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Advantages and Disadvantages of Pre-emptive Kidney Transplantation: Results From a Single Transplantation Center
Advantages and Disadvantages of Pre-emptive Kidney Transplantation: Results From a Single Transplantation Center T. Nakamuraa,*, H. Ushigomea, T. Nakaoa, S. Haradaa, K. Koshinoa, T. Suzukib, T. Itoa, S. Noboria, and N. Yoshimuraa,b a Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan; and bDepartment of Organ Interaction Research Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
ABSTRACT Background. There is a growing tendency to perform pre-emptive kidney transplantation (PKT). However, less research has been performed on outcomes of PKT and kidney transplantation (KT) after long-term dialysis (LD). Methods. To elucidate advantages of PKT to KTLD, 96 patients who underwent livingdonor KT at our university from 2000 to 2011 were enrolled for this study: 64 patients in the PKT0 (0 months dialysis) group; 14 patients in the PKT-3 group (less than 3 months dialysis); 18 patients in the LD (dialysis > 120 months) group. All recipients were assessed for patients’ survival, graft survival, urinary tract infection, laboratory data, episodes of acute rejection, cytomegalovirus-related diseases, and other significant infectious diseases which required hospitalization. Results. Although there were no significant differences in 5-year graft survival (93.8% in PKT0, 85.7% in PKT-3, and 83.7% in control), 5-year patient survival is better in the PKT0 group (96.9%) and the PKT-3 group (92.9%) compared to 88.9% in the control group. Urinary tract infection is clearly correlated with the LD group (44.4% in the LD group vs 19.2% in the PKT group) primarily due to atrophic bladder and subsequent vesicoureteral reflux. Slightly higher rates of acute rejection were found in the PKT groups (30.8% vs 26.3%). Conclusion. This study revealed that there are both advantages and disadvantages of PKT. It is clear, therefore, that PKT can be recommended for end-stage renal disease patients provided enough attention is paid to the onset of acute rejection.
T
HERE are a growing number of end-stage renal disease (ESRD) patients on hemodialysis or peritoneal dialysis, which has a negative influence on both individual patients and the government. Recent data revealed that there are almost 300,000 patients on hemodialysis, which is a considerable burden on the government [1]. Although there is no doubt that kidney transplantation (KT) is a superior renal replacement therapy, a chronic shortage of donors hinders us from performing KT in Japan [2]. Despite the current situation, pre-emptive kidney transplantation (PKT) has gained popularity and has been increasing every year to avoid various complications due to hemodialysis as well as reducing medical expenses. It is also true that PKT has better impact on ESRD patients in terms of quality of life and mortality [3,4]. Thus, it has been considered as the best renal replacement therapy for ESRD patients. It is still 0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2014.09.179
626
controversial, however, which component of PKT leads to better outcomes. Therefore, to clarify factors of PKT associated with superior outcomes, we investigated 96 patients who underwent KT at our university hospital, and each differential element was analyzed retrospectively. MATERIALS AND METHODS A total of 96 patients who had undergone living-donor KT at our university hospital, Kyoto Prefectural University of Medicine,
*Address correspondence to Tsukasa Nakamura, MD, Department of Organ Transplantation and General Surgery, Kyoto Prefectural Under University of Medicine, 602-8566, Kajii-cho 465, Kamigyo-ku, Kyoto-prefecture, Japan. E-mail: tsukasa@koto. kpu-m.ac.jp ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 47, 626e629 (2015)
PRE-EMPTIVE KIDNEY TRANSPLANTATION
Fig 1. Immunosuppressive regimens. Abbreviations: DFPP, double filtration plasmapheresis; PE, plasma exchange; CsA, cyclosporine A; Tac, tacrolimus; MMF, mycophenolate mofetil; Mz, mizoribine; PSL, prednisolone. from 2000 to 2011, were retrospectively enrolled. The Ethics Committee approval was obtained from the internal research ethics committee of the Kyoto Prefectural University of Medicine. The patients were divided into the following three groups according to their duration of dialysis: 64 patients in the PKT0 (0 months dialysis) group; 14 patients in the PKT1e3 group (1 to 3 months dialysis); and 18 patients in the long-term dialysis (LD; dialysis > 120 months) group.
Immunosuppressive Drug Regimen Recipients were treated with cyclosporine A (trough level 200 ng/mL during the first week and 150e200 ng/mL 1 week after transplantation) or tacrolimus (trough level 15 ng/mL) and mycophenolate mofetil (25 mg/kg/d) or mizoribine (6 mg/kg/d, given orally twice a day), and prednisolone (PSL; maintenance dose 10 mg/d, after the initial dose reduction). In addition, basiliximab (20 mg/body) was administered on days 0 and 4 as a standard protocol from 2005 (Fig 1). In case of ABO-incompatible KT, rituximab (100e200 mg) was administered on days 14 and 7 with monitoring population of CD19 or 20 positive B cells. Each of the patients gave informed consent. The study was approved by the Institutional Review Board and complied with the Declaration of Helsinki.
Laboratory Data The laboratory data related with renal function (creatinine, estimate glomerular filtration rate [eGFR], proteinuria, and hematocrit) was monitored at 0, 1, 6, 12, 36, and 60 months from transplantation.
Statistical Analysis A log-rank test was applied for comparing Kaplan-Meier survival curves. Means of continuous measures were analyzed by using a Student t-test. Dunnette’s or Tukey’s tests were used for multiple comparisons. All statistical analyses were performed using GraphPad Prism 6 (GraphPad Software, Inc., San Diego, Calif, United States).
RESULTS
Sixty-five male and 31 female KT recipients were enrolled in the study. They were divided as follows: 64 patients in the PKT0 (0 months dialysis) group; 14 patients in the PKT3 group (1e3 months dialysis); and 18 patients in the control (dialysis > 120 months) group. Patient demographic
627
characteristics are summarized in Table 1. A distinct followup period was determined as a 5-year study. Results from the three different groups were compared statistically. Firstly, during the year after KT, only 1 patient of a total 96 recipients had died (in the PKT0 group). Secondly, during the 5-year follow-up period, 5 patients of a 96 recipients had died (2 patients in the PKT0 group; 1 patient in the PKT-3 group; and 2 patients in the LD group). During the follow-up period, the PKT0 and PKT-3 groups indicated slightly preferable outcomes in patient survival compared to the LD group (P ¼ .379; Fig 2). Causes of death are described in Table 1. Importantly, all causes of death (2 patients) in the LD group were related to infectious diseases. Including nonfatal cases, systemic infection determined as requiring hospitalization in KT recipients might be correlated with the LD group (P ¼ .103). Moreover, the total number of cytomegalovirus (CMV) infectious diseases was relatively higher in the LD group with 17.2% in the PKT0 group, 7.1 in the PKT-3 group, and 27.8 in the LD group (P ¼ .301). The 5-year graft survival rates were as follows: 93.8% in the PKT0 group, 85.7% in the PKT-3 group, and 83.3% in the LD group. A total of 9 graft losses were observed during the 5 years after KT (4 recipients in the PKT0 group, 2 recipients in the PKT-3 group, and 3 recipients in the LD group; P ¼ .323). There were no significant differences in graft loss between the Table 1. Demographics of Recipients PKT-0 (n ¼ 64)
PKT-3 (n ¼ 14)
Age at KT (y) 38 17.0 38 10.7 Male (%) 70.30 78.60 Diagnosis (%) Diabetes 4.7 28.6 Glomerular diseases 34.3 21.5 Polycystic 4.7 7.1 Congenital 21.9 7.1 Unknown 28.1 35.7 Other 6.3 0 Donor (%) Parent or child 56.3 57.2 Spouse 31.2 21.4 Cadaver 0 0 Other 12.5 21.4 ABO incompatible (%) 18.8 14.3 1-year survival (%) 98.4 100 5-year survival (%) 96.9 92.9 1-year graft survival (%) 98.4 100 5-year graft survival (%) 93.8 85.7 Cause of death (%) Infection 0 0 Cardiovascular disease 0 0 Cancer 0 100 (1/1) Suicide 50 (1/2) 0 Other 50 (1/2) 0 Acute rejection (%) 29.8 35.7 Urinary tract infection (%) 20.3 14.3 CMV antigenemia (%) 37.5 28.6 CMV infection (%) 17.2 7.1 Systemic infection (%) 12.5 14.3
LD (living-related) (18)
51 10.1 50.00 5.5 66.7 5.5 5.5 11/3 5.5 27.8 61.1 0 11.1 42.1 100 88.9 100 83.3 100 (2/2) 0 0 0 0 26.3 44.4 38.9 27.8 33.3
628
NAKAMURA, USHIGOME, NAKAO ET AL
Fig 2. Patient survival (A) and graft survival (B) in the three distinct groups including the PKT0 group, the PKT-3 group, and the LD group.
three groups. Laboratory parameters of all recipients were compared between the three groups. Transitions of laboratory data (serum creatinine, eGFR, hematocrit, and proteinuria) were not correlated with a particular group. With regard to acute rejection, there was a higher tendency to experience the onset of acute graft rejection in both the PKT0 (29.7%) and PKT-3 (35.7%) groups compared with the LD group (26.3%), although there were not distinct differences in rates of acute rejection (P ¼ .878). Urinary tract infection, determined as bacteria in urine (105 cfu/mL), cystitis, or pyelitis after ureteroneocystostomy was highly associated with the LD group (44.4%). This figure was significantly lower in the PKT0 (20.3%) and PKT-3 (14.3%) groups (P ¼ .0223). DISCUSSION
Although there are various barriers to performing PKT, recently it has gained popularity as one of the renal replacement therapies [5,6]. On the other hand, it is also true that a severe shortage of cadaveric organ donors and subsequent increased number of patients who undergo LD while awaiting transplantation still remains a paramount problem in Japan. Thus, it is of vital importance to elucidate these characteristics and outcomes. First of all, this study revealed that recipients who had experienced LD tended to undergo ABOincompatible KT. However, outcomes of ABO-incompatible KT have significantly improved primarily owing to advanced immunosuppressive regimens [7]. Therefore, these differences would have minimal impact on our results. A retrospective cohort study was conducted to provide insight into characteristic differences between PKT and LD groups’ patient survival, graft survival, acute rejection, urinary tract complication/infection, and severe systemic infection. With regard to comorbidities before KT, generally higher prevalence rates in heart disease, calcification of blood vessels [8], and low-capacity of the bladder were observed in the LD group. It is reasonable to believe that these comorbidities have negative impact on recipients’ outcomes. Practically, these comorbidities before KT are clearly correlated with complications after KT. However, according to our results, it can be argued that patient survival and graft survival in the LD group are slightly lower but barely comparable with PKT groups. This result might be due to contributions of preoperative intensive assessment and postoperative
appropriate care for LD patients. In contrast, unfortunately, it is also true that the rates of infectious complication in the LD group are significantly higher. In terms of post-transplantation urinary tract complications, a prominent difference in urinary tract infection was observed. It can be argued that the bladders of LD patients have changed into severely atrophic bladders primarily due to disuse syndrome. Subsequently, an atrophic bladder triggers various urinary tract infections. To address this issue, the method of ureteroneocystostomy must be considered in terms of its complications. Although there are some variations in ureteroneocystostomy, Politano-Leadbetter re-implants indicated a better outcome in terms of vesicoureteral reflux [9]. Therefore, in case of performing KTLD, Politano-Leadbetter ureteroneocystostomy might be a better option. However, it is also true that performing Politano-Leadbetter in patients with an atrophic bladder might be difficult. Therefore, it seems to be a good surgical strategy to follow the following procedure: 1) Politano-Leadbetter ureteroneocystostomy is recommended for a poor compliance bladder; 2) For cases in which a severe atrophic bladder is an obstacle to performing the above procedure, it is better to use the Lich-Gregoire technique with or without temporal external urine drainage, depending on each case. Furthermore, an increased frequency of systemic infectious diseases and CMV-related diseases in the LD group was observed, and finally these infections can lead to fatality in transplant recipients. Although our study contains a limited number of deceased recipients, the main causes of death were due to infectious diseases in the LD group. Given the fact that CMV pneumonia tends to cause severe deterioration of patients’ condition and can be fatal, it is important to minimize calcineurin inhibitor concentration in serum to prevent overimmunosuppression. Simultaneously, prevention of CMV should be considered especially for patients in the LD group because a preventive therapy produced certain efficiency [10]. In contrast, LD seemed to be correlated with a favorable outcome in terms of acute rejection (a slightly lower incidence was observed). However, it can be considered that this result reflected the immunocompromised status of LD patients. Although continuous uremia also has a negative impact on immunity [11], the effect of LD on immune reaction cannot be ignored and might be much more severe. Taken together, it is reasonable to believe that to address infectious complication leads to better immunosuppressive
PRE-EMPTIVE KIDNEY TRANSPLANTATION
therapy; consequently, it might result in a better patient survival rate in organ transplantation patients. CONCLUSIONS
This study showed that PKT had favorable outcomes of survival, systemic infection, and urinary tract infection, whereas a higher tendency toward acute rejection episodes was observed. For LD patients, there must be more preoperative consideration concerning deterioration of cardiovascular function and bladder compliance due to LD. Although these results would not give full support for performing PKT, generally these components bring better outcomes in PKT recipients, providing that a careful followup of the onset of acute rejection is conducted. ACKNOWLEDGMENTS Tsukasa Nakamura thanks Lyn Child, RN, Holborn Church, Leeds, United Kingdom, for her English editing and proofreading.
REFERENCES [1] Yamagata K, Yagisawa T, Nakai S, Nakayama M, Imai E, Hattori M, et al. Prevalence and incidence of chronic kidney disease stage G5 in Japan. Clin Exp Nephrol 2015;19(1):54e64. [2] Yoshimura N, Okajima H, Ushigome H, Sakamoto S, Fujiki M, Okamoto M. Current status of organ transplantation in Japan and worldwide. Surg Today 2010;40(6):514e25.
629 [3] Meier-Kriesche HU, Port FK, Ojo AO, Rudich SM, Hanson JA, Cibrik DM, et al. Effect of waiting time on renal transplant outcome. Kidney Int 2000;58(3):1311e7. [4] 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;344(10): 726e31. [5] Knight RJ, Teeter LD, Graviss EA, Patel SJ, DeVos JM, Moore LW, et al. Barriers to preemptive renal transplantation: a single center questionnaire study. Transplantation 2015;99(3):576e9. [6] Kallab S, Bassil N, Esposito L, Cardeau-Desangles I, Rostaing L, Kamar N. Indications for and barriers to preemptive kidney transplantation: a review. Transplant Proc 2010;42(3): 782e4. [7] Kaihara S, Okamoto M, Akioka K, Ogino S, Higuchi A, Kadotani Y, et al. Improved graft survival in ABO-incompatible living donor kidney transplantation. Transplant Proc 2005;37(4): 1804e5. [8] Goldsmith DJ, Covic A, Sambrook PA, Ackrill P. Vascular calcification in long-term haemodialysis patients in a single unit: a retrospective analysis. Nephron 1997;77(1):37e43. [9] Whang M, Yballe M, Geffner S, Fletcher HS, Palekar S, Mulgaonkar S. Urologic complications in more than 2500 kidney transplantations performed at the Saint Barnabas healthcare system. Transplant Proc 2011;43(5):1619e22. [10] Meije Y, Fortun J, Len O, Aguado JM, Moreno A, Cisneros JM, et al. Prevention strategies for cytomegalovirus disease and long-term outcomes in the high-risk transplant patient (Dþ/R-): experience from the RESITRA-REIPI cohort. Transpl Infect Dis 2014;16(3):387e96. [11] Girndt M, Sester M, Sester U, Kaul H, Kohler H. Molecular aspects of T- and B-cell function in uremia. Kidney Int Suppl 2001;78:S206e11.
ABSTRACT Background. There is a growing tendency to perform pre-emptive kidney transplantation (PKT). However, less research has been performed on outcomes of PKT and kidney transplantation (KT) after long-term dialysis (LD). Methods. To elucidate advantages of PKT to KTLD, 96 patients who underwent livingdonor KT at our university from 2000 to 2011 were enrolled for this study: 64 patients in the PKT0 (0 months dialysis) group; 14 patients in the PKT-3 group (less than 3 months dialysis); 18 patients in the LD (dialysis > 120 months) group. All recipients were assessed for patients’ survival, graft survival, urinary tract infection, laboratory data, episodes of acute rejection, cytomegalovirus-related diseases, and other significant infectious diseases which required hospitalization. Results. Although there were no significant differences in 5-year graft survival (93.8% in PKT0, 85.7% in PKT-3, and 83.7% in control), 5-year patient survival is better in the PKT0 group (96.9%) and the PKT-3 group (92.9%) compared to 88.9% in the control group. Urinary tract infection is clearly correlated with the LD group (44.4% in the LD group vs 19.2% in the PKT group) primarily due to atrophic bladder and subsequent vesicoureteral reflux. Slightly higher rates of acute rejection were found in the PKT groups (30.8% vs 26.3%). Conclusion. This study revealed that there are both advantages and disadvantages of PKT. It is clear, therefore, that PKT can be recommended for end-stage renal disease patients provided enough attention is paid to the onset of acute rejection.
T
HERE are a growing number of end-stage renal disease (ESRD) patients on hemodialysis or peritoneal dialysis, which has a negative influence on both individual patients and the government. Recent data revealed that there are almost 300,000 patients on hemodialysis, which is a considerable burden on the government [1]. Although there is no doubt that kidney transplantation (KT) is a superior renal replacement therapy, a chronic shortage of donors hinders us from performing KT in Japan [2]. Despite the current situation, pre-emptive kidney transplantation (PKT) has gained popularity and has been increasing every year to avoid various complications due to hemodialysis as well as reducing medical expenses. It is also true that PKT has better impact on ESRD patients in terms of quality of life and mortality [3,4]. Thus, it has been considered as the best renal replacement therapy for ESRD patients. It is still 0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2014.09.179
626
controversial, however, which component of PKT leads to better outcomes. Therefore, to clarify factors of PKT associated with superior outcomes, we investigated 96 patients who underwent KT at our university hospital, and each differential element was analyzed retrospectively. MATERIALS AND METHODS A total of 96 patients who had undergone living-donor KT at our university hospital, Kyoto Prefectural University of Medicine,
*Address correspondence to Tsukasa Nakamura, MD, Department of Organ Transplantation and General Surgery, Kyoto Prefectural Under University of Medicine, 602-8566, Kajii-cho 465, Kamigyo-ku, Kyoto-prefecture, Japan. E-mail: tsukasa@koto. kpu-m.ac.jp ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 47, 626e629 (2015)
PRE-EMPTIVE KIDNEY TRANSPLANTATION
Fig 1. Immunosuppressive regimens. Abbreviations: DFPP, double filtration plasmapheresis; PE, plasma exchange; CsA, cyclosporine A; Tac, tacrolimus; MMF, mycophenolate mofetil; Mz, mizoribine; PSL, prednisolone. from 2000 to 2011, were retrospectively enrolled. The Ethics Committee approval was obtained from the internal research ethics committee of the Kyoto Prefectural University of Medicine. The patients were divided into the following three groups according to their duration of dialysis: 64 patients in the PKT0 (0 months dialysis) group; 14 patients in the PKT1e3 group (1 to 3 months dialysis); and 18 patients in the long-term dialysis (LD; dialysis > 120 months) group.
Immunosuppressive Drug Regimen Recipients were treated with cyclosporine A (trough level 200 ng/mL during the first week and 150e200 ng/mL 1 week after transplantation) or tacrolimus (trough level 15 ng/mL) and mycophenolate mofetil (25 mg/kg/d) or mizoribine (6 mg/kg/d, given orally twice a day), and prednisolone (PSL; maintenance dose 10 mg/d, after the initial dose reduction). In addition, basiliximab (20 mg/body) was administered on days 0 and 4 as a standard protocol from 2005 (Fig 1). In case of ABO-incompatible KT, rituximab (100e200 mg) was administered on days 14 and 7 with monitoring population of CD19 or 20 positive B cells. Each of the patients gave informed consent. The study was approved by the Institutional Review Board and complied with the Declaration of Helsinki.
Laboratory Data The laboratory data related with renal function (creatinine, estimate glomerular filtration rate [eGFR], proteinuria, and hematocrit) was monitored at 0, 1, 6, 12, 36, and 60 months from transplantation.
Statistical Analysis A log-rank test was applied for comparing Kaplan-Meier survival curves. Means of continuous measures were analyzed by using a Student t-test. Dunnette’s or Tukey’s tests were used for multiple comparisons. All statistical analyses were performed using GraphPad Prism 6 (GraphPad Software, Inc., San Diego, Calif, United States).
RESULTS
Sixty-five male and 31 female KT recipients were enrolled in the study. They were divided as follows: 64 patients in the PKT0 (0 months dialysis) group; 14 patients in the PKT3 group (1e3 months dialysis); and 18 patients in the control (dialysis > 120 months) group. Patient demographic
627
characteristics are summarized in Table 1. A distinct followup period was determined as a 5-year study. Results from the three different groups were compared statistically. Firstly, during the year after KT, only 1 patient of a total 96 recipients had died (in the PKT0 group). Secondly, during the 5-year follow-up period, 5 patients of a 96 recipients had died (2 patients in the PKT0 group; 1 patient in the PKT-3 group; and 2 patients in the LD group). During the follow-up period, the PKT0 and PKT-3 groups indicated slightly preferable outcomes in patient survival compared to the LD group (P ¼ .379; Fig 2). Causes of death are described in Table 1. Importantly, all causes of death (2 patients) in the LD group were related to infectious diseases. Including nonfatal cases, systemic infection determined as requiring hospitalization in KT recipients might be correlated with the LD group (P ¼ .103). Moreover, the total number of cytomegalovirus (CMV) infectious diseases was relatively higher in the LD group with 17.2% in the PKT0 group, 7.1 in the PKT-3 group, and 27.8 in the LD group (P ¼ .301). The 5-year graft survival rates were as follows: 93.8% in the PKT0 group, 85.7% in the PKT-3 group, and 83.3% in the LD group. A total of 9 graft losses were observed during the 5 years after KT (4 recipients in the PKT0 group, 2 recipients in the PKT-3 group, and 3 recipients in the LD group; P ¼ .323). There were no significant differences in graft loss between the Table 1. Demographics of Recipients PKT-0 (n ¼ 64)
PKT-3 (n ¼ 14)
Age at KT (y) 38 17.0 38 10.7 Male (%) 70.30 78.60 Diagnosis (%) Diabetes 4.7 28.6 Glomerular diseases 34.3 21.5 Polycystic 4.7 7.1 Congenital 21.9 7.1 Unknown 28.1 35.7 Other 6.3 0 Donor (%) Parent or child 56.3 57.2 Spouse 31.2 21.4 Cadaver 0 0 Other 12.5 21.4 ABO incompatible (%) 18.8 14.3 1-year survival (%) 98.4 100 5-year survival (%) 96.9 92.9 1-year graft survival (%) 98.4 100 5-year graft survival (%) 93.8 85.7 Cause of death (%) Infection 0 0 Cardiovascular disease 0 0 Cancer 0 100 (1/1) Suicide 50 (1/2) 0 Other 50 (1/2) 0 Acute rejection (%) 29.8 35.7 Urinary tract infection (%) 20.3 14.3 CMV antigenemia (%) 37.5 28.6 CMV infection (%) 17.2 7.1 Systemic infection (%) 12.5 14.3
LD (living-related) (18)
51 10.1 50.00 5.5 66.7 5.5 5.5 11/3 5.5 27.8 61.1 0 11.1 42.1 100 88.9 100 83.3 100 (2/2) 0 0 0 0 26.3 44.4 38.9 27.8 33.3
628
NAKAMURA, USHIGOME, NAKAO ET AL
Fig 2. Patient survival (A) and graft survival (B) in the three distinct groups including the PKT0 group, the PKT-3 group, and the LD group.
three groups. Laboratory parameters of all recipients were compared between the three groups. Transitions of laboratory data (serum creatinine, eGFR, hematocrit, and proteinuria) were not correlated with a particular group. With regard to acute rejection, there was a higher tendency to experience the onset of acute graft rejection in both the PKT0 (29.7%) and PKT-3 (35.7%) groups compared with the LD group (26.3%), although there were not distinct differences in rates of acute rejection (P ¼ .878). Urinary tract infection, determined as bacteria in urine (105 cfu/mL), cystitis, or pyelitis after ureteroneocystostomy was highly associated with the LD group (44.4%). This figure was significantly lower in the PKT0 (20.3%) and PKT-3 (14.3%) groups (P ¼ .0223). DISCUSSION
Although there are various barriers to performing PKT, recently it has gained popularity as one of the renal replacement therapies [5,6]. On the other hand, it is also true that a severe shortage of cadaveric organ donors and subsequent increased number of patients who undergo LD while awaiting transplantation still remains a paramount problem in Japan. Thus, it is of vital importance to elucidate these characteristics and outcomes. First of all, this study revealed that recipients who had experienced LD tended to undergo ABOincompatible KT. However, outcomes of ABO-incompatible KT have significantly improved primarily owing to advanced immunosuppressive regimens [7]. Therefore, these differences would have minimal impact on our results. A retrospective cohort study was conducted to provide insight into characteristic differences between PKT and LD groups’ patient survival, graft survival, acute rejection, urinary tract complication/infection, and severe systemic infection. With regard to comorbidities before KT, generally higher prevalence rates in heart disease, calcification of blood vessels [8], and low-capacity of the bladder were observed in the LD group. It is reasonable to believe that these comorbidities have negative impact on recipients’ outcomes. Practically, these comorbidities before KT are clearly correlated with complications after KT. However, according to our results, it can be argued that patient survival and graft survival in the LD group are slightly lower but barely comparable with PKT groups. This result might be due to contributions of preoperative intensive assessment and postoperative
appropriate care for LD patients. In contrast, unfortunately, it is also true that the rates of infectious complication in the LD group are significantly higher. In terms of post-transplantation urinary tract complications, a prominent difference in urinary tract infection was observed. It can be argued that the bladders of LD patients have changed into severely atrophic bladders primarily due to disuse syndrome. Subsequently, an atrophic bladder triggers various urinary tract infections. To address this issue, the method of ureteroneocystostomy must be considered in terms of its complications. Although there are some variations in ureteroneocystostomy, Politano-Leadbetter re-implants indicated a better outcome in terms of vesicoureteral reflux [9]. Therefore, in case of performing KTLD, Politano-Leadbetter ureteroneocystostomy might be a better option. However, it is also true that performing Politano-Leadbetter in patients with an atrophic bladder might be difficult. Therefore, it seems to be a good surgical strategy to follow the following procedure: 1) Politano-Leadbetter ureteroneocystostomy is recommended for a poor compliance bladder; 2) For cases in which a severe atrophic bladder is an obstacle to performing the above procedure, it is better to use the Lich-Gregoire technique with or without temporal external urine drainage, depending on each case. Furthermore, an increased frequency of systemic infectious diseases and CMV-related diseases in the LD group was observed, and finally these infections can lead to fatality in transplant recipients. Although our study contains a limited number of deceased recipients, the main causes of death were due to infectious diseases in the LD group. Given the fact that CMV pneumonia tends to cause severe deterioration of patients’ condition and can be fatal, it is important to minimize calcineurin inhibitor concentration in serum to prevent overimmunosuppression. Simultaneously, prevention of CMV should be considered especially for patients in the LD group because a preventive therapy produced certain efficiency [10]. In contrast, LD seemed to be correlated with a favorable outcome in terms of acute rejection (a slightly lower incidence was observed). However, it can be considered that this result reflected the immunocompromised status of LD patients. Although continuous uremia also has a negative impact on immunity [11], the effect of LD on immune reaction cannot be ignored and might be much more severe. Taken together, it is reasonable to believe that to address infectious complication leads to better immunosuppressive
PRE-EMPTIVE KIDNEY TRANSPLANTATION
therapy; consequently, it might result in a better patient survival rate in organ transplantation patients. CONCLUSIONS
This study showed that PKT had favorable outcomes of survival, systemic infection, and urinary tract infection, whereas a higher tendency toward acute rejection episodes was observed. For LD patients, there must be more preoperative consideration concerning deterioration of cardiovascular function and bladder compliance due to LD. Although these results would not give full support for performing PKT, generally these components bring better outcomes in PKT recipients, providing that a careful followup of the onset of acute rejection is conducted. ACKNOWLEDGMENTS Tsukasa Nakamura thanks Lyn Child, RN, Holborn Church, Leeds, United Kingdom, for her English editing and proofreading.
REFERENCES [1] Yamagata K, Yagisawa T, Nakai S, Nakayama M, Imai E, Hattori M, et al. Prevalence and incidence of chronic kidney disease stage G5 in Japan. Clin Exp Nephrol 2015;19(1):54e64. [2] Yoshimura N, Okajima H, Ushigome H, Sakamoto S, Fujiki M, Okamoto M. Current status of organ transplantation in Japan and worldwide. Surg Today 2010;40(6):514e25.
629 [3] Meier-Kriesche HU, Port FK, Ojo AO, Rudich SM, Hanson JA, Cibrik DM, et al. Effect of waiting time on renal transplant outcome. Kidney Int 2000;58(3):1311e7. [4] 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;344(10): 726e31. [5] Knight RJ, Teeter LD, Graviss EA, Patel SJ, DeVos JM, Moore LW, et al. Barriers to preemptive renal transplantation: a single center questionnaire study. Transplantation 2015;99(3):576e9. [6] Kallab S, Bassil N, Esposito L, Cardeau-Desangles I, Rostaing L, Kamar N. Indications for and barriers to preemptive kidney transplantation: a review. Transplant Proc 2010;42(3): 782e4. [7] Kaihara S, Okamoto M, Akioka K, Ogino S, Higuchi A, Kadotani Y, et al. Improved graft survival in ABO-incompatible living donor kidney transplantation. Transplant Proc 2005;37(4): 1804e5. [8] Goldsmith DJ, Covic A, Sambrook PA, Ackrill P. Vascular calcification in long-term haemodialysis patients in a single unit: a retrospective analysis. Nephron 1997;77(1):37e43. [9] Whang M, Yballe M, Geffner S, Fletcher HS, Palekar S, Mulgaonkar S. Urologic complications in more than 2500 kidney transplantations performed at the Saint Barnabas healthcare system. Transplant Proc 2011;43(5):1619e22. [10] Meije Y, Fortun J, Len O, Aguado JM, Moreno A, Cisneros JM, et al. Prevention strategies for cytomegalovirus disease and long-term outcomes in the high-risk transplant patient (Dþ/R-): experience from the RESITRA-REIPI cohort. Transpl Infect Dis 2014;16(3):387e96. [11] Girndt M, Sester M, Sester U, Kaul H, Kohler H. Molecular aspects of T- and B-cell function in uremia. Kidney Int Suppl 2001;78:S206e11.