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Supplemental Table S1. Average Annual Incidence of de novo DSA according to donor type and post- transplant time, First 5-Years Post-Transplant results.

Post-Transplant

Year Overall Living Donor Deceased Donor

Person-Year Experience

Number of Cases

Rate /1000 /Year

Person-Year Experience

Number of Cases

Rate /1000 /Year

Person-Year Experience

Number.

of Cases

Rate /1000 /Year

Cases /Year Cases /Year Cases /Year

0-1 177.1 20 112.9 104.3 9 86.3 72.8 9 123.7

1-2 165.2 5 30.3 99.8 1 10.0 65.3 4 61.2

2-3 156.9 8 50.9 96.4 4 41.5 60.5 4 66.1

3-4 146.8 2 13.6 92.1 1 10.8 54.6 1 18.3

4-5 140.7 2 14.2 88.7 1 11.2 51.9 1 19.2

>5 459.4 10 21.8 308.8 5 16.1 150.6 5 33.2

Total 1246.2 47 37.7 790.4 21 26.5 455.8 26 52.6

(2)

Supplemental Table S2. Average Annual Incidence of de novo DSA according to transplant age and post-transplant time, First 3-Years Post-Transplant results.

Post-Transplant Year

Age at Transplant 18 – 35 years

Age at Transplant 36-50 years

Age at Transplant 51-60 years

Age at Transplant

>60 years

N b R N b R N b R N b R

Person-Year Experience

Number of Cases

Rate /1000 /Year

Person-Year Experience

Number of Cases

Rate /1000 /Year

Person-Year Experience

Number of Cases

Rate /1000 /Year

Person-Year Experience

Number of Cases

Rate /1000 /Year

0-1 26.7 7 262.4 62.6 7 111.8 55.2 4 72.4 32.7 2 61.2

1-2 22.3 2 89.6 58.3 2 34.2 52.6 1 19.0 31.7 0 0

2-3 21.0 1 47.7 56.7 2 35.3 50.9 2 39.3 28.4 3 105.7

>3 123.5 4 32.4 281.5 2 7.1 230.0 7 30.4 111.9 1 8.9

Total 193.5 14 72.3 459.4 13 28.3 388.7 14 36.0 204.6 6 29.3

(3)

Pt No. Gender AA Race

Txp Type

Age at Txp

No. of HLA Mismatches HLA Pre- Txp

No. of DSA at

onset

DSAmax Spec.

DSAmax Initial MFI

Persistent DSAmax

Months To DSA Onset

New DSA after Initial

Acute Rejection

Lost Graft Multiple Pre-DSA With/

Post-DSA A B DR DQ Total

1 F Y LRD 47 1 1 1 1 4 Y 1 DQ7 12202 Y 1.6 N N N Y N

2 F Y DD 49 1 1 1 1 4 Y 1 DQ3 21764 Y 12 8 N N N Y N

Supplemental Table S3. DSA Detail for Each Positive Patient.

2 F Y DD 49 1 1 1 1 4 Y 1 DQ3 21764 Y 12.8 N N N Y N

3 M Y LURD 41 1 2 1 1 5 N 4 DQ6 6793 Y 9.3 Y N N Y Y

4 F Y DD 16 2 0 1 1 4 N 1 DQ7 14571 Y 9.2 N N Y N Y

5 F N DD 58 0 0 0 2 2 Y 1 DQ3 2212 Y 3.6 N Y N Y Y

6 M N LRD 32 1 1 1 1 4 Y 1 DQ2 4643 Y 5.9 N N N Y N

7 F N LRD 36 1 1 1 1 4 N 1 A26 4816 Y 8.4 N N N Y Y

8 M Y LRD 23 2 2 2 1 7 N 1 DQ5 5689 Y 70.9 Y Y Y N N

9 M Y LURD 33 0 2 2 1 5 N 3 A2 7707 Y 1.0 N Y N Y N

10 F Y DD 34 2 2 1 1 6 N 1 DQ7 10671 Y 17 5 N N N N Y

10 F Y DD 34 2 2 1 1 6 N 1 DQ7 10671 Y 17.5 N N N N Y

11 F N DD 67 2 1 1 2 6 N 1 DQ2 14104 Y 7.0 Y N N Y N

12 M Y DD 52 0 0 0 2 2 N 1 DQ7 3357 N 123.2 N N N N Y

13 M Y LRD 27 1 1 2 0 4 Y 1 A29 4674 Y 95.2 Y N Y N N

14 M N LRD 48 0 1 1 2 4 N 1 DQ4 7280 Y 26.5 N N N N N

15 M Y LRD 23 1 0 1 1 3 Y 1 DQ6 3017 Y 3.9 Y N N N N

16 M Y DD 41 2 1 1 2 6 N 1 DQ7 10791 Y 87.7 N N N N N

17 M Y LRD 49 0 1 1 1 3 N 1 B8 5648 N 77.4 N N N N N

18 M N LURD 30 1 1 2 1 5 N 1 A1 1929 Y 9 4 N N N Y Y

18 M N LURD 30 1 1 2 1 5 N 1 A1 1929 Y 9.4 N N N Y Y

19 M N LRD 35 1 2 2 2 7 Y 1 DQ4 4036 N 93.3 N N N N N

20 M Y DD 51 2 2 0 2 6 N 1 DQ7 6127 Y 108.2 N N N N N

21 M Y LRD 31 2 2 1 1 6 N 1 DQ2 7276 Y 22.5 Y N N Y Y

22 F Y DD 52 2 1 1 1 5 Y 1 DQ7 5344 Y 19.5 Y N N N N

23 M Y DD 41 2 1 2 1 6 Y 1 A30 1013 Y 18.0 Y N N N N

24 F Y DD 42 2 2 0 1 5 Y 1 DR12 1029 N 1.4 Y N N N N

25 M N LRD 23 2 0 1 0 3 N 1 DR53 23576 Y 97.5 N N N N N

26 M Y LRD 29 1 1 1 1 4 N 1 DQ3 13057 Y 11 0 N N N N N

26 M Y LRD 29 1 1 1 1 4 N 1 DQ3 13057 Y 11.0 N N N N N

27 M Y LURD 63 1 2 2 2 7 N 2 DQ8 14814 Y 30.3 N N N N N

28 M N LRD 61 1 1 0 1 3 Y 1 DQ6 4212 Y 30.4 N N N N N

29 F Y DD 51 1 2 2 1 6 Y 1 DQ2 18773 Y 11.2 N N N N N

30 F Y DD 52 1 0 1 1 3 N 1 DQ6 1510 Y 67.4 N N N N N

31 F Y LURD 58 1 1 2 1 5 N 1 DQ2 7710 Y 46.0 N N N N N

32 M Y DD 68 1 2 1 1 5 N 1 A1 4924 Y 54.4 N N N N N

33 M Y DD 42 2 2 2 1 7 Y 1 A1 1152 N 5.0 N N N N Y

34 M N LURD 64 2 2 2 1 7 Y 1 B7 2641 Y 1 2 Y N N N Y

34 M N LURD 64 2 2 2 1 7 Y 1 B7 2641 Y 1.2 Y N N N Y

35 F Y DD 51 0 2 0 2 4 N 1 DQ2 1950 N 68.4 N N N N N

36 M N LRD 60 1 1 1 0 3 N 1 A3 2302 N 57.3 N N Y N N

37 F Y DD 51 2 1 2 1 6 N 1 A2 2828 Y 1.3 N N N N N

38 M Y DD 49 2 2 1 2 7 N 1 DQ9 15816 Y 34.6 N N N N Y

39 M Y DD 35 1 2 1 1 5 N 1 DQ7 11729 Y 35.8 N N N N N

40 F Y DD 47 2 2 2 1 7 Y 1 A2 1279 N 4.7 N N N N N

41 F N DD 66 2 2 1 1 6 Y 1 A1 12163 Y 26.3 Y N N N N

42 M Y DD 52 2 2 1 1 6 Y 1 A1 4506 Y 1 0 N N N N N

42 M Y DD 52 2 2 1 1 6 Y 1 A1 4506 Y 1.0 N N N N N

43 M Y LRD 51 2 2 1 0 5 Y 1 B7 7674 Y 26.3 Y N N Y Y

44 M N DD 19 1 2 2 2 7 Y 1 DQ7 1435 N 3.8 N N N N N

45 M Y DD 55 1 2 2 2 7 Y 1 DQ1 1006 Y 39.9 Y N N N N

46 M Y DD 42 1 2 2 2 7 Y 1 DQ8 1283 Y 1.0 N N N Y N

47 M N DD 58 1 2 1 0 4 N 1 DR53 4894 Y 33.2 N N N N N

Pt=patient, M=male, F=female, AA=African-American, Txp=transplant, LRD=living related donor, LURD=living-unrelated donor, DD=deceased donor, Y=yes, N=no, No.=number

(4)

Living Donor Deceased Donor P-value

Number of Subjects 109 80

Number of Subjects with De novo DSA 21 (19) 26 (33) 0.04

Patient Characteristics

Supplemental Table S4. Comparison of Patient Characteristics for Living and Deceased Donor Transplants

Patient Characteristics

Mean Age (SD) 48.3 (12.3) 49.3 (11.1) NS

Age at transplant 18-35 21 (19) 9 (11) NS

Age at transplant 36-50 38 (35) 29 (36) NS

Age at transplant 51-60 30 (28) 28 (35) NS

Age at transplant over 60 20 (19) 14 (18) NS

M l (%) 72 (66) 39 (49) 0 01

Male, n(%) 72 (66) 39 (49) 0.01

African-American, n(%) 56 (51) 65 (81) <0.01

Transplant Characteristics

Delayed Graft Function, n(%) 1 (<1) 5 (6) 0.04

Pre-Transplant HLA IgG Antibody Positive (non-DSA) 30 (28) 28 (35) NS

Mean Total HLA Mismatch (SD) 4 2 (1 7) 4 7 (1 7) 0 02

Mean Total HLA Mismatch (SD) 4.2 (1.7) 4.7 (1.7) 0.02

A-locus mismatches >0 90 (83) 66 (83) NS

B-locus mismatches >0 100 (92) 63 (79) 0.01

DR-locus mismatches >0 91 (83) 67 (84) NS

DQ-locus mismatches >0 79 (72) 64 (80) NS

Immunosuppression Induction n(%) Induction, n(%) Daclizumab Thymoglobulin

105 (97) 3 (3)

57 (71) 22 (28)

<0.01 Calcineurin Inhibitor, n(%)

Cyclosporine Tacrolimus

81 (75) 27 (25)

48 (60) 30 (38)

0.04

D t d i i li (%)

Documented immunosuppression non-compliance, n(%) 4 (4) 3 (4) NS

Rejection

T-Cell Mediated 21 (19) 13 (16) NS

Pure Antibody Mediated (AMR) 0 0 NS

Mixed (TCMR with AMR) 8 (7) 6 (8) NS

Median Serum Creatinine at 1 month Post-Transplant (range) p ( g ) 1 6 (0 8 – 3 0) 1.6 (0.8 – 3.0) 1 3 (0 8 – 3 7) 1.3 (0.8 – 3.7) NS NS Months of Follow-up

Mean (SD) Median (range)

99 (31) 98 (10 – 149)

83 (34) 78 (10 – 152)

<0.01

(5)

0 90

rvival 1.00

HLA Antibody Negative ib d ( ) ( )

0.60 0.70 0.80 0.90

ograft Su r

DSA Positive

HLA Antibody (+), DSA (-)

0 20 0.30 0.40 0.50 0.60

ity o f Al lo

0.00 0.10 0.20

Probabil i

0 1 2 3 4 5

Log-rank p<0.01

99 98 98 94 92 91

HLA (+) DSA (-) 43 43 42 42 39 35

HLA Antibody (-)

Number at risk

0 1 2 3 4 5

Years after Transplant

47 46 44 39 35 32

DSA (+) 99 98 98 94 92 91

HLA (+), DSA ( )

Supplemental Figure S1 The death censored graft survival is shown from time of transplant showing that

Supplemental Figure S1. The death-censored graft survival is shown from time of transplant showing that

de novo DSA positive patients are at a higher risk of failure than DSA negative patients and HLA antibody

positive patients. Survival for HLA antibody positive (DSA negative) patients is not statistically different

than HLA antibody negative patients at 5 years post-transplant.

(6)

S C ti i ≤ 1 6 /dL t S C ti i > 1 6 /dL t

0 90 1.00

val 0 90

val 1.00

DSA Negative (n=58) DSA Negative (n=84)

Serum Creatinine ≤ 1.6 mg/dL at DSA Appearance

Serum Creatinine > 1.6 mg/dL at DSA Appearance

0.50 0.60 0.70 0.80 0.90

Allograf t Survi v

0.50 0.60 0.70 0.80 0.90

Allograf t Survi v

DSA Positive (n=19)

DSA Positive (n=28)

0 00 0.10 0.20 0.30 0.40

Probability of

0 00 0.10 0.20 0.30 0.40

Probability of Log-rank p=0.013 Log-rank p=0.02

0.00

0 1 2 3 4 5

Years after Transplant 0.00

0 1 2 3 4 5

Years after Transplant

Supplemental Figure S2.The effect of de novo DSA stratified by early dysfunction. In patients with a 1

month serum creatinine ≤1.6 mg/dL are divided into DSA positive and DSA negative groupings. Patients with normal baseline function (serum creatinine ≤1.6 mg/dL at 1 month post-transplant) are at higher risk of

allograft loss if they have DSA. Similarly, in even in patients with some degree of dysfunction (serum

creatinine >1.6 mg/dL) at 1 month post-transplant, DSA still leads to poorer outcomes. For both analyses

patients all survival is death-censored.

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