Background
Methods
Study population and design
Dialysis settings
Clinical and laboratory measurements
Plasma mannose-binding lectin levels
Quantification of the antigenic levels of C3d, C3, Properdin and C5b-9
Definition of endpoint
Statistics
Results
Patients characteristics
MBL, properdin, C3d and C5b-9 levels in hemodialysis patients
Plasma concentration | At start hemodialysis | At end hemodialysis | P-valuea
| Controls | P-valueb
|
---|---|---|---|---|---|
MBL | 879 (255–1572) | 821 (319–1477) |
0.005
| 784 (277–1449) | 0.9 |
Properdin | 16.8 (13.6–22.4) | 18.0 (14.2–23.8) |
0.01
| 13.0 (10.8–14.7) | <0.0001
|
C3d | 7.3 (5.6–10.1) | 10.3 (7.4–16.9) | <0.0001
| 2.7 (2.3–3.4) | <0.0001
|
C5b-9 | 214 (166–419) | 253 (187–487) | <0.0001
| 141 (107–262) | <0.0001
|
Plasma concentration | No CV-event | CV-event | P-valuec
| ||
---|---|---|---|---|---|
MBL | 1074 (428–1722) | 464 (111–1102) |
0.006
| ||
Properdin | 18.6 (14.0–24.0) | 17.3 (15.1–23.4) | 0.8 | ||
C3d | 10.3 (7.3–16.7) | 10.8 (7.4–17.2) | 0.8 | ||
C3d/C3 | 8.2 (6.3–13.7) | 8.6 (6.0–15.6) | 0.5 | ||
C3 | 1.28 (1.08–1.53) | 1.32 (1.14–1.55) | 0.6 | ||
C5b-9 | 249 (182–513) | 266 (194–473) | 0.8 |
% CV event-free survival | Low level (%) | High level (%) | P-valued
| ||
---|---|---|---|---|---|
MBLe
| 42.30 | 74.10 |
0.003
| ||
MBLf
| 48.50 | 74.30 |
0.02
| ||
Properdine
| 65.40 | 74.10 | 0.6 | ||
C3dg
| 67.50 | 66.70 | 0.8 | ||
C3d/C3g
| 67.50 | 66.70 | 0.9 | ||
C3g
| 68.80 | 63.00 | 0.7 | ||
C5b-9g
| 67.50 | 69.20 | 0.4 |
Hemodialysis patients with versus hemodialysis patients without cardiovascular events
Cardiovascular risk according to MBL levels
MBL range (ng/mL) | Patients | P
*
< 0.001 |
R
| P
#
| ||
---|---|---|---|---|---|---|
All (n = 107) | MBL low 319 < ng/mL (n = 26) | MBL high 319 ≥ ng/mL (n = 81) | ||||
821[319–1477] | 98[33–146] | 1290[671–1848] | ||||
Demographics
| ||||||
Age, years | 62.5 ± 15.6 | 65.3 ± 12.1 | 61.56 ± 16.6 | 0.3 | –0.26 |
0.007
|
Male gender, n (%) | 71 (66) | 17 (65) | 54 (67) | 1.0 | ||
Current diabetes, n (%) | 25 (24) | 9 (35) | 16 (20) | 0.2 | ||
Hypertension, n (%) | 85 (84) | 22 (88) | 63 (83) | 0.8 | ||
Cardiovascular history, n (%) | 26 (25) | 9 (35) | 15 (19) | 0.1 | ||
BMI, kg/m2
| 25.8 ± 4.4 | 27.0 ± 4.5 | 25.4 ± 4.4 | 0.1 | –0.03 | 0.8 |
Hemodialysis
| ||||||
Dialysis vintage, months | 25.5 [8.5–52.3] | 18.2 [7.0–47.7] | 32.8 [9.1–53.3] | 0.2 | –0.01 | 0.9 |
Primary renal disease, n (%)
| ||||||
Hypertension | 18 (17) | 4 (15) | 14 (17) | 1.0 | ||
Diabetes | 14 (13) | 5 (19) | 9 (11) | 0.3 | ||
ADPKD | 13 (12) | 3 (12) | 10 (12) | 1.0 | ||
FSGS | 9 (8) | 4 (15) | 5 (6) | 0.2 | ||
IgA nephropathy | 4 (4) | 0 (0) | 4 (5) | 0.6 | ||
Chronic pyelonephritis | 3 (3) | 0 (0) | 3 (4) | 1.0 | ||
Glomerulonephritis | 13 (12) | 2 (8) | 11 (14) | 0.7 | ||
Other diagnoses | 16 (16) | 6 (23) | 10 (12) | 0.2 | ||
Unknown | 17 (16) | 2 (8) | 15 (19) | 0.2 | ||
Ultrafiltration volume, L | 2.55 ± 0.78 | 2.54 ± 0.82 | 2.56 ± 0.78 | 0.9 | –0.01 | 0.9 |
Ultrafiltration rate, ml/kg/h | 8.56 ± 2.63 | 7.81 ± 2.39 | 8.80 ± 2.67 | 0.1 | 0.04 | 0.7 |
Systolic blood pressure
| ||||||
Predialysis, mmHg | 140.4 ± 25.1 | 144.7 ± 26.4 | 139.1 ± 24.7 | 0.3 | –0.17 | 0.08 |
Postdialysis, mmHg | 131.8 ± 25.6 | 136 ± 24.3 | 130.4 ± 26.0 | 0.4 | –0.24 |
0.02
|
Heart rate
| ||||||
Predialysis, bpm | 73 [63–82] | 71 [62–82] | 74 [64–82] | 0.3 | 0.11 | 0.3 |
Postdialysis, bpm | 79 [69–87] | 75 [65–86] | 79 [69–88] | 0.4 | 0.13 | 0.2 |
Kidney transplant, n (%) | 21 (20) | 4 (15) | 17 (21) | 0.8 | ||
Laboratory measurements
| ||||||
Hematocrit, % | 34.9 ± 3.8 | 34.5 ± 4.1 | 35.0 ± 3.7 | 0.6 | 0.04 | 0.7 |
HbA1c, mmol/mol | 5.68 ± 0.98 | 5.80 ± 0.97 | 5.63 ± 0.98 | 0.5 | –0.15 | 0.2 |
Albumin, g/L | 39 [37–42] | 39 [37–42] | 39 [37–42] | 0.9 | 0.01 | 0.9 |
pH | 7.37 [7.34–7.39] | 7.37 [7.32–7.39] | 7.37 [7.34–7.39] | 0.7 | 0.05 | 0.6 |
Calcium, mmol/L | 2.31 ± 0.16 | 2.31 ± 0.15 | 2.32 ± 0.16 | 0.9 | 0.03 | 0.7 |
Phosphate, mmol/L | 1.67 ± 0.53 | 1.82 ± 0.47 | 1.65 ± 0.54 | 0.2 | –0.00 | 0.9 |
hsCRP, mg/L | 6.7 [2.8–10.9] | 6.1 [1.4–12.0] | 6.7 [3.0–10.9] | 0.7 | 0.10 | 0.3 |
Medication
| ||||||
Aspirin, n (%) | 57 (54) | 11 (42) | 46 (64) | 0.3 | ||
Calcium channel blockers, n (%) | 14 (13) | 3 (12) | 11 (14) | 1.0 | ||
β-Blocker, n (%) | 61 (57) | 18 (69) | 43 (53) | 0.2 | ||
ACE inhibitor, n (%) | 10 (10) | 3 (12) | 7 (9) | 0.7 | ||
AT2-receptor antagonists, n (%) | 14 (13) | 2 (8) | 12 (15) | 0.5 | ||
Statin, n (%) | 20 (19) | 5 (19) | 15 (19) | 1.0 | ||
Diuretics, n (%) | 8 (8) | 3 (12) | 5 (6) | 0.4 |
Cardiovascular events | ||||||
---|---|---|---|---|---|---|
Low MBL | Log MBL continuous | |||||
HR | 95 % CI |
P
| HR (per SD) | 95 % CI |
P
| |
Model 1 | 2.64 | 1.36–5.13 |
0.004
| 0.64 | 0.46–0.90 |
0.01
|
Model 2 | 2.75 | 1.39–5.44 |
0.004
| 0.61 | 0.43–0.88 |
0.008
|
Model 3 | 2.94 | 1.45–5.94 |
0.003
| 0.61 | 0.42–0.89 |
0.01
|
Model 4 | 3.55 | 1.70–7.40 |
0.001
| 0.58 | 0.40–0.84 |
0.004
|
Model 5 | 3.98 | 1.88–8.42 | <0.001
| 0.56 | 0.38–0.81 |
0.002
|
Cardiac events | ||||||
---|---|---|---|---|---|---|
Model 1 | 2.60 | 1.10–6.18 |
0.03
| 0.71 | 0.46–1.10 | 0.1 |
Model 2 | 2.49 | 1.04–5.96 |
0.04
| 0.73 | 0.46–1.16 | 0.2 |
Model 3 | 2.65 | 1.08–6.55 |
0.03
| 0.74 | 0.47–1.18 | 0.2 |
Model 4 | 3.82 | 1.48–9.87 |
0.006
| 0.62 | 0.38–1.01 | 0.06 |
Model 5 | 3.96 | 1.49–10.54 |
0.006
| 0.59 | 0.35–0.98 |
0.04
|
Cardiovascular events | ||||||
---|---|---|---|---|---|---|
Acute coronary syndrome | CABG/PCI | Congestive heart failure | Sudden death | CVA | Peripheral vascular disease | |
Low MBL levels | 4 (15 %) | 5 (19 %) | 0 (0 %) | 2 (8 %) | 2 (8 %) | 4 (15 %) |
High MBL levels | 4 (5 %) | 5 (6 %) | 3 (4 %) | 3 (4 %) | 2 (2 %) | 8 (10 %) |
Mortality | |||||
---|---|---|---|---|---|
Cardiovascular | Infection | Stopping dialysis therapy | Others | Unknown | |
Low MBL levels | 4 (15 %) | 1 (4 %) | 0 (0 %) | 0 (0 %) | 6 (23 %) |
High MBL levels | 7 (9 %) | 1 (1 %) | 7 (9 %) | 2 (2 %) | 9 (11 %) |
Predictive Value of MBL
Harrell’s C (95 % CI) | Change (95 % CI)a
| IDI (%) | P | ||
---|---|---|---|---|---|
Without MBL | With MBL | ||||
Model 1 | 0.56 (0.46–0.66) | 0.64 (0.53–0.76) | 0.085 (0.072–0.098) | 5.93 | 0.01 |
Model 2 | 0.64 (0.55–0.73) | 0.67 (0.57–0.77) | 0.033 (0.028–0.038) | 5.35 | 0.01 |
Model 3 | 0.71 (0.63–0.80) | 0.74 (0.65–0.83) | 0.027 (0.026–0.028) | 6.05 | 0.01 |
Model 4 | 0.73 (0.64–0.82) | 0.76 (0.68–0.85) | 0.033 (0.033–0.033) | 6.92 | 0.01 |