.001; 0.82 (0.71-0.94), P = 0.005, respectively}. In the longitudinal cohort, the uEGF:MCP-1 ratio correlated more closely with the percentage change of eGFR slope (r = 0.33, P < 0.001) as compared with uEGF/Cr or uMCP-1/Cr alone. The composite endpoint was defined as end-stage renal disease or 30% reduction of eGFR. These three markers were independently associated with composite endpoint after adjusting for potential confounders [hazard ratio 0.76 (0.59-1.00), P = 0.047 for uEGF/Cr; 1.18 (1.02-1.38), P = 0.028 for uMCP-1/Cr; 0.79 (0.68-0.91), P = 0.001 for uEGF/MCP-1].

Conclusion:

In Chinese patients, urinary EGF/MCP-1 was negatively associated with the occurrence of DKD. Moreover, uEGF/MCP-1 had a better ability to predict the composite endpoint and correlated more closely with kidney function decline in advanced DKD as compared with uEGF/Cr or uMCP-1/Cr alone.

PMID:
30357416
DOI:
10.1093/ndt/gfy314

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