HLA Matching Trumps Donor Age: Donor-Recipient Pairing Characteristics That Impact Long-Term Success in Living Donor Kidney Transplantation in the Era of Paired Kidney Exchange

Milner, John; Melcher, Marc L.; Lee, Brian; Veale, Jeff; Ronin, Matthew; D'Alessandro, Tom; Hil, Garet; Fry, Phillip C.; Shannon, Patrick

doi:10.1097/txd.0000000000000597

Cited by 23 publications

(9 citation statements)

References 24 publications

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“…HLA-A/B/DRB1 or HLA-A/B/DR/DQB1 was used to quantitate the hydrophobic (HMS), electrostatic (EMS), and amino acid (AMS) mismatch scores: IM scores for each transplant were calculated as averages for class I (HLA-A/B) and class II (DR ± DQ) loci. That way, 50% of the IM score was contributed by DR alone or DR/DQ combination, as was suggested before (28).…”

Section: Imputation Of High-resolution Hla Types and Calculation Of Immunogenicitysupporting

confidence: 51%

Low Hydrophobic Mismatch Scores Calculated for HLA-A/B/DR/DQ Loci Improve Kidney Allograft Survival

Bekbolsynov

Mierzejewska

Borucka³

et al. 2020

Front. Immunol.

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We evaluated the impact of human leukocyte antigen (HLA) disparity (immunogenicity; IM) on long-term kidney allograft survival. The IM was quantified based on physicochemical properties of the polymorphic linear donor/recipient HLA amino acids (the Cambridge algorithm) as a hydrophobic, electrostatic, amino acid mismatch scores (HMS\AMS\EMS) or eplet mismatch (EpMM) load. High-resolution HLA-A/B/DRB1/DQB1 types were imputed to calculate HMS for primary/re-transplant recipients of deceased donor transplants. The multiple Cox regression showed the association of HMS with graft survival and other confounders. The HMS integer 0-10 scale showed the most survival benefit between HMS 0 and 3. The Kaplan-Meier analysis showed that: the HMS=0 group had 18.1-year median graft survival, a 5-year benefit over HMS>0 group; HMS ≤ 3.0 had 16.7-year graft survival, a 3.8-year better than HMS>3.0 group; and, HMS ≤ 7.8 had 14.3-year grafts survival, a 1.8-year improvement over HMS>7.8 group. Stratification based on EMS, AMS or EpMM produced similar results. Additionally, the importance of HLA-DR with/without -DQ IM for graft survival was shown. In our simulation of 1,000 random donor/recipient pairs, 75% with HMS>3.0 were re-matched into HMS ≤ 3.0 and the remaining 25% into HMS≥7.8: after re-matching, the 13.5 years graft survival would increase to 16.3 years. This approach matches donors to recipients with low/medium IM donors thus preventing transplants with high IM donors.

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Section: Imputation Of High-resolution Hla Types and Calculation Of Immunogenicitysupporting

confidence: 51%

Low Hydrophobic Mismatch Scores Calculated for HLA-A/B/DR/DQ Loci Improve Kidney Allograft Survival

Bekbolsynov

Mierzejewska

Borucka³

et al. 2020

Front. Immunol.

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“…Although multiple factors contribute to prolonged graft survival for LDKT recipients, human leukocyte antigen (HLA) matching remains a very impactful determinant of long-term outcome (5–8). First-degree genetic relatives (i.e.…”

Section: Introductionmentioning

confidence: 99%

Inferior long-term allograft and patient outcomes among recipients of offspring living donor kidneys

Cohen

Owei

Sawinski

et al. 2018

American Journal of Transplantation

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While offspring-to-parent living donor kidney transplantations may represent an ideal donor-recipient combination to optimize long-term transplantation outcomes, the sex-specific long-term success of these transplantations remains unclear. We hypothesize that allograft and recipient survivals in offspring-to-parent living donor kidney transplantation differ between men and women due to donor-specific alloimmunization during pregnancy. We retrospectively analyzed long-term allograft and patient survival among men and women who received an offspring living donor kidney compared with those who received other haplotype-matched living donor kidneys. Based on multivariable Cox proportional hazards modeling of Organ Procurement and Transplantation Network data from 2001 to 2015, we found that both men and women who received offspring living donor kidneys had significantly increased mortality compared with recipients who received nonoffspring living donor kidneys. While male recipients of any living donor kidney had greater risk of mortality and allograft failure than female recipients, there was no significant difference in all-cause allograft failure or mortality in male versus female recipients of offspring living donor kidney transplantations. Our analysis demonstrated no significant interaction between recipient sex and donor offspring status. We conclude that nonoffspring living donors should be considered whenever feasible for both men and women with multiple donor options.

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“…If the median graft survival in each immunogenicity category is multiplied by the number of recipients, the resulting kidney life-years (KLY) can be used as a measure of outcomes of kidney transplantation ( 26 ). We then multiplied the projected graft survival in years by the number of transplants with our race-specific HMS thresholds: Black recipients gained 2,300 KLY at HMS=0 over their current outcomes, 4,400 KLY at HMS ≤ 1.0, and 9,800 KLY at HMS ≤ 3.0.…”

Section: Resultsmentioning

confidence: 99%

Improving Access to HLA-Matched Kidney Transplants for African American Patients

et al. 2022

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IntroductionKidney transplants fail more often in Black than in non-Black (White, non-Black Hispanic, and Asian) recipients. We used the estimated physicochemical immunogenicity for polymorphic amino acids of donor/recipient HLAs to select weakly immunogenic kidney transplants for Black vs. White or non-Black patients.MethodsOPTN data for 65,040 donor/recipient pairs over a 20-year period were used to calculate the individual physicochemical immunogenicity by hydrophobic, electrostatic and amino acid mismatch scores (HMS, EMS, AMS) and graft-survival outcomes for Black vs. White or vs. non-Black recipients, using Kaplan-Meier survival and Cox regression analyses. Simulations for re-matching recipients with donors were based on race-adjusted HMS thresholds with clinically achievable allocations.ResultsThe retrospective median kidney graft survival was 12.0 years in Black vs. 18.6 years in White (6.6-year difference; p>0.001) and 18.4 years in non-Black (6.4-year difference; p>0.01) recipients. Only 0.7% of Blacks received transplants matched at HLA-A/B/DR/DQ (HMS=0) vs. 8.1% in Whites (p<0.001). Among fully matched Blacks (HMS=0), graft survival was 16.1-years and in well-matched Blacks (HMS ≤ 3.0) it was 14.0-years. Whites had 21.6-years survival at HMS ≤ 3.0 and 18.7-years at HMS ≤ 7.0 whereas non-Blacks had 22.0-year at HMS ≤ 3.0 and 18.7-year at HMS ≤ 7.0, confirming that higher HMS thresholds produced excellent survival. Simulation of ABO-compatible donor-recipient pairs using race-adjusted HMS thresholds identified weakly immunogenic matches at HMS=0 for 6.1% Blacks and 18.0% at HMS ≤ 3.0. Despite prioritizing Black patients, non-Black patients could be matched at the same level as in current allocation (47.0% vs 56.5%, at HMS ≤ 7.0).ConclusionsRace-adjusted HMS (EMS, AMS)-based allocation increased the number of weakly immunogenic donors for Black patients, while still providing excellent options for non-Black recipients.

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HLA Matching Trumps Donor Age: Donor-Recipient Pairing Characteristics That Impact Long-Term Success in Living Donor Kidney Transplantation in the Era of Paired Kidney Exchange

Cited by 23 publications

References 24 publications

Low Hydrophobic Mismatch Scores Calculated for HLA-A/B/DR/DQ Loci Improve Kidney Allograft Survival

Low Hydrophobic Mismatch Scores Calculated for HLA-A/B/DR/DQ Loci Improve Kidney Allograft Survival

Inferior long-term allograft and patient outcomes among recipients of offspring living donor kidneys

Improving Access to HLA-Matched Kidney Transplants for African American Patients

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