Effect of Early Steroid Withdrawal on Posttransplant Diabetes Among Kidney Transplant Recipients Differs by Recipient Age

Ahn, JiYoon B.; Bae, Sunjae; Hess, Gregory P.; Lentine, Krista L.; Segev, Dorry L.; McAdams‐DeMarco, Mara

doi:10.1097/txd.0000000000001260

Cited by 6 publications

(5 citation statements)

References 53 publications

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“…However, this observation also raises important clinical questions such as to what extent the intensity of the immune suppressive drugs could be lowered, specifically in the long term. Such a question is important in elderly recipients with an aged immune system, who are prone to infectious, metabolic, and cardiovascular side effects of immune suppressive medication [31][32][33].…”

Section: Discussionmentioning

confidence: 99%

The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients

Betjes,

Kal-van Gestel,

Roodnat

et al. 2023

Transpl Int

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It is not known whether antibody-mediated rejection (ABMR) is age-related, whether it plateaus late after transplantation, and to what extent it contributes to graft loss in older recipients. Patients transplanted between 2010 and 2015 (n = 1,054) in a single center had regular follow-up until January 2023. Recipients were divided into age groups at transplantation: 18–39 years (“young”), 40–55 years (“middle age”), and >55 years (“elderly”). Ten years after transplantation the cumulative % of recipients with ABMR was 17% in young, 15% in middle age, and 12% in elderly recipients (p < 0.001). The cumulative incidence of ABMR increased over time and plateaued 8–10 years after transplantation. In the elderly, with a median follow-up of 7.5 years, on average 30% of the recipients with ABMR died with a functional graft and ABMR contributed only 4% to overall graft loss in this group. These results were cross-validated in a cohort of recipients with >15 years follow-up. Multivariate cox-regression analysis showed that increasing recipient age was independently associated with decreasing risk for ABMR. In conclusion, the cumulative risk for ABMR is age-dependent, plateaus late after transplantation, and contributes little to overall graft loss in older recipients.

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Section: Discussionmentioning

confidence: 99%

The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients

Betjes,

Kal-van Gestel,

Roodnat

et al. 2023

Transpl Int

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“…Early steroid withdrawal may have differential impact stratified by age, with older SOT recipients in a population-cohort study demonstrating more favourable responses to steroid withdrawal (e.g. lower PTDM and mortality) but increased risk for rejection [ 35 ]. Balancing PTDM versus graft-related concerns with steroid avoidance/withdrawal is essential, although patient/graft survival should take priority.…”

Section: Opinion Statement 5: Choose An Immunosuppression Regimen For...mentioning

confidence: 99%

International consensus on post-transplantation diabetes mellitus

Sharif,

Chakkera,

de Vries

et al. 2024

Nephrology Dialysis Transplantation

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Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held between 6–8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous report. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed making GRADE recommendations would be flawed Although kidney-allograft centric, we suggest these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this personal viewpoint reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.

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“…For instance, early steroid withdrawal especially benefits older adults in terms of posttransplant diabetes mellitus prevention. Ahn et al have demonstrated in USRDS data in over 12,000 kidney transplant recipients that recipients over 55 years had a significantly higher benefit of steroid withdrawal than younger recipients (aHR for diabetes: 0.71 for >55 years vs. 1.18 in the age category 18–29 years) ( 107 ). Furthermore, a major competitive risk factor for graft loss in older adults is death with a functioning graft.…”

Section: Managing Maintenance Immune Suppression Regimens In Relation...mentioning

confidence: 99%

Lowering maintenance immune suppression in elderly kidney transplant recipients; connecting the immunological and clinical dots

Betjes

Weerd

2023

Front. Med.

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The management of long-term immune suppressive medication in kidney transplant recipients is a poorly explored field in the area of transplant medicine. In particular, older recipients are at an increased risk for side effects and have an exponentially increased risk of infection-related death. In contrast, an aged immune system decreases the risk of acute T-cell-mediated rejection in older recipients. Recent advances in alloimmunity research have shown a rapid and substantial decline in polyfunctional, high-risk CD4+ T cells post-transplantation. This lowers the direct alloreactivity responsible for T-cell-mediated rejection, also known as donor-specific hyporesponsiveness. Chronic antibody-mediated rejection (c-aABMR) is the most frequent cause of kidney graft loss in the long term. However, in older adults, c-aABMR as a cause of graft loss is outnumbered by death with a functioning graft. In addition, DSA development and a diagnosis of c-aABMR plateau ~10 years after transplantation, resulting in a very low risk for rejection thereafter. The intensity of immune suppression regimes could likely be reduced accordingly, but trials in this area are scarce. Tacrolimus monotherapy for 1 year after transplantation seems feasible in older kidney transplant recipients with standard immunological risk, showing the expected benefits of fewer infections and better vaccination responses.

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Effect of Early Steroid Withdrawal on Posttransplant Diabetes Among Kidney Transplant Recipients Differs by Recipient Age

Abstract: Supplemental Digital Content is available in the text.

Cited by 6 publications

References 53 publications

The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients

The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients

International consensus on post-transplantation diabetes mellitus

Lowering maintenance immune suppression in elderly kidney transplant recipients; connecting the immunological and clinical dots

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