Increased immunosuppressive vulnerability in elderly renal transplant recipients.

Abstract

The results of renal transplantation have improved steadily over the last 10 years. This improvement is in large part attributable to improvements in immunosuppressive pharmacotherapy. Several phase III clinical trials have demonstrated decreased acute rejection rates with relatively little, if any, increase in infectious complications in a broad cross-section of patients (1‐12). It is possible, however, that in certain subpopulations of patients, such as elderly renal transplant recipients, the risk/benefit ratio of acute rejection versus infection may be different from that of the general renal transplant population. If this were the case, the appropriate immunosuppressive regimen for that population should be reconsidered. Renal transplantation is a relatively safe option for renal replacement therapy in elderly patients with end-stage renal disease (ESRD). In 1976, Tersigni et al. (13) reported a series of nine ESRD patients above the age of 60 years successfully treated with renal transplantation. Shortly thereafter, Wedel et al. (14) published a series of 41 geriatric renal transplant recipients, and pointed out that the risk to these patients was not graft loss from rejection but, rather, death with a functioning graft. This author also reported that there was an increased risk for serious infectious complications in the older age group. With the advent of cyclosporine and more selective immunosuppression, the results of renal transplantation improved in high-risk groups, such as elderly patients. In 1989, Pirsch et al (15) concluded that cadaveric renal transplantation with cyclosporine immunosuppression was safe and an effective therapeutic modality in elderly ESRD patients. Subsequent studies have reinforced that concept (16) but have also reinforced the idea that elderly patients have a degree of immune incompetence (17) and require less aggressive immunosuppressive therapy (17). That theory was supported by the continuing observation of lower rejection rates (17, 18) and lower incidence of chronic rejection (18, 19), but higher risk of infections (19, 20) noted in elderly transplant recipients. Reinforcement of the practice of transplantation in elderly patients came from a study that showed significantly greater survival probability in ESRD patients over the age of 60 who received transplants as opposed to matched patients who remained on dialysis (9). Recent data demonstrate a very similar 5-year graft (54 ‐74%) and patient survival (52‐74%), confirming the improvement made but also the concept that most patients in this high-risk group die with functioning grafts (19). In this study, posttransplant morbidity was attributed primarily to infectious complications and an increased prevalence of malignancy (19). We demonstrated previously, in a single-center study, that intensification of immunosuppressive therapy in elderly transplant recipients increased infectious complications without decreasing the incidence of acute rejection or improvement in graft survival (21). Given the above data, it is possible that the vulnerability to immunosuppression of older renal transplant patients may be very different from that of younger patients. To test this hypothesis, we analyzed a large group of renal transplant recipients with regard to their balance of acute rejection versus death due to infection.