PMID- 33857535
OWN - NLM
STAT- MEDLINE
DCOM- 20210913
LR  - 20220902
IS  - 1523-6838 (Electronic)
IS  - 0272-6386 (Print)
IS  - 0272-6386 (Linking)
VI  - 78
IP  - 3
DP  - 2021 Sep
TI  - Biomarkers of Kidney Tubule Health, CKD Progression, and Acute Kidney Injury in 
      SPRINT (Systolic Blood Pressure Intervention Trial) Participants.
PG  - 361-368.e1
LID - S0272-6386(21)00513-8 [pii]
LID - 10.1053/j.ajkd.2021.01.021 [doi]
AB  - RATIONALE & OBJECTIVE: The Systolic Blood Pressure Intervention Trial (SPRINT) 
      compared the effect of intensive versus standard systolic blood pressure targets 
      on cardiovascular morbidity and mortality. In this ancillary study, we evaluated 
      the use of exploratory factor analysis (EFA) to combine biomarkers of kidney 
      tubule health in urine and plasma and then study their role in longitudinal 
      estimated glomerular filtration rate (eGFR) change and risk of acute kidney 
      injury (AKI). STUDY DESIGN: Observational cohort nested in a clinical trial. 
      SETTING & PARTICIPANTS: 2,351 SPRINT participants with eGFR < 60 mL/min/1.73 m(2) 
      at baseline. EXPOSURE: Levels of neutrophil gelatinase-associated lipocalin 
      (NGAL), interleukin 18 (IL-18), chitinase-3-like protein (YKL-40), kidney injury 
      molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), 
      alpha(1)-microglobulin (A1M) and beta(2)-microglobulin (B2M), uromodulin (UMOD), 
      fibroblast growth factor 23 (FGF-23), and intact parathyroid hormone (PTH). 
      OUTCOME: Longitudinal changes in eGFR and risk of AKI. ANALYTICAL APPROACH: We 
      performed EFA to capture different tubule pathophysiologic processes. We used 
      linear mixed effects models to evaluate the association of each factor with 
      longitudinal changes in eGFR. We evaluated the association of the tubular factors 
      scores with AKI using Cox proportional hazards regression. RESULTS: From 10 
      biomarkers, EFA generated 4 factors reflecting tubule injury/repair (NGAL, IL-18, 
      and YKL-40), tubule injury/fibrosis (KIM-1 and MCP-1), tubule reabsorption (A1M 
      and B2M), and tubule reserve/mineral metabolism (UMOD, FGF-23, and PTH). Each 
      1-SD higher tubule reserve/mineral metabolism factor score was associated with a 
      0.58% (95% CI, 0.39%-0.67%) faster eGFR decline independent of baseline eGFR and 
      albuminuria. Both the tubule injury/repair and tubule injury/fibrosis factors 
      were independently associated with future risk of AKI (per 1 SD higher, HRs of 
      1.18 [95% CI, 1.10-1.37] and 1.23 [95% CI, 1.02-1.48], respectively). 
      LIMITATIONS: The factors require validation in other settings. CONCLUSIONS: EFA 
      allows parsimonious subgrouping of biomarkers into factors that are 
      differentially associated with progressive eGFR decline and AKI. These subgroups 
      may provide insights into the pathological processes driving adverse kidney 
      outcomes.
CI  - Published by Elsevier Inc.
FAU - Bullen, Alexander L
AU  - Bullen AL
AD  - Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA.
FAU - Katz, Ronit
AU  - Katz R
AD  - Department of Obstetrics & Gynecology, University of Washington, Seattle, WA.
FAU - Jotwani, Vasantha
AU  - Jotwani V
AD  - Kidney Health Research Collaborative, Department of Medicine, University of 
      California-San Francisco, San Francisco, CA; Department of Medicine, San 
      Francisco VA Medical Center, San Francisco, CA.
FAU - Garimella, Pranav S
AU  - Garimella PS
AD  - Division of Nephrology and Hypertension, Department of Medicine, University of 
      California-San Diego, San Diego, CA.
FAU - Lee, Alexandra K
AU  - Lee AK
AD  - Kidney Health Research Collaborative, Department of Medicine, University of 
      California-San Francisco, San Francisco, CA.
FAU - Estrella, Michelle M
AU  - Estrella MM
AD  - Kidney Health Research Collaborative, Department of Medicine, University of 
      California-San Francisco, San Francisco, CA; Department of Medicine, San 
      Francisco VA Medical Center, San Francisco, CA.
FAU - Shlipak, Michael G
AU  - Shlipak MG
AD  - Kidney Health Research Collaborative, Department of Medicine, University of 
      California-San Francisco, San Francisco, CA; Department of Epidemiology and 
      Biostatistics, University of California-San Francisco, San Francisco, CA; 
      Department of Medicine, San Francisco VA Medical Center, San Francisco, CA.
FAU - Ix, Joachim H
AU  - Ix JH
AD  - Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA; 
      Division of Nephrology and Hypertension, Department of Medicine, University of 
      California-San Diego, San Diego, CA; Division of Preventive Medicine, Department 
      of Family Medicine and Public Health, University of California-San Diego, San 
      Diego, CA. Electronic address: joix@ucsd.edu.
LA  - eng
GR  - R01 DK098234/DK/NIDDK NIH HHS/United States
GR  - IK2 BX004986/BX/BLRD VA/United States
GR  - U01 DK102730/DK/NIDDK NIH HHS/United States
GR  - T32 DK104717/DK/NIDDK NIH HHS/United States
GR  - P30 DK079337/DK/NIDDK NIH HHS/United States
GR  - K24 DK110427/DK/NIDDK NIH HHS/United States
GR  - R01 DK119528/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210420
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)
RN  - 0 (FGF23 protein, human)
RN  - 7Q7P4S7RRE (Fibroblast Growth Factor-23)
SB  - IM
CIN - Am J Kidney Dis. 2021 Sep;78(3):335-337. PMID: 34023146
MH  - Acute Kidney Injury/*metabolism/pathology/physiopathology
MH  - Aged
MH  - Biomarkers/urine
MH  - Blood Pressure/*physiology
MH  - Disease Progression
MH  - Female
MH  - Fibroblast Growth Factor-23
MH  - Glomerular Filtration Rate/*physiology
MH  - Humans
MH  - Kidney Function Tests
MH  - Kidney Tubules/*metabolism/pathology
MH  - Male
MH  - Middle Aged
PMC - PMC8384678
MID - NIHMS1716909
OTO - NOTNLM
OT  - Acute kidney injury (AKI)
OT  - CKD progression
OT  - chronic kidney disease (CKD)
OT  - eGFR trajectory
OT  - estimated glomerular filtration rate (eGFR)
OT  - kidney tubule
OT  - plasma biomarker
OT  - renal function
OT  - tubular dysfunction
OT  - tubular marker
OT  - urine biomarker
COIS- Financial Disclosure: The authors declare that they have no relevant financial 
      interests.
EDAT- 2021/04/16 06:00
MHDA- 2021/09/14 06:00
PMCR- 2022/09/01
CRDT- 2021/04/15 20:12
PHST- 2020/08/14 00:00 [received]
PHST- 2021/01/25 00:00 [accepted]
PHST- 2021/04/16 06:00 [pubmed]
PHST- 2021/09/14 06:00 [medline]
PHST- 2021/04/15 20:12 [entrez]
PHST- 2022/09/01 00:00 [pmc-release]
AID - S0272-6386(21)00513-8 [pii]
AID - 10.1053/j.ajkd.2021.01.021 [doi]
PST - ppublish
SO  - Am J Kidney Dis. 2021 Sep;78(3):361-368.e1. doi: 10.1053/j.ajkd.2021.01.021. Epub 
      2021 Apr 20.