Age, Exclusion Criteria, and Generalizability of Randomized Trials Enrolling Kidney Transplant Recipients

Abstract

Background The proportion of elderly (≥65 years) kidney transplant recipients (KTRs) doubled in the United States (US) from 1999 – 2008. Given higher mortality, more medication side effects, and less rejection among elderly KTRs, optimal care of these patients may require tailored decisions about transplant therapeutics. It is unknown whether participants in transplant clinical trials – which generate the best evidence for patient care – are representative of the aging population of KTRs. Methods Using PubMed, we identified randomized trials involving KTRs from 1999 – 2008 and determined age-exclusion criteria and the mean age of participants. The mean age of these trial participants was compared to the mean age of the overall population of incident KTRs in the US. Results The 87,222 participants in 573 trials were significantly younger than the US KTR population (p<0.05). This age discrepancy worsened over the study period (during the years 2006 – 2008, the mean age was 45 years for trial participants versus 50 years for US KTRs, p<0.05). Thirty percent of trials had an exclusion criterion based on older age, and 16% excluded recipients ≥65 years. In multivariable regression, immunosuppression trials (p<0.01) and trials in higher-impact journals (p=0.03) were more likely to exclude the elderly, but there was no significant difference in exclusion of elderly patients based on a trial’s geographic location. Conclusions Trial participants are younger than KTRs in the US and many trials exclude older patients. Transplant investigators should make strong efforts to recruit patients across the total age spectrum.

Age-Dependent Metabolic and Immunosuppressive Effects of Tacrolimus

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A Rationale for Age-Adapted Immunosuppression in Organ Transplantation

“…43 A recent meta-analysis revealed that kidney transplant recipients participating in clinical trials in the US were significantly younger. 44 Older age as an exclusion criterion was evident in 30% of studies. Obviously, clinical trials in transplant medicine do not consider the clinical reality of a steadily increasing volume of older transplant recipients.…”

Lower Calcineurin Inhibitor Doses in Older Compared to Younger Kidney Transplant Recipients Yield Similar Troughs

“…Importantly, older recipients have been underrepresented in pivotal immunosuppression trials but clinically are usually treated with those same regimens. (4) Therefore we studied CNI disposition in a large population of kidney transplant recipients in three adult age groups; young (18–34 years), middle (35–64 years) and older (65–84 years) to define age related drug disposition changes adjusting for important demographic, clinical, and genetic factors.…”