Improvements in Long-term Renal Transplant Graft Survival (2005)

To the Editor: A recent article by Meier–Kriesche et al., published in the American Journal of Transplantation raises fundamental differences between kidney transplant long-term graft survival projected by us in the year 2000 using UNOS database (1Hariharan S Johnson CP Bresnahan BA et al.Improved graft survival after renal transplantations in recipient in the United States, 1988 to 1996..N Engl J Med. 2000; 342: 605-612Crossref PubMed Scopus (1634) Google Scholar) and the long-term graft survival analyzed using the USRDS database (2Meier-Kriesche HU Schold JD Kaplan B Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strategies?.Am J Transplantation. 2004; 4: 1289-1295Abstract Full Text Full Text PDF PubMed Scopus (535) Google Scholar). The final analyses revealed a much lower Kaplan-Meier half-life. However, there are fundamental differences between these two analyses even though they are derived from similar but not the same databases. We would like to point out these differences as they are critical for further enhancing long-term graft survival. We used United Network of Organ Sharing (UNOS) database, while the recent analysis used USRDS database. These databases are derived from the same patients and should not be different. However, in our study a total of 93 934 kidney and combined kidney-pancreas and kidney-liver were included. These included both living and cadaveric recipients transplanted from 1988 to 1996. After exclud-ing patients transplanted in 1996 there were a total of 82 168 recipients included in our study, which is much higher than the 77 937 recipients who were analyzed by Meier-Kriesche et al. in their study. Differences of a total of 4231 (5.1%) transplant recipients would contribute to the different results. Long-term renal transplant graft survival measured as halflife is estimated for recipients who have a functioning graft at 1 year. Hence, our calculation of half-life was conditioned on survival for 1 year post-transplant. However, Meier-Kriesche et al. in their analysis calculated the graft half-lives from the time of transplantation. Such an analysis is applicable only when the transplant graft survival is linear from the time of transplantation, which is not true for patients transplanted from 1988 to 1995 as well as in recent years. Historically, renal transplant graft survival becomes linear around 6–12 months posttransplantation. Hence, the half-life calculation should be performed after 1 year post-transplantation. Interpretation of long-term graft survival as half-life from the time of transplantation by Meier-Kriesche et al, would give lower values compared to our projected survival in the year 2000. In addition, Kaplan–Meier half-life values shown by Meier–Kriesche et al. included both primary and repeat transplant recipients. However, this was compared to our projected half-life that included only primary renal transplant recipients. Inclusion of repeat transplants will show lower Kaplan–Meier half-lives. In addition, our review of the UNOS files showed a bias in reporting of events as graft failures appear to be reported quickly while there is a lag in accumulation of follow-up time from patients with continued function. While this bias is not important when comparing groups such as age/sex, the terminal part of any annual cohort-based curve is negatively biased. Annual cohort analyses should consider these data reporting issue. Thus, there are fundamental differences between these two analyses. These include different data sets, patient population, calculation of half-life from the time of trans-plantation versus 1 year post-transplant, inclusion versus exclusion of repeat transplant recipients and handling of reporting biases. However, Meier–Kriesche et al., do acknowledge improvements in graft survival for recipients who have undergone repeat transplants as well as in African American population. In their analysis they also noted improvements in halflife from 6 to 8 years, which contributed 33% better survival in 1995 compared to 1988 for all renal transplants. It is important to recognize and convey these improvements in kidney transplant graft survival. This positive message has not been conveyed in their manuscript. It is critical to note that these improvements occurred prior to the introduction of mycophenolate mofetil and tacrolimus. In conclusion, there has been progressive, small but measurable improvements in long-term graft survival in recent years. The methodology used for such a measurement may be different from one another. However, further improvements are perhaps restricted due to donor characteristics, recipient comorbid conditions as well as multisource progressive injury to the kidney.