- Email: [email protected]
Kidney Retransplantation in Comparison With First Kidney Transplantation
Kidney Retransplantation in Comparison With First Kidney Transplantation F. Pour-Reza-Gholi, M. Nafar, A. Saeedinia, F. Farrokhi, A. Firouzan, N. Simforoosh, A. Basiri, and B. Einollahi ABSTRACT Introduction. The aim of this study was to depict the outcome of second and third kidney allografts in comparison with first kidney allografts. Methods. Among 2150 kidney transplantations are 103 second and 5 third transplantations. Demographic characteristics and survivals of retransplanted patients were compared with a randomly selected group of first kidney recipients, consisting of two cases matched with each retransplanted patient for age, gender, and date of transplantation. Results. Retransplanted patients consisted of 78 men and 30 women of mean age 32.63 ⫾ 11.92 years. They had received kidneys from 91 living-unrelated and 17 living-related donors. Median followup was 27 months. One-, 2-, 3-, and 5-year graft survivals were 81.4%, 78.9%, 78.9%, and 73.7% among retransplants, versus 92.9%, 91.5%, 89.8%, and 85.3% in the control group, respectively (P ⫽ .0037). Patient survival was 96%, 94.6%, 92.4%, and 87.8% in the retransplant group versus 93.1%, 92.4%, 90.9%, 87.4% in the control group, respectively (P ⫽ .63). Also, graft survivals were slightly lower in female compared to male retransplant patients (P ⫽ .09). No significant difference in survival rates was seen in different age groups. Conclusion. It seems that kidney retransplantation can yield desirable outcomes, albeit relatively lower graft survivals.
N
OWADAYS, KIDNEY retransplantation, although considered to be a high-risk procedure, is increasingly performed worldwide. Second graft survival rates seem to be 10% lower than that of first grafts, although recently the survival difference has been reduced to 1%.1 Rejection and early graft loss may be more common, especially in highly sensitized patients, but the overall short-term outcome has been reported to be desirable.2,3 The cost effectiveness of this medical intervention for end-stage renal disease patients shows considerable benefits.4 However, most studies have been done on a restricted number of patients and they lack long term follow-up: We compared the outcomes of patients with second or third kidney allografts with recipients of a first kidney transplant. MATERIALS AND METHODS Among 2117 kidney transplantations were 108 retransplant cases, including 5 recipients of a third kidney allograft. The first retransplantation was performed in 1988; this study covered transplants up to March 2004. The retransplanted patients included 78 (72.2%) males and 30
(27.8%) females. Their mean age at the time of the procedure was 32.63 ⫾ 11.92 (range 11 to 63) years. Most patients were in the 25 to 45 year age group: ⬍25, 26.9%; 25 to 45; 58.3%; ⬎45; 14.8%. Ninety-one patients (84.2%) received a kidney from a livingunrelated donor and 17 (15.8%) from a living-related one. Laparoscopic donor nephrectomy was performed in 23 cases (21.3%). Before their first transplantation 51 patients (48.1%) had undergone dialysis for less than 24 months and 20 (18.9%) for 24 months or more. The previous allograft had shown graft function for less than 48 months in 28 (26.4%) patients and for 48 months or more in 25 (23.6%). Immunosuppression therapy consisted of cyclosporine and prednisolone in 15 (13.8%) and with azathioprime in 66 (61.1%) patients. Thirteen percent of patients were HCV-antibody positive and 2.8% were HBs-antigen positive. From the Urology and Nephrology Research Center, Shaheed Labbafinejad Medical Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran (F.P., M.N., A.S., F.F., A.F., N.S., A.B., B.E.). Address reprint requests to Farhat Farrokhi, Urology/Nephrology Research Center (UNRC), No. 44, 9th Boustan, Pasdaran, Tehran, Iran 1666679951. E-mail: [email protected]
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.08.034
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2962
Transplantation Proceedings, 37, 2962–2964 (2005)
RETRANSPLANTATION VS FIRST TRANSPLANTATION
2963
Table 1. Graft Survival Rate* in Different Groups of Kidney Transplant Patients
Number of cases Survival (%) 1 year 2 year 3 year 5 year 10 year
Total
First Transplant
Control
Retransplant
Second Transplant
Male Retransplant
Female Retransplat
2117
2009
216
108
103
78
30
91.8 89.3 86.1 80.8 67.7
92.4 89.8 86.5 81.2 67.7
92.9 91.5 89.8 85.3 66.2
81.4 78.9 78.9 73.7 —
82.5 79.9 79.9 74.5 —
85.3 83.8 83.8 77.7 —
71.3 65.4 65.4 65.4 —
*Kaplan-Meier (death censored).
Patient and graft survival rates in this group were compared with all recipients of a first allograft and also with a randomly selected cohort of first transplant patients, consisting of two controls matched with each retransplant patient for age, gender, and date of transplantation, (216 control cases g). Statistical analysis used Student t and chi-square tests for comparisons of variants, and Kaplan-Meier and log-rank tests for survival analyses. Deathcensored graft survival was considered in this study.
RESULTS
Median follow-up was 27 (range 1 to 151) months. Seventyfour patients (68.5%) had functional grafts, 23 (21.3%) were chronic dialysis dependent, 7 (6.5%) had died, and 3 (2.8%) were lost to follow-up. The median last serum creatinine level was 1.30 mg/dl in patients with a functional graft. Among the recipients of third kidney allografts (n ⫽ 5), two had lost their graft function within 2 months and the others had active allografts for at least 60 months. Graft survival rates are listed in Table 1. One to 10-year survivals in the control group were not different from those in the overall transplanted patients or the first transplant patients. Showing a significant difference in the first year and in the following years, retransplanted patients displayed a lower 5-year graft survival rate than recipients of a first kidney transplant (73.7% versus 81.2%, P ⫽ .0063) or than the control group (73.7% versus 85.3%, P ⫽ .0037). The difference remained when recipients of a third kidney transplant were excluded (74.5% versus 85.3%, P ⫽ .0076). Graft survivals were slightly lower in female compared to male retransplant patients (P ⫽ .09). After dividing the patients into the age groups of ⬍25, 25 to 45, and ⬎45 years, graft survivals were compared but failed to show a significant difference. Also, graft survival rates were not different in patients under 30 compared to those above 30 years (Table 2). Five-year patient survivals were not different in retransplanted group (Table 3). DISCUSSION
Retransplantation is often a necessity for some cases, such as children.5 Hoenberger et al4 have shown that the lifetime cost of medical care per first transplant candidate is $1,210 higher with a retransplantation policy compared with a no-retransplantation policy; its societal cost-effectiveness is estimated to be $9,656 per quality-adjusted life-year saved.4 Delmonico et al6 reviewed their experience on second
transplants concluding that because excellent second renal allograft survival is attainable and because the costs are comparable, restricting suitable patients to subsequent lifelong dialysis becomes unethical. However, retransplantation rates are low in most centers. In a study of more than 400 cases, relatively few patients who had lost their kidney transplants were returned to the cadaveric waiting list (39%) and even fewer (less than half) underwent retransplantation.7 In our center, 108 patients were recipients of a nonprimary allograft, which was only 5.1% of our 2117 transplants. Comparing 51 retransplanted patients with 96 first transplant patients, matched for age, gender, and date of transplantation, Mouquet et al3 observed no difference in terms of acute rejection episodes (33% for Group 1 versus 48% for Group 2), serum creatinine values at last review, 5-year and 8-year patient (92% versus 82% and 92% versus 76%), and graft survivals (85% versus 75% and 59% versus 61%).3 In our study, although the difference between the two groups was significant, the 5-year graft survival was approximately the same as the results in their study with comparable creatinine levels. In a study in Switzerland, survival rates at 1, 2, and 5 years were 75%, 68%, and 60% for second grafts in 271 cases, which was lower than our findings (82.5%, 79.9%, and 79.9%, respectively).8 In Delmonico’s study, the 1-, 3-, and 5-year actuarial allograft survival rates were 86%, 78%, and 69%, respectively. In a study by Stratta et al,2 over a 42-month period, 76 nonprimary renal transplants (66 second, 7 third, 3 fourth allografts) were reviewed in 73 recipients. Graft survival was 63.6% for secondary grafts and 28.6% for tertiary grafts.2 Our second transplant results are comparable to theirs. Patient survival was high in all of the above studies; ours agree with them. Graft outcome was slightly better in male retransplant Table 2. Graft Survival Rates in Different Age Groups of Retransplant Patients Age (yr)
⬍25
25–45
⬎45
⬍30
Graft Survival Rate (%)* 1 year 2 year 3 year 5 year
74.1 70.2 70.2 60.2
82.9 80.6 80.6 80.6 P ⫽ .36
88.5 88.5 88.5 70.8
81.1 76.5 76.5 72.0 P⫽
*Kaplan-Meier (death censored).
ⱖ30
81.9 81.9 81.9 76.9 .72
2964
POUR-REZA-GHOLI, NAFAR, SAEEDINIA ET AL Table 3. Patient Survival Rate in Different Groups of Kidney Transplant Patients
Number of cases Patient survival rate (%)* 1 year 2 year 3 year 5 year 10 year
Total
First transplant
Control
Retransplant
2117
2009
216
108
93.9 92.5 91.3 88.0 83.2
93.8 92.4 91.2 87.9 83.2
93.1 92.4 90.9 87.4 82.2
96.0 94.6 92.4 87.8 82.9
*Kaplan-Meier.
patients; however, this requires more investigation to be confirmed and the possible causes of this difference should be assessed. In summary, a better life quality with acceptable longterm outcomes may be provided by retransplantation. But, we should consider ways to achieve similar results of primary and nonprimary kidney transplantations. REFERENCES 1. Hirata M, Terasaki PI: Renal retransplantation. Clin Transpl xx:419, 1994 2. Stratta RJ, Oh CS, Sollinger HW, et al: Kidney retransplantation in the cyclosporine era. Transplantation 45:40, 1988 3. Mouquet C, Benalia H, Chartier-Kastler E, et al: Renal retransplantation in adults. Comparative prognostic study. Prog Urol 9:239, 1999
4. Hornberger JC, Best JH, Garrison LP Jr: Cost-effectiveness of repeat medical procedures: kidney transplantation as an example. Med Decis Making 17:363, 1997 5. De Meester J, Smits JM, Offner G, et al: Renal retransplantation of children: is a policy ‘first cadaver donor, then live donor’ an acceptable option? Pediatr Transplant 5:179, 2001 6. Delmonico FL, Tolkoff-Rubin N, Auchincloss H Jr, et al: Second renal transplantations. Ethical issues clarified by outcome; outcome enhanced by a reliable crossmatch. Arch Surg 129:354, 1994 7. Howard RJ, Reed AI, Van Der Werf WJ, Hemming AW, et al: What happens to renal transplant recipients who lose their grafts? Am J Kidney Dis 38:31, 2001 8. Etienne T, Goumaz C, Ruedin P, et al: Renal retransplantation in Switzerland: poor HLA matching of first and subsequent allografts does not appear to affect overall graft survival. Transpl Int 5 (Suppl 1) S65, 1992
N
OWADAYS, KIDNEY retransplantation, although considered to be a high-risk procedure, is increasingly performed worldwide. Second graft survival rates seem to be 10% lower than that of first grafts, although recently the survival difference has been reduced to 1%.1 Rejection and early graft loss may be more common, especially in highly sensitized patients, but the overall short-term outcome has been reported to be desirable.2,3 The cost effectiveness of this medical intervention for end-stage renal disease patients shows considerable benefits.4 However, most studies have been done on a restricted number of patients and they lack long term follow-up: We compared the outcomes of patients with second or third kidney allografts with recipients of a first kidney transplant. MATERIALS AND METHODS Among 2117 kidney transplantations were 108 retransplant cases, including 5 recipients of a third kidney allograft. The first retransplantation was performed in 1988; this study covered transplants up to March 2004. The retransplanted patients included 78 (72.2%) males and 30
(27.8%) females. Their mean age at the time of the procedure was 32.63 ⫾ 11.92 (range 11 to 63) years. Most patients were in the 25 to 45 year age group: ⬍25, 26.9%; 25 to 45; 58.3%; ⬎45; 14.8%. Ninety-one patients (84.2%) received a kidney from a livingunrelated donor and 17 (15.8%) from a living-related one. Laparoscopic donor nephrectomy was performed in 23 cases (21.3%). Before their first transplantation 51 patients (48.1%) had undergone dialysis for less than 24 months and 20 (18.9%) for 24 months or more. The previous allograft had shown graft function for less than 48 months in 28 (26.4%) patients and for 48 months or more in 25 (23.6%). Immunosuppression therapy consisted of cyclosporine and prednisolone in 15 (13.8%) and with azathioprime in 66 (61.1%) patients. Thirteen percent of patients were HCV-antibody positive and 2.8% were HBs-antigen positive. From the Urology and Nephrology Research Center, Shaheed Labbafinejad Medical Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran (F.P., M.N., A.S., F.F., A.F., N.S., A.B., B.E.). Address reprint requests to Farhat Farrokhi, Urology/Nephrology Research Center (UNRC), No. 44, 9th Boustan, Pasdaran, Tehran, Iran 1666679951. E-mail: [email protected]
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.08.034
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2962
Transplantation Proceedings, 37, 2962–2964 (2005)
RETRANSPLANTATION VS FIRST TRANSPLANTATION
2963
Table 1. Graft Survival Rate* in Different Groups of Kidney Transplant Patients
Number of cases Survival (%) 1 year 2 year 3 year 5 year 10 year
Total
First Transplant
Control
Retransplant
Second Transplant
Male Retransplant
Female Retransplat
2117
2009
216
108
103
78
30
91.8 89.3 86.1 80.8 67.7
92.4 89.8 86.5 81.2 67.7
92.9 91.5 89.8 85.3 66.2
81.4 78.9 78.9 73.7 —
82.5 79.9 79.9 74.5 —
85.3 83.8 83.8 77.7 —
71.3 65.4 65.4 65.4 —
*Kaplan-Meier (death censored).
Patient and graft survival rates in this group were compared with all recipients of a first allograft and also with a randomly selected cohort of first transplant patients, consisting of two controls matched with each retransplant patient for age, gender, and date of transplantation, (216 control cases g). Statistical analysis used Student t and chi-square tests for comparisons of variants, and Kaplan-Meier and log-rank tests for survival analyses. Deathcensored graft survival was considered in this study.
RESULTS
Median follow-up was 27 (range 1 to 151) months. Seventyfour patients (68.5%) had functional grafts, 23 (21.3%) were chronic dialysis dependent, 7 (6.5%) had died, and 3 (2.8%) were lost to follow-up. The median last serum creatinine level was 1.30 mg/dl in patients with a functional graft. Among the recipients of third kidney allografts (n ⫽ 5), two had lost their graft function within 2 months and the others had active allografts for at least 60 months. Graft survival rates are listed in Table 1. One to 10-year survivals in the control group were not different from those in the overall transplanted patients or the first transplant patients. Showing a significant difference in the first year and in the following years, retransplanted patients displayed a lower 5-year graft survival rate than recipients of a first kidney transplant (73.7% versus 81.2%, P ⫽ .0063) or than the control group (73.7% versus 85.3%, P ⫽ .0037). The difference remained when recipients of a third kidney transplant were excluded (74.5% versus 85.3%, P ⫽ .0076). Graft survivals were slightly lower in female compared to male retransplant patients (P ⫽ .09). After dividing the patients into the age groups of ⬍25, 25 to 45, and ⬎45 years, graft survivals were compared but failed to show a significant difference. Also, graft survival rates were not different in patients under 30 compared to those above 30 years (Table 2). Five-year patient survivals were not different in retransplanted group (Table 3). DISCUSSION
Retransplantation is often a necessity for some cases, such as children.5 Hoenberger et al4 have shown that the lifetime cost of medical care per first transplant candidate is $1,210 higher with a retransplantation policy compared with a no-retransplantation policy; its societal cost-effectiveness is estimated to be $9,656 per quality-adjusted life-year saved.4 Delmonico et al6 reviewed their experience on second
transplants concluding that because excellent second renal allograft survival is attainable and because the costs are comparable, restricting suitable patients to subsequent lifelong dialysis becomes unethical. However, retransplantation rates are low in most centers. In a study of more than 400 cases, relatively few patients who had lost their kidney transplants were returned to the cadaveric waiting list (39%) and even fewer (less than half) underwent retransplantation.7 In our center, 108 patients were recipients of a nonprimary allograft, which was only 5.1% of our 2117 transplants. Comparing 51 retransplanted patients with 96 first transplant patients, matched for age, gender, and date of transplantation, Mouquet et al3 observed no difference in terms of acute rejection episodes (33% for Group 1 versus 48% for Group 2), serum creatinine values at last review, 5-year and 8-year patient (92% versus 82% and 92% versus 76%), and graft survivals (85% versus 75% and 59% versus 61%).3 In our study, although the difference between the two groups was significant, the 5-year graft survival was approximately the same as the results in their study with comparable creatinine levels. In a study in Switzerland, survival rates at 1, 2, and 5 years were 75%, 68%, and 60% for second grafts in 271 cases, which was lower than our findings (82.5%, 79.9%, and 79.9%, respectively).8 In Delmonico’s study, the 1-, 3-, and 5-year actuarial allograft survival rates were 86%, 78%, and 69%, respectively. In a study by Stratta et al,2 over a 42-month period, 76 nonprimary renal transplants (66 second, 7 third, 3 fourth allografts) were reviewed in 73 recipients. Graft survival was 63.6% for secondary grafts and 28.6% for tertiary grafts.2 Our second transplant results are comparable to theirs. Patient survival was high in all of the above studies; ours agree with them. Graft outcome was slightly better in male retransplant Table 2. Graft Survival Rates in Different Age Groups of Retransplant Patients Age (yr)
⬍25
25–45
⬎45
⬍30
Graft Survival Rate (%)* 1 year 2 year 3 year 5 year
74.1 70.2 70.2 60.2
82.9 80.6 80.6 80.6 P ⫽ .36
88.5 88.5 88.5 70.8
81.1 76.5 76.5 72.0 P⫽
*Kaplan-Meier (death censored).
ⱖ30
81.9 81.9 81.9 76.9 .72
2964
POUR-REZA-GHOLI, NAFAR, SAEEDINIA ET AL Table 3. Patient Survival Rate in Different Groups of Kidney Transplant Patients
Number of cases Patient survival rate (%)* 1 year 2 year 3 year 5 year 10 year
Total
First transplant
Control
Retransplant
2117
2009
216
108
93.9 92.5 91.3 88.0 83.2
93.8 92.4 91.2 87.9 83.2
93.1 92.4 90.9 87.4 82.2
96.0 94.6 92.4 87.8 82.9
*Kaplan-Meier.
patients; however, this requires more investigation to be confirmed and the possible causes of this difference should be assessed. In summary, a better life quality with acceptable longterm outcomes may be provided by retransplantation. But, we should consider ways to achieve similar results of primary and nonprimary kidney transplantations. REFERENCES 1. Hirata M, Terasaki PI: Renal retransplantation. Clin Transpl xx:419, 1994 2. Stratta RJ, Oh CS, Sollinger HW, et al: Kidney retransplantation in the cyclosporine era. Transplantation 45:40, 1988 3. Mouquet C, Benalia H, Chartier-Kastler E, et al: Renal retransplantation in adults. Comparative prognostic study. Prog Urol 9:239, 1999
4. Hornberger JC, Best JH, Garrison LP Jr: Cost-effectiveness of repeat medical procedures: kidney transplantation as an example. Med Decis Making 17:363, 1997 5. De Meester J, Smits JM, Offner G, et al: Renal retransplantation of children: is a policy ‘first cadaver donor, then live donor’ an acceptable option? Pediatr Transplant 5:179, 2001 6. Delmonico FL, Tolkoff-Rubin N, Auchincloss H Jr, et al: Second renal transplantations. Ethical issues clarified by outcome; outcome enhanced by a reliable crossmatch. Arch Surg 129:354, 1994 7. Howard RJ, Reed AI, Van Der Werf WJ, Hemming AW, et al: What happens to renal transplant recipients who lose their grafts? Am J Kidney Dis 38:31, 2001 8. Etienne T, Goumaz C, Ruedin P, et al: Renal retransplantation in Switzerland: poor HLA matching of first and subsequent allografts does not appear to affect overall graft survival. Transpl Int 5 (Suppl 1) S65, 1992