Independent and incremental prognostic value of novel cardiac biomarkers in chronic hemodialysis patients.
End-stage renal disease is a major clinical and public health problem, and cardiovascular disease accounts for half of the mortality in hemodialysis patients. An existing mortality risk score (AROii score) or N-terminal pro-brain natriuretic peptide (NT-proBNP) level have modest predictive power, but there is room for improvement. There are emerging cardiac biomarkers (soluble isoforms of ST2 [sST2], galectin-3 [Gal-3]), and uremic toxicity (indoxyl sulfate). We sought to determine whether these biomarkers predict cardiovascular outcomes in hemodialysis patients and have incremental prognostic value over the clinical score and NT-proBNP level.



A total of 423 hemodialysis patients were prospectively followed up for primary (all-cause death) and secondary end points (a composite of all-cause death or cerebrocardiovascular events).



During a mean follow-up of 2.1 ± 0.4 years, there were 48 all-cause deaths and 78 composite outcomes. Soluble isoforms of ST2, Gal-3, and NT-proBNP were associated with all-cause deaths but indoxyl sulfate was not in both log-rank test and receiver operating characteristic analysis. Both sST2 and Gal-3 had independent and incremental prognostic value for both outcomes over the AROii score and NT-proBNP. Although adding sST2 did not reclassify over the model-based AROii score and NT-proBNP for all-cause death, further addition of Gal-3 did. Subgroup analyses of patients with left ventricular ejection fraction measurement (n = 301) corroborated these results, where the 2 biomarkers remained independent and incremental for both all-cause death and composite outcome after adjusting for the risk score and the ejection fraction.



Both sST2 and Gal-3 had independent and incremental prognostic values over NT-proBNP and an established risk score in patients with hemodialysis. Assessment of sST2 and Gal-3 further enhances risk stratification.
Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Masaru
M
Obokata
Menzies Research Institute Tasmania, Hobart, Australia.
Hiroaki
H
Sunaga
Hidaka Hospital, Takasaki, Gunma, Japan.
Hideki
H
Ishida
Hidaka Hospital, Takasaki, Gunma, Japan; Department of Nephrology, Heisei-Hidaka Clinic, Takasaki, Gunma, Japan.
Kyoko
K
Ito
Hidaka Hospital, Takasaki, Gunma, Japan; Department of Medicine, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
Tetsuya
T
Ogawa
Hidaka Hospital, Takasaki, Gunma, Japan.
Yoshitaka
Y
Ando
Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Masahiko
M
Kurabayashi
Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan; Menzies Research Institute Tasmania, Hobart, Australia. Electronic address: kazz.negishi@nifty.com.
Kazuaki
K
Negishi
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D002423:Cause of Death; D005260:Female; D037502:Galectin 3 / Q000097:blood*; D006801:Humans; D007200:Indican / Q000097:blood*; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009026:Mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D006435:Renal Dialysis; D012307:Risk Factors; D013318:Stroke Volume
D015415:Biomarkers; D037502:Galectin 3; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D007200:Indican