Preemptive Kidney Transplantation: Why should we avoid a trial of dialysis?

New York, NY
July 31, 2007

As kidney function declines, patient preferences for renal replacement therapy are paramount in caring for patients with chronic kidney disease (CKD). While hemodialysis (home, in-center), peritoneal dialysis, and transplantation are viable options, transplantation has emerged as the preferred treatment due to marked improvements in survival and quality of life (1). However, timing of transplantation deserves particular attention (2,3).

In past years, there was a tendency among nephrologists and transplant surgeons to allow patients to experience dialysis for some time prior to transplantation, often in an effort to improve post-transplant adherence to treatment plans. The reasoning was that after experiencing dialysis, patients would work harder to maintain a transplant. However, the concept of “preemptive kidney transplantation” – transplanting a patient before they require dialysis – has achieved greater importance as evidence of benefit accrues – between 30 and 40% of transplants are currently preemptive. Here we discuss the case for preemptive transplantation.

Investigators have been interested in outcomes of preemptive transplantation since the early 1990s. While single center reports appeared to demonstrate benefits, the availability of data in national registries for transplant recipients meant that transplant outcomes could be analyzed more easily. In 2000, a USRDS registry analysis on 73,103 primary transplants demonstrated that preemptive transplantation conferred a substantial survival benefit (4). Similarly, this report documented a beneficial effect of preemptive transplantation on death-censored graft survival. Later, Mange et al. demonstrated that this survival benefit not only exists at one year, but improves and persists during long-term follow-up (5).

Another important conclusion of Meier-Kreische’s report (4) and follow-up studies (6) widened the concept of the benefit preemptive transplant with the finding that time on dialysis is a critical independent predictor of renal transplant outcome. Specifically, patients transplanted preemptively have the most benefit, and there is a graded, stepwise decline in post-transplant graft and patient survival for each year spent on dialysis. This effect of dialysis time was a highly significant even after adjusting for other plausible factors. While mechanisms for the benefit are unclear, T-cell function and immune response seemed to be provoked by extended dialysis exposure, and avoidance of the adverse impact of dialysis on cardiovascular outcomes is another prime candidate (2,3)  Residual kidney function has been ruled out as a factor (7).

While the association between preemptive transplant and improved survival is a robust association that survives multivariate analysis, it is important to note that patients who receive preemptive transplants are qualitatively different than patients who do not. In a study of 38,836 transplant recipients, it was noted that preemptive recipients were more likely to be white than black, able to work, covered by private insurance, college-educated, and with higher levels of HLA mismatching (8). Thus, even though the benefit of preemptive transplantation applies broadly to various patient groups, it is not made available equally among all patient demographics. A referral to a transplant program will generally include screening by a social worker and financial counselor, who can determine eligibility and insurance status for the transplant. For many patients without coverage, it may still be possible to proceed with transplant if they are eligible for Medicare on the day of transplantation. 

While most preemptive transplants are from a living donor, up to a quarter of these transplants occur with deceased donors. Therefore, it is critically important for patients to have early access to the transplant list whether or not they have a living donor. Similar to timely nephrologists’ referral in CKD, early referral for transplant can have an appreciable impact on early transplantation and improved outcomes (9). 

In conclusion, for a patient with GFR <30 (stage IV CKD), during discussions regarding renal replacement therapy, preemptive kidney transplantation should be a main focus of efforts, including workup and referral to a transplant center. Preemptive transplant with a living donor is the optimal approach, but even patients without kidney donors should be referred early for transplantation.  

Eric M. Gibney, M.D.
Assistant Professor of Medicine
Division of Nephrology and the Hume-Lee Transplant Center
Virginia Commonwealth University

References
               
1. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ, Port FK. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999 Dec 2;341(23):1725-30.

2. Meier-Kriesche HU, Schold JD.  The impact of pretransplant dialysis on outcomes in renal transplantation. Semin Dial. 2005 Nov-Dec;18(6):499-504. Review.

3. Mange KC, Weir MR.  Preemptive renal transplantation: why not?  Am J Transplant. 2003 Nov;3(11):1336-40. Review.

4. Meier-Kriesche HU, Port FK, Ojo AO, Rudich SM, Hanson JA, Cibrik DM, Leichtman AB, Kaplan B.  Effect of waiting time on renal transplant outcome. Kidney Int. 2000 Sep;58(3):1311-7.

5. Mange KC, Joffe MM, Feldman HI.  Effect of the use or nonuse of long-term dialysis on the subsequent survival of renal transplants from living donors. N Engl J Med. 2001 Mar 8;344(10):726-31.

6. Meier-Kriesche HU, Kaplan B.  Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis. Transplantation. 2002 Nov 27;74(10):1377-81.

7. Gill JS, Tonelli M, Johnson N, Pereira BJ.  Why do preemptive kidney transplant recipients have an allograft survival advantage?  Transplantation. 2004 Sep 27;78(6):873-9.

8. Kasiske BL, Snyder JJ, Matas AJ, Ellison MD, Gill JS, Kausz AT.  Preemptive kidney transplantation: the advantage and the advantaged. J Am Soc Nephrol. 2002 May;13(5):1358-64.

9. Weng FL, Mange KC.  A comparison of persons who present for preemptive and nonpreemptive kidney transplantation. Am J Kidney Dis. 2003 Nov;42(5):1050-7.