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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

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... Full description

Journal Title: Diabetologia 2014, Vol.58 (1), p.188-198
Main Author: Fufaa, Gudeta D
Other Authors: 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
Format: Electronic Article Electronic Article
Language: English
Subjects:
Acute-Phase Proteins - urine
Adolescent
Adult
Aged
Analysis
Article
Biomarkers
Chronic kidney failure
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - ethnology
Diabetes Mellitus, Type 2 - mortality
Diabetes Mellitus, Type 2 - urine
Diabetic Nephropathies - ethnology
Diabetic Nephropathies - mortality
Diabetic Nephropathies - urine
End-stage renal disease
Fatty Acid-Binding Proteins - urine
Fatty acids
Female
Hepatitis A Virus Cellular Receptor 1
Human Physiology
Humans
Incidence
Indians, North American - statistics & numerical data
Internal Medicine
Kidney Failure, Chronic - ethnology
Kidney Failure, Chronic - mortality
Kidney Failure, Chronic - urine
Lipocalin-2
Lipocalins - urine
Male
Medicine
Medicine & Public Health
Membrane Glycoproteins - urine
Metabolic Diseases
Middle Aged
Mortality
Native Americans
Neoplasm Proteins - urine
Protein binding
Proto-Oncogene Proteins - urine
Receptors, Virus
Type 2 diabetes
Young Adult
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 0012-186X
Link: https://www.ncbi.nlm.nih.gov/pubmed/25316431
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4258130
title: 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
format: Article
creator:
  • 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
subjects:
  • Acute-Phase Proteins - urine
  • Adolescent
  • Adult
  • Aged
  • Analysis
  • Article
  • Biomarkers
  • Chronic kidney failure
  • Diabetes Mellitus, Type 2 - complications
  • Diabetes Mellitus, Type 2 - ethnology
  • Diabetes Mellitus, Type 2 - mortality
  • Diabetes Mellitus, Type 2 - urine
  • Diabetic Nephropathies - ethnology
  • Diabetic Nephropathies - mortality
  • Diabetic Nephropathies - urine
  • End-stage renal disease
  • Fatty Acid-Binding Proteins - urine
  • Fatty acids
  • Female
  • Hepatitis A Virus Cellular Receptor 1
  • Human Physiology
  • Humans
  • Incidence
  • Indians, North American - statistics & numerical data
  • Internal Medicine
  • Kidney Failure, Chronic - ethnology
  • Kidney Failure, Chronic - mortality
  • Kidney Failure, Chronic - urine
  • Lipocalin-2
  • Lipocalins - urine
  • Male
  • Medicine
  • Medicine & Public Health
  • Membrane Glycoproteins - urine
  • Metabolic Diseases
  • Middle Aged
  • Mortality
  • Native Americans
  • Neoplasm Proteins - urine
  • Protein binding
  • Proto-Oncogene Proteins - urine
  • Receptors, Virus
  • Type 2 diabetes
  • Young Adult
ispartof: Diabetologia, 2014, Vol.58 (1), p.188-198
description: 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  
language: eng
source:
identifier: ISSN: 0012-186X
fulltext: no_fulltext
issn:
  • 0012-186X
  • 1432-0428
url: Link


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titleAssociation 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
creatorFufaa, 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
creatorcontribFufaa, 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 ; Chronic Kidney Disease Biomarkers Consortium Investigators ; for the Chronic Kidney Disease Biomarkers Consortium Investigators
descriptionAims/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.
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0ISSN: 0012-186X
1EISSN: 1432-0428
2DOI: 10.1007/s00125-014-3389-3
3PMID: 25316431
languageeng
publisherBerlin/Heidelberg: Springer Berlin Heidelberg
subjectAcute-Phase Proteins - urine ; Adolescent ; Adult ; Aged ; Analysis ; Article ; Biomarkers ; Chronic kidney failure ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - ethnology ; Diabetes Mellitus, Type 2 - mortality ; Diabetes Mellitus, Type 2 - urine ; Diabetic Nephropathies - ethnology ; Diabetic Nephropathies - mortality ; Diabetic Nephropathies - urine ; End-stage renal disease ; Fatty Acid-Binding Proteins - urine ; Fatty acids ; Female ; Hepatitis A Virus Cellular Receptor 1 ; Human Physiology ; Humans ; Incidence ; Indians, North American - statistics & numerical data ; Internal Medicine ; Kidney Failure, Chronic - ethnology ; Kidney Failure, Chronic - mortality ; Kidney Failure, Chronic - urine ; Lipocalin-2 ; Lipocalins - urine ; Male ; Medicine ; Medicine & Public Health ; Membrane Glycoproteins - urine ; Metabolic Diseases ; Middle Aged ; Mortality ; Native Americans ; Neoplasm Proteins - urine ; Protein binding ; Proto-Oncogene Proteins - urine ; Receptors, Virus ; Type 2 diabetes ; Young Adult
ispartofDiabetologia, 2014, Vol.58 (1), p.188-198
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1Weil, E. Jennifer
2Nelson, Robert G
3Hanson, Robert L
4Bonventre, Joseph V
5Sabbisetti, Venkata
6Waikar, Sushrut S
7Mifflin, Theodore E
8Zhang, Xiaoming
9Xie, Dawei
10Hsu, Chi-yuan
11Feldman, Harold I
12Coresh, Josef
13Vasan, Ramachandran S
14Kimmel, Paul L
15Liu, Kathleen D
16Chronic Kidney Disease Biomarkers Consortium Investigators
17for the Chronic Kidney Disease Biomarkers Consortium Investigators
title
0Association 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
1Diabetologia
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0Diabetologia
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descriptionAims/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.
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9Diabetes Mellitus, Type 2 - ethnology
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12Diabetic Nephropathies - ethnology
13Diabetic Nephropathies - mortality
14Diabetic Nephropathies - urine
15End-stage renal disease
16Fatty Acid-Binding Proteins - urine
17Fatty acids
18Female
19Hepatitis A Virus Cellular Receptor 1
20Human Physiology
21Humans
22Incidence
23Indians, North American - statistics & numerical data
24Internal Medicine
25Kidney Failure, Chronic - ethnology
26Kidney Failure, Chronic - mortality
27Kidney Failure, Chronic - urine
28Lipocalin-2
29Lipocalins - urine
30Male
31Medicine
32Medicine & Public Health
33Membrane Glycoproteins - urine
34Metabolic Diseases
35Middle Aged
36Mortality
37Native Americans
38Neoplasm Proteins - urine
39Protein binding
40Proto-Oncogene Proteins - urine
41Receptors, Virus
42Type 2 diabetes
43Young Adult
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1Weil, E. Jennifer
2Nelson, Robert G
3Hanson, Robert L
4Bonventre, Joseph V
5Sabbisetti, Venkata
6Waikar, Sushrut S
7Mifflin, Theodore E
8Zhang, Xiaoming
9Xie, Dawei
10Hsu, Chi-yuan
11Feldman, Harold I
12Coresh, Josef
13Vasan, Ramachandran S
14Kimmel, Paul L
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titleAssociation 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
authorFufaa, 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
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0Acute-Phase Proteins - urine
1Adolescent
2Adult
3Aged
4Analysis
5Article
6Biomarkers
7Chronic kidney failure
8Diabetes Mellitus, Type 2 - complications
9Diabetes Mellitus, Type 2 - ethnology
10Diabetes Mellitus, Type 2 - mortality
11Diabetes Mellitus, Type 2 - urine
12Diabetic Nephropathies - ethnology
13Diabetic Nephropathies - mortality
14Diabetic Nephropathies - urine
15End-stage renal disease
16Fatty Acid-Binding Proteins - urine
17Fatty acids
18Female
19Hepatitis A Virus Cellular Receptor 1
20Human Physiology
21Humans
22Incidence
23Indians, North American - statistics & numerical data
24Internal Medicine
25Kidney Failure, Chronic - ethnology
26Kidney Failure, Chronic - mortality
27Kidney Failure, Chronic - urine
28Lipocalin-2
29Lipocalins - urine
30Male
31Medicine
32Medicine & Public Health
33Membrane Glycoproteins - urine
34Metabolic Diseases
35Middle Aged
36Mortality
37Native Americans
38Neoplasm Proteins - urine
39Protein binding
40Proto-Oncogene Proteins - urine
41Receptors, Virus
42Type 2 diabetes
43Young Adult
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1Weil, E. Jennifer
2Nelson, Robert G
3Hanson, Robert L
4Bonventre, Joseph V
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6Waikar, Sushrut S
7Mifflin, Theodore E
8Zhang, Xiaoming
9Xie, Dawei
10Hsu, Chi-yuan
11Feldman, Harold I
12Coresh, Josef
13Vasan, Ramachandran S
14Kimmel, Paul L
15Liu, Kathleen D
16Chronic Kidney Disease Biomarkers Consortium Investigators
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1Weil, E. Jennifer
2Nelson, Robert G
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6Waikar, Sushrut S
7Mifflin, Theodore E
8Zhang, Xiaoming
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atitleAssociation 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
jtitleDiabetologia
stitleDiabetologia
addtitleDiabetologia
date2014-10-15
risdate2014
volume58
issue1
spage188
epage198
pages188-198
issn0012-186X
eissn1432-0428
notesGudeta D. Fufaa and E. Jennifer Weil contributed equally to this paper.
abstractAims/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.
copBerlin/Heidelberg
pubSpringer Berlin Heidelberg
pmid25316431
doi10.1007/s00125-014-3389-3
oafree_for_read