Unacceptable human leucocyte antigens for organ offers in the era of organ shortage: influence on waiting time before kidney transplantation

Ziemann, Malte; Heßler, Nicole; König, Inke R.; Lachmann, Nils; Dick, Andrea; Ditt, Vanessa; Budde, Klemens; Reinke, Petra; Eisenberger, Ute; Suwelack, Barbara; Klein, Thomas; Westhoff, Timm H.; Arns, Wolfgang; Ivens, Katrin; Habicht, Antje; Renders, Lutz; Stippel, Dirk L.; Bös, Dominik; Sommer, Florian; Görg, Siegfried; Nitschke, Martin; Feldkamp, Thorsten; Heinemann, Falko M.; Kelsch, Reinhard

doi:10.1093/ndt/gfw462

Cited by 16 publications

(21 citation statements)

References 8 publications

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“…This has already been addressed by Ziemann et al . [13], who found that the waiting time is extended by 1.3 weeks if the PRA value is increased by 1% within the regular allocation and prolonged by 5 weeks within ESP. The cPRA did not impact relisting but did affect retransplantation in our cox regression model.…”

Section: Discussionmentioning

confidence: 99%

“…Kidney transplant candidates with prior graft loss are known to be highly sensitized and have more anti‐HLA antibodies, irrespective if they underwent allograft nephrectomy or only withdrawal of immunosuppression [11,12]. As a consequence, the fear comes that dnDSA lead to a higher number of unacceptable antigens, which might as a consequence lead to a longer waiting time [13]. But whether this causality between dnDSA and waiting time also considering Eurotransplant Acceptable Mismatch (AM) program in the case of retransplantation is true is not clear.…”

Section: Introductionmentioning

confidence: 99%

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What happens after graft loss? A large, long‐term, single‐center observation

et al. 2021

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Summary The number of patients returning to dialysis after graft failure increases. Surprisingly, little is known about the clinical and immunological outcomes of this cohort. We retrospectively analyzed 254 patients after kidney allograft loss between 1997 and 2017 and report clinical outcomes such as mortality, relisting, retransplantations, transplant nephrectomies, and immunization status. Of the 254 patients, 49% had died 5 years after graft loss, while 27% were relisted, 14% were on dialysis and not relisted, and only 11% were retransplanted 5 years after graft loss. In the complete observational period, 111/254 (43.7%) patients were relisted. Of these, 72.1% of patients were under 55 years of age at time of graft loss and only 13.5% of patients were ≥65 years. Age at graft loss was associated with relisting in a logistic regression analysis. In the complete observational period, 42 patients (16.5%) were retransplanted. Only 4 of those (9.5%) were ≥65 years at time of graft loss. Nephrectomy had no impact on survival, relisting, or development of dnDSA. Patients after allograft loss have a high overall mortality. Immunization contributes to long waiting times. Only a very limited number of patients are retransplanted especially when ≥65 years at time of graft loss.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

What happens after graft loss? A large, long‐term, single‐center observation

et al. 2021

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“…The average waiting time for dialysis patients to receive kidney grafts in Japan is 13 years, as opposed to the 4 to 6 years prevailing in most countries. 21 , 22 The number of recipients on a waiting list for KTx has been increasing. Therefore, DCD donors have become an accepted organ resource to alleviate the chronic shortage of kidney grafts.…”

Section: Discussionmentioning

confidence: 99%

Single Graft Utilization From Donors With Severe Acute Kidney Injury After Circulatory Death

Tomita

Iwadoh

Ogawa

et al. 2018

Transplantation Direct

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Chronic shortages of organs for transplantation have led to the use of marginal kidneys from donors after circulatory death with acute kidney injury (AKI), but the utilization of kidneys with severe AKI is not well established. We retrospectively analyzed eight kidney transplantation (KTx) cases from donation after circulatory death (DCD) with terminal creatinine (t-Cr) concentrations higher than 10.0 mg/dL and/or oliguria for more than 5 days (AKI network criteria: stage III). Although all patients showed delayed graft function, no cases of primary nonfunction (PNF) were found. Five patients maintained stable renal function for approximately 15.5, 10, 10, 5, and 0.5 years after KTx. Only 1 patient showed biopsy-proven acute rejection. Also, 2 patients developed graft failure: one attributable to chronic antibody mediated rejection at 11.3 years after KTx, and one attributable to recurrence of IgA nephropathy at 4.6 years after KTx. Kidneys with AKI stage III yielded great outcomes without the risk of primary nonfunction and rejection. Although the AKI kidneys were associated with delayed graft function, these results suggest that even the most severe kidneys with AKI stage III from DCD donors can be considered a valid alternative for recipients on a waiting list for KTx.

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“…In addition, all patients were tested with a Luminex-based LABScreen Mixed bead assay (One Lambda; Thermo Fisher Scientific, Inc.). In step-by-step analysis, 29 the anti-HLA class I and/or II positive sera with positive were subsequently specified with LABScreen single-antigen bead assays (One Lambda; Thermo Fisher Scientific Inc.). All beads with normalized median fluorescence intensity (MFI) values higher than 1000 were considered to be positive for anti-HLA antibodies.…”

Section: Methodsmentioning

confidence: 99%

Development of De Novo Donor-specific HLA Antibodies and AMR in Renal Transplant Patients Depends on CYP3A5 Genotype

et al. 2021

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Background. The single-nucleotide polymorphism CYP3A5 rs776746 is related to a reduction in the metabolizing activity of the CYP3A5 enzyme. People carrying at least one copy of the wild-type allele, defined as CYP3A5 expressers, exhibit higher clearance and lower trough concentrations of tacrolimus than homozygous nonexpressers, and this difference may affect alloimmunization and allograft function. Methods. We retrospectively studied 400 kidney transplant recipients treated with a tacrolimus-based immunosuppression regimen to detect CYP3A5 genotype, de novo formation of HLA antibodies and donor-specific antibodies (DSAs), and clinical outcome up to 5 y after transplant. Results. We found that 69 (17%) of the 400 patients were CYP3A5 expressers. During the first 3 y after transplant, CYP3A5 expressers tended to have lower tacrolimus trough levels than nonexpressers, although their tacrolimus dosage was as much as 80% higher. De novo DSAs were found more frequently in CYP3A5 expressers than in nonexpressers (13/69 [19%] versus 33/331 [10%], P = 0.02). De novo DSA-free survival rates ( P = 0.02) were significantly lower for expressers than for nonexpressers. CYP3A5 genotype had no effect on allograft failure, but CYP3A5 expressers exhibited a significantly higher frequency of antibody-mediated rejection. CYP3A5 expresser status was an independent risk factor for the development of de novo DSAs (relative risk, 2.34, P = 0.01). Conclusions. Early detection of CYP3A5 expressers, enabling genotype-based dose adjustment of tacrolimus immediately after renal transplant, may be a useful strategy for reducing the risk of de novo DSA production and antibody-mediated rejection.

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Unacceptable human leucocyte antigens for organ offers in the era of organ shortage: influence on waiting time before kidney transplantation

Cited by 16 publications

References 8 publications

What happens after graft loss? A large, long‐term, single‐center observation

What happens after graft loss? A large, long‐term, single‐center observation

Single Graft Utilization From Donors With Severe Acute Kidney Injury After Circulatory Death

Development of De Novo Donor-specific HLA Antibodies and AMR in Renal Transplant Patients Depends on CYP3A5 Genotype

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