Association of urinary KIM-1, L-FABP, NAG and NGAL with incident end-stage renal disease and mortality in American Indians with type 2 diabetes mellitus

作者：Fufaa Gudeta D; Weil E Jennifer; Nelson Robert G^*; Hanson Robert L; Bonventre Joseph V; Sabbisetti Venkata; Waikar Sushrut S; Mifflin Theodore E; Zhang Xiaoming; Xie Dawei; Hsu Chi yuan; Feldman Harold I; Coresh Josef; Vasan Ramachandran S; Kimmel Paul L; Liu Kathleen D

来源：Diabetologia, 2015, 58(1): 188-198.

DOI：10.1007/s00125-014-3389-3

• Biomarkers
• End-stage renal disease
• Mortality
• Type 2 diabetes

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.

• 出版日期2015-1