Transplant management

The immune system of older KT recipients is less efficient at generating primary responses to neoantigens yet able to elicit strong T- and B-cell anamnestic responses.  Older individuals previously exposed to HLA antigens through transplantation, blood transfusions, pregnancies, or ventricular-assisted devices are theoretically at a high risk for developing T-cell and antibody-mediated rejection.

Although the bioavailability of drugs in older individuals can be affected by many factors, it appears that variables such as higher gastric pH, reduced gastric emptying, decreased splanchnic circulation, and changes in fat distribution have little influence in the pharmacodynamics of immunosuppressants in elderly KT recipients.


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Immunosuppression in transplantation is divided in two phases: induction therapy and long-term maintenance immunosuppression. Induction involves the use of lymphocyte depleting agents or non-depleting interleukin-2 receptor antagonists (IL2-RA). Rabbit anti-thymocyte globulin (rATG) and alemtuzumab are potent depleting agents associated with lower rates of acute rejection but higher incidences of infections and malignancy. Non-depleting agents, such as IL2-RA although less efficient in preventing acute rejection have a lower risk of post transplant malignancies and infection.11

With regard to maintenance immunosuppression, the standard combination includes permutations of calcineurin inhibitors, antiproliferative agents and prednisone. As suggested by Danovitch and colleagues, immune risk stratification is pivotal in the choice of immunosuppression in the elderly.

In elderly KT recipients with low immunologic risk profile and receiving a kidney from young donor, clinicians should consider IL2-RA for induction as well as steroid withdrawal or minimization protocols. In elderly KT recipients with a high risk of rejection, standard induction with lymphocyte depleting agents and standard immunosuppression are recommended.

For elder KT recipients of an ECD kidney or older living donor, the choice of induction should primarily depend on the immunological risk. Given the high risk of calcineurin inhibitor (CNI) nephrotoxicity in these grafts, clinicians should consider using CNI avoidance or minimization protocols.

Despite these general guidelines, immunosuppression in KT recipients should be tailored and individualized. Careful institutional protocols should be adapted to the elderly population and a customized rather than a “one size fits all” approach should be sought.

Predicting outcomes

Several studies have attempted to identify variables that would predict outcomes in elderly KT recipients. Doyle et al found that a pre-KT history of non-skin malignancy, vascular disease, and current smoking were risk factors for decreased graft and patient survival.12

In a single-center cohort study, Yango and coworkers found that a history of chronic obstructive pulmonary disease and peripheral vascular disease also predicted higher mortality among older recipients. Most recently, Heldal found that acute rejection in the first 90 days and a donor age of 60 years and older predicted lower patient survival whereas delayed graft function, donor age of 60 or older, and HLA antibodies were associated with death-censored graft loss.13

In a cohort of 436 KT patients, Kutner et al found that patients older than 55 years were more likely to have lower physical functioning score. In multivariate analysis, age older than 55 years and lower pre-KT physical functioning were the only predictors of hospitalization or death post-KT. All these studies highlight the importance of adequate patient selection of older KT candidates (Table 1).

Improving outcomes

Transplant programs should perform a comprehensive evaluation of older KT candidates, including assessment of cardiovascular, infection, and malignancy risk and evaluation of patients’ psychosocial network and support, mobility and functional status, cognition, immune system reactivity, and patient and family expectations. Older patients have more comorbidities than younger recipients, so they should be warned about the risks and likelihood of delisting after initial clearance for KT.

As suggested by Danovitch and Savransky, older waitlisted patients should be seen at least twice a year to optimize their status. Geriatricians should participate in both the initial evaluation and subsequent follow-up pre-KT visits as they can provide insights into the functional and mental status of the elderly candidates by picking-up subtle cues indicative of declining performance.14

Conclusions

Altogether, the current literature supports KT in elderly recipients. Survival of older patients undergoing KT is substantially better than that of those who remain on dialysis.  This benefit persists even in individuals older than 70 years old. Elderly recipients transplanted with LD kidneys have better graft and patient survival than those who receive an SCD or ECD KT. 

Among recipients of LD kidneys, those transplanted with organs from donors younger than 55 have the best outcomes. For selected elderly candidates facing long waiting times, ECD transplantation is a more suitable alternative than continuation of dialysis.

The success of transplantation in any KT recipient is incumbent upon strict and thorough selection criteria. The selection of older candidates for KT is a complex task that should be customized to each patient and should involve a formal geriatric evaluation. Management of immunosuppression in older KT should be tailored to avoid acute rejection while minimizing the risk of infection and malignancy. To that end, standard immunosuppression protocols may not fulfill the needs of elderly KT recipients, and biological rather than chronological age should be used as frame of reference when designing immunosuppressive regimens for the elderly.

Dr. Barrantes is a clinical lecturer and Dr. Samaniego-Picota is an associate professor in the Department of Internal Medicine at the University of Michigan in Ann Arbor, where also is Medical Director of Kidney and Kidney-Pancreas Transplantation.

References

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