Baseline characteristics
The overall study population included 83 patients receiving SPKT in our department between 2000 and 2016. At the time of transplantation, 64 patients obtained HD and nineteen patients used PD. Continuous ambulatory peritoneal dialysis was used by fourteen patients (74 %) and automatic peritoneal dialysis was used by five patients (26%) among the PD group. Recipient, donor and graft characteristics according to the different dialysis types prior to transplantation are summarized in Table 1. The two groups were similar for the majority of their pre-transplant characteristics, while the number of female recipients was higher in the PD group (P = 0.017), and a history of depression was more frequent in the HD group (P = 0.049). HLA mismatches, post-transplant immunosuppressive regimes and lengths of hospital stay did not show significant differences between the two groups (data not shown).
Table 1 Demographic and clinicopathologic characteristics of the study cohort prior to transplantation. Data are shown as mean ± SD. ALT, antilymphocyte globulin; ATG, anti-thymocyte globulin; BMI, body mass index; CMV, cytomegalovirus; D+, donor positive; R+ recipient positive; HbA1c, glycated hemoglobin; HD, hemodialysis; IL-2 RA, Interleukin-2 receptor antagonist; PD, peritoneal dialysis; SPKT, simultaneous pancreas-kidney transplantation.
Variables
|
HD (N = 64)
|
PD (N = 19)
|
P-value
|
|
|
|
|
|
Recipient
|
|
|
|
|
Age, years
|
43.8 ± 9.1
|
43.2 ± 9.7
|
0.845
|
|
Gender
|
|
|
|
|
|
Male
|
40 (62. 5%)
|
6 (31.6 %)
|
0.017
|
|
|
Female
|
24 (37.5 %)
|
13 (68.4 %)
|
|
BMI, kg/m²
|
25.8 ± 4.4
|
24 ± 3.6
|
0.105
|
|
Duration diabetes mellitus, years
|
27.1 ± 8.4
|
26.1 ± 8.6
|
0.685
|
|
Time on dialysis, months
|
30.5 ± 21.3
|
27.0 ± 22.1
|
0.536
|
|
HbA1c pre-transplantation, %
|
7.7 ± 1.8
|
7.7 ± 1.2
|
0.940
|
|
Time on waiting list, months
|
10.9 ± 13.6
|
7.2 ± 6.9
|
0.242
|
|
Comorbidities
|
|
|
|
|
|
Diabetic retinopathy
|
56 (87.5 %)
|
13 (68.4 %)
|
0.050
|
|
|
Diabetic neuropathy
|
39 (60.9 %)
|
11 (57.9 %)
|
0.812
|
|
|
Arterial obstructive disease
|
12 (18.8 %)
|
2 (10.5 %)
|
0.401
|
|
|
Coronary heart disease
|
21 (32.8 %)
|
2 (10.5 %)
|
0.050
|
|
|
Depression
|
21 (32.8 %)
|
2 (10.5 %)
|
0.049
|
|
Taking aspirin pre-SPKT
|
23 (35.9 %)
|
9 (47.4 %)
|
0.367
|
|
|
|
|
|
Donor
|
|
|
|
|
Age, years
|
24.1 ± 11.8
|
19.2 ± 7.8
|
0.109
|
|
Gender
|
|
|
|
|
|
Male
|
37 (57.8 %)
|
14 (73.3 %)
|
0.212
|
|
|
Female
|
27 (42.2 %)
|
5 (26.3 %)
|
|
BMI, kg/m²
|
22.4 ± 3.1
|
22.1 ± 2.8
|
0.987
|
|
|
|
|
|
Graft
|
|
|
|
|
Kidney cold ischemia, hours
|
11.0 ± 3.3
|
11.1 ± 2.6
|
0.978
|
|
Pancreas cold ischemia, hours
|
10.1 ± 1.9
|
10.9 ± 3.9
|
0.294
|
|
|
|
|
|
CMV status
|
|
|
|
|
CMV D +
|
31 (48.4 %)
|
11 (64.7 %)
|
0.211
|
|
CMV R +
|
36 (56.3 %)
|
13 (68.4 %)
|
0.343
|
|
|
|
|
|
Induction Therapy
|
|
|
|
|
ALG/ ATG
|
54 (84.4 %)
|
15 (78.9 %)
|
0.864
|
|
IL2-RA
|
7 (10.9 %)
|
3 (15.8 %)
|
0.568
|
|
None
|
3 (4.7 %)
|
1 (5.3 %)
|
0.916
|
|
|
|
|
|
Outcome
Complications
There were no significant differences in the frequency of peri- and postoperative complications between HD and PD SPKT recipients (Table 2). The global relaparotomy rate was similar between the two groups (HD: 35% versus PD: 36%; P = 0.77).
After transplantation, eighteen patients developed intra-abdominal infections (HD: 20% versus PD: 26%; P = 0.577). There were eight bacterial infections, two fungal infections and eight cultured positive for both bacteria and fungi. Intra-abdominal infections were complicated with graft pancreatitis in nine cases (HD: 10% versus PD: 11%; P = 0.89) and relaparotomy was necessary in ten cases (HD: 13% versus PD: 11%; P = 0.76). Four out of nineteen PD patients had a history of peritonitis during their time on dialysis, including two patients with two or more episodes of peritonitis. A history of peritonitis was not associated with an increased risk of complications after transplantation, whereby only one of these patients had an intra-abdominal infection and one patient developed pancreatitis post-transplant.
Table 2 Post-transplant complications and causes of relaparotomy. CMV, cytomegalovirus; GI, gastrointestinal; HD, hemodialysis; PD, peritoneal dialysis; SPKT, simultaneous pancreas-kidney transplantation.
Variables
|
HD (N = 64)
|
PD (N = 19)
|
P-value
|
|
|
|
|
|
|
|
Acute combined graft rejection
|
12 (19 %)
|
3 (16 %)
|
0.769
|
|
Delayed graft function kidney
|
10 (16 %)
|
2 (11 %)
|
0.80
|
|
Anastomotic leak
|
2 (3 %)
|
1 (5 %)
|
0.66
|
|
Graft thrombosis
|
7 (11 %)
|
4 (21 %)
|
0.254
|
|
GI-bleeding
|
7 (11 %)
|
1 (5 %)
|
0.426
|
|
Other major bleeding
|
9 (14 %)
|
2 (11 %)
|
0.69
|
|
Intra-abdominal infection
|
13 (20 %)
|
5 (26 %)
|
0.577
|
|
Graft pancreatitis
|
11 (17 %)
|
3 (16 %)
|
0.88
|
|
CMV infection
|
21 (33.3 %)
|
5 (26.3 %)
|
0.564
|
|
Wound infections
|
9 (14 %)
|
3 (16 %)
|
0.851
|
|
|
|
|
|
|
Re-operation/ relaparotomy
|
23 (35 %)
|
7 (36 %)
|
0.77
|
|
Causes relaparotomy
|
|
|
|
|
|
Infection
|
8 (13 %)
|
2 (11 %)
|
0.76
|
|
|
Bleeding
|
6 (9 %)
|
1 (5 %)
|
0.51
|
|
|
Thrombosis
|
7 (11 %)
|
3 (16 %)
|
0.54
|
|
|
Others
|
2 (3 %)
|
1 (5 %)
|
0.66
|
|
|
|
|
|
|
Patient and graft survival
The 3- and 5-year patient survival rates for patients after SPKT showed no significant differences between the HD and PD group (98.2% and 96.1% in HD versus 92.9% and 92.9% in PD, respectively; P = 0.559). Similarly, the 1-, 3- and 5- year pancreas graft survival rates (94.6%, 90.3% and 85.8% in HD versus 88.2%, 81.9% and 81.9% in PD, respectively; P = 0.901) and kidney graft survival rates (98.2%, 96.4% and 84.3% in HD versus 88.2%, 88.2% and 80.2% in PD, respectively; P = 0.712) did not show any significant differences between the two groups (Figure 1).
As shown in Table 3, no significant differences were found between the type of pre-transplant dialysis modality and causes for patient death and graft failure. However, we noted a tendency of higher graft losses due to thrombosis in PD patients (HD: 4.7% versus PD: 15.8%; P = 0.10).
Table 3 Causes of patient death and pancreas and kidney graft loss after simultaneous pancreas-kidney transplantation.
Variables
|
HD (N = 64)
|
PD (N = 19)
|
P-value
|
|
|
|
|
|
Patient death
|
|
|
|
|
Total
|
12 (19 %)
|
3 (16 %)
|
0.78
|
|
Cardiovascular
|
6 (9.4 %)
|
2 (10.5 %)
|
0.88
|
|
Infection
|
4 (6.3 %)
|
1 (5.3 %)
|
0.87
|
|
Other
|
2 (3.1 %)
|
0 (0 %)
|
0.43
|
|
|
|
|
|
Pancreas graft failure
|
|
|
|
Total
|
15 (23 %)
|
5 (26 %)
|
0.79
|
|
Rejection
|
3 (4.7 %)
|
0 (0 %)
|
0.33
|
|
Thrombosis
|
3 (4.7 %)
|
3 (15.8 %)
|
0.10
|
|
Bleeding
|
2 (3.1 %)
|
0 (0 %)
|
0.43
|
|
Infection
|
5 (7.8 %)
|
2 (10.5 %)
|
0.70
|
|
Other
|
2 (3.1 %)
|
0 (0 %)
|
0.43
|
|
|
|
|
|
Kidney graft failure
|
|
|
|
|
Total
|
13 (20 %)
|
3 (16 %)
|
0.19
|
|
Rejection
|
6 (9 %)
|
1 (5 %)
|
0.32
|
|
Thrombosis
|
2 (3 %)
|
1 (5 %)
|
0.66
|
|
Infection
|
3 (5 %)
|
1 (5 %)
|
0.91
|
|
Other
|
2 (3 %)
|
0 (0 %)
|
0.45
|
|
|
|
|
|
Multivariate Cox regression analysis of the total study population revealed that the presence of cardiovascular disease is an independent predictor of patient death. Moreover, the preoperative presence of cardiovascular disease, recipient age, BMI, duration of pre-transplant dialysis and surgical complications could be identified as independent predictors of pancreas and kidney graft loss (Table 4).
Table 4 Multivariate Cox regression analysis of predictors of patient death and pancreas graft loss. BMI, body mass index; HD, hemodialysis; HR (95CI), hazard ratio (95% confidence interval); PD, peritoneal dialysis.
Variables
|
HR (95 CI)
|
P-value
|
|
|
|
|
Patient death
|
|
|
|
Cardiovascular disease
|
6.12 (1.7 - 21.19
|
0.005
|
|
Dialysis modality (PD vs HD)
|
1.72 (0.3 7- 7.71)
|
0.70
|
|
Recipient age
|
0.96 (0.90 - 1.04)
|
0.33
|
|
Recipient gender (male vs female)
|
1.36 (0.41 - 4.44)
|
0.60
|
|
Months on dialysis
|
1.01 (0.9 - 1.0)
|
0.25
|
|
Years of diabetes
|
1.01 (0.9 - 1.2)
|
0.65
|
|
Recipient BMI
|
1.02 (0.88 - 1.18)
|
0.75
|
|
|
|
|
Pancreas graft failure
|
|
|
|
Cardiovascular disease
|
3.36 (1.14 - 9.89)
|
0.02
|
|
Dialysis modality (PD vs HD)
|
1.35 (0.43 - 4.27)
|
0.60
|
|
Recipient age
|
1.2 (0.99 - 1.12)
|
0.01
|
|
Recipient gender (male vs female)
|
2.01 (0.81 - 4.92)
|
0.129
|
|
Months on dialysis
|
0.98 (0.96 - 1.10)
|
0.001
|
|
Years of diabetes
|
1.02 (0.94 - 1.06)
|
0.95
|
|
Surgical complications
|
6.48 (2.66 - 15.74)
|
0.001
|
|
Recipient BMI
|
1.2 (1.08 - 1.35)
|
0.01
|
|
|
|
|
Kidney graft failure
|
|
|
|
Cardiovascular disease
|
2.53 (0.82 - 7.46)
|
0.019
|
|
Dialysis modality (PD vs HD)
|
1.01 (0.28 - 3.59)
|
0.986
|
|
Recipient age
|
1.2 (0.99 - 1.12)
|
0.01
|
|
Recipient gender (male vs female)
|
2.1 (0.75 - 6.1)
|
0.15
|
|
Months on dialysis
|
0.96 (0.93 - 1.2)
|
0.001
|
|
Years of diabetes
|
1.1 (0.95 - 1.08)
|
0.74
|
|
Surgical complications
|
3.4 (1.5 - 6.9)
|
0.03
|
|
Recipient BMI
|
1.19 (1.06 - 1.33)
|
0.003
|
|
|
|
|
Health-related quality of life (HRQoL)
Impact of pre-transplant dialysis modality
Tables 5 compares the HRQoL scores of SPKT recipients according to their dialysis modality before and after transplantation. Both groups showed an improvement of HRQoL in all SF-36 domains after transplantation. There were statistically significant improvements in six of the eight SF-36 domains in the HD group, and in seven of the eight SF-36 domains in the PD group.
Before transplantation, benefits were seen for the PD patients, with statistically significant differences in terms of physical functioning (P = 0.028), bodily pain (P = 0.034), and in the physical component summary (PCS) (P = 0.013) compared with patients receiving HD prior to transplantation (Table 5). After SPKT, PD patients showed significantly better results in four of the eight SF-36 domains compared with HD patients: physical functioning (P < 0.01), bodily pain (P < 0.01), general health (P = 0.04), vitality (P = 0.04) and PCS (P < 0.01).
Table 5 Comparison of HRQoL between HD and PD patients before and after SPKT. Data are shown as mean ± SD. HD, hemodialysis; MCS, mental component summary; MD, mean difference; PCS, physical component summary; PD, Peritoneal dialysis; SF-36, Short Form 36; SPKT, simultaneous pancreas-kidney transplantation.
|
|
Groups
|
|
HD - PD
|
SF-36 dimensions
|
|
HD (N = 64)
|
|
PD (N = 19)
|
|
Before SPKT
|
|
After SPKT
|
|
|
Before SPKT
|
After SPKT
|
P-value
|
Before SPKT
|
After SPKT
|
P-value
|
|
MD
|
P-value
|
|
MD
|
P-value
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Physcial functioning
|
|
48.3 ± 13.3
|
68.9 ± 8.9
|
<0.01
|
|
63.8 ± 17.7
|
81.3 ± 15.9
|
0.030
|
|
-15.2 ± 7.1
|
0.028
|
|
-12.4 ± 4.9
|
<0.01
|
Role limitations- physical
|
|
38.3 ± 31.3
|
60.7 ± 25.4
|
0.040
|
|
56.2 ± 43.8
|
72.9 ± 19.8
|
<0.01
|
|
-17.9 ± 16.4
|
0.267
|
|
-12.2 ± 9.1
|
0.49
|
Bodily Pain
|
|
44.2 ± 21.2
|
71.1 ± 8.5
|
<0.01
|
|
64.1 ± 17.6
|
85.3 ± 9.8
|
<0.01
|
|
-19.9 ± 9.3
|
0.034
|
|
-14.2 ± 6.3
|
<0.01
|
General health
|
|
36.5 ± 16.1
|
61.6 ± 7.5
|
<0.01
|
|
48.8 ± 7.0
|
67.9 ± 6.8
|
<0.01
|
|
-12.3 ± 6.3
|
0.053
|
|
-6.3 ± 2.8
|
0.04
|
Social function
|
|
55.8 ± 17.6
|
65.2 ± 12.2
|
0.110
|
|
68.8 ± 11.6
|
73.9 ± 11.2
|
0.329
|
|
-13.0 ± 7.4
|
0.077
|
|
-8.7 ± 4.6
|
0.15
|
Vitality
|
|
42.7 ± 11.2
|
61.1 ± 7.4
|
<0.01
|
|
48.8 ± 18.5
|
67.9 ± 5.4
|
<0.01
|
|
-6.1 ± 6.6
|
0.333
|
|
-6.8 ± 2.6
|
0.04
|
Role limitations- emotional
|
|
44.4 ± 29.9
|
61.9 ± 28.8
|
0.122
|
|
66.7 ± 30.9
|
83.3 ± 22.5
|
0.178
|
|
-22.3 ± 12.9
|
0.109
|
|
-21.4 ± 10.3
|
0.36
|
Mental Health
|
|
51.4 ± 16.4
|
63.4 ± 5.8
|
0.010
|
|
49.5 ± 2.8
|
62.3 ± 8.2
|
<0.01
|
|
-1.9 ± 4.9
|
0.681
|
|
-1.1 ± 2.7
|
0.96
|
PCS
|
|
34.9 ± 5.8
|
45.6 ± 4.6
|
<0.01
|
|
43.1 ± 8.6
|
50.8 ± 2.5
|
<0.01
|
|
-8.2 ± 3.1
|
0.013
|
|
-5.2 ± 1.5
|
<0.01
|
MCS
|
|
40.2 ± 6.6
|
44.7 ± 4.5
|
0.042
|
|
41.6 ± 5.4
|
46.8 ± 3.8
|
0.021
|
|
-1.4 ± 2.9
|
0.624
|
|
-2.1 ± 1.6
|
0.32
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Impact of demographical and clinical variables
We separately analyzed the possible impact of three factors – age, gender and graft loss – on the HRQoL of the overall study population after SPKT (Table 6). Regarding patients’ age, there was a significant difference in physical functioning (P = 0.04), general health (P < 0.01) and role limitations (P = 0.03). In the univariate analysis, patients’ gender showed no influence on HRQoL after SPKT. Graft loss (kidney or pancreas) led to a significant decrease in all physical components (each P < 0.01) and mental health status (P = 0.01) of the SF-36.
Table 6 Univariate analysis: impact of clinical and demographical variables on SF-36 results of all patients after transplantation (n = 83). Data are shown as mean ± SD.
SF-36 dimensions
|
|
Age
|
|
Gender
|
|
Graft loss
|
|
|
<45 years
|
>45 years
|
P-value
|
|
Male
|
Female
|
P-value
|
|
No
|
Yes
|
P-value
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Physcial functioning
|
|
80.1 ± 11.2
|
69.8 ± 14.3
|
0.04
|
|
77.8 ± 13.4
|
74.2 ± 14.3
|
0.499
|
|
86.8 ± 6.8
|
65.6 ± 10.3
|
<0.01
|
Role limitations- physical
|
|
73.5± 20.6
|
61.1 ± 13.1
|
0.09
|
|
69.3 ± 17.6
|
67.6 ± 20.1
|
0.308
|
|
76.3 ± 15.1
|
45.8 ± 10.2
|
<0.01
|
Bodily Pain
|
|
80.1 ± 11.7
|
72.2. ± 9.6
|
0.1
|
|
79.8 ± 12.3
|
76.1 ± 11.1
|
0.416
|
|
81.8 ± 8.9
|
67.9 ± 7.7
|
<0.01
|
General health
|
|
67.9 ± 5.8
|
59.8 ± 7.6
|
<0.01
|
|
63.1 ± 9.1
|
66.4± 5.2
|
0.276
|
|
82.8 ± 8.5
|
46.7 ± 5.8
|
<0.01
|
Social function
|
|
72.1 ± 10.4
|
63.9 ± 14.6
|
0.11
|
|
68.2 ± 15.6
|
70.0 ± 10.4
|
0.719
|
|
73.9 ± 11.2
|
65.0 ± 12.1
|
0.08
|
Vitality
|
|
66.2 ± 5.7
|
61.8 ± 9.2
|
0.15
|
|
67.3 ± 7.2
|
61.3 ± 6.7
|
0.047
|
|
66.4 ± 5.9
|
55.2 ± 5.1
|
0.06
|
Role limitations- emotional
|
|
82.1 ± 22.4
|
61.5 ± 23.7
|
0.03
|
|
68.9 ± 29.4
|
75.8 ± 21.6
|
0.545
|
|
80.1 ± 5.1
|
61.1 ± 20.3
|
0.09
|
Mental Health
|
|
63.3 ± 7.9
|
62.4 ± 5.6
|
0.66
|
|
63.7 ± 7.5
|
61.8 ± 6.3
|
0.498
|
|
65.1 ± 5.6
|
57.1 ± 1.3
|
0.01
|
|
|
|
|
|
|
|
|
|
|
|
|
|