PMID- 34544821
OWN - NLM
STAT- MEDLINE
DCOM- 20211206
LR  - 20230301
IS  - 1533-3450 (Electronic)
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 32
IP  - 10
DP  - 2021 Oct
TI  - Urine Biomarkers of Kidney Tubule Health, Injury, and Inflammation are Associated 
      with Progression of CKD in Children.
PG  - 2664-2677
LID - 10.1681/ASN.2021010094 [doi]
AB  - BACKGROUND: Novel urine biomarkers may improve identification of children at 
      greater risk of rapid kidney function decline, and elucidate the pathophysiology 
      of CKD progression. METHODS: We investigated the relationship between urine 
      biomarkers of kidney tubular health (EGF and alpha-1 microglobulin), tubular injury 
      (kidney injury molecule-1; KIM-1), and inflammation (monocyte chemoattractant 
      protein-1 [MCP-1] and YKL-40) and CKD progression. The prospective CKD in 
      Children Study enrolled children aged 6 months to 16 years with an eGFR of 
      30-90ml/min per 1.73m(2). Urine biomarkers were assayed a median of 5 months 
      [IQR: 4-7] after study enrollment. We indexed the biomarker to urine creatinine 
      by dividing the urine biomarker concentration by the urine creatinine 
      concentration to account for the concentration of the urine. The primary outcome 
      was CKD progression (a composite of a 50% decline in eGFR or kidney failure) 
      during the follow-up period. RESULTS: Overall, 252 of 665 children (38%) reached 
      the composite outcome over a median follow-up of 6.5 years. After adjustment for 
      covariates, children with urine EGF concentrations in the lowest quartile were at 
      a seven-fold higher risk of CKD progression versus those with concentrations in 
      the highest quartile (fully adjusted hazard ratio [aHR], 7.1; 95% confidence 
      interval [95% CI], 3.9 to 20.0). Children with urine KIM-1, MCP-1, and alpha-1 
      microglobulin concentrations in the highest quartile were also at significantly 
      higher risk of CKD progression versus those with biomarker concentrations in the 
      lowest quartile. Addition of the five biomarkers to a clinical model increased 
      the discrimination and reclassification for CKD progression. CONCLUSIONS: After 
      multivariable adjustment, a lower urine EGF concentration and higher urine KIM-1, 
      MCP-1, and alpha-1 microglobulin concentrations were each associated with CKD 
      progression in children.
CI  - Copyright (c) 2021 by the American Society of Nephrology.
FAU - Greenberg, Jason H
AU  - Greenberg JH
AUID- ORCID: 0000-0001-5874-1109
AD  - Department of Pediatrics, Yale University School of Medicine, New Haven, 
      Connecticut.
AD  - Department of Medicine Clinical and Translational Research Accelerator, Yale 
      University School of Medicine, New Haven, Connecticut.
FAU - Abraham, Alison G
AU  - Abraham AG
AD  - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 
      Baltimore, Maryland.
FAU - Xu, Yunwen
AU  - Xu Y
AD  - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 
      Baltimore, Maryland.
FAU - Schelling, Jeffrey R
AU  - Schelling JR
AD  - Department of Internal Medicine, Case Western Reserve University School of 
      Medicine, Cleveland, Ohio.
FAU - Feldman, Harold I
AU  - Feldman HI
AUID- ORCID: 0000-0003-4572-2608
AD  - Department of Medicine, Perelman School of Medicine at the University of 
      Pennsylvania, Philadelphia, Pennsylvania.
FAU - Sabbisetti, Venkata S
AU  - Sabbisetti VS
AD  - Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Ix, Joachim H
AU  - Ix JH
AD  - Division of Nephrology-Hypertension, University of California San Diego, San 
      Diego, California.
AD  - Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, 
      California.
FAU - Jogalekar, Manasi P
AU  - Jogalekar MP
AD  - Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Coca, Steven
AU  - Coca S
AUID- ORCID: 0000-0002-0928-9168
AD  - Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New 
      York, New York.
FAU - Waikar, Sushrut S
AU  - Waikar SS
AUID- ORCID: 0000-0003-4004-326
AD  - Section of Nephrology, Boston University School of Medicine and Boston Medical 
      Center, Boston, Massachusetts.
FAU - Shlipak, Michael G
AU  - Shlipak MG
AD  - UCSF Division of General Internal Medicine at the VA, Kidney Health Research 
      Collaborative, San Francisco Veterans Affairs Health Care System and University 
      of California, San Francisco, California.
FAU - Warady, Bradley A
AU  - Warady BA
AUID- ORCID: 0000-0003-1812-6587
AD  - Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri.
FAU - Vasan, Ramachandran S
AU  - Vasan RS
AD  - Departments of Medicine and Epidemiology, Boston University Schools of Medicine 
      and Public Health, Boston, Massachusetts.
FAU - Kimmel, Paul L
AU  - Kimmel PL
AD  - National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, 
      Maryland.
FAU - Bonventre, Joseph V
AU  - Bonventre JV
AD  - Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Denburg, Michelle
AU  - Denburg M
AD  - Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, 
      Pennsylvania.
FAU - Parikh, Chirag R
AU  - Parikh CR
AUID- ORCID: 0000-0001-9051-7385
AD  - Department of Internal Medicine, Johns Hopkins School of Medicine, Baltimore, New 
      York.
FAU - Furth, Susan
AU  - Furth S
AD  - National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, 
      Maryland.
CN  - CKD Biomarkers Consortium
CN  - CKD Biomarker consortium
LA  - eng
GR  - K08 DK110536/DK/NIDDK NIH HHS/United States
GR  - U01 DK066143/DK/NIDDK NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - U24 DK066116/DK/NIDDK NIH HHS/United States
GR  - U01 DK082185/DK/NIDDK NIH HHS/United States
GR  - R37 DK039773/DK/NIDDK NIH HHS/United States
GR  - L40 DK110937/DK/NIDDK NIH HHS/United States
GR  - R01 DK072381/DK/NIDDK NIH HHS/United States
GR  - K24 DK078737/DK/NIDDK NIH HHS/United States
GR  - R01 HL085757/HL/NHLBI NIH HHS/United States
GR  - U01 DK085689/DK/NIDDK NIH HHS/United States
GR  - K24 DK090203/DK/NIDDK NIH HHS/United States
GR  - U01 DK082194/DK/NIDDK NIH HHS/United States
GR  - U01 DK066116/DK/NIDDK NIH HHS/United States
GR  - U01 DK102730/DK/NIDDK NIH HHS/United States
GR  - U01 DK085660/DK/NIDDK NIH HHS/United States
GR  - U01 DK066174/DK/NIDDK NIH HHS/United States
GR  - P30 DK079310/DK/NIDDK NIH HHS/United States
GR  - U01 DK106982/DK/NIDDK NIH HHS/United States
GR  - K23 DK118198/DK/NIDDK NIH HHS/United States
GR  - U01 DK103225/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210920
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Alpha-Globulins)
RN  - 0 (Biomarkers)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CHI3L1 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chitinase-3-Like Protein 1)
RN  - 0 (HAVCR1 protein, human)
RN  - 0 (Hepatitis A Virus Cellular Receptor 1)
RN  - 0 (alpha-1-microglobulin)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Adolescent
MH  - Albuminuria/urine
MH  - Alpha-Globulins/*urine
MH  - Biomarkers/urine
MH  - Chemokine CCL2/*urine
MH  - Child
MH  - Chitinase-3-Like Protein 1/urine
MH  - Creatinine/urine
MH  - *Disease Progression
MH  - Epidermal Growth Factor/*urine
MH  - Female
MH  - Follow-Up Studies
MH  - Glomerular Filtration Rate
MH  - Hepatitis A Virus Cellular Receptor 1/*metabolism
MH  - Humans
MH  - Kidney Tubules/injuries/pathology
MH  - Male
MH  - Nephritis/urine
MH  - Prospective Studies
MH  - Renal Insufficiency, Chronic/physiopathology/*urine
PMC - PMC8722795
OTO - NOTNLM
OT  - children
OT  - chronic kidney disease
OT  - end-stage kidney disease
OT  - pediatric nephrology
FIR - Ramachandran, Vasan S
IR  - Ramachandran VS
FIR - Schelling, Jeffrey
IR  - Schelling J
FIR - Denburg, Michelle
IR  - Denburg M
FIR - Furth, Susan
IR  - Furth S
FIR - Warady, Bradley
IR  - Warady B
FIR - Bonventre, Joseph
IR  - Bonventre J
FIR - Waikar, Sushrut
IR  - Waikar S
FIR - Sabbisetti, Venkata
IR  - Sabbisetti V
FIR - Coresh, Josef
IR  - Coresh J
FIR - Grams, Morgan
IR  - Grams M
FIR - Rebholz, Casey
IR  - Rebholz C
FIR - Abraham, Alison
IR  - Abraham A
FIR - Parikh, Chirag
IR  - Parikh C
FIR - Coca, Steven
IR  - Coca S
FIR - Rhee, Eugene
IR  - Rhee E
FIR - Kimmel, Paul L
IR  - Kimmel PL
FIR - Kusek, John W
IR  - Kusek JW
FIR - Rovin, Brad
IR  - Rovin B
FIR - Shlipak, Michael G
IR  - Shlipak MG
FIR - Sarnak, Mark
IR  - Sarnak M
FIR - Gutierrez, Orlando M
IR  - Gutierrez OM
FIR - Ix, Joachim
IR  - Ix J
FIR - Dubin, Ruth
IR  - Dubin R
FIR - Hostetter, Tom
IR  - Hostetter T
FIR - Deo, Rajat
IR  - Deo R
FIR - Feldman, Harold I
IR  - Feldman HI
FIR - Xie, Dawei
IR  - Xie D
FIR - Shou, Haochang
IR  - Shou H
FIR - Ballard, Shawn
IR  - Ballard S
FIR - Whitehead, Krista
IR  - Whitehead K
FIR - Collins, Heather
IR  - Collins H
FIR - Greenberg, Jason H
IR  - Greenberg JH
FIR - Ganz, Peter
IR  - Ganz P
EDAT- 2021/09/22 06:00
MHDA- 2021/12/15 06:00
PMCR- 2022/10/01
CRDT- 2021/09/21 05:49
PHST- 2021/01/24 00:00 [received]
PHST- 2021/06/28 00:00 [accepted]
PHST- 2021/09/22 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/09/21 05:49 [entrez]
PHST- 2022/10/01 00:00 [pmc-release]
AID - 00001751-202110000-00029 [pii]
AID - 2021010094 [pii]
AID - 10.1681/ASN.2021010094 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2021 Oct;32(10):2664-2677. doi: 10.1681/ASN.2021010094. Epub 
      2021 Sep 20.