figure s1, sdcdownload.lww.com/wolterskluwer_vitalstream_com/... · figure s1, sdc figure s1, sdc:...
TRANSCRIPT
P a g e | 1
Figure S1, SDC
Figure S1, SDC: A sample of 66,596 first adult kidney transplants with organs from living donors were performed between 1987 and 2013 with a projected median survival of 24.4 years. These are compared with 189,141 transplants during the same period with kidneys from deceased donors with a projected median survival of 18.0 years.10 Median survival was calculated from unadjusted data that span the 25 years duration, 1987-2013. Therefore their projected median values are not expected to match K-M curves that are calculated only from a shorter, more recent period in which the survival of allografts in both strata has improved.
P a g e | 2
Figure S2, SDC
Figure S2, SDC: The mean of the 32 z values was -0.02 and was not significantly different from 0.0 by t-test (p = 0.95); the standard deviation is 1.50, 95% empirical confidence interval is estimated with the bootstrap (b=1000), (1.05, 1.86); the tests for normality—Shapiro-Wilk (p = 0.52), Kolmogorov-Smirnov (p > 0.15), Cramer-von Mises (p > 0.25), and Anderson-Darling (p > 0.25)—do not reject the null hypothesis of a normal distribution. Therefore, the Cox fully adjusted regression for all living donors for first adult kidney transplants 1987-2013 is well specified.
P a g e | 3
Figure S3, SDC
Figure S3, SDC: The mean of the 124 z values was -0.07 and was not significantly different from 0.0 by t-test (p = 0.54); the standard deviation is 1.23 with 95% empirical confidence interval estimated with the bootstrap (b=1000), (1.08, 1.38); the tests for normality—Shapiro-Wilk (p = 0.89), Kolmogorov-Smirnov (p > 0.15), Cramer-von Mises (p > 0.25), and Anderson-Darling (p > 0.25)—do not reject the null hypothesis of a normal distribution. Therefore, the Cox fully adjusted regression for all first adult kidney transplants, 1987-2013, is well specified.
P a g e | 4
Figure S4, SDC
Figure S4, SDC: A Cox multivariate regression was performed with the survival time of kidney allografts from living donors as the dependent variable and an HLA mismatch categorical variable with categories as the primary explanatory variable with category living-related 0-mismatch as the reference. HR values for the full model are presented in Table 3. The blue line is fitted to the full model observed values with intercept 1.26 (1.04, 1.48), p < 0.0001, and slope of 0.14 (0.08, 0.20), p = 0.0004.
Table S1, SDC
Ordinary Least Square Regression of Schoenfeld Residuals of Individual Cox Model Variables
on Survival Time of First Adult Kidneys from Living Donors to Test the Proportional Hazards
Assumptiona
All Living Donors (N=66,596)
7,726 Events
Variable Beta R-Square P
Recipient Age 0.0000 0.0014 0.0011
Donor Age 0.0000 0.0000 0.8272
Recipient Gender -0.0000 0.0000 0.6321
Donor Gender -0.0000 0.0000 0.8971
Five Year Intervals -0.0000 0.0000 0.5774
Ethnicity -0.0000 0.0001 0.4185
Peak PRA -0.0000 0.0021 <.0001
Education -0.0000 0.0012 0.0025
Recipient BMI 0.0000 0.0009 0.0054
Working at Tx 0.0000 0.0002 0.1764
Dialysis Duration 0.0000 0.0001 0.2956
Dialysis Type 0.0000 0.0008 0.0149
Induction 0.0000 0.0003 0.1377
Immunosuppression 0.0000 0.0006 0.0348
HLA Mismatch 0.0000 0.0001 0.4396
a. The beta coefficient was never larger than 0.0001 and R-square did not exceed
0.0021. The large size of the sample for each regression created very small standard
errors. Therefore beta was significantly greater than 0.0 for a number of variables but
the low R-square demonstrated a lack of correlation between the 2 variables in each
instance.
Table S2, SDC
Z Table for the Goodness of Fit Test for the Cox Proportional Hazards Fully
Adjusted Model for all Allografts from Living Donors with 33 Categoriesa
Group Observed
Events
Expected
Events
z
1 19 25.996 -1.37206
2 42 36.432 0.92245
3 65 46.868 3.21696
4 88 57.304 5.51147
5 111 67.74 7.80598
6 134 78.176 10.10049
7 157 88.612 12.395
8 180 99.048 14.68951
9 203 109.484 16.98402
10 226 119.92 19.27853
11 249 130.356 21.57304
12 272 140.792 23.86755
13 295 151.228 26.16206
14 318 161.664 28.45657
15 341 172.1 30.75108
16 364 182.536 33.04559
17 387 192.972 35.3401
18 410 203.408 37.63461
19 433 213.844 39.92912
20 456 224.28 42.22363
21 479 234.716 44.51814
22 502 245.152 46.81265
23 525 255.588 49.10716
24 548 266.024 51.40167
25 571 276.46 53.69618
26 594 286.896 55.99069
27 617 297.332 58.2852
28 640 307.768 60.57971
29 663 318.204 62.87422
30 686 328.64 65.16873
31 709 339.076 67.46324
32 732 349.512 69.75775
a: adjustment for recipient age, donor age, recipient sex, donor sex, transplant era,
recipient ethnicity, recipient peak PRA, recipient education, recipient BMI, recipient
dialysis type, recipient working for income at transplant, years on dialysis greater than
or equal to the median, induction, immunosuppression at discharge, and HLA
mismatch.
Table S3, SDC
Ordinary Least Square Regression of Schoenfeld Residuals of Individual Cox Model
Variables on Survival Time of First Adult Kidneys to Test the Proportional Hazards
Assumptiona
All Donors (N=255,737)
49,713 Events
Variable Beta R-Square p
Recipient Age 0.0000 0.0004 <.0001
Donor Age 0.0000 0.0000 >0.05
Donor Gender 0.0000 0.0006 <.0001
Five Year Intervals 0.0000 0.0008 <.0001
Ethnicity 0.0000 0.0002 0.0012
Cold Ischemia Time -0.0000 0.0001 >0.05
Peak PRA -0.0000 0.0004 <.0001
Education 0.0000 0.0016 <.0001
Recipient BMI 0.0000 0.0001 0.0334
Donor BMI 0.0000 0.0000 >0.05
Diabetes Pre-transplant 0.0000 0.0001 0.0102
Working at Tx 0.0000 0.0003 <.0001
Drug Treatment COPD 0.0000 0.0001 0.0205
Dialysis Type 0.0000 0.0007 <.0001
Donor Type 0.0000 0.0000 >0.05
Waiting Time 0.0000 0.0000 >0.05
Induction -0.0000 0.0000 <.0001
Immunosuppression -0.0000 0.0013 <.0001
HLA Mismatch 0.0000 0.0000 >0.05
a. The beta coefficient was never larger than 0.0001 and R-square did not exceed
0.0018. The large size of the sample for each regression, 41987, created very small
standard errors. Therefore beta was significantly greater than 0.0 for a number of
variables but the low R-square demonstrated a lack of correlation between the 2
variables in each instance.
Table S4, SDC
Z Table for the Goodness of Fit Test for the Cox Proportional Hazards Fully Adjusted
Model for the 0-Mismatch Categorical Variable across all Strata of Donor Source
(N=255,737) with 125 Categoriesa
Group Observed Events Expected Events z
1 19 29.39 -1.917
2 33 38.52 -0.89004
3 34 43.72 -1.47059
4 44 49.89 -0.83386
5 53 54 -0.13607
6 54 57.64 -0.47914
7 42 61.84 -2.52309
8 54 66.97 -1.58543
9 56 67.72 -1.42475
10 72 71.84 0.01887
11 66 74.02 -0.93235
12 63 80.93 -1.99263
13 57 86.02 -3.12889
14 85 88.42 -0.36325
15 80 91.95 -1.24573
16 83 98.07 -1.52168
17 77 97.52 -2.07776
18 91 102.56 -1.14137
19 120 105.87 1.37299
20 104 108.13 -0.39698
21 88 114.41 -2.46937
22 98 117.24 -1.77657
23 99 122.3 -2.10706
24 139 124.9 1.26157
25 130 126.62 0.30006
26 120 132.26 -1.06635
27 115 134.98 -1.71974
28 151 139.13 1.00671
29 159 145.7 1.1016
30 157 144.6 1.03109
31 140 154.96 -1.20212
32 146 156.54 -0.84244
33 159 158.07 0.07384
34 160 164.26 -0.33255
35 183 170.66 0.94496
36 176 169.35 0.51062
37 171 174.85 -0.29099
38 161 175.33 -1.08219
39 203 189.58 0.97457
40 180 189.66 -0.70124
41 176 195.88 -1.42035
42 194 194.41 -0.02951
43 233 195.99 2.6438
44 212 211.46 0.03703
45 211 212.84 -0.12636
46 219 221.09 -0.14087
47 213 223.98 -0.73364
48 225 229.93 -0.32501
49 233 231.91 0.07157
50 236 238.59 -0.16784
51 243 250.97 -0.50333
52 252 244.63 0.4713
53 248 256.77 -0.54748
54 254 266.13 -0.74363
55 262 271.36 -0.56848
56 261 269.78 -0.53443
57 292 274.83 1.03553
58 292 287.42 0.27042
59 279 294.35 -0.8948
60 281 298.69 -1.02378
61 296 295.04 0.0559
62 366 302.28 3.66492
63 338 316.4 1.21439
64 311 323.46 -0.69281
65 330 332.53 -0.13883
66 354 334.36 1.07382
67 346 335.58 0.56859
68 340 357.07 -0.90343
69 361 345.31 0.84455
70 363 363.45 -0.02356
71 375 365.12 0.51715
72 348 378.13 -1.54935
73 386 390.1 -0.20738
74 353 392.71 -2.00384
75 406 381.94 1.23093
76 420 403.75 0.80889
77 445 403.96 2.04195
78 452 414.56 1.83891
79 431 417.14 0.67881
80 445 429.9 0.72815
81 484 438.78 2.15886
82 448 462.51 -0.67487
83 468 473.19 -0.23838
84 468 461.71 0.29252
85 443 490.47 -2.14351
86 518 496.96 0.94368
87 516 500.34 0.70025
88 499 521.15 -0.97047
89 520 523.57 -0.15605
90 509 516.46 -0.32814
91 561 534.88 1.1293
92 560 545.8 0.60775
93 580 553.09 1.14439
94 588 566.93 0.8848
95 602 565.17 1.54924
96 608 581 1.12006
97 629 595.39 1.37743
98 638 607.35 1.24355
99 647 643.62 0.1333
100 650 668.92 -0.73148
101 671 665.49 0.21374
102 694 676.62 0.66832
103 739 679.67 2.27576
104 761 695.61 2.47923
105 713 732.41 -0.71711
106 748 702.53 1.71542
107 776 727.63 1.7931
108 757 749.41 0.27721
109 770 734.44 1.31208
110 772 780.08 -0.28923
111 803 790.67 0.43851
112 829 799.32 1.04989
113 817 809.71 0.25614
114 859 844.35 0.50422
115 848 855.03 -0.24046
116 930 886.72 1.45326
117 903 912.66 -0.31986
118 977 948.19 0.93565
119 976 1038.54 -1.94077
120 1011 1070.36 -1.8143
121 995 1060.07 -1.99846
122 1087 1112.58 -0.76696
123 1182 1168.19 0.40395
124 1194 1251.31 -1.62026
a. adjustment for recipient age, donor age, donor sex, transplant era, recipient ethnicity,
recipient diabetes, cold ischemia time, recipient peak PRA, recipient education,
recipient BMI, donor BMI, recipient working for income at transplant, recipient COPD,
recipient dialysis type, donor source, waiting time for transplant, induction and
immunosuppression at discharge, HLA mismatch.
Table S5, SDC
Hazard ratio for risk of allograft failure by HLA mismatch with 0-Mismatch as the reference among adult (age ≥18 years),
first kidney only transplant recipients receiving organs from living donors. Reduced model with adjustment for recipient
age, recipient sex, and transplant era.
All Living Donors Living-Related Donors Living-Unrelated Donors
HLA
Mismatch N H.R. 95% C.I. p N H.R. 95% C.I. p N H.R. 95% C.I. p
0 5916 1.00 Reference 5770 1.00 Reference 146 1.00 Reference
1 3557 1.45 1.27,1.65 <.0001 3327 1.44 1.26, 1.64 <.0001 230 1.64 0.79, 3.42 >0.05
2 11036 1.70 1.54,1.88 <.0001 9857 1.71 1.54, 1.89 <.0001 1179 1.69 0.93, 3.08 >0.05
3 18424 1.94 1.77, 2.13 <.0001 14681 1.94 1.76, 2.14 <.0001 3743 2.12 1.18, 3.78 0.0114
4 9856 1.78 1.60,1.98 <.0001 2753 1.92 1.69, 2.19 <.0001 7103 1.94 1.09, 3.46 0.0242
5 11515 1.93 1.74, 2.14 <.0001 2773 2.06 1.81, 2.35 <.0001 8742 2.14 1.21, 3.81 0.0094
6 6292 2.17 1.94, 2.43 <.0001 1435 2.17 1.85, 2.55 <.0001 4857 2.49 1.39, 4.43 0.0021
a: adjustment for recipient age, sex, and transplant era.
P a g e | 15
Table S6, SDC
Hazard ratio for risk of allograft Failure for HLA mismatch triple with [0,0,0] as the
reference among adult (age ≥18 years), first kidney only transplant recipients receiving
organs from a living donora
All Living Donors
Mismatch
Category
Triple
[A,B,DR]
Number H.R. 95% C.I. p
0 [0,0,0] 5916 1.00 Reference
1 [0,0,1] 1149 1.49 1.24, 1.79 <.0001
1 [0,1,0] 1377 1.41 1.18, 1.69 0.0002
1 [1,0,0] 1031 1.43 1.16, 1.75 0.0006
2 [0,0,2] 75 1.37 0.77, 2.43 >0.05
2 [0,1,1] 4752 1.69 1.51, 1.91 <.0001
2 [0,2,0] 99 1.81 1.02, 3.21 0.0419
2 [1,0,1] 1938 1.77 1.53, 2.06 <.0001
2 [1,1,0] 4123 1.58 1.40, 1.79 <.0001
2 [2,0,0] 49 0.73 0.23, 2.26 >0.05
3 [0,1,2] 450 1.92 1.45, 2.56 <.0001
3 [0,2,1] 724 1.86 1.46, 2.36 <.0001
3 [1,0,2] 167 2.33 1.57, 3.45 <.0001
3 [1,1,1] 16028 1.90 1.73, 2.09 <.0001
3 [1,2,0] 535 1.23 0.89, 1.69 >0.05
P a g e | 16
3 [2,0,1] 171 1.22 0.69, 2.16 >0.05
3 [2,1,0] 349 1.66 1.18, 2.32 0.0035
4 [0,2,2] 854 1.42 1.10, 1.82 0.0065
4 [1,1,2] 2302 1.81 1.56, 2.10 <.0001
4 [1,2,1] 4021 1.72 1.51, 1.96 <.0001
4 [2,0,2] 109 2.22 1.33, 3.71 0.0024
4 [2,1,1] 2016 1.93 1.66, 2.26 <.0001
4 [2,2,0] 554 1.84 1.40, 2.40 <.0001
5 [1,2,2] 5182 2.04 1.81, 2.30 <.0001
5 [2,1,2] 1908 1.80 1.53, 2.12 <.0001
5 [2,2,1] 4425 1.79 1.57, 2.03 <.0001
6 [2,2,2] 6292 2.12 1.89, 2.37 <.0001
a: adjustment for recipient age, donor age, recipient sex, donor sex, transplant era,
recipient ethnicity, recipient peak PRA, recipient education, recipient BMI, recipient
dialysis type, recipient working for income at transplant, years on dialysis greater than
or equal to the median, induction and immunosuppression at discharge.
P a g e | 17
Table S7, SDC
Tests of Equality (1 d.f.) for the Triples of HLA Mismatch for all First Adult Kidney
Transplants from Living Donors in a Full Model Cox Multivariate Regression and with a
Holm-Bonferroni Correction for Multiple Testsa
Test Mismatch
Category Test
Chi
squaredp Adjusted p
1 3 [111]:[120] 7.59 0.0059 0.0009
2 3 [102]:[120] 6.46 0.0110 0.0009
3 3 [022]:[211] 5.12 0.0236 0.0009
4 3 [012]:[120] 4.58 0.0323 0.0009
5 3 [021]:[120] 4.55 0.0330 0.0009
6 3 [122]:[221] 4.48 0.0342 0.0010
7 3 [102]:[201] 3.44 0.0636 0.0010
8 3 [022]:[112] 3.24 0.0718 0.0010
9 3 [022]:[202] 2.45 0.1178 0.0010
10 3 [122]:[212] 2.36 0.1245 0.0010
11 5 [101]:[200] 2.35 0.1249 0.0011
12 2 [111]:[201] 2.35 0.1249 0.0011
13 3 [022]:[121] 2.18 0.1394 0.0011
14 3 [101]:[110] 2.18 0.1395 0.0011
15 3 [011]:[200] 2.1 0.1438 0.0012
16 5 [022]:[220] 2.10 0.1469 0.0012
P a g e | 18
17 4 [012]:[201] 2.04 0.1534 0.0012
18 3 [020]:[200] 2.00 0.1572 0.0013
19 4 [121]:[211] 2.00 0.1577 0.0013
20 2 [021]:[201] 1.85 0.1735 0.0013
21 1 [110]:[200] 1.80 0.1794 0.0014
22 4 [102]:[210] 1.74 0.1870 0.0014
23 2 [120]:[210] 1.70 0.1926 0.0014
24 4 [011]:[110] 1.26 0.2615 0.0015
25 3 [102]:[111] 1.06 0.3034 0.0015
26 3 [021]:[102] 0.98 0.3211 0.0016
27 2 [002]:[200] 0.96 0.3282 0.0016
28 4 [121]:[202] 0.92 0.3370 0.0017
29 1 [201]:[210] 0.85 0.3559 0.0017
30 1 [002]:[101] 0.76 0.3832 0.0018
31 4 [111]:[210] 0.66 0.4165 0.0019
32 2 [012]:[102] 0.63 0.4288 0.0019
33 3 [112]:[202] 0.58 0.4450 0.0020
34 2 [112]:[211] 0.56 0.4554 0.0021
35 2 [002]:[011] 0.53 0.4653 0.0022
36 4 [012]:[210] 0.48 0.4904 0.0023
37 3 [002]:[020] 0.47 0.4923 0.0024
38 4 [202]:[220] 0.43 0.5145 0.0025
39 3 [112]:[121] 0.40 0.5294 0.0026
P a g e | 19
40 4 [011]:[101] 0.36 0.5466 0.0028
41 4 [021]:[210] 0.32 0.5704 0.0029
42 4 [202]:[211] 0.26 0.6095 0.0031
43 4 [002]:[110] 0.25 0.6204 0.0033
44 2 [020]:[110] 0.22 0.6425 0.0036
45 2 [121]:[220] 0.21 0.6462 0.0038
46 3 [001]:[010] 0.20 0.6532 0.0042
47 2 [010]:[100] 0.20 0.6532 0.0045
48 2 [211]:[220] 0.13 0.7182 0.0050
49 2 [001]:[100] 0.12 0.7307 0.0056
50 4 [011]:[020] 0.05 0.8180 0.0063
51 3 [012]:[021] 0.04 0.8455 0.0071
52 4 [021]:[111] 0.03 0.8500 0.0083
53 2 [112]:[220] 0.01 0.9216 0.0100
54 2 [012]:[111] 0.01 0.9260 0.0125
55 2 [020]:[101] 0.01 0.9398 0.0167
56 4 [212]:[221] 0.01 0.9401 0.0250
57 5 [120]:[201] 0.00 0.9754 0.0500
a. adjustment for recipient age, donor age, recipient sex, donor sex, transplant era,
recipient ethnicity, recipient peak PRA, recipient education, recipient BMI, recipient
dialysis type, recipient working for income at transplant, years on dialysis greater than
or equal to the median, induction and immunosuppression at discharge.
P a g e | 20
Table S8, SDC
Tests of Equality (1 d.f.) for the Triples of HLA Mismatch for all (N=255,737) First Adult
Kidney Transplants in a Full Model Cox Multivariate Regression and with a Holm-
Bonferroni Correction for Multiple Testsa
Test Mismatch
Category Test
Chi
squaredp Adjusted p
1 3 [012]:[210] 15.0527 0.0001 0.0009
2 3 [111]:[210] 11.2004 0.0008 0.0009
3 3 [012]:[120] 10.2267 0.0014 0.0009
4 3 [102]:[210] 9.5637 0.002 0.0009
5 3 [021]:[210] 7.741 0.0054 0.0009
6 3 [102]:[120] 6.3716 0.0116 0.0010
7 3 [012]:[111] 4.8542 0.0276 0.0010
8 3 [111]:[120] 4.551 0.0329 0.0010
9 3 [012]:[201] 4.2702 0.0388 0.0010
10 3 [021]:[120] 4.0442 0.0443 0.0010
11 5 [122]:[221] 3.8755 0.049 0.0011
12 2 [011]:[110] 3.3793 0.066 0.0011
13 3 [201]:[210] 2.6853 0.1013 0.0011
14 3 [102]:[201] 2.5947 0.1072 0.0011
15 3 [102]:[111] 2.4378 0.1184 0.0012
16 5 [122]:[212] 2.2773 0.1313 0.0012
P a g e | 21
17 4 [112]:[211] 2.2185 0.1364 0.0012
18 3 [012]:[021] 1.8771 0.1707 0.0013
19 4 [202]:[211] 1.736 0.1876 0.0013
20 2 [020]:[110] 1.6432 0.1999 0.0013
21 1 [001]:[100] 1.5243 0.217 0.0014
22 4 [202]:[220] 1.4516 0.2283 0.0014
23 4 [112]:[220] 1.1804 0.2773 0.0014
24 2 [011]:[101] 1.1639 0.2807 0.0015
25 4 [121]:[202] 0.9687 0.325 0.0015
26 2 [020]:[101] 0.9585 0.3276 0.0016
27 3 [021]:[102] 0.9373 0.333 0.0016
28 3 [120]:[201] 0.9114 0.3398 0.0017
29 4 [121]:[211] 0.8984 0.3432 0.0017
30 1 [001]:[010] 0.8557 0.355 0.0018
31 1 [010]:[100] 0.8557 0.355 0.0019
32 2 [002]:[020] 0.7639 0.3821 0.0019
33 3 [021]:[201] 0.7257 0.3943 0.0020
34 3 [120]:[210] 0.6219 0.4303 0.0021
35 4 [022]:[202] 0.5982 0.4393 0.0022
36 2 [110]:[200] 0.5822 0.4454 0.0023
37 2 [002]:[011] 0.5618 0.4535 0.0024
38 4 [112]:[121] 0.5068 0.4765 0.0025
39 4 [112]:[202] 0.4413 0.5065 0.0026
P a g e | 22
40 3 [021]:[111] 0.4078 0.5231 0.0028
41 4 [022]:[211] 0.3759 0.5398 0.0029
42 4 [121]:[220] 0.3501 0.5541 0.0031
43 3 [111]:[201] 0.2592 0.6107 0.0033
44 2 [101]:[110] 0.2401 0.6242 0.0036
45 4 [022]:[220] 0.2393 0.6247 0.0038
46 2 [101]:[200] 0.2121 0.6451 0.0042
47 2 [002]:[200] 0.1968 0.6573 0.0045
48 2 [020]:[200] 0.1955 0.6584 0.0050
49 2 [011]:[020] 0.1752 0.6755 0.0056
50 4 [022]:[112] 0.0876 0.7673 0.0063
51 3 [012]:[102] 0.0486 0.8255 0.0071
52 2 [002]:[110] 0.0356 0.8504 0.0083
53 2 [011]:[200] 0.0242 0.8763 0.0100
54 4 [022]:[121] 0.0161 0.899 0.0125
55 4 [211]:[220] 0.0097 0.9215 0.0167
56 2 [002]:[101] 0.009 0.9244 0.0250
57 5 [212]:[221] 0.0004 0.9849 0.0500
a. adjustment for recipient age, donor age, donor sex, transplant era, recipient ethnicity,
recipient diabetes, cold ischemia time, recipient peak PRA, recipient education,
recipient BMI, donor BMI, recipient working for income at transplant, recipient COPD,
recipient dialysis type, kidney source for all persons, waiting time for transplant,
induction and immunosuppression at discharge.