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Kidney Transplantation in Patients Receiving Dialysis Treatment for More Than 10 Years
Outcomes
Kidney Transplantation in Patients Receiving Dialysis Treatment for More Than 10 Years H. Kishikawa, Y. Ichikawa, N. Arichi, S. Tokugawa, I. Yoshioka, K. Nishimura, A. Okuno, N. Fujii, and M. Nojima ABSTRACT In the present single center study, we analyzed 277 kidney transplant patients (procedures performed between February 1984 and February 2006) to determine the impact of long-term dialysis on kidney transplant outcomes. Forty-four had been treated prior to renal transplantation with dialysis for more than 10 years (range, 10.0 –32.5 years, average, 16.6 years; Group I), while the remaining 233 recipients showed an average end-stage renal disease period of 2.8 years (range, 0 –9.8 years; Group II). There were no significant differences in patient survivals between the 2 groups: 97.3% vs 97.4% at 1 year; 85.7% vs 92.4% at 5 years; 85.7% vs 90.7% at 10 years (P ⫽ .2347). Five Group I patients died: 2 from infections, 2 from liver dysfunction, and 1 from cerebral bleeding. These causes of death were similar to those among Group II patients. Graft survival was not significantly different between the 2 groups: 95% vs 88.8% at 1 year; 75.5% vs 76.5% at 5 years; 75.5% vs 65.5% at 10 years (P ⫽ .6264). Our results suggested that dialysis treatment for more than 10 years did not have negative effects on posttransplantation patient and graft survival.
T
HERE IS an extreme shortage of living and cadaveric kidney donors in Japan. Therefore, a great number of patients with end-stage renal disease (ESRD) awaiting transplantation must remain on hemodialysis for several years. While improvements in dialysis techniques and materials have recently increased, the long-term survival of these patients has been reported to be associated with various complications: cardio- and cerebro-vascular disease, immune system impairment, malignancy, and amyloidosis. The effects of long-term dialysis on patient survival and allograft function are not well known, although it has been suggested that preemptive transplantation provides good results. In the present single center study, we analyzed 277 kidney transplant patients to determine the impact of long-term dialysis on kidney transplant outcomes.
PATIENTS AND METHODS Between February 1984 and February 2006, 277 kidney transplant procedures were performed at our hospital. Forty-four patients had been treated with dialysis prior to renal transplantation for more than 10 years (range, 10.0 –32.5 years, average, 16.6 years; Group I), while the remaining 233 recipients had an average ESRD period
From the Department of Renal Transplantation Center, Hyogo Prefectural Nishinomiya Hospital, Hyogo, Japan (H.K., Y.I., N.A., S.T., I.Y., K.N., A.O., N.F.), and the Department of Urology, Hyogo College of Medicine, Hyogo, Japan (M.N.). Address reprint requests to Hidefumi Kishikawa, MD, Department of Renal Transplantation Center, Hyogo Prefectural Nishinomiya Hospital, Rokutanji-cho 13-9, Nishinomiya, Hyogo 6620918, Japan.
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.10.138
Transplantation Proceedings, 38, 3445–3447 (2006)
3445
3446
KISHIKAWA, ICHIKAWA, ARICHI ET AL Table 1. Patient Demographics and Characteristics Feature
No. of patients Gender (M/F) Age (y) Dialysis duration (y) Range (y) Donor source Cadaveric donor Living donor HLA mismatch AB DR Donor age (y) HCV carrier (%) Follow-up period (y)
Group I
Group II
44 31/13 44.8 ⫾ 8.5 16.6 ⫾ 4.8 10–32.5
233 132/101 34.4 ⫾ 9.6 2.8 ⫾ 2.6 0–9.8
37 7
49 184
1.568 ⫾ 1.043 0.614 ⫾ 0.538 49.7 ⫾ 14.9 31 5.0 ⫾ 5.0
1.384 ⫾ 0.827 0.662 ⫾ 0.520 52.4 ⫾ 11.5 8.1 11.6 ⫾ 7
P
.088 ⬍.0001
⬍.0001
.1219 .9196 .1663 .0006 ⬍.0001
Table 2. Cox Proportional Hazard Model for Relative Risk (RR) of Patient Death Variable
RR
95% CI
P
ESRD duration (per 1 year) Cadaveric donor (living donation) Acute rejection episode HCV infection Cyclosporine (tacrolimus) Recipient age (per 1 year) Donor age (per 1 year)
0.971 1.246 2.365 1.985 1.193 1.076 1.019
0.882–1.061 0.734–2.051 0.965–5.841 0.572–6.100 0.744–1.972 1.027–1.130 0.987–1.057
NS NS NS NS NS .0019 NS
Patient characteristics are shown in Table 1 The age of the recipients in Group I was significantly older (44.8 vs 34.4 years, P ⬍ .0001), while the incidence of cadaveric donor transplantation (P ⬍ .0001) and percentage of HCV carriers (P ⫽ .0006) were higher in that group. In contrast, recipient gender distribution was similar and HLA matching not significantly different between the groups. All Group I patients survived more than 3 months after transplantation and, other than a single primary nonfunction in a kidney from a cadaveric donor, all grafts functioned for
more than 3 months. There were 7 wound infections, 5 CMV infections, and 3 Herpes-Zoster virus infections among Group I patients within 3 months after transplantation, although none was a serious complication. Acute rejection episodes developed in 28.6% of Group I and 43.6% of Group II patients (P ⫽ .1013). Actuarial patient survival for the 2 groups is shown in Figure 1. There were no significant differences in patient survival: 97.3% vs 97.4% at 1 year; 85.7% vs 92.4% at 5 years; 85.7% vs 90.7% at 10 years (P ⫽ .2347). The effects of ESRD time prior to transplantation, age, donor age, acute rejection episodes, HCV infection, type of calcineurin inhibitor, and donor source on patient survival were analyzed using Cox proportionate hazard regression (Table 2). Higher recipient age was the only significant risk factor for patient death after kidney transplantation (P ⫽ .0019), while increased ESRD time was not significant (P ⫽ .5307). Five patients in Group I died: 2 from infections, 2 from liver dysfunction, and 1 from cerebral bleeding. In contrast, 30 died in Group II: 10 from malignancy, 7 from infection, 6 from cardio- or cerebrovascular disease, 4 from liver dysfunction, and 3 from other diseases. The causes of death were similar in both groups, however, no patient in Group I died of a malignancy. Graft survival was not significantly different between the 2 groups: 95% vs 88.8% at 1 year; 75.5% vs 76.5% at 5 years; 75.5% vs 65.5% at 10 years (P ⫽ .6264; Fig 2). The possible risk factors for graft survival were analyzed by Cox
Fig 1. Unadjusted patient survival by length of dialysis treatment before transplantation.
Fig 2. Unadjusted graft survival by length of dialysis treatment before transplantation.
of 2.8 years (range, 0 –9.8 years; Group II). All patients received calcineurin inhibitor-based immunosuppressing. Acute rejection episodes were diagnosed by the clinical course, including a rise in serum creatinine level with histological confirmation. OKT3 monoclonal antibody treatment was employed for steroid-resistant rejection episodes. Both patient and graft survival rates were calculated using the Kaplan-Meier method and compared with a log-rank test. In addition, we used a Cox proportional hazard model to detect independent risk factors for graft and patient survival. An unpaired Student t test and chi-square analysis were utilized where appropriate. P ⬍ .05 was considered statistically significant.
RESULTS
LONG-TERM DIALYSIS AND TRANSPLANTATION
3447
Table 3. Cox Proportional Hazard Model for Relative Risk (RR) of Graft Loss Variable
RR
95% CI
P
ESRD duration (per 1 year) Cadaveric donor (living donation) Acute rejection episode HCV infection Cyclosporine (tacrolimus) Recipient age (per 1 year) Donor age (per 1 year)
0.932 1.426 3.624 2.459 1.472 1.071 1.023
0.850–1.014 0.844–2.336 1.526–8.781 0.767–7.037 0.942–2.381 1.025–1.121 0.988–1.063
NS NS .0037 NS NS .0021 NS
proportionate hazard regression (Table 3). Significant risk factors for graft loss after kidney transplantation were greater recipient age (P ⫽ .0021) and acute rejection episodes (P ⫽ .0037), whereas increased ESRD time was not significant (P ⫽ .1062). DISCUSSION
Approximately 250,000 ESRD patients were treated with dialysis in 2005 in Japan. Further, 12,000 ESRD patients are on the waiting list for cadaveric transplantation, a quarter of whom have been receiving dialysis for more than 10 years, because of the growing discrepancy between the number of donors versus potential recipients. In 2005, only 160 cadaveric and 834 living renal transplantations were performed in Japan. There is some evidence that patients who receive a preemptive renal transplant show graft and patient survival advantages, as opposed to those who receive a renal transplant after a period of maintenance dialysis therapy.1,2 ESRD patients on dialysis have been reported to suffer poor nutrition, a chronic inflammatory state, and altered immunologic functions.3,4 Meier-Kriesche et al5 hypothesized that the longer one waits on dialysis, the greater the exposure to chronic effects of end-stage renal failure and dialysis, making ESRD a time-dependent risk factor associated with patient death and graft loss. Patients who survived on dialysis for a longer period have been noted to show good compliance and proper self-control, while improvements in dialysis materials and techniques also have had a significant effect. Nevertheless, the effects of longterm dialysis with regard to patient survival and allograft function are not well known. Some studies have reported the negative impact of long-term ESRD on kidney transplant outcome.5–7 In contrast, Cacciarelli et al8 reported no differences in graft and patient survival after 1 and 5 years associated with the length of time of pretransplantation dialysis treatment. Further, Vianello et al9 reported no significant difference in patient and graft survival between patients receiving dialysis for more than 15 years versus those less than 2 years, while Arend et al10 also did not observe any effect of length of pretransplantation dialysis on patient survival. In the present study, long-term pretransplantation dialysis did not have a negative impact on either patient or graft survival. We found that recipient age was the only independent risk factor for patient death, while recipient age and
acute rejection episodes were independent risk factors for graft loss. There has been evidence of immunological impairments associated with chronic kidney failure during long-term dialysis treatment.11,12 Although there was no lethal infection within 3 months of transplantation among the present patients with an ESRD period of more than 10 years, 15 of 44 suffered some form of infection, including wound infections, CMV infection, and HZV infection. In contrast, an acute rejection episode was a risk factor for graft loss. In our analysis, the incidence of acute rejection episodes tended to be higher among patients with shorter ESRD periods, although it was not statistically significant. Thus, the impaired immune system of patients with an ESRD period of greater than 10 years may have contributed to the graft survival and wound healing results. The causes of death in our patients were not characteristic of patients with longer compared with shorter ESRD periods. No patient died of malignancy among Group I, probably because of the relatively short follow-up period, while the cumulative incidence of malignancy increased markedly with longer posttransplantation periods.13 In conclusion, our results suggested that dialysis for more than 10 years did not have negative effects on posttransplantation patient and graft survival. Thus, renal transplantation can be confidently performed in long-term dialysis patients. REFERENCES 1. Roake JA, Cahill AP, Gray CM, et al: Preemptive cadaveric renal transplantation: clinical outcome. Transplantation 62:1411, 1996 2. Asderakis A, Augustine T, Dyer P, et al: Pre-emptive kidney transplantation: the attractive alternative. Nephrol Dial Transplant 13:1799, 1998 3. Kaufmann P, Smolle KH, Horina JH, et al: Impact of long-term hemodialysis on nutritional status in patients with endstage renal failure. Clin Invest Med 72:754, 1994 4. Miyata T, Wada Y, Cai Z, et al: Implication of an increased oxidative stress in the formation of advanced glycation end products in patients with end-stage renal failure. Kidney Int 51:1170, 1997 5. Meier-Kriesche HU, Port FK, Ojo AO, et al: Effect of waiting time on renal transplant outcome. Kidney Int 58:1311, 2000 6. Goldfarb-Rumyantzev AS, Hurdle JF, Scandling J, et al: Duration of end-stage renal disease and kidney transplant outcome. Nephrol Dial Transplant 20:167, 2004 7. Cosio FG, Alamir A, Yim S, et al: Patient survival after renal transplantation. I. The impact of dialysis pre-transplant. Kidney Int 53:767, 1998 8. Cacciarelli TV, Sumrani N, DiBenedetto A, et al: Influence of length of time on dialysis before transplantation on long-term renal allograft outcome. Transplant Proc 25:2474, 1998 9. Vianello A, Padoan MV, Calconi G, et al: Influence of length of time on dialysis before grafting on kidney transplant results. Renal Fail 18:279, 1996 10. Arend SM, Mallat MJ, Westendorp RJ, et al: Patient survival after renal transplantation: more than 25 years follow-up. Nephrol Dial Transplant 12:1672, 1997 11. Ota Z, Amano T: Immunological impairment in chronic kidney failure with long-term dialysis. Nippon Rinsho 50:637, 1992 12. Descampus-Latscha B, Herbelin A, Nguyen AT, et al: Immune system dysreguration in uremia. Semin Nephrol 14:253, 1994 13. Kishikawa H, Ichikawa Y, Yazawa K, et al: Malignant neoplasm in kidney transplantation. Int J Urol 5:521, 1998
Kidney Transplantation in Patients Receiving Dialysis Treatment for More Than 10 Years H. Kishikawa, Y. Ichikawa, N. Arichi, S. Tokugawa, I. Yoshioka, K. Nishimura, A. Okuno, N. Fujii, and M. Nojima ABSTRACT In the present single center study, we analyzed 277 kidney transplant patients (procedures performed between February 1984 and February 2006) to determine the impact of long-term dialysis on kidney transplant outcomes. Forty-four had been treated prior to renal transplantation with dialysis for more than 10 years (range, 10.0 –32.5 years, average, 16.6 years; Group I), while the remaining 233 recipients showed an average end-stage renal disease period of 2.8 years (range, 0 –9.8 years; Group II). There were no significant differences in patient survivals between the 2 groups: 97.3% vs 97.4% at 1 year; 85.7% vs 92.4% at 5 years; 85.7% vs 90.7% at 10 years (P ⫽ .2347). Five Group I patients died: 2 from infections, 2 from liver dysfunction, and 1 from cerebral bleeding. These causes of death were similar to those among Group II patients. Graft survival was not significantly different between the 2 groups: 95% vs 88.8% at 1 year; 75.5% vs 76.5% at 5 years; 75.5% vs 65.5% at 10 years (P ⫽ .6264). Our results suggested that dialysis treatment for more than 10 years did not have negative effects on posttransplantation patient and graft survival.
T
HERE IS an extreme shortage of living and cadaveric kidney donors in Japan. Therefore, a great number of patients with end-stage renal disease (ESRD) awaiting transplantation must remain on hemodialysis for several years. While improvements in dialysis techniques and materials have recently increased, the long-term survival of these patients has been reported to be associated with various complications: cardio- and cerebro-vascular disease, immune system impairment, malignancy, and amyloidosis. The effects of long-term dialysis on patient survival and allograft function are not well known, although it has been suggested that preemptive transplantation provides good results. In the present single center study, we analyzed 277 kidney transplant patients to determine the impact of long-term dialysis on kidney transplant outcomes.
PATIENTS AND METHODS Between February 1984 and February 2006, 277 kidney transplant procedures were performed at our hospital. Forty-four patients had been treated with dialysis prior to renal transplantation for more than 10 years (range, 10.0 –32.5 years, average, 16.6 years; Group I), while the remaining 233 recipients had an average ESRD period
From the Department of Renal Transplantation Center, Hyogo Prefectural Nishinomiya Hospital, Hyogo, Japan (H.K., Y.I., N.A., S.T., I.Y., K.N., A.O., N.F.), and the Department of Urology, Hyogo College of Medicine, Hyogo, Japan (M.N.). Address reprint requests to Hidefumi Kishikawa, MD, Department of Renal Transplantation Center, Hyogo Prefectural Nishinomiya Hospital, Rokutanji-cho 13-9, Nishinomiya, Hyogo 6620918, Japan.
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.10.138
Transplantation Proceedings, 38, 3445–3447 (2006)
3445
3446
KISHIKAWA, ICHIKAWA, ARICHI ET AL Table 1. Patient Demographics and Characteristics Feature
No. of patients Gender (M/F) Age (y) Dialysis duration (y) Range (y) Donor source Cadaveric donor Living donor HLA mismatch AB DR Donor age (y) HCV carrier (%) Follow-up period (y)
Group I
Group II
44 31/13 44.8 ⫾ 8.5 16.6 ⫾ 4.8 10–32.5
233 132/101 34.4 ⫾ 9.6 2.8 ⫾ 2.6 0–9.8
37 7
49 184
1.568 ⫾ 1.043 0.614 ⫾ 0.538 49.7 ⫾ 14.9 31 5.0 ⫾ 5.0
1.384 ⫾ 0.827 0.662 ⫾ 0.520 52.4 ⫾ 11.5 8.1 11.6 ⫾ 7
P
.088 ⬍.0001
⬍.0001
.1219 .9196 .1663 .0006 ⬍.0001
Table 2. Cox Proportional Hazard Model for Relative Risk (RR) of Patient Death Variable
RR
95% CI
P
ESRD duration (per 1 year) Cadaveric donor (living donation) Acute rejection episode HCV infection Cyclosporine (tacrolimus) Recipient age (per 1 year) Donor age (per 1 year)
0.971 1.246 2.365 1.985 1.193 1.076 1.019
0.882–1.061 0.734–2.051 0.965–5.841 0.572–6.100 0.744–1.972 1.027–1.130 0.987–1.057
NS NS NS NS NS .0019 NS
Patient characteristics are shown in Table 1 The age of the recipients in Group I was significantly older (44.8 vs 34.4 years, P ⬍ .0001), while the incidence of cadaveric donor transplantation (P ⬍ .0001) and percentage of HCV carriers (P ⫽ .0006) were higher in that group. In contrast, recipient gender distribution was similar and HLA matching not significantly different between the groups. All Group I patients survived more than 3 months after transplantation and, other than a single primary nonfunction in a kidney from a cadaveric donor, all grafts functioned for
more than 3 months. There were 7 wound infections, 5 CMV infections, and 3 Herpes-Zoster virus infections among Group I patients within 3 months after transplantation, although none was a serious complication. Acute rejection episodes developed in 28.6% of Group I and 43.6% of Group II patients (P ⫽ .1013). Actuarial patient survival for the 2 groups is shown in Figure 1. There were no significant differences in patient survival: 97.3% vs 97.4% at 1 year; 85.7% vs 92.4% at 5 years; 85.7% vs 90.7% at 10 years (P ⫽ .2347). The effects of ESRD time prior to transplantation, age, donor age, acute rejection episodes, HCV infection, type of calcineurin inhibitor, and donor source on patient survival were analyzed using Cox proportionate hazard regression (Table 2). Higher recipient age was the only significant risk factor for patient death after kidney transplantation (P ⫽ .0019), while increased ESRD time was not significant (P ⫽ .5307). Five patients in Group I died: 2 from infections, 2 from liver dysfunction, and 1 from cerebral bleeding. In contrast, 30 died in Group II: 10 from malignancy, 7 from infection, 6 from cardio- or cerebrovascular disease, 4 from liver dysfunction, and 3 from other diseases. The causes of death were similar in both groups, however, no patient in Group I died of a malignancy. Graft survival was not significantly different between the 2 groups: 95% vs 88.8% at 1 year; 75.5% vs 76.5% at 5 years; 75.5% vs 65.5% at 10 years (P ⫽ .6264; Fig 2). The possible risk factors for graft survival were analyzed by Cox
Fig 1. Unadjusted patient survival by length of dialysis treatment before transplantation.
Fig 2. Unadjusted graft survival by length of dialysis treatment before transplantation.
of 2.8 years (range, 0 –9.8 years; Group II). All patients received calcineurin inhibitor-based immunosuppressing. Acute rejection episodes were diagnosed by the clinical course, including a rise in serum creatinine level with histological confirmation. OKT3 monoclonal antibody treatment was employed for steroid-resistant rejection episodes. Both patient and graft survival rates were calculated using the Kaplan-Meier method and compared with a log-rank test. In addition, we used a Cox proportional hazard model to detect independent risk factors for graft and patient survival. An unpaired Student t test and chi-square analysis were utilized where appropriate. P ⬍ .05 was considered statistically significant.
RESULTS
LONG-TERM DIALYSIS AND TRANSPLANTATION
3447
Table 3. Cox Proportional Hazard Model for Relative Risk (RR) of Graft Loss Variable
RR
95% CI
P
ESRD duration (per 1 year) Cadaveric donor (living donation) Acute rejection episode HCV infection Cyclosporine (tacrolimus) Recipient age (per 1 year) Donor age (per 1 year)
0.932 1.426 3.624 2.459 1.472 1.071 1.023
0.850–1.014 0.844–2.336 1.526–8.781 0.767–7.037 0.942–2.381 1.025–1.121 0.988–1.063
NS NS .0037 NS NS .0021 NS
proportionate hazard regression (Table 3). Significant risk factors for graft loss after kidney transplantation were greater recipient age (P ⫽ .0021) and acute rejection episodes (P ⫽ .0037), whereas increased ESRD time was not significant (P ⫽ .1062). DISCUSSION
Approximately 250,000 ESRD patients were treated with dialysis in 2005 in Japan. Further, 12,000 ESRD patients are on the waiting list for cadaveric transplantation, a quarter of whom have been receiving dialysis for more than 10 years, because of the growing discrepancy between the number of donors versus potential recipients. In 2005, only 160 cadaveric and 834 living renal transplantations were performed in Japan. There is some evidence that patients who receive a preemptive renal transplant show graft and patient survival advantages, as opposed to those who receive a renal transplant after a period of maintenance dialysis therapy.1,2 ESRD patients on dialysis have been reported to suffer poor nutrition, a chronic inflammatory state, and altered immunologic functions.3,4 Meier-Kriesche et al5 hypothesized that the longer one waits on dialysis, the greater the exposure to chronic effects of end-stage renal failure and dialysis, making ESRD a time-dependent risk factor associated with patient death and graft loss. Patients who survived on dialysis for a longer period have been noted to show good compliance and proper self-control, while improvements in dialysis materials and techniques also have had a significant effect. Nevertheless, the effects of longterm dialysis with regard to patient survival and allograft function are not well known. Some studies have reported the negative impact of long-term ESRD on kidney transplant outcome.5–7 In contrast, Cacciarelli et al8 reported no differences in graft and patient survival after 1 and 5 years associated with the length of time of pretransplantation dialysis treatment. Further, Vianello et al9 reported no significant difference in patient and graft survival between patients receiving dialysis for more than 15 years versus those less than 2 years, while Arend et al10 also did not observe any effect of length of pretransplantation dialysis on patient survival. In the present study, long-term pretransplantation dialysis did not have a negative impact on either patient or graft survival. We found that recipient age was the only independent risk factor for patient death, while recipient age and
acute rejection episodes were independent risk factors for graft loss. There has been evidence of immunological impairments associated with chronic kidney failure during long-term dialysis treatment.11,12 Although there was no lethal infection within 3 months of transplantation among the present patients with an ESRD period of more than 10 years, 15 of 44 suffered some form of infection, including wound infections, CMV infection, and HZV infection. In contrast, an acute rejection episode was a risk factor for graft loss. In our analysis, the incidence of acute rejection episodes tended to be higher among patients with shorter ESRD periods, although it was not statistically significant. Thus, the impaired immune system of patients with an ESRD period of greater than 10 years may have contributed to the graft survival and wound healing results. The causes of death in our patients were not characteristic of patients with longer compared with shorter ESRD periods. No patient died of malignancy among Group I, probably because of the relatively short follow-up period, while the cumulative incidence of malignancy increased markedly with longer posttransplantation periods.13 In conclusion, our results suggested that dialysis for more than 10 years did not have negative effects on posttransplantation patient and graft survival. Thus, renal transplantation can be confidently performed in long-term dialysis patients. REFERENCES 1. Roake JA, Cahill AP, Gray CM, et al: Preemptive cadaveric renal transplantation: clinical outcome. Transplantation 62:1411, 1996 2. Asderakis A, Augustine T, Dyer P, et al: Pre-emptive kidney transplantation: the attractive alternative. Nephrol Dial Transplant 13:1799, 1998 3. Kaufmann P, Smolle KH, Horina JH, et al: Impact of long-term hemodialysis on nutritional status in patients with endstage renal failure. Clin Invest Med 72:754, 1994 4. Miyata T, Wada Y, Cai Z, et al: Implication of an increased oxidative stress in the formation of advanced glycation end products in patients with end-stage renal failure. Kidney Int 51:1170, 1997 5. Meier-Kriesche HU, Port FK, Ojo AO, et al: Effect of waiting time on renal transplant outcome. Kidney Int 58:1311, 2000 6. Goldfarb-Rumyantzev AS, Hurdle JF, Scandling J, et al: Duration of end-stage renal disease and kidney transplant outcome. Nephrol Dial Transplant 20:167, 2004 7. Cosio FG, Alamir A, Yim S, et al: Patient survival after renal transplantation. I. The impact of dialysis pre-transplant. Kidney Int 53:767, 1998 8. Cacciarelli TV, Sumrani N, DiBenedetto A, et al: Influence of length of time on dialysis before transplantation on long-term renal allograft outcome. Transplant Proc 25:2474, 1998 9. Vianello A, Padoan MV, Calconi G, et al: Influence of length of time on dialysis before grafting on kidney transplant results. Renal Fail 18:279, 1996 10. Arend SM, Mallat MJ, Westendorp RJ, et al: Patient survival after renal transplantation: more than 25 years follow-up. Nephrol Dial Transplant 12:1672, 1997 11. Ota Z, Amano T: Immunological impairment in chronic kidney failure with long-term dialysis. Nippon Rinsho 50:637, 1992 12. Descampus-Latscha B, Herbelin A, Nguyen AT, et al: Immune system dysreguration in uremia. Semin Nephrol 14:253, 1994 13. Kishikawa H, Ichikawa Y, Yazawa K, et al: Malignant neoplasm in kidney transplantation. Int J Urol 5:521, 1998