Table 2 Proteins inversely associated with mortality in CRIC and PACE, measured in participants at least one year after dialysis initiation

From: Risk factors for mortality in patients with kidney failure on hemodialysis identified by proteomic analysis of CRIC and PACE studies

Protein

CRIC

PACE

Molecular weight (MW) pathobiology

 

HR per log2

p

HR per log2

p

 

Myocilin

0.69

5.30 × 10−6

0.49

0.00010

55 kDa Induces skeletal muscle growth89

Insulin-like growth factor-binding protein complex acid labile subunit

0.67

3.29 × 10−5

0.66

0.0077

86 kDa Complexes with IGF/IGFB binary units, forming a reservoir of IGF1 and 2 in the circulation90

Proactivator polypeptide-like 1

0.65

3.85 × 10−5

0.49

3.1 × 10−6

58 kDa AKA prosaposin, precursor to sphingolipid activator proteins91

Kallikrein-7

0.60

2.76 × 10−5

0.46

7.26 × 10−5

27 kDa Cleaves kinin causing vasodilation92

Insulin-like growth factor I

0.59

6.19 × 10−5

0.57

0.00017

7.6 kDa Protective of endothelial function, vascular smooth muscle26

Carbonyl reductase [NADPH] 3

0.54

6.15 × 10−9

0.63

0.013

31 kDa Overexpression in heart aggravates anthracycline cardiotoxicity93

Collagen alpha-1(XV) chain

0.51

8.1 × 10−6

0.35

5.98 × 10−5

29 kDa Found in cardiac and skeletal muscle

Kit ligand

0.50

3.0 × 10−5

0.42

0.00013

22 kDa Cytokine that stimulates hematopoiesis

Growth differentiation factor 11/8

0.47

1.66 × 10−6

0.41

0.00034

25 kDa GDF11 negatively associated with age-related left ventricular hypertrophy94,95,96 41 kDa GDF8 inhibits skeletal muscle growth97

Complement C1q tumor necrosis factor-related protein 3

0.45

7.41 × 10−5

0.39

0.0067

26 kDa Potentially cardioprotective adipokine98

Tetranectin

0.29

2.52 × 10−10

0.30

0.0043

60 kDa Found in myocardium, circulating level is low in HF31 Associated with CVD outcomes32

  1. Proteins shown were selected from those significant at FDR < 0.05 in both cohorts in association with mortality using all follow-up time, in participants undergoing HD ≥ 1 year. (14 years in CRIC; 6.9 years in PACE). Proteins were chosen among 50 with most extreme HRs per MAD unit, and here we show HR per log2 for interpretability. Bold indicates p < 7 × 10−6 in CRIC. Associations tested with Cox HR and two-sided p-values.
  2. IGF insulin-like growth factor, IGFBP insulin-like growth factor binding protein, GDF growth differentiation factor.
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