PMID- 24200462
OWN - NLM
STAT- MEDLINE
DCOM- 20140519
LR  - 20220310
IS  - 1523-6838 (Electronic)
IS  - 0272-6386 (Print)
IS  - 0272-6386 (Linking)
VI  - 63
IP  - 4
DP  - 2014 Apr
TI  - Urine stability studies for novel biomarkers of acute kidney injury.
PG  - 567-72
LID - S0272-6386(13)01285-7 [pii]
LID - 10.1053/j.ajkd.2013.09.013 [doi]
AB  - BACKGROUND: The study of novel urinary biomarkers of acute kidney injury has 
      expanded exponentially. Effective interpretation of data and meaningful 
      comparisons between studies require awareness of factors that can adversely 
      affect measurement. We examined how variations in short-term storage and 
      processing might affect the measurement of urine biomarkers. STUDY DESIGN: 
      Cross-sectional prospective. SETTING & PARTICIPANTS: Hospitalized patients from 2 
      sites: Yale New Haven Hospital (n=50) and University of California, San Francisco 
      Medical Center (n=36). PREDICTORS: We tested the impact of 3 urine processing 
      conditions on these biomarkers: (1) centrifugation and storage at 4 degrees C for 48 
      hours before freezing at -80 degrees C, (2) centrifugation and storage at 25 degrees C for 48 
      hours before freezing at -80 degrees C, and (3) uncentrifuged samples immediately frozen 
      at -80 degrees C. OUTCOMES: Urine concentrations of 5 biomarkers: neutrophil 
      gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury 
      molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and cystatin 
      C. MEASUREMENTS: We measured urine biomarkers by established enzyme-linked 
      immunosorbent assay methods. Biomarker values were log-transformed, and agreement 
      with a reference standard of immediate centrifugation and storage at -80 degrees C was 
      compared using concordance correlation coefficients (CCCs). RESULTS: Neither 
      storing samples at 4 degrees C for 48 hours nor centrifugation had a significant effect 
      on measured levels, with CCCs higher than 0.9 for all biomarkers tested. For 
      samples stored at 25 degrees C for 48 hours, excellent CCC values (>0.9) also were noted 
      between the test sample and the reference standard for NGAL, cystatin C, L-FABP 
      and KIM-1. However, the CCC for IL-18 between samples stored at 25 degrees C for 48 hours 
      and the reference standard was 0.81 (95% CI, 0.66-0.96). LIMITATIONS: No 
      comparisons to fresh, unfrozen samples; no evaluation of the effect of protease 
      inhibitors. CONCLUSIONS: All candidate markers tested using the specified assays 
      showed high stability with both short-term storage at 4 degrees C and without 
      centrifugation prior to freezing. For optimal fidelity, urine for IL-18 
      measurement should not be stored at 25 degrees C before long-term storage or analysis.
CI  - Copyright (c) 2014 National Kidney Foundation, Inc. All rights reserved.
FAU - Parikh, Chirag R
AU  - Parikh CR
AD  - Section of Nephrology, Department of Medicine, Yale University School of 
      Medicine, New Haven, CT; Program of Applied Translational Research, Yale 
      University School of Medicine, New Haven, CT. Electronic address: 
      chirag.parikh@yale.edu.
FAU - Butrymowicz, Isabel
AU  - Butrymowicz I
AD  - Section of Nephrology, Department of Medicine, Yale University School of 
      Medicine, New Haven, CT; Program of Applied Translational Research, Yale 
      University School of Medicine, New Haven, CT.
FAU - Yu, Angela
AU  - Yu A
AD  - Section of Nephrology, Department of Medicine, Yale University School of 
      Medicine, New Haven, CT; Program of Applied Translational Research, Yale 
      University School of Medicine, New Haven, CT.
FAU - Chinchilli, Vernon M
AU  - Chinchilli VM
AD  - Department of Public Health Sciences, Penn State College of Medicine, Hershey, 
      PA.
FAU - Park, Meyeon
AU  - Park M
AD  - Division of Nephrology, Department of Medicine, University of California, San 
      Francisco, CA.
FAU - Hsu, Chi-Yuan
AU  - Hsu CY
AD  - Division of Nephrology, Department of Medicine, University of California, San 
      Francisco, CA; Division of Research, Kaiser Permanente of Northern California, 
      Oakland, CA.
FAU - Reeves, W Brian
AU  - Reeves WB
AD  - Department of Medicine, Division of Nephrology, Penn State College of Medicine, 
      Hershey, PA.
FAU - Devarajan, Prasad
AU  - Devarajan P
AD  - Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
FAU - Kimmel, Paul L
AU  - Kimmel PL
AD  - Division of Kidney, Urologic, and Hematologic Diseases, National Institute of 
      Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 
      Bethesda, MD.
FAU - Siew, Edward D
AU  - Siew ED
AD  - Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt 
      University Medical Center, Nashville, TN.
FAU - Liu, Kathleen D
AU  - Liu KD
AD  - Division of Nephrology, Department of Medicine, University of California, San 
      Francisco, CA.
CN  - ASSESS-AKI Study Investigators
LA  - eng
GR  - K24 DK92291/DK/NIDDK NIH HHS/United States
GR  - U01 DK082183/DK/NIDDK NIH HHS/United States
GR  - P30 DK079310/DK/NIDDK NIH HHS/United States
GR  - UL1 RR024131/RR/NCRR NIH HHS/United States
GR  - 5K23DK088964-02/DK/NIDDK NIH HHS/United States
GR  - U01 DK084012/DK/NIDDK NIH HHS/United States
GR  - P50 DK096418/DK/NIDDK NIH HHS/United States
GR  - U01 DK082185/DK/NIDDK NIH HHS/United States
GR  - UL1 TR000077/TR/NCATS NIH HHS/United States
GR  - UL1 TR000004/TR/NCATS NIH HHS/United States
GR  - K24 DK090203/DK/NIDDK NIH HHS/United States
GR  - U01 DK082223/DK/NIDDK NIH HHS/United States
GR  - U01DK082192/DK/NIDDK NIH HHS/United States
GR  - R01 HL085757/HL/NHLBI NIH HHS/United States
GR  - U01DK082183/DK/NIDDK NIH HHS/United States
GR  - K23 DK088964/DK/NIDDK NIH HHS/United States
GR  - U01 DK082192/DK/NIDDK NIH HHS/United States
GR  - U01-DK082185/DK/NIDDK NIH HHS/United States
GR  - U01-DK082223/DK/NIDDK NIH HHS/United States
GR  - K24 DK092291/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, American Recovery and Reinvestment Act
PT  - Research Support, N.I.H., Extramural
DEP - 20131105
PL  - United States
TA  - Am J Kidney Dis
JT  - American journal of kidney diseases : the official journal of the National Kidney 
      Foundation
JID - 8110075
RN  - 0 (Biomarkers)
SB  - IM
CIN - Am J Kidney Dis. 2014 Apr;63(4):543-6. PMID: 24670481
MH  - Acute Kidney Injury/*urine
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers/*urine
MH  - Centrifugation
MH  - Cross-Sectional Studies
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Freezing
MH  - Humans
MH  - Male
MH  - Prospective Studies
MH  - Urine Specimen Collection/methods/standards
PMC - PMC3969397
MID - NIHMS528074
OTO - NOTNLM
OT  - Proteins
OT  - acute kidney injury (AKI)
OT  - acute renal failure (ARF)
OT  - biospecimen handling
OT  - concordance
OT  - handling
OT  - protein stability
OT  - storage
OT  - urine biomarker
COIS- Financial Disclosure: CRP is a co-inventor on a patent for the use of IL-18 as a 
      marker of AKI (no financial value). PD is a co-inventor on a patent for the use 
      of NGAL as a marker of AKI. EDS is a consultant for Alere Inc. KDL is a 
      consultant for Astute Biomedical. The other authors declare that they have no 
      other relevant financial interests.
FIR - Chinchilli, Vernon M
IR  - Chinchilli VM
FIR - Go, Alan S
IR  - Go AS
FIR - Himmelfarb, Jonathan
IR  - Himmelfarb J
FIR - Ikizler, T Alp
IR  - Ikizler T
FIR - Kaufman, James S
IR  - Kaufman JS
FIR - Kimmel, Paul L
IR  - Kimmel PL
FIR - Parikh, Chirag R
IR  - Parikh CR
FIR - Stokes, John B
IR  - Stokes JB
FIR - Coca, Steven
IR  - Coca S
FIR - Garg, Amit
IR  - Garg A
FIR - Ordonez, Juan D
IR  - Ordonez JD
FIR - Zheng, Sijie
IR  - Zheng S
FIR - Ghahramani, Nasrollah
IR  - Ghahramani N
FIR - Lewis, Julia B
IR  - Lewis JB
FIR - Ware, Lorraine
IR  - Ware L
FIR - Krawczeski, Catherine
IR  - Krawczeski C
FIR - Bennett, Michael
IR  - Bennett M
FIR - Zappitelli, Michael
IR  - Zappitelli M
FIR - Wurfel, Mark
IR  - Wurfel M
EDAT- 2013/11/10 06:00
MHDA- 2014/05/20 06:00
PMCR- 2015/04/01
CRDT- 2013/11/09 06:00
PHST- 2013/05/27 00:00 [received]
PHST- 2013/09/13 00:00 [accepted]
PHST- 2013/11/09 06:00 [entrez]
PHST- 2013/11/10 06:00 [pubmed]
PHST- 2014/05/20 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - S0272-6386(13)01285-7 [pii]
AID - 10.1053/j.ajkd.2013.09.013 [doi]
PST - ppublish
SO  - Am J Kidney Dis. 2014 Apr;63(4):567-72. doi: 10.1053/j.ajkd.2013.09.013. Epub 
      2013 Nov 5.