Demographic data and baseline characteristics are presented in Table 1. Eighty percent were men and average age for all patients was 60.3 (11.1) years. The procedures were 51% CABG (n=48), 28% (n=27) isolated valve replacements or repairs and 21% (n=20) combined procedures, all performed on average 7.1 (5.6) years after transplantation. The most common valve procedure was aortic valve replacement (AVR). Twenty-four isolated AVRs and 18 combined CABG and AVR procedures were performed. Three KTR and seven controls had active endocarditis at time of surgery (p=0.33). Thirteen KTR had experienced graft loss and were established on chronic dialysis treatment at time of heart surgery. In those not on dialysis (n=82), the CKD-EPI estimated GFR at time of surgery was lower compared to controls; 45 vs 77 mL/min/1.73m2 (p<0.001).
Table 1. Demographics and baseline characteristics of 95 kidney transplant recipients (including three simultaneous kidney pancreas recipients) who underwent heart surgery (48 CABG, 27 valve replacements or repairs and 20 combined procedures) and 95 controls.
|
Transplant recipients
(n=95)
|
Controls
(n=95)
|
P value
|
Men
|
76/19 (80%)
|
76/19 (80%)
|
NA
|
Age, years
|
60.3 (11.1)
|
60.4 (11.1)
|
NA
|
Hypertension
|
87
|
64
|
<0.001
|
Diabetes mellitus
Type 1
Type 2
Post-transplant
|
36
12
21
3
|
27
0
27
0
|
0.17
<0.001
0.40
N.A.
|
Pulmonary disease
|
6
|
13
|
0.09
|
Cerebrovascular disease
|
10
|
14
|
0.38
|
Family history of CVDa
|
20
|
32
|
0.05
|
Atrial fibrillation
|
24
|
19
|
0.39
|
VF/VT
|
6
|
8
|
0.58
|
Earlier CABG/Valve
|
5
|
5
|
1.0
|
Angina
|
66
|
64
|
0.76
|
Dyspnea
|
66
|
68
|
0.75
|
NYHA class (average)
AMI last 90 days
|
2.85
12
|
2.84
17
|
0.93
0.31
|
Active endocarditis
|
3
|
7
|
0.33
|
Pulmonary hypertensionb
|
14 (n=93)
|
43
|
<0.001
|
Ejection fraction % (SD)
|
53.1 (13.3) (n=93)
|
53.8 (18.4) (n=95)
|
0.78
|
Body surface (m2)
|
1.96 (0.24) (n=92)
|
1.95 (0.29) (n=91)
|
0.76
|
Serum creatinine mg/dLc
|
1.84 (0.81) (n=78)
|
1.07 (0.46) (n=82)
|
<0.001
|
Estimated GFR3
|
45.4 (21.8) (n=78)
|
76.8 (21.7) (n=82)
|
<0.001
|
Chronic dialysisd
|
13
|
0
|
NA
|
Years since transplantation
Range
|
7.1 (5.6)
23 days – 22 years
|
NA
|
NA
|
Emergency oper.e
|
17
|
14
|
0.70
|
aAcute myocardial infarction in first-degree male relative before age of 55 or in first-degree female relative before age of 65. bPulmonary arterial systolic pressure above 35 mmHg. Two missing values in KTR.
cEstimated glomerular filtration rate based on CKD-EPI creatinine formula. Patients on maintenance dialysis treatment were excluded from the calculation. Additionally, four missing values in KTR and 13 missing values in controls.
d Established on maintenance hemodialysis or peritoneal dialysis at time of heart surgery.
e Heart surgery within 24-hours from diagnosis.
Thirty-day mortality was 6.3% in KTR and 2.1% in controls (p=0.14; Log rank test), see Figure 1.
Figure 1. Kaplan-Meier actuarial 30-day survival after heart surgery in 95 kidney transplant recipients versus controls. Overall comparison with long-rank (Mantel-Cox) test, chi-square 2.13, df=1, p=0.14.
There was no difference in mortality rates in the 13 KTR on chronic dialysis versus those with a functioning kidney graft; 7.7% (n=1) vs 6.1% (n=5) (p=1.00). Three of the six KTR who died within first 30-days underwent CABG, two had valve surgery and one had a combined procedure. The causes of death were identified in all but one KTR: cardiac arrest after bleeding, progressive heart failure after perioperative AMI, cerebral infarction, Enterococcus endocarditis and bacterial pneumonia. In the control patients two died within the first 30-days; one had CABG surgery and died of postoperative myocardial infarction and progressive heart failure and the other underwent a combined procedure and died of Pseudomonas septicemia.
The frequency of acute kidney injury (AKI) was significantly higher in KTR, 57% vs. 23% (p<0.001), driven mainly by a higher incidence of AKI stage 1, i.e. an absolute increase in serum creatinine of ³0.3 mg/dL or 25%. See Table 2. The incidence of AKI requiring dialysis was similar between groups (7 vs. 5 patients, p=0.76). In two KTR the kidney function did not recover and maintenance dialysis was established. In a univariate logistic regression, likelihood ratio (LR) for AKI in KTR vs. controls was 4.46 (2.33-8.62, p<0.001). After adjustment for preoperative estimated GFR, there was still an increased risk of AKI in KTR, LR 2.4 (1.11-5.17, p=0.025).
Average serum creatinine at admission in the KTR group was 1.84 (0.81) mg/dL (n=78, 5 missing values and 13 patients on maintenance dialysis) and for controls 1.07 (0.46) mg/dL (n=82, excluding 13 controls that matched the 13 patients with non-functioning graft). See Table 1. The average peak in-hospital creatinine for KTR was 2.44 (1.22) mg/dL and for all controls 1.29 (0.80) mg/dL (p<0.001) while the mean discharge creatinine was 2.15 (1.17) mg/dL and 1.15 (0.78) mg/dL, respectively. The difference between creatinine at discharge versus admission of 0.3 mg/dL was significant for KTR (p<0.001) only.
KTR experienced also more postoperative bleeding, 1288 (1081) mL vs 957 (548) mL (p=0.01) and received a higher number of postoperative red cell transfusions than matched controls, 4.9 (5.6) vs 3.2 (5.4) (p=0.04). There was no difference in the use of acetylic salicylic acid, warfarin or low-molecular weight heparin among KTR vs. controls (72% vs 65%, p=0.35, 21% vs 18%, p=0.58 and 12% vs 12%, p=1.00, respectively). Although borderline significant, postoperative infections were more common in KTR, 29 (30.5%) vs. 19 (20.0%) patients (p=0.10), mainly driven by the increased frequency of wound infections (10 (10.5%) vs. 3 (3.2%), p=0.09). Postoperative data are presented in Table 2.
Table 2. Postoperative data in 95 kidney transplant recipients who underwent open heart surgery and 95 matched controls.
Postoperative data
|
Transplant recipients (n=95)
|
Controls
(n=95)
|
P value
|
30-day mortality
|
6 (6.3%)
|
2 (2.1%)
|
0.14
|
Any AKI (AKINa criteria)
Stage 1
Stage 2
Stage 3
|
47/82 (57%)
37
2
8 (7 dialysis)
|
21/91 (23%)
15
0
6 (5 dialysis)
|
<0.001
<0.001
0.50
0.58
|
Readmission within 30 days
|
13 (13.7%)
|
9 (9.5%)
|
0.36
|
Hemorrhage (ml)
|
1288 (1081)
|
957 (548)
|
0.01
|
Red cells (units)
Plasma (units)
Platelets (units)
Whole blood
Any blood product
|
4.9 (5.6)
3.9 (5.0)
0.9 (1.8)
0.1 (0.6)
9.7 (10.8)
|
3.2 (5.4)
3.6 (8.3)
0.6 (2.0)
0.1 (0.4)
7.4 (15.4)
|
0.04
0.77
0.29
0.41
0.23
|
Reoperation for hemorrhage
|
8 (8.4%)
|
10 (10.5%)
|
0.62
|
Sepsis
Pneumonia
Wound infection
Mediastinitis
Any postoperative infection
|
8
15
10
2
29 (30.5%)
|
5
16
3
1
19 (20%)
|
0.54
0.84
0.09
1.00
0.10
|
Postoperative arrhythmiab
|
42
|
38
|
0.56
|
Ventilation support (hours)
|
13.0 (29.1)
|
15.5 (41.0)
|
0.62
|
ICU days
|
2.0 (2.8)
|
1.8 (2.4)
|
0.51
|
Length of stay (days)
|
7.2 (7.5)
|
6.0 (3.0)
|
0.15
|
aAcute Kidney Injury Network bNew onset postoperative atrial fibrillation, atrial flutter, ventricular tachycardia, ventricular fibrillation
There was no statistical difference in intraoperative data and perioperative complications. However, perioperative stroke occurred in 6 KTR (6.3%) and in only 1 control patient (1.1%), p=0.12, see Table 3.
Table 3. Intraoperative data and perioperative complications in 95 kidney transplant recipients who underwent open heart surgery (48 CABG, 27 valve replacements or repairs and 20 combined procedures) and 95 controls.
|
Transplant recipients
(n=95)
|
Controls
(n=95)
|
P value
|
Perfusion time (min)
|
91 (35)
|
99 (50)
|
0.22
|
Ischemia time (min)
|
59 (29)
|
62.6 (39)
|
0.48
|
Perioperative myocardial infarction
|
6
|
3
|
0.50
|
Perioperative cerebrovascular accident
|
6
|
1
|
0.12
|
Number of distal coronary anastomosesa
|
2.8 (1.15)
|
2.9 (1.03)
|
0.70
|
Use of internal thoracic arterya
|
91% (n=62)
|
85% (n=58)
|
0.29
|
aCABG only, n=68
Uni- and multivariable logistic regression analyses of preoperative risk factors for 30-day mortality in KTR are presented in Tables 4 and 5, respectively.
Table 4. Univariable logistic regression. Preoperative risk factors for 30-day mortality after heart surgery in 95 kidney transplant patients.
Risk factor
|
Odds ratio (95% CI)
|
P value
|
Age per year
|
1.05 (0.96-1.14)
|
0.29
|
Age (<70 vs =>70 years)a
|
3.45 (0.65-18.44)
|
0.15
|
Chronic lung disease
|
0.0 (0.00-.)
|
1.00
|
Pulmonary hypertensionb
|
1.17 (0.13-10.83)
|
0.89
|
Diabetes mellitus
|
1.70 (0.32-8.90)
|
0.53
|
Dialysis
|
1.28 (0.14 -11.95)
|
0.83
|
Estimated GFRc
|
1.02 (0.98-1.06)
|
0.29
|
Statin use
|
2.68 (0.30-23.90)
|
0.38
|
Ejection fraction £ 35%
|
0.0 (0.00-.)
|
1.00
|
NYHA Class III/IV vs I/II
|
2.18 (0.24-19.54)
|
0.49
|
Previous AMI
|
2.45 (0.43-14.07)
|
0.32
|
AMI within 90 days before surgery
|
8.89 (1.56-50.76)
|
0.01
|
Previous cerebrovascular event
|
1.78 (0.19-16.95)
|
0.62
|
Smoking current
|
12.12 (1.35-108.81)
|
0.03
|
Period of surgeryd
|
0.26 (0.03-2.29)
|
0.22
|
Previous heart surgery
|
0.0 (0.00-.)
|
1.00
|
Emergency surgery
|
2.47 (0.41-14.71)
|
0.32
|
Valve surgery
|
1.02 (0.20-5.34)
|
0.98
|
Kidney-pancreas transplant
|
0.0 (0.000-.)
|
1.00
|
an=23 versus n=72, respectively bSystolic pulmonary artery pressure > 35 mmHg cEstimated glomerular filtration rate based on CKD-EPI creatinine formula d1989-2002 versus 2003-2016
Table 5. Multivariable logistic regressiona. Preoperative risk factors for 30-day mortality in 95 kidney transplant recipients.
Risk factor
|
Odds ratio (95% CI)
|
P value
|
Current smoker
|
17.32 (1.62-185.63)
|
0.02
|
AMI within 90 days before surgery
|
12.49 (1.60-97.40)
|
0.02
|
aBackward Wald selection procedure was used to identify the final multivariable model.