Plasma kidney injury molecule-1 in heart failure: renal mechanisms and clinical outcome.
Urinary kidney injury molecule-1 (KIM-1) is a marker of tubular damage and associated with worse outcome in heart failure (HF). Plasma KIM-1 has not been described in HF.



In a renal mechanistic cohort of 120 chronic HF patients, we established the association between plasma KIM-1, renal invasive haemodynamic parameters {renal blood flow ([(131) I]hippuran clearance) and measured glomerular filtration rate (GFR; [(125) I]iothalamate)} and urinary tubular damage markers. The association between plasma KIM-1, plasma creatinine, and clinical outcome was further explored in a cohort of 2033 acute HF patients. Median plasma KIM-1 was 171.5 pg/mL (122.8-325.7) in chronic (n = 99) and 295.1 pg/mL (182.2-484.2) in acute HF (n = 1588). In chronic HF, plasma KIM-1 was associated with GFR (P < 0.001), creatinine, and cystatin C. Plasma KIM-1 was associated with urinary N-acetyl-β-d-glucosaminidase (NAG), but not with other urinary tubular damage markers. Log plasma KIM-1 predicted adverse clinical outcome after adjustment for age, gender, and GFR [hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.07-3.53, P = 0.030]. Statistical significance was lost after correction for NT-proBNP (HR 1.61, 95% CI 0.81-3.20, P = 0.175). In acute HF, higher plasma KIM-1 levels were associated with higher creatinine, lower albumin, and presence of diabetes. Log plasma KIM-1 predicted 60-day HF rehospitalization (HR 1.27, 95% CI 1.03-1.55, P = 0.024), but not 180-day mortality or 60-day death or renal or cardiovascular rehospitalization.



Plasma KIM-1 is associated with glomerular filtration and urinary NAG, but not with other urinary tubular damage markers. Plasma KIM-1 does not predict outcome in chronic HF after correction for NT-proBNP. In acute HF, plasma KIM-1 predicts HF rehospitalization in multivariable analysis.
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
Johanna E
JE
Emmens
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
Jozine M
JM
Ter Maaten
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
Yuya
Y
Matsue
University of Brescia, Brescia, Italy.
Marco
M
Metra
Duke University Medical Center, Durham, NC, USA.
Christopher M
CM
O'Connor
Medical University, Clinical Military Hospital, Wroclaw, Poland.
Piotr
P
Ponikowski
University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
John R
JR
Teerlink
Momentum Research, Durham, NC, USA.
Gad
G
Cotter
Momentum Research, Durham, NC, USA.
Beth
B
Davison
University of Hull, Kingston upon Hull, UK.
John G
JG
Cleland
Brigham and Women's Hospital, Boston, MA, USA.
Michael M
MM
Givertz
Merck Research Laboratories, Rahway, NJ, USA.
Daniel M
DM
Bloomfield
University of Iowa Carver College of Medicine Cardiovascular Research Center, Iowa City, IA, USA.
Howard C
HC
Dittrich
Singulex Inc., Alameda, CA, USA.
John
J
Todd
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
Dirk J
DJ
van Veldhuisen
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.|University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
Hans L
HL
Hillege
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
Kevin
K
Damman
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
Peter
P
van der Meer
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
Adriaan A
AA
Voors
D000118:Acetylglucosaminidase / Q000652:urine; D000208:Acute Disease; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood*; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism; D000071068:Lipocalin-2 / Q000652:urine; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D012079:Renal Circulation; D012709:Serum Albumin / Q000378:metabolism*
D055316:Cystatin C; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D010446:Peptide Fragments; D012709:Serum Albumin; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D003404:Creatinine; D000118:Acetylglucosaminidase
Heart failure; Plasma KIM-1; Prognosis