Preemptive Living-Donor Renal Transplantation: Outcome and Clinical Advantages S.W. Yoo, O.J. Kwon, and C.M. Kang ABSTRACT Introduction. Kidney transplant recipients have a higher quality of life and consume fewer health care resources compared with patients on dialysis. However, optimal timing of transplantation has been controversial. Recent studies have clearly demonstrated that preemptive renal transplantation is associated with better graft survival, lower complications, and better cost-effective outcomes. We evaluated differential effects on long-term outcomes according to dialysis type/duration versus no dialysis. Materials and Methods. We retrospectively analyzed 499 cases of first living-donor kidney transplantations performed in our center from January 1990 to January 2007. We compared 3 groups according to graft survival, acute and chronic rejection, postoperative complication, and delayed graft function rates. The mean duration of follow-up was 119.1 ⫾ 47.2 months. Results. Among 499 cases, 81 cases were preemptive renal transplantations with 418 cases hemodialysis [HD], 343 cases, peritoneal dialysis [PD] 75 cases) performed after dialysis. The 1-, 5-, and 10-year graft survival rates were 98.8%, 89.5%, 79.4% among the preemptive renal transplantation group and 92.4%, 78.2%, and 69.2% and 85.3%, 74.5%, and 68.2% (P ⫽ .03) in the dialysis groups (HD, PD), respectively. The differential effect of pretransplantation HD or PD was not significant. However, the graft survival rates in the HD group were not significantly higher than the PD group (P ⫽ .61). The duration of dialysis was not associated with graft survival. Conclusion. We suggest that preemptive renal transplantation should be the first choice of treatment for patients with end-stage renal disease.
T
HE inadequate pool of donor organs makes patients a waiting transplantation use renal replacement treatment in the form of either hemodialysis (HD) or peritoneal dialysis (PD), even though kidney transplantation in eligible patients with end-stage renal disease is related to higher survival rates than long-term dialysis. Some retrospective studies from individual transplantation centers have reported that preemptive transplantation (transplantation performed before the initiation of long-term dialysis) has little effect on outcomes,1–5 but other reports show improved graft survival.6 – 8 We studied differential effects on long-term outcomes according to dialysis type and duration versus no dialysis, evaluating the outcome and clinical advantages among the 3 groups. MATERIALS AND METHODS Eligible patients of 15 years of age or older who received a first kidney transplant from a living donor between 1990 and 2007 (N ⫽ © 2009 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 41, 117–120 (2009)
499) were subdivided into 3 groups: preemptive transplant (n ⫽ 81), HD (n ⫽ 343), or PD group (n ⫽ 75). Graft failure was defined as the initiation of long-term dialysis therapy after transplantation. When increased serum creatinine level was ⬎0.3 mg/dL a day or in case of oliguria (low urine output ⬍1000 mL during the initial 24 hours after transplantation), we performed renal Duplex scan. Rejection was confirmed by a resistance index ⬎0.8. Prednisone, Cyclosporine/Tacrolimus (FK 506), and Mycophenolic acid/Azathioprine were used as immunosuppressive agents in the 3 groups. We compared the 3 groups (preemptive, HD, and PD) according to graft survival rates, acute and chronic rejection rates, postoperative complication rates, and frequency of delayed graft function.
From the Transplantation Center, Hanyang University Hospital, Seoul, Korea. Address reprint requests to Oh Jung Kwon, MD, PhD, Professor of Surgery, Hanyang University Hospital, Department of Surgery, SeoungdongKu HaengdangDong 17, 133-792 Seoul, Korea. E-mail:
[email protected] 0041-1345/09/$–see front matter doi:10.1016/j.transproceed.2008.09.063 117
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We used chi-square tests to compare postoperative complication rates. Kaplan-Meier analysis was performed for patient and graft survivals. The value of P ⬍ .05 was considered statistically significant. We used SPSS version 12.0 (SPSS, Chicago, Ill, United States).
RESULTS
There were a number of characteristics associated with the 3 groups (Table 1). At the time of transplantation, recipient and donor ages were similar. The number of related donors type was 72.8%, 41.4%, and 25.3% in the 3 groups. The mean duration of dialysis therapy before transplantation was 29.3 ⫾ 36.9 months in the HD group and 33.1 ⫾ 34.2 months in the PD group. The overall patient survival rates were 98.2%, 96.7%, and 96.2% at 1, 5, and 10 years after transplantation, respectively. Graft survival rates of 499 patients were 92.4%, 79.5%, and 70.7% at 1, 5, and 10 years, respectively. Patient survival rates at 5 and 10 years of recipients who underwent preemptive transplantations were not different from those of recipients who experienced dialysis therapy before transplantation (preemptive vs dialysis; 96.2% vs 96.8%, 94.7% vs 96.5%; P ⬎ .05). But graft survival rates at 5 and 10 years were better among the preemptive group than those of
recipients on dialysis therapy before transplantation (89.5% vs 77.6%, 79.4% vs 69.1%; P ⫽ .03; Fig 1). Pretransplantation dialysis modality did not affect patient or graft survivals; the 5-year graft survival rates were 78.2% versus 74.5%; 10-year graft survival rates were 69.2% versus 68.2% for HD versus PD, respectively (P ⫽ .61; Fig 2). In comparing preemptive with nonpreemptive transplantation, the former mode was associated with a lower rate of delayed graft function (DGF) which occurred in the preemptive group at 4.9%; the HD group at 9.6%; and the PD group at 8.0%. Acute rejection episodes occurred in 18.5% of patients in the preemptive group; 32.4% of HD patients; and 37.3% of PD patients (P ⫽ .009). The infection rates of Pneumonia, urinary tract, cytomegalovirus, and Herpes zoster were 13.6%, 14.3%, and 21.3% among preemptive, HD, and PD patients. Malignancy including Kaposi sarcoma, lymphoma, and lung cancer, occurred in 1.2% of the preemptive group, 3.5% of the HD and 4% of the PD group. DISCUSSION
Currently, patients awaiting transplantation need to use renal replacement therapy as the second best treatment due
Table 1. Characteristics of the Transplant Recipients and Complications After Transplantation Characteristics
Recipient age (yr) Range (yr) Gender of recipient (% male/female) Primary cause of ESRD (%) Hypertension (%) Diabetes mellitus (%) Glomerulonephritis (%) IgA nephropathy (%) Others (%) Unknown (%) Donor age (yr) Range Gender of donor (% male/female) Donor type Related Unrelated No. of HLA-A, B matched (%) 0 1 2 3 4 No. of HLA-DR matched (%) 0 1 2 Duration of dialysis (mo) Mean follow-up (mo) DGF (%) Acute rejection (%) Infection (%) Malignancy (%)
Preemptive Group (n ⫽ 81)
HD Group (n ⫽ 343)
PD Group (n ⫽ 75)
37.5 ⫾ 9.5 17–59 51.9/48.1
39.0 ⫾ 10.8 15–66 65.9/34.1
39.1 ⫾ 10.9 16–59 69.3/30.7
9.9 1.2 3.7 7.4 7.4 70.4 38.9 ⫾ 13.0 17–71 62.5/37.5
8.4 4.4 7.6 6.4 16.9 56.3 39.9 ⫾ 11.3 16–73 56.6/43.4
12.0 9.3 6.7 5.3 2.7 64.0 39.9 ⫾ 11.3 16–64 66.7/33.3
72.8 27.2
41.4 58.6
25.3 74.7
2.5 19.8 50.6 18.5 8.6
5.8 36.4 43.4 9.6 4.7
5.3 41.3 45.3 5.3 2.7
3.7 71.6 24.7 (-) 121.3 ⫾ 58.3 4.9 18.5 13.6 1.2
5.2 81.3 12.8 29.3 ⫾ 36.9 117.0 ⫾ 46.1 9.6 32.4 14.3 3.5
9.3 81.3 9.3 33.1 ⫾ 34.2 126.7 ⫾ 37.1 8.0 37.3 21.3 4
Abbreviations: ESRD, end-stage renal disease; Ig, immunoglobulin.
PREEMPTIVE RENAL TRANSPLANTATION
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the cost and morbidity of placement of a permanent HD access. Dialysis is often initiated in the hospital, for this reason preemptive transplantation could also decrease the need for hospitalization. Some retrospective studies1–5 from individual transplantation centers have reported that preemptive transplantation had little effect on outcomes, but other workers6 – 8 have reported improved graft survival. The North American Pediatric Renal Transplant Cooperative Study group9 reported that graft survival was improved for children who received preemptive transplants compared with those receiving transplants after initiating chronic maintenance dialysis. A study of 8481 adult, living-donor transplants from 1994 to 199719 also reported a 52% reduction in the risk of graft failure associated with preemptive transplantation. However, in the European Dialysis and Transplantation Association-European Renal Association registry study10 of 35,511 adult, cadaver and living-donor transplants from 1985 to 1992, 5-year patient and graft survival rates were not affected by preemptive transplantation. In our study, we found that preemptive transplantation lead to the best allograft survival. The results of our study were consistent with previous studies19,20 wherein preemptive transplantation from living donors as compared with that after initiation of long-term dialysis, was associated with better allograft survival. Fig 1. Relationship between preemptive transplantation group and dialysis group.
to the inadequate pool of donor organs. Past studies have shown various rates of graft survival among the preemptive, HD, or PD groups.9,10 We performed a retrospective cohort study to examine the relationship between prior dialysis, dialysis modality, dialysis duration, and patient survival. The long-term outcome of kidney transplantation depends on several conditions: the age of the donor and the recipient; previous transplantation or transfusion; comorbidity conditions; and other immunologic factors.11–14 We have studied the long-term outcome of kidney transplantation according to the initiation of pretransplantation dialysis and its duration. We found that the initiation of pretransplantation dialysis affected allograft outcomes, but the dialysis modality, PD or HD, did not influence it. There are some theoretical detriments to preemptive transplantation: failure to maximize native kidney function and to take advantage of putative immunosuppressive effects of uremia,15 which theoretically help to prevent early posttransplantation rejection. It is possible that preemptive transplantation may increase the chances for patients who finally recover renal function to undergo transplantation unnecessarily. Although uncommon, at least some patients who begin dialysis for end-stage renal disease ultimately recover renal function.16,17 But transplantation is ultimately less expensive than dialysis18; avoiding dialysis may reduce overall costs. Preemptive transplantation may also obviate
Fig 2. Relationship between hemodialysis group and peritoneal dialysis group. HD, hemodialysis group; PD, peritoneal dialysis group.
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Although many confounding factors may be connected with this observation, immunologic mechanisms may at least in part be associated with this result. The initiation of dialysis has been reported to diminish immune dysfunction,21,22 thus increasing the risk for rejection, leading to the poorer outcomes compared with preemptive transplantation. Descamps-Latscha et al21 provided evidence of a greater degree of impairment in the immune system among patients not undergoing dialysis compared with those undergoing long-term dialysis. Kaul et al22 confirmed that the initiation of HD leads to a significant improvement in T-cell proliferation. These consequences suggest that exposure to dialysis may diminish the severity of immune dysfunction and thus increase the risk of acute rejection and graft failure. We observed that preemptive transplantation was associated with lower rates of DGF postoperative infection, and malignancy incidence. Also, acute rejection occurred significantly less often in the preemptive than the dialysis group. In conclusion, preemptive transplantation may be the first choice of treatment for patients who need transplantation, because preemptive renal transplantation from living donors without the previous initiation of dialysis is associated with a better allograft survival rate and may be associated with lower complication rates; it is a costeffective option. REFERENCES 1. Katz SM, Kermann RH, Golden D, et al: Preemptive transplantation-an analysis of benefits and hazards in 85 cases. Transplantation 51:351, 1991 2. Flom LS, Reisman EM, Donovan JM, et al: Favorable experience with pre-emptive renal transplantation in children. Pediatr Nephrol 6:258, 1992 3. Offiner G, Hoyer PF, Meyer B, et al: Preemptive renal transplantation in children and adolescents. Transpl Int 6:125, 1993 4. Mahmoud A, Said MH, Dawahra M, et al: Outcome of preemptive renal transplantation and pretransplantation dialysis in children (published erratum appears in Pediatr Nephrol 11:777, 1997). Pediatr Nephrol 11:573, 1997 5. John AG, Rao M, Jacob CK: Preemptive live-related renal transplantation. Transplantation 66:204, 1998 6. Roake JA, Cahill AP, Gray CM, et al: Preemptive cadaveric renal transplantation-clinical outcome. Transplantation 62:1411, 1996
YOO, KWON, AND KANG 7. Asderakis A, Augustine T, Dyer P, et al: Pre-emptive kidney transplantation, the attractive alternative. Nephrol Dial Transplant 13:1799, 1998 8. Papalois VE, Moss A, Gillingham KJ, et al: Pre-emptive transplants for patients with renal failure, an argument against waiting until dialysis. Transplantation 70:625, 2000 9. Vats AN, Donaldson L, Fine RN, et al: Pretransplant dialysis status and outcome of renal transplantation in North American children, a NAPRTCS Study, North American Pediatric Renal Transplant Cooperative Study. Transplantation 69:1414, 2000 10. Berthoux FC, Jones EH, Mehls O, et al: Transplantation report. 2, pre-emptive renal transplantation in adults aged over 15 years. The EDTA-ERA Registry, European Dialysis and Transplant Association-European Renal Association. Nephrol Dial Transplant 11:41, 1996 11. Ojo AO, Leichtman AB, Punch JD, et al: Impact of preexisting donor hypertension and diabetes mellitus on cadaveric renal transplant outcomes. Am J Kidney Dis 36:153, 2000 12. Mouquet C, Benalia H, Chartier-Kastler E, et al: Renal retransplantation in adults: comparative prognostic study. Prog Urol 9:239, 1999 13. Chavers BM, Sullivan EK, Tejani A, et al: Pre-transplant blood transfusion and renal allograft outcome: a report of the North American Pediatric Renal Transplant Cooperative study. Pediatr Transplant 1:22, 1997 14. Donoghue DO, Manos J, Pearson R, et al: Continuous ambulatory peritoneal dialysis and renal transplantation: a ten-year experience in a single center. Perit Dial Int 12:242, 1992 15. Girndt M, Sester M, Sester U, et al: Molecular aspects of Tand B-cell function in uremia. Kidney Int 78:206, 2001 16. Sekkarie MA, Port FK, Wolfe RA, et al: Recovery from end-stage renal disease. Am J Kidney Dis 15:61, 1990 17. Pichette V, Querin S, Desmeules M, et al: Renal function recovery in end-stage renal disease. Am J Kidney Dis 22:398, 1993 18. Kasiske BL, Cohen D, Lucey MR, et al: Payment for immunosuppression after organ transplantation. American Society of Transplantation. JAMA 283:2445, 2000 19. Mange KC, Joffe MM, Feldmann 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 344:726, 2001 20. Schurmann SJ, McEnery PT: Factors influencing short-term and long-term pediatric renal transplant survival. J Pediatr 30:455, 1997 21. Descamps-Latscha B, Herbelin A, Nguyen AT, et al: Balance between IL-1 beta, TNF-alpha, and their specific inhibitors in chronic renal failure and maintenance dialysis: relationships with activation markers of T cells, B cells, and monocytes. J Immunol 154:882, 1995 22. Kaul H, Girndt M, Sester U, et al: Initiation of hemodialysis treatment leads to improvement of T-cell activation in patients with end-stage renal disease. Am J Kidney Dis 35:611, 2000
