Immunosuppression of the Elderly Kidney Transplant Recipient

Danovitch, Gabriel M.; Gill, Jagbir; Bunnapradist, Suphamai

doi:10.1097/01.tp.0000275423.69689.dc

Cited by 88 publications

(86 citation statements)

References 60 publications

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“…The validation process provided support for the robustness of the risk assessment principle. The potential usefulness of this strategy is broad and ranges from the definition of personalized target levels of immunosuppressants, the duration of antibiotic/antiviral prophylaxis, and the identification of patients who might benefit from immunosuppression minimization or tolerance induction protocols to the optimization of organ allocation systems (2,(20)(21)(22)(23)(24). Depending on the preferred application, different end points should be considered.…”

Section: Discussionmentioning

confidence: 99%

Risk Stratification for Rejection and Infection after Kidney Transplantation

Cippà¹,

Schiesser²,

Ekberg

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Definition of individual risk profile is the first step to implement strategies to keep the delicate balance between under-and overimmunosuppression after kidney transplantation. Results Despite different temporal dynamics, rejections and severe infections had similar overall incidences in the first year after transplantation (23.4% and 25.5%, respectively), and infections were the principal cause of death (43.2% of all deaths). Recipient older age, deceased donor, higher number of HLA mismatches, and high risk for cytomegalovirus disease were associated with infection; deceased donor, higher number of HLA mismatches, and immunosuppressive therapy including cyclosporin A (compared with tacrolimus), with rejection. These factors were integrated into a two-dimensional risk stratification model, which defined four risk groups: low risk for infection and rejection (30.8%), isolated risk for rejection (36.1%), isolated risk for infection (7.0%), and high risk for infection and rejection (26.1%). In internal validation, this model significantly discriminated the subgroups in terms of composite end point (low risk for infection/rejection, 24.4%; isolated risk for rejection and isolated risk for infection, 31.3%; high risk for infection/rejection, 54.4%; P,0.001), rejection episodes (isolated risk for infection and low risk for infection/rejection, 13.0%; isolated risk for rejection and high risk for infection/ rejection, 24.2%; P=0.001), and infection episodes (low risk for infection/rejection and isolated risk for rejection, 12.0%; isolated risk for infection and high risk for infection/rejection, 37.6%; P,0.001). External validation confirmed the applicability of the model to an independent cohort.Conclusions We propose a two-dimensional risk stratification model able to disentangle the individual risk for rejection and infection in the first year after kidney transplantation. This concept can be applied to implement a personalized immunosuppressive and antimicrobial treatment approach.

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Section: Discussionmentioning

confidence: 99%

Risk Stratification for Rejection and Infection after Kidney Transplantation

Cippà¹,

Schiesser²,

Ekberg

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…The elderly comprise the largest growing segment of patients with End Stage Renal Disease (ESRD) and are the fasting growing segment of transplant recipients (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

Induction Immunosuppressive Therapy in the Elderly Kidney Transplant Recipient in the United States

Gill¹,

Sampaio²,

Gill³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives The choice of induction agent in the elderly kidney transplant recipient is unclear. Results In high-risk recipients with high-risk donors there was a higher risk of rejection and functional graft loss with IL2RA versus rATG. Among low-risk recipients with low-risk donors there was no difference in outcomes between IL2RA and rATG. In the two groups in which donor or recipient was high risk, there was a higher risk of rejection but not functional graft loss with IL2RA. Among low-risk recipients with high-risk donors, there was a trend toward a higher risk of death with IL2RA.Conclusions rATG may be preferable in high-risk recipients with high-risk donors and possibly low-risk recipients with high-risk donors. In the remaining groups, although rATG is associated with a lower risk of acute rejection, long-term outcomes do not appear to differ. Prospective comparison of these agents in an elderly cohort is warranted to compare the efficacy and adverse consequences of these agents to refine the use of induction immunosuppressive therapy in the elderly population.

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“…20 Elderly recipients are more prone to the consequences of enhanced immunosuppression such as infection, malignancy, or metabolic complications. 21 A recent study by Ducloux and associates showed an association between r-ATG use and increased risk for cardiovascular events. 22 The authors postulated that r-ATG induced infectious risk burden with activation of CD8-positive T cells and immune reconstitution with expansion of proinflammatory cytokine producing CD8-positive T cells as factors contributing to atherosclerosis burden.…”

Section: Sabiha M Hussain Et Al/experimental and Clinical Transplantmentioning

confidence: 99%

Untitled

2016

Exp Clin Transplant

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Objectives: This study explored the safety of early steroid withdrawal in recipients of expanded criteria deceased-donor kidney transplants. Materials and Methods: Using the Organ Procurement and Transplant Network-United Network of Organ Sharing database, we identified patients who underwent expanded criteria deceased-donor kidney transplant between January 2000 and December 2008 after receiving induction with rabbit-antithymocyte globulin (n = 3717), alemtuzumab (n = 763), or interleukin 2 blocking agent (n = 2600) followed by calcineurin inhibitor and mycophenolate mofetilbased maintenance with and without steroid therapy. Results: Adjusted overall graft survival (hazard ratio 1.32; 95% confidence interval, 1.1-1.56; P = .002) and patient survival (hazard ratio 1.46, 95% confidence interval, 1.16-1.83, P = .001) were inferior, whereas death-censored graft survival (hazard ratio 1.13; 95% confidence interval, 0.87-1.47; P = .35) was similar for chronic steroid maintenance versus early steroid withdrawal groups in rabbit-antithymocyte globulininduced patients. Graft and patient outcomes were similar for chronic steroid maintenance versus early steroid withdrawal groups among alemtuzumab and interleukin 2 blocking agent-induced patients. Among rabbit-antithymocyte globulin-induced patients, adjusted overall graft survival (hazard ratio 1.57; 95% confidence interval, 1.2-2.0; P < .001) and patient survival (hazard ratio 1.5; 95% CI, 1.15-2.1; P = .004) were inferior, whereas death-censored graft survival (hazard ratio 1.5; 95% confidence interval, 0.97-2.43; P = .07) trended inferior for chronic steroid maintenance versus early steroid withdrawal groups in recipients > 60 years old (n = 1729). Conclusions: Our study showed safety of early steroid withdrawal in recipients of expanded criteria deceaseddonor kidney transplants who underwent perioperative induction followed by calcineurin inhibitor and mycophenolate mofetil maintenance. Among rabbitantithymocyte globulin-induced patients, chronic steroid maintenance was associated with inferior graft and patient outcomes, an effect limited to older recipients.

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Immunosuppression of the Elderly Kidney Transplant Recipient

Cited by 88 publications

References 60 publications

Risk Stratification for Rejection and Infection after Kidney Transplantation

Risk Stratification for Rejection and Infection after Kidney Transplantation

Induction Immunosuppressive Therapy in the Elderly Kidney Transplant Recipient in the United States

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