Article Figures & Data
Figures
- Figure 1.
Treatment with a tacrolimus regimen was associated with a lower prevalence of dnDSA development.
- Figure 2.
Each HLA-DR and -DQ whole-antigen mismatch was associated with a broad range of eplet mismatches. Data points each represent one recipient's HLA-DR or DQ mismatch.
- Figure 3.
HLA-DR or -DQ eplet mismatch thresholds outperformed traditional whole-antigen HLA-DR or -DQ mismatch (zero, one, or two mismatches) to predict Class II dnDSA-free survival post-transplant. HLA locus specific Kaplan-Meier dnDSA free survival curves shown stratified by eplet mismatch (top) or whole-antigen mismatch (bottom).
- Figure 4.
Recipients who developed dnDSA had a greater percentage of tacrolimus levels below thresholds of 5 ng/ml or less. For each tacrolimus threshold the percentage of trough levels measured below that threshold for each patient were analyzed. Values shown are the mean percentage below each threshold with 95% confidence intervals.
- Figure 5.
In recipients who developed dnDSA, mean tacrolimus trough levels dropped significantly in the 6 months prior to dnDSA onset compared with their earlier trough levels. Mean tacrolimus levels in the six months prior to dnDSA onset were compared to all previous levels within distinct time epochs to show the consistency of association irrespective of the timing of dnDSA onset. Tacrolimus levels within the No dnDSA group are included for reference. Values represent the mean tacrolimus trough levels and their 95% confidence intervals.
- Figure 6.
Eplet mismatch modulates the effect of tacrolimus trough levels on the development of dnDSA. High risk: HLA-DR or -DQ eplet mismatch >11; low risk: HLA-DR and -DQ eplet mismatch ≤11. P values represent a comparison of high-risk patients who developed dnDSA with high-risk patients who did not develop dnDSA and a comparison of high-risk patients who developed dnDSA with low-risk patients who did not develop dnDSA. Values represent the mean percentages of tacrolimus trough levels below each threshold and their corresponding 95% confidence intervals.
Tables
HLA-DR or -DQ dnDSA, n=66 No HLA-DR or -DQ dnDSA, n=530 P Value First transplant, % 97 96 0.92 Recipient age at transplant, yr 33.6±17.6 44.6±15.6 <0.001 Donor age, yr 36.6±14.9 40.7±14.7 0.04 Living donor, % 41 50 0.17 Recipient ethnicity, white versus other, % 76 65 0.07 Cold ischemic time, h 8.7±5.7 6.8±5.4 0.004 Delayed graft function, % 14 12 0.65 Nonadherence, % 41 11 <0.001 Cyclosporin versus tacrolimus regime, % 39 11 <0.001 Calcineurin inhibitor coefficient of variation 39.6±13.5 33.7±13.3 0.01 HLA-A whole-antigen mismatch 1.0±0.7 1.1±0.8 0.17 HLA-B whole-antigen mismatch 1.2±0.6 1.2±0.7 0.52 HLA-C whole-antigen mismatch 0.8±0.8 1.1±0.8 0.12 HLA-DRβ1 whole-antigen mismatch 1.4±0.5 1.2±0.7 0.14 HLA-DRβ1/3/4/5 whole-antigen mismatch 2.4±0.9 2.1±1.3 0.18 HLA-DQβ1 whole-antigen mismatch 1.2±0.5 1.1±0.7 0.25 HLA-DQα1/β1 whole-antigen mismatch 2.3±0.9 2.2±1.4 0.54 HLA-DRβ1/3/4/5 eplet mismatch 14.1±7.3 11.0±9.2 0.001 HLA-DQα1/β1 eplet mismatch 17.5±8.1 13.0±10.4 0.002 Episodes of TCMR greater than or equal to borderline in 0–12 mo 1.4±1.4 0.6±1.1 <0.001 Episodes of TCMR≥Banff 1A in 0–12 mo 0.6±0.8 0.2±0.5 <0.001 Total Cohort DR dnDSA n=596, 29 Events DQ dnDSA n=596, 51 Events DR or DQ dnDSA n=596, 66 Events HR (95% CI) P Value HR (95% CI) P Value HR (95% CI) P Value Recipient age at transplant, yr 0.97 (0.95 to 0.99) 0.02 0.97 (0.95 to 0.98) 0.002 0.97 (0.96 to 0.99) 0.001 Nonadherence 3.07 (1.40 to 6.52) <0.01 3.11 (1.71 to 5.58) <0.001 3.09 (1.83 to 5.15) <0.001 Cyclosporin versus tacrolimus 2.14 (0.93 to 4.70) 0.07 1.97 (1.06 to 3.52) 0.03 2.28 (1.35 to 3.78) 0.002 HLA-DRβ1/3/4/5 eplet mismatch/ten mismatches 2.79 (1.84 to 4.27) <0.001 HLA-DQα1/β1 eplet mismatch/ten mismatches 2.00 (1.52 to 2.67) <0.001 HLA-DRβ1/3/4/5 + HLA-DQα1/β1 eplet mismatch/ten mismatches 1.37 (1.18 to 1.58) <0.001 - Table 3.
Multivariate correlates of dnDSA development: Subset with histology 0–12 mo post-transplant
Subset with Histology 0–12 mo Post-Transplant DR dnDSA n=439, 29 Events DQ dnDSA n=439, 48 Events DR or DQ dnDSA n=439, 63 Events HR (95% CI) P Value HR (95% CI) P Value HR (95% CI) P Value Recipient age at transplant, yr 0.98 (0.96 to 1.00) 0.09 0.97 (0.96 to 0.99) 0.003 0.98 (0.96 to 0.99) 0.003 Nonadherence 3.38 (1.53 to 7.28) 0.003 3.78 (2.08 to 6.79) <0.001 3.28 (1.93 to 5.51) <0.001 HLA-DRβ1/3/4/5 eplet mismatch/ten mismatches 3.16 (1.96 to 5.24) <0.001 HLA-DQα1/β1 eplet mismatch/ten mismatches 1.46 (1.12 to 1.93) <0.001 HLA-DRβ1/3/4/5 + HLA-DQα1/β1 eplet mismatch/ten mismatches 1.34 (1.14 to 1.57) 0.003 TCMR greater than or equal to borderline in 0–12 mo 1.37 (1.08 to 1.69) 0.01 1.31 (1.08 to 1.56) 0.001 1.22 (1.03 to 1.43) 0.02 - Table 4.
Multivariate correlates of dnDSA development: Subset treated with tacrolimus regime
Subset Treated with Tacrolimus Regime DR dnDSA n=492, 19 Events DQ dnDSA n=492, 34 Events DR or DQ dnDSA n=492, 44 Events HR (95% CI) P Value HR (95% CI) P Value HR (95% CI) P Value Recipient age at transplant, yr 0.95 (0.91 to 0.98) 0.002 0.95 (0.93 to 0.98) <0.001 0.96 (0.94 to 0.97) <0.001 Nonadherence 4.42 (1.74 to 11.41) 0.002 3.59 (1.73 to 7.43) 0.001 4.30 (2.29 to 8.08) <0.001 HLA-DRβ1/3/4/5 eplet mismatch/ten mismatches 2.70 (1.64 to 4.53) <0.001 HLA-DQα1/β1 eplet mismatch/ten mismatches 2.24 (1.56 to 3.29) <0.001 HLA-DRβ1/3/4/5 + HLA-DQα1/β1 eplet mismatch/ten mismatches 1.34 (1.13 to 1.60) 0.001
Supplemental Data
In this issue
Jump to section
More in this TOC Section
Cited By...
- Beyond the Biopsy: Monitoring Immune Status in Kidney Recipients
- Long-Term Immunosuppression Management: Opportunities and Uncertainties
- Eplet Mismatch Load and De Novo Occurrence of Donor-Specific Anti-HLA Antibodies, Rejection, and Graft Failure after Kidney Transplantation: An Observational Cohort Study
- Molecular Mismatch--the Renaissance of HLA in Kidney Transplantation
- Evaluation and Treatment of Acute Rejection in Kidney Allografts