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

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

Research output: Contribution to journalArticle

Abstract

Aims/hypothesis: Kidney injury molecule 1 (KIM-1), liver fatty acid-binding protein (L-FABP), N-acetyl-β-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 macroalbuminuria (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).

Conclusions/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.

Original languageEnglish (US)
Pages (from-to)188-198
Number of pages11
JournalDiabetologia
Volume58
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Fufaa, G. D., Weil, E. J., Nelson, R. G., Hanson, R. L., Bonventre, J. V., Sabbisetti, V., Waikar, S. S., Mifflin, T. E., Zhang, X., Xie, D., Hsu, C. Y., Feldman, H. I., Coresh, J., Vasan, R. S., Kimmel, P. L., & Liu, K. D. (2015). 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. Diabetologia, 58(1), 188-198. https://doi.org/10.1007/s00125-014-3389-3