期刊
DIABETOLOGIA
卷 58, 期 1, 页码 188-198出版社
SPRINGER
DOI: 10.1007/s00125-014-3389-3
关键词
Biomarkers; End-stage renal disease; Mortality; Type 2 diabetes
资金
- Chronic Kidney Disease Biomarker Consortium - NIDDK [U01DK85649, U01DK085673, U01DK085660, U01DK085688, U01DK085651, U01DK085689]
- National Institute of Diabetes and Digestive and Kidney Diseases
Aims/hypothesis Kidney injury molecule 1 (KIM-1), liver fatty acid-binding protein (L-FABP), N-acetyl-beta-D-glucosaminidase (NAG) and neutrophil gelatinase-associated lipocalin (NGAL) are urinary biomarkers of renal tubular injury. We examined their association with incident end-stage renal disease (ESRD) and all-cause mortality in American Indians with type 2 diabetes. Methods Biomarker concentrations were measured in baseline urine samples in 260 Pima Indians who were followed for a median of 14 years. HRs were reported per SD of creatinine (Cr)-normalised log-transformed KIM-1, NAG and NGAL, and for three categories of L-FABP. Results During follow-up, 74 participants developed ESRD and 101 died. Median concentrations of KIM-1/Cr, NAG/Cr and NGAL/Cr and the proportion of detectable L-FABP were highest in those with macro albuminuria (p < 0.001 for KIM-1/Cr, NAG/Cr and L-FABP; p = 0.006 for NGAL/Cr). After multivariable adjustment, NGAL/Cr was positively associated with ESRD (HR 1.59, 95% CI 1.20, 2.11) and mortality (HR 1.39, 95% CI 1.06, 1.82); L-FABP/Cr was inversely associated with ESRD (HR [for highest vs lowest tertile] 0.40, 95% CI 0.19, 0.83). Addition of NGAL/Cr to models that included albuminuria and glomerular filtration rate increased the c-statistic for predicting ESRD from 0.828 to 0.833 (p=0.001) and for death from 0.710 to 0.722 (p=0.018). Addition of L-FABP/Cr increased the c-statistic for ESRD from 0.828 to 0.832 (p=0.042). Conclusion/interpretation In Pima Indians with type 2 diabetes, urinary concentrations of NGAL and L-FABP are associated with important health outcomes, but they are unlikely to add to risk prediction with standard markers in a clinically meaningful way given the small increase in the c-statistic.
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