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Pairs of Kidneys Transplanted From the Same Donor: Is There Any Difference?
Pairs of Kidneys Transplanted From the Same Donor: Is There Any Difference? C. García-Sánchez, M. Fajardo-Paneque, E. León-Dueñas, J. Martínez-Rodríguez, J.S. Leal-Arenas, I. Osmán-García, and R.A. Medina-López ABSTRACT Objectives. The aim of this study was to compare the evolution of the first kidney in relation to the second kidney transplanted from the same donor, focusing on the impact that a longer cold ischemia time may have as an independent variable. Material and Methods. The study included 44 pairs of kidneys transplanted from the same donor between February 2008 and October 2010, divided into Groups 1 and 2 according to the graft placement order. The variables analyzed were age, sex, comorbidities, number of transfusions, length of hospital stay, maximum peak PRA, immunologic incompatibility, ischemia time, delayed graft function (DGF), presence of rejection, creatinine clearance at first week, at 3 months and at 1 year, and vascular and tract complications in each group. Results. The mean cold ischemia time was 15.6 hours in Group 1 and 20.1 hours in Group 2 (P ⬍ .001). The average recipient age was 52.79 years in Group 1 and 54.52 years in Group 2, with an equal sex ratio in the two groups; an average of 2.06 PRC were transfused prior to transplantation in Group 1 and 0.93 PRC in Group 2; the average length of stay was similar in the two groups. Major DR incompatibility was only found in Group 2 (P ⬍ .03). Creatinine clearance at first week, DGF and acute rejection showed worse results in Group 2, but these differences were not significant. Vascular complications were present in 4.5% and 2.3% of Groups 1 and 2, respectively, and tract complications were 6.8% and 11.4%. Conclusions. A greater tendency to DGF, early rejection and tract complications were found in the group with longer ischemia time, although the difference was not statistically significant. Larger series will be necessary to confirm our results. IDNEY transplantation improves survival of patients with end-stage renal failure on hemodialysis.1 Nevertheless, the technique is not free from medical and surgical complications that may ultimately lead to graft loss and the need for reintroduction into the dialysis program. Many risk factors have been studied, related to both graft and patient function such as donor and recipient age, sex, etiology of renal failure, ischemia time, and HLA incompatibility.2,3 Cold ischemia time is one of the main modifiable risk factors. The aim of this study was to analyze the relationship between ischemia time and the transplanted kidney function as well as the surgical technique and medical complications, minimizing the differences in recipient-dependent risk factors by studying pairs of kidneys transplanted from the same donor.
K
MATERIALS AND METHODS We studied retrospectively 44 pairs of transplants (88 recipients) from the same donor between February 2008 and October 2010 at our center. Implantation of the “twin kidneys” in each recipient was performed consecutively by the same surgical team. The 88 patients were divided into Groups 1 and 2 according to the graft placement order. The variables analyzed were donor and recipient age, number of transfusions prior to transplantation, length of hospital stay, maxFrom the Hospital Universitario Virgen del Rocio, Sevilla, Spain. Address correspondence to Cristina García Sánchez, Hospital Universitario Virgen del Rocío Avenida Manuel Siurot sn 41013 Sevilla. E-mail: [email protected]
© 2012 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter http://dx.doi.org/10.1016/j.transproceed.2012.07.089
Transplantation Proceedings, 44, 2057–2059 (2012)
2057
2058
SÁNCHEZ, PANEQUE, DUEÑAS ET AL
imum peak reactive antibody panel (% PRA), immunological HLA incompatibilities in A, B and DR loci, cold ischemia time, initial delayed graft function (DGF) considered to be the requirement for dialysis during the first week after transplantation, creatinine clearance at first week, at 3 months and one year after transplantation, vascular and tract complications and the presence or absence of rejection. The descriptive and comparative statistical analysis between the groups was done with SPSS version 17.0.
RESULTS
The descriptive analysis of the two groups confirmed that they were homogeneous. No differences were found in age or in male/female ratio, or in the average number of transfusions before transplantation or the mean length of hospital stay (Table 1). The mean cold ischemia times were 15.6 and 20.1 hours in Groups 1 and 2, respectively (P ⬍ .001). In the comparative study of incompatibilities, only a greater DR incompatibility was found in Group 2 (P ⬍ .03) (Table 2). Worse results for creatinine clearance at first week, DGF and acute rejection were found in Group 2, but the differences were not significant (Table 3). The presence of vascular complications was 4.5% and 2.3% in Groups 1 and 2, respectively. The first percentage corresponded to two patients who suffered venous thrombosis in the early postoperative period and therefore required transplantectomy. The 2.3% corresponds to a single case of graft atheroembolism, where transplantectomy was also required. Tract complications in Group 1 occurred in 6.8% of cases: two cases of urinary leaks in the ureterovesical reimplantation anastomosis occurred after removal of the ureteral tutor on the 10th day (in both cases ureteral reimplantation was performed again); and one case of stenosis a month after the transplant that was satisfactorily resolved endoscopically by interventional radiologists at our center. In Group 2, tract complications occurred in 4 patients (11.4%): 2 stenosis and 2 urinary leaks. In this group, one of the cases of stenosis was at the proximal ureter. Endoscopic treatment was not possible due to the stenotic ureter length, so a uretero-ureteral anastomosis to the native ureter was performed. One of the cases of a leak was at the ureterovesical anastomosis and the other was due to ureteral necrosis, requiring the use of the native tract to resolve this complication. DISCUSSION
In recent years, different working groups have tried to clarify the impact that cold ischemia time and ischemia-
Table 2. Mean Incompatibilities in Groups 1 and 2 Variable
Group 1
Group 2
Incompatibility A Incompatibility B Incompatibility DR Percent max PRA
1.70 1.48 0.89 0.17
1.64 1.61 1.25 0.07
reperfusion phenomena may have on acute rejection, graft function and survival.4 –5 Although it has been assumed that ischemia time negatively affects the function and survival of the transplanted kidney, not all studies were able to confirm the long-term differences. Ischemia time is not related as a continuous variable to graft survival, and several studies have described a cutoff between 12 and 18 hours of ischemia time, after which survival decreases significantly.4 There is also a worse initial function (first week after transplantation) in those kidneys implanted with a longer ischemia time, although the medium to long-term functional outcome of grafts transplanted with longer ischemia times are similar to those implanted with fewer hours of ischemia.4,6 – 8 By obviating donor-dependent factors and studying just pairs of transplanted kidneys we were able to relate independently ischemia time with graft function and complications after transplantation. Our results suggest a greater tendency to DGF, acute failure and worse initial creatinine clearance in the Group 2 patients, whose kidneys were transplanted in second place. Although not statistically significant, these results are consistent with a similar study conducted by Reguiro et al8 who analyzed 278 pairs of kidneys from the same donor and also found worse initial results (not significant) in patients with the second-placed transplanted kidneys, reaching homogenized functionality over time in both groups. However, some studies have demonstrated a direct detrimental effect between DGF and graft survival.8 –12 With regards to urinary tract and vascular complications, we found no significant differences between the two groups. In the group with a longer ischemia time, the percentage of tract problems was higher. However, we have found no studies that relate the ischemia time to these complications and that could support our results. Possible tract complications have only been associated with tissue ischemia due to incorrect kidney removal or, when located in the bladder, caused by a deficient suture in defunctionalized bladders.8 Our two study groups were homogeneous, except for graft ischemia time before implantation. We tried to demonstrate possible complications and functional differences
Table 1. Characteristics of the Two Groups Variable
Age Female Male Transfusions Hospital stay
Group 1
52.79 50% 50% 2.06 16.36
Table 3. Means of Creatinine
Group 2
54.52 34.1% 65.9% 0.93 16.35
Variable
Cr Cr Cr Cr
CI first week Cl 3 months Cl 6 months Cl 12 months
Group 1
Group 2
36.65 68.83 76 85.60
28.14 67.63 76.83 82.58
PAIRS OF KIDNEYS TRANSPLANTED
but obtained practically similar results in both groups (although there was a tendency to a worse DGF and acute rejection in the second group). Even though the ischemia times were significantly different between the two groups (the means were 15.6 and 20.1 hours in Groups 1 and 2, respectively), both were very close to the interval (12–18h) suggested in different studies as a cutoff for the presence of differences in functional outcomes. In our series there was a greater tendency to DGF and early rejection in the group with a longer ischemia time, although the difference was not significant. Larger series will be necessary to confirm our results. REFERENCES 1. Wolfe RA, Ashby VB, Milford EL, et al: Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 341:1725, 1999 2. Light JA, Gage F, Kowalski AE, et al: Immediate function and cost comparison between static and pulsatile preservation in kidney recipients. Clin Transplant. 10:233, 1996 3. Cho YW, Cecka JM: Cadaver-donor renal retransplants. Clin Transpl: 469, 1993
2059 4. Barba J, Zudaire JJ, Robles JE, et al: Is there a safe cold ischemia time interval for the renal graft? Actas Urol Esp 35:475, 2011 5. Cicciarelli J, Iwaki Y, Mendez R, et al: Effects of cold ischemia time on cadaver renal allografts. Transplant Proc 25:1543, 1993 6. Kyllönen LE, Salmela KT, Eklund BH, et al: Long-term results of 1047 cadaveric kidney transplantations with special emphasis on initial graft function and rejection. Transpl Int 13:122, 2000 7. Mikhalski D, Wissing KM, Ghisdal L, et al: Cold ischemia is a major determinant of acute rejection and renal graft survival in the modern era of immunosuppression. Transplantation. 85(Suppl)S3, 2008 8. Regueiro López RC, Leva Vallejo M, Prieto Castro R, et al: Paired kidneys in transplant. Actas Urol Esp 33:182, 2009 9. Schneider A, Toledo-Pereyra LH, Zeichner WD, et al: Effect of dopamine and pitressin on kidneys procured and harvested for transplantation. Transplantation 36:110, 1983 10. Terasaki PI, Cecka JM, Gjertson DW, et al: A ten-year prediction for kidney transplant survival. Clin Transpl 501, 1992 11. Jang HJ, Kim SC, Kim SK, Han DJ: Paired kidneys as a study model for the analysis of factors affecting cadaveric renal allograft survival. Transplant Proc 30:3669, 1998 12. Marcén R, Orofino L, Pascual J, et al: Delayed graft function does not reduce the survival of renal transplant allografts. Transplantation 66:461, 1998
K
MATERIALS AND METHODS We studied retrospectively 44 pairs of transplants (88 recipients) from the same donor between February 2008 and October 2010 at our center. Implantation of the “twin kidneys” in each recipient was performed consecutively by the same surgical team. The 88 patients were divided into Groups 1 and 2 according to the graft placement order. The variables analyzed were donor and recipient age, number of transfusions prior to transplantation, length of hospital stay, maxFrom the Hospital Universitario Virgen del Rocio, Sevilla, Spain. Address correspondence to Cristina García Sánchez, Hospital Universitario Virgen del Rocío Avenida Manuel Siurot sn 41013 Sevilla. E-mail: [email protected]
© 2012 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter http://dx.doi.org/10.1016/j.transproceed.2012.07.089
Transplantation Proceedings, 44, 2057–2059 (2012)
2057
2058
SÁNCHEZ, PANEQUE, DUEÑAS ET AL
imum peak reactive antibody panel (% PRA), immunological HLA incompatibilities in A, B and DR loci, cold ischemia time, initial delayed graft function (DGF) considered to be the requirement for dialysis during the first week after transplantation, creatinine clearance at first week, at 3 months and one year after transplantation, vascular and tract complications and the presence or absence of rejection. The descriptive and comparative statistical analysis between the groups was done with SPSS version 17.0.
RESULTS
The descriptive analysis of the two groups confirmed that they were homogeneous. No differences were found in age or in male/female ratio, or in the average number of transfusions before transplantation or the mean length of hospital stay (Table 1). The mean cold ischemia times were 15.6 and 20.1 hours in Groups 1 and 2, respectively (P ⬍ .001). In the comparative study of incompatibilities, only a greater DR incompatibility was found in Group 2 (P ⬍ .03) (Table 2). Worse results for creatinine clearance at first week, DGF and acute rejection were found in Group 2, but the differences were not significant (Table 3). The presence of vascular complications was 4.5% and 2.3% in Groups 1 and 2, respectively. The first percentage corresponded to two patients who suffered venous thrombosis in the early postoperative period and therefore required transplantectomy. The 2.3% corresponds to a single case of graft atheroembolism, where transplantectomy was also required. Tract complications in Group 1 occurred in 6.8% of cases: two cases of urinary leaks in the ureterovesical reimplantation anastomosis occurred after removal of the ureteral tutor on the 10th day (in both cases ureteral reimplantation was performed again); and one case of stenosis a month after the transplant that was satisfactorily resolved endoscopically by interventional radiologists at our center. In Group 2, tract complications occurred in 4 patients (11.4%): 2 stenosis and 2 urinary leaks. In this group, one of the cases of stenosis was at the proximal ureter. Endoscopic treatment was not possible due to the stenotic ureter length, so a uretero-ureteral anastomosis to the native ureter was performed. One of the cases of a leak was at the ureterovesical anastomosis and the other was due to ureteral necrosis, requiring the use of the native tract to resolve this complication. DISCUSSION
In recent years, different working groups have tried to clarify the impact that cold ischemia time and ischemia-
Table 2. Mean Incompatibilities in Groups 1 and 2 Variable
Group 1
Group 2
Incompatibility A Incompatibility B Incompatibility DR Percent max PRA
1.70 1.48 0.89 0.17
1.64 1.61 1.25 0.07
reperfusion phenomena may have on acute rejection, graft function and survival.4 –5 Although it has been assumed that ischemia time negatively affects the function and survival of the transplanted kidney, not all studies were able to confirm the long-term differences. Ischemia time is not related as a continuous variable to graft survival, and several studies have described a cutoff between 12 and 18 hours of ischemia time, after which survival decreases significantly.4 There is also a worse initial function (first week after transplantation) in those kidneys implanted with a longer ischemia time, although the medium to long-term functional outcome of grafts transplanted with longer ischemia times are similar to those implanted with fewer hours of ischemia.4,6 – 8 By obviating donor-dependent factors and studying just pairs of transplanted kidneys we were able to relate independently ischemia time with graft function and complications after transplantation. Our results suggest a greater tendency to DGF, acute failure and worse initial creatinine clearance in the Group 2 patients, whose kidneys were transplanted in second place. Although not statistically significant, these results are consistent with a similar study conducted by Reguiro et al8 who analyzed 278 pairs of kidneys from the same donor and also found worse initial results (not significant) in patients with the second-placed transplanted kidneys, reaching homogenized functionality over time in both groups. However, some studies have demonstrated a direct detrimental effect between DGF and graft survival.8 –12 With regards to urinary tract and vascular complications, we found no significant differences between the two groups. In the group with a longer ischemia time, the percentage of tract problems was higher. However, we have found no studies that relate the ischemia time to these complications and that could support our results. Possible tract complications have only been associated with tissue ischemia due to incorrect kidney removal or, when located in the bladder, caused by a deficient suture in defunctionalized bladders.8 Our two study groups were homogeneous, except for graft ischemia time before implantation. We tried to demonstrate possible complications and functional differences
Table 1. Characteristics of the Two Groups Variable
Age Female Male Transfusions Hospital stay
Group 1
52.79 50% 50% 2.06 16.36
Table 3. Means of Creatinine
Group 2
54.52 34.1% 65.9% 0.93 16.35
Variable
Cr Cr Cr Cr
CI first week Cl 3 months Cl 6 months Cl 12 months
Group 1
Group 2
36.65 68.83 76 85.60
28.14 67.63 76.83 82.58
PAIRS OF KIDNEYS TRANSPLANTED
but obtained practically similar results in both groups (although there was a tendency to a worse DGF and acute rejection in the second group). Even though the ischemia times were significantly different between the two groups (the means were 15.6 and 20.1 hours in Groups 1 and 2, respectively), both were very close to the interval (12–18h) suggested in different studies as a cutoff for the presence of differences in functional outcomes. In our series there was a greater tendency to DGF and early rejection in the group with a longer ischemia time, although the difference was not significant. Larger series will be necessary to confirm our results. REFERENCES 1. Wolfe RA, Ashby VB, Milford EL, et al: Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 341:1725, 1999 2. Light JA, Gage F, Kowalski AE, et al: Immediate function and cost comparison between static and pulsatile preservation in kidney recipients. Clin Transplant. 10:233, 1996 3. Cho YW, Cecka JM: Cadaver-donor renal retransplants. Clin Transpl: 469, 1993
2059 4. Barba J, Zudaire JJ, Robles JE, et al: Is there a safe cold ischemia time interval for the renal graft? Actas Urol Esp 35:475, 2011 5. Cicciarelli J, Iwaki Y, Mendez R, et al: Effects of cold ischemia time on cadaver renal allografts. Transplant Proc 25:1543, 1993 6. Kyllönen LE, Salmela KT, Eklund BH, et al: Long-term results of 1047 cadaveric kidney transplantations with special emphasis on initial graft function and rejection. Transpl Int 13:122, 2000 7. Mikhalski D, Wissing KM, Ghisdal L, et al: Cold ischemia is a major determinant of acute rejection and renal graft survival in the modern era of immunosuppression. Transplantation. 85(Suppl)S3, 2008 8. Regueiro López RC, Leva Vallejo M, Prieto Castro R, et al: Paired kidneys in transplant. Actas Urol Esp 33:182, 2009 9. Schneider A, Toledo-Pereyra LH, Zeichner WD, et al: Effect of dopamine and pitressin on kidneys procured and harvested for transplantation. Transplantation 36:110, 1983 10. Terasaki PI, Cecka JM, Gjertson DW, et al: A ten-year prediction for kidney transplant survival. Clin Transpl 501, 1992 11. Jang HJ, Kim SC, Kim SK, Han DJ: Paired kidneys as a study model for the analysis of factors affecting cadaveric renal allograft survival. Transplant Proc 30:3669, 1998 12. Marcén R, Orofino L, Pascual J, et al: Delayed graft function does not reduce the survival of renal transplant allografts. Transplantation 66:461, 1998