Effect of initial immunosuppression on long-term kidney transplant outcome in immunological low-risk patients

Michielsen, Laura A.; Zuilen, Arjan D. van; Verhaar, Marianne C.; Wisse, Bram W.; Kamburova, Elena G.; Joosten, Irma; Allebes, Wil A.; Meer, Arnold van der; Baas, Marije C.; Spierings, Eric; Hack, C. E.; Reekum, Franka E. van; Bots, Michiel L.; Drop, Adriaan C.A.D.; Plaisier, Loes; Seelen, Marc A.; Sanders, Jan-Stephan; Hepkema, Bouke; Lambeck, Annechien J. A.; Bungener, Laura; Roozendaal, Caroline; Tilanus, Marcel G.J.; Voorter, C. E. M.; Wieten, Lotte; Duijnhoven, Elly M. van; Gelens, M.; Christiaans, Maarten H. L.; Ittersum, Frans J. van; Nurmohamed, Shaikh A.; Lardy, Neubury M.; Swelsen, Wendy; Pant, Karlijn A. van der; Weerd, Neelke C. van der; Berge, Ineke J. M. ten; Bemelman, Fréderike J.; Hoitsma, Andries J.; Boog, Paul J.M. van der; Fijter, Johan W. de; Betjes, M.; Heidt, Sebastiaan; Roelen, Dave L.; Claas, Frans H.J.; Otten, H.G.; Hilbrands, Luuk B.

doi:10.1093/ndt/gfy377

Cited by 7 publications

(7 citation statements)

References 39 publications

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“…Graft survival censored for death is significantly better for the elderly group as compared to the young and middle aged groups ( Figure 2C ) explaining the similar all-cause graft survival curves between age groups with the first 10 years after transplantation. Of note, the type of maintenance immune suppressive regimen (in particular ciclosporin or tacrolimus-based) was not associated with graft survival in the different age groups, in accordance with a previous analysis of the total PROCARE cohort ( 19 ). The majority of young recipients received a graft from a living donor as opposed to the elderly group and most of the deceased donor kidneys were from brain death donors.…”

Section: Resultssupporting

confidence: 90%

Causes of Kidney Graft Failure in a Cohort of Recipients With a Very Long-Time Follow-Up After Transplantation

Betjes¹,

Roelen

Agteren³

et al. 2022

Front. Med.

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BackgroundBiopsy-proven causes of graft loss many years after kidney transplantation are scarcely documented.MethodsPatients transplanted between 1995 and 2005 (n = 737) in a single center were followed on a regular basis until 2021. The recipients were divided according to age at transplantation into 3 groups; 18–39 years (young), 40–55 years (middle age), and older than 55 years (elderly). For cause biopsies of renal transplants were clustered into the categories, rejection, IFTA, return original disease, and diagnosis of de novo kidney disease.ResultsRejection was the main cause of graft failure censored for death at every time period after transplantation. The incidence of T cell-mediated rejection (TCMR) became rare 6 years after transplantation while the cumulative incidence of antibody-mediated rejection (ABMR) increased over time (1.1% per year). ABMR was not diagnosed anymore beyond 15 years of follow-up in recipients without pre-transplant donor-specific antibodies (DSA). An episode of TCMR was associated with an increased incidence of ABMR diagnosis in the short-term but did not increase the overall incidence of AMBR not in the long-term. Death as a cause of graft failure was an important competitive risk factor long after transplantation and resulted in a significantly lower frequency of rejection-related graft loss in the elderly group (11 vs. 23% in the young group at 15 year follow-up).ConclusionRejection is a major cause of graft loss but recipient’s age, time after transplantation, and the presence of DSA before transplantation determine the relative contribution to overall graft loss and the type of rejection involved.

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Section: Resultssupporting

confidence: 90%

Causes of Kidney Graft Failure in a Cohort of Recipients With a Very Long-Time Follow-Up After Transplantation

Betjes¹,

Roelen

Agteren³

et al. 2022

Front. Med.

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“…In this comprehensive, retrospective CTS analysis, we compared the impact of Tac- and CsA-based immunosuppression on the outcome of European KT recipients aged ≥60 y. Our findings are in line with previous studies‚ which, in general, did not report any significant effect of the type of CNI on short- or long-term death-censored graft survival or mortality; 12,17-23 however, these studies focused on comparatively young recipients with a mean age of approximately 45 y, whereas recipients aged ≥60 y were underrepresented. 17 We now analyzed >30 000 European kidney transplantations specifically from this growing group of elderly KT recipients and found that the choice of CNI did not have any significant impact on graft loss and patient mortality in these patients either.…”

Section: Discussionsupporting

confidence: 81%

“…Regarding the risk of rejection treatment, we report a significantly reduced risk for recipients on Tac therapy, an observation which is also similar to results of previous studies in younger recipients. 6,18,20 This effect was confirmed in almost all subgroups. Importantly, we demonstrated that the association between Tac-based immunosuppression and a reduced risk of rejection treatment was significant for transplants with both 0 to 3 and 4 to 6 HLA mismatches.…”

Section: Discussionsupporting

confidence: 52%

Influence of Calcineurin Inhibitor Choice on Outcomes in Kidney Transplant Recipients Aged ≥60 Y: A Collaborative Transplant Study Report

et al. 2022

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“…Initial immunosuppression was categorized as prednisolone/cyclosporine with or without mycophenolate mofetil (MMF) with or without interleukin (IL)-2 receptor antagonist (IL2RA) versus prednisolone/tacrolimus/MMF with or without IL2RA based on a previous study on the complete PROCARE cohort. 12 Graft function was categorized on direct or delayed function, and HLA mismatches were divided into equal categories.…”

Section: Data Handlingmentioning

confidence: 99%

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Heidt

Haasnoot

Witvliet

et al. 2019

American Journal of Transplantation

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Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long‐term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995‐2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6‐month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA‐B plus 1 HLA‐DR, or 2 HLA‐DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low‐risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.

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Effect of initial immunosuppression on long-term kidney transplant outcome in immunological low-risk patients

Cited by 7 publications

References 39 publications

Causes of Kidney Graft Failure in a Cohort of Recipients With a Very Long-Time Follow-Up After Transplantation

Causes of Kidney Graft Failure in a Cohort of Recipients With a Very Long-Time Follow-Up After Transplantation

Influence of Calcineurin Inhibitor Choice on Outcomes in Kidney Transplant Recipients Aged ≥60 Y: A Collaborative Transplant Study Report

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

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