The Effects of Cytomegalovirus Serology on Graft and Recipient Survival in Cadaveric Renal Transplantation: Implications for Organ Allocation Mark A. Schnitzler, PhD, Robert S. Woodward, PhD, Daniel C. Brennan, MD, Edward L. Spitznagel, PhD, William C. Dunagan, MD, and Thomas C. Bailey, MD 0 The potential benefits from allocating donated cadaveric kidneys based on donor and recipient cytomegalovirus (CMV) serology remain controversial. We estimated graft survival and recipient survival using bivariate Kaplan- Meier models and multivariate Cox proportional hazards models for 24,643 first cadaveric renal transplantations performed in the United States between 1989, coinciding with the introduction of ganciclovir, and 1994. The effects of donor and recipient CMV serology were estimated, and the implications of these estimates for CM/-based allocation of cadaveric kidneys were considered. From Kaplan-Meier estimates, the a-year impact of CMV-sero- positive donor kidneys was a 3.6% reduction in graft survival and a 2.4% reduction in recipient survival for CMV- seronegative recipients, and a 3.9% reduction in graft survival and a 3.0% reduction in recipient survival for CMV- seropositive recipients. Multivariate Cox analysis demonstrated an adverse impact of donor CMV seropositivity regardless of recipient CMV status. D-/R- CMV serologic pairs had the best 3-year outcomes, with 73.4% graft survival and 67.7% recipient survival. D+/R+ CMV serologic pairs were found to have the worst 3-year outcomes, with 66.4% graft survival and 63.1% recipient survival, and were significantly worse than D+/R- pairs in terms of recipient survival. The maximum estimated impact of a program allocating donor kidneys to maximize the number of D-/R- CMV serologic pairs, assuming no impact on HLA mismatches, was a 0.1% reduction in aggregate g-year graft survival and a 0.2% reduction in aggregate recipient survival. An alternative program allocating donor kidneys to minimize the number of D+/R+ pairs had no estimated effect on either graft or recipient survival. We conclude that during the ganciclovir era, CMV continues to have an important impact on first cadaveric renal transplantation. However, even under ideal conditions, CMV-based kidney allocation to either maximize the number of D-/R- pairs or minimize the number of D+/R+ pairs is likely to provide little benefit to the population of cadaveric renal transplant recipients. 0 1997 by the National Kidney Foundation, Inc. INDEX WORDS: Renal transplantation; cytomegalovirus; multivariate survival analysis. C YTOMEGALOVIRUS (CMV), a member of the herpes group of viruses, is associated with increased risk of bacterial and opportunistic infections, acute and chronic rejection, allograft loss, and death in renal transplant recipients.‘” The reason CMV infection decreases graft sur- vival is unclear, but proposed mechanisms have From The Health Administration Program and the Depart- ment of Internal Medicine, School of Medicine, and the De- partment of Mathematics, Washington University, St Louis, MO. Received August I, 1996; accepted in revisedform Novem- ber 12, 1996. Supported in part by a grant (ROl-DK-47801-OIAI) from the National Institute of Diabetes and Digestive and Kidney Diseases. The data reported here have been supplied by the US Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an oflcial policy or interpretation of the US government. Address reprint requests to Mark A. Schnitzler, PhD, The Health Administration Program, Washington University School of Medicine, 4547 Clayton Ave, St Louis, MO 63110. 0 1997 by the National Kidney Foundation, Inc. 0272-6386/97/2903-0014$3.00/O included direct cytopathic effects of the virus,4 local cytokine production causing upregulation of class I and II major histocompatibility antigens leading to increased risk of rejection,536 immuno- logic cross-reactivity between the immediate early CMV antigen and HLA-DR antigen,’ the production of a glycoprotein homologous to MHC class I antigens by CMV-infected cells,8 and the practice of reducing immunosuppressive agents when symptomatic CMV infection is pres- ent. As with other herpes viruses, CMV may per- sist in a latent state that may be transmitted with organ, blood, and tissue donation. Thus, CMV- seronegative allograft recipients (R-) of CMV- seropositive (D+) organs or blood are at risk of primary infection.’ Cytomegalovirus-seroposi- tive recipients of seropositive organs or blood are at risk of reinfection as well.]’ In addition, seropositive recipients are susceptible to reacti- vation of endogenous latent virus as a result of immunosuppression. There is evidence of benefit from organ alloca- tion based on CMV serology in heart-lung” and liver” transplants. However, the potential for benefit for renal transplantation from systematic 428 American Journal of Kidney Diseases, Vol29, No 3 (March), 1997: pp 428-434