PMID- 31378102
OWN - NLM
STAT- MEDLINE
DCOM- 20191125
LR  - 20240214
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Print)
IS  - 0194-911X (Linking)
VI  - 74
IP  - 4
DP  - 2019 Oct
TI  - Distinct Dimensions of Kidney Health and Risk of Cardiovascular Disease, Heart 
      Failure, and Mortality.
PG  - 872-879
LID - 10.1161/HYPERTENSIONAHA.119.13339 [doi]
AB  - Chronic kidney disease is a strong risk factor for cardiovascular disease (CVD), 
      but clinical kidney measures (estimated glomerular filtration rate and 
      albuminuria) do not fully reflect the multiple aspects of kidney tubules 
      influencing cardiovascular health. Applied methods are needed to integrate 
      numerous tubule biomarkers into useful prognostic scores. In SPRINT (Systolic 
      Blood Pressure Intervention Trial) participants with chronic kidney disease at 
      baseline (estimated glomerular filtration rate(cr&cys) <60 mL/minute per 1.73 
      m(2)), we measured 8 biomarkers from urine (alpha1M [alpha1M microglobulin], beta2M [beta2M 
      microglobulin], umod [uromodulin], KIM-1 [kidney injury molecule-1], MCP-1 
      [monocyte chemoattractant protein-1], YKL-40 [chitinase-3-like protein-1], NGAL 
      [neutrophil gelatinase-associated lipocalin], and IL-18 [interleukin 18]) and 2 
      biomarkers from serum (intact parathyroid hormone, iFGF-23 [intact fibroblast 
      growth factor-23]). We used an unsupervised method, exploratory factor analysis, 
      to create summary scores of tubule health dimensions. Adjusted Cox models 
      evaluated each tubule score with CVD events, heart failure, and all-cause 
      mortality. We examined CVD discrimination using Harrell C-statistic. Factor 
      analysis of 10 biomarkers from 2376 SPRINT-chronic kidney disease participants 
      identified 4 unique dimensions of tubular health: tubule injury/repair (NGAL, 
      IL-18, YKL-40), tubule injury/fibrosis (KIM-1, MCP-1), tubule reabsorption (alpha1M, 
      beta2M), and tubular reserve/mineral metabolism (umod, intact parathyroid hormone, 
      iFGF-23). After adjustment for CVD risk factors, estimated glomerular filtration 
      rate, and albumin-to-creatinine ratio, 2 of the 4 tubule scores were associated 
      with CVD (hazard ratio per SD; reabsorption, 1.21 [1.06-1.38]; reserve, 1.24 
      (1.08-1.38]), 1 with heart failure (reserve, 1.41 [1.13-1.74]), and none with 
      mortality. Compared with a base model (C-statistic=0.674), adding estimated 
      glomerular filtration rate and albumin-to-creatinine ratio improved the 
      C-statistic (C=0.704; P=0.001); further adding tubule scores additionally 
      improved the C-statistic (C=0.719; P=0.009). In the setting of chronic kidney 
      disease, dimensions of tubule health quantified using factor analysis improved 
      CVD discrimination beyond contemporary kidney measures. Clinical Trial 
      Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.
FAU - Lee, Alexandra K
AU  - Lee AK
AD  - From the Department of Medicine, University of California San Francisco (A.K.L., 
      V.J., M.G.S.).
FAU - Katz, Ronit
AU  - Katz R
AD  - Division of Nephrology, University of Washington, Seattle (R.K.).
FAU - Jotwani, Vasantha
AU  - Jotwani V
AD  - From the Department of Medicine, University of California San Francisco (A.K.L., 
      V.J., M.G.S.).
FAU - Garimella, Pranav S
AU  - Garimella PS
AD  - Division of Nephrology-Hypertension, University of California San Diego (P.S.G., 
      J.H.I).
FAU - Ambrosius, Walter T
AU  - Ambrosius WT
AD  - Department of Biostatistics and Data Science, Wake Forest School of Medicine, 
      Winston-Salem, NC (W.T.A.).
FAU - Cheung, Alfred K
AU  - Cheung AK
AD  - Division of Nephrology (A.K.C., K.L.R.), University of Utah, Salt Lake City.
AD  - Medical Service, Veterans Affairs Salt Lake City Healthcare System, UT (A.K.C.).
FAU - Gren, Lisa H
AU  - Gren LH
AD  - Division of Public Health (L.H.G.), University of Utah, Salt Lake City.
FAU - Neyra, Javier A
AU  - Neyra JA
AD  - Division of Nephrology, University of Texas Southwestern, Dallas (J.A.N.).
AD  - Division of Nephrology, Bone, and Mineral Metabolism, University of Kentucky, 
      Lexington (J.A.N.).
FAU - Punzi, Henry
AU  - Punzi H
AD  - Punzi Medical Center Carrollton, TX (H.P.).
FAU - Raphael, Kalani L
AU  - Raphael KL
AD  - Division of Nephrology (A.K.C., K.L.R.), University of Utah, Salt Lake City.
FAU - Shlipak, Michael G
AU  - Shlipak MG
AD  - From the Department of Medicine, University of California San Francisco (A.K.L., 
      V.J., M.G.S.).
FAU - Ix, Joachim H
AU  - Ix JH
AD  - Division of Nephrology-Hypertension, University of California San Diego (P.S.G., 
      J.H.I).
LA  - eng
SI  - ClinicalTrials.gov/NCT01206062
GR  - UL1 TR000433/TR/NCATS NIH HHS/United States
GR  - UL1 TR000445/TR/NCATS NIH HHS/United States
GR  - R01 DK098234/DK/NIDDK NIH HHS/United States
GR  - UL1 TR000064/TR/NCATS NIH HHS/United States
GR  - UL1 TR000075/TR/NCATS NIH HHS/United States
GR  - K23 DK114556/DK/NIDDK NIH HHS/United States
GR  - UL1 TR000093/TR/NCATS NIH HHS/United States
GR  - T32 AG000212/AG/NIA NIH HHS/United States
GR  - UL1 TR000003/TR/NCATS NIH HHS/United States
GR  - UL1 TR000050/TR/NCATS NIH HHS/United States
GR  - UL1 TR001420/TR/NCATS NIH HHS/United States
GR  - K24 DK110427/DK/NIDDK NIH HHS/United States
GR  - UL1 RR024134/RR/NCRR NIH HHS/United States
GR  - HHSN268200900048C/HL/NHLBI NIH HHS/United States
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - HHSN268200900040C/HL/NHLBI NIH HHS/United States
GR  - UL1 TR002548/TR/NCATS NIH HHS/United States
GR  - HHSN268200900046C/HL/NHLBI NIH HHS/United States
GR  - P30 GM103337/GM/NIGMS NIH HHS/United States
GR  - UL1 TR001064/TR/NCATS NIH HHS/United States
GR  - UL1 RR025752/RR/NCRR NIH HHS/United States
GR  - UL1 RR025771/RR/NCRR NIH HHS/United States
GR  - HHSN268200900049C/HL/NHLBI NIH HHS/United States
GR  - HHSN268200900047C/HL/NHLBI NIH HHS/United States
GR  - UL1 TR000439/TR/NCATS NIH HHS/United States
GR  - UL1 TR000073/TR/NCATS NIH HHS/United States
GR  - UL1 RR025755/RR/NCRR NIH HHS/United States
GR  - UL1 TR002003/TR/NCATS NIH HHS/United States
GR  - UL1 TR000002/TR/NCATS NIH HHS/United States
GR  - UL1 TR002240/TR/NCATS NIH HHS/United States
GR  - UL1 TR000105/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190805
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Biomarkers)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers/metabolism
MH  - Blood Pressure/physiology
MH  - Cardiovascular Diseases/*epidemiology/mortality/physiopathology
MH  - Creatinine/metabolism
MH  - Female
MH  - Glomerular Filtration Rate/physiology
MH  - Humans
MH  - Kidney/metabolism
MH  - Male
MH  - Middle Aged
MH  - Renal Insufficiency, Chronic/*epidemiology/mortality/physiopathology
MH  - Risk
MH  - Survival Rate
PMC - PMC6739187
MID - NIHMS1533002
OTO - NOTNLM
OT  - albuminuria
OT  - biomarker
OT  - cardiovascular diseases
OT  - epidemiology
OT  - kidney
EDAT- 2019/08/06 06:00
MHDA- 2019/11/26 06:00
PMCR- 2020/10/01
CRDT- 2019/08/06 06:00
PHST- 2019/08/06 06:00 [pubmed]
PHST- 2019/11/26 06:00 [medline]
PHST- 2019/08/06 06:00 [entrez]
PHST- 2020/10/01 00:00 [pmc-release]
AID - 10.1161/HYPERTENSIONAHA.119.13339 [doi]
PST - ppublish
SO  - Hypertension. 2019 Oct;74(4):872-879. doi: 10.1161/HYPERTENSIONAHA.119.13339. 
      Epub 2019 Aug 5.