Renal Transplantation Using Kidneys Procured From Elderly Donors Older Than 70 Years A. Jozwika, P. Domagalaa,*, R. Kieszeka, M. Wszolaa, M. Serwanska-Swieteka, E. Karpetaa, L. Gorskia, M. Bieniasza, M. Jonasa, A. Bermana, L. Paczekb, M. Durlikc, A. Chmuraa, and A. Kwiatkowskia a Departments of General Surgery and Transplantology, Medical University of Warsaw, Warsaw, Poland; bDepartments of Immunology, Transplantology, and Internal Medicine, Medical University of Warsaw, Warsaw, Poland; and cDepartments of Transplantology and Nephrology, Medical University of Warsaw, Warsaw, Poland
ABSTRACT Aim. A major problem for the transplant society is a shortage of organs for transplantation compared with the number of patients on the waiting list. This study aimed to assess the results of the transplantation of kidneys procured from older donors. Patients and Methods. A total of 27 kidneys procured from donors age 70 years or older were transplanted between January 1, 2010, and April 25, 2015. These represented only 4.1% of the 657 kidneys transplanted from deceased donors during this period at the same center. Results. Delayed graft function (DGF) in the recipients of kidneys procured from donors age 70 or older occurred in 46.1% of patients, whereas the recipients of kidneys from younger donors showed DGF at a frequency of 32.7% (P ¼ NS). The annual and 3-year survival rates of kidneys in the study group were 85% and 80%, respectively, and in the control group were 92.5% and 88.6%, respectively (P ¼ NS). According to the Polish National Organ Procurement Organization (Poltransplant), the annual survival rate of a transplanted kidney in Poland stands at 89%, whereas the 3-year survival rate is 82%. We detected no significant posttransplantation differences in the serum creatinine concentration and in the estimated glomerular filtration rate between the study and control groups. The donor age and donor creatinine were the variables independently associated with DGF. Conclusions. The results of transplantation of kidneys from elderly donors were comparable to those of transplantation from younger donors. Kidneys harvested from elderly donors should be used for a transplant after a preliminary assessment.
K
IDNEY transplantation is the best-known method for treating patients with end-stage renal failure. A major issue for the transplant society is the shortage of organs compared with the number of patients on the waiting list for transplantation. Furthermore, many transplanted kidneys are now obtained from living donors; this approach gives much better results, whether tissues are harvested from young or old donors. However, not every patient can receive a kidney from a living donor. According to the Polish National Organ Procurement Organization (Poltransplant), the average waiting time for a first kidney transplant is 9 months and for a subsequent transplant is 13 months [1]. The number of patients on the waiting list for transplantation [2] and many patients on dialysis before addition
to the waiting list die every year. To increase the pool of available organs, broader criteria for donor selection have been used. Indeed, the concept of extended donor criteria has been used for many years. Expanded-criteria donor kidneys have been defined as kidneys from donors age 60 years and older, or from donors age 50 to 59 years who meet at least 2 of the following criteria: cerebrovascular accident as a cause of death, serum creatinine levels above
*Address correspondence to Piotr Domagala, Departments of General Surgery and Transplantology, Medical University of Warsaw, 59 Nowogrodzka St., 02-006 Warsaw, Poland. E-mail:
[email protected]
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0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.03.017
Transplantation Proceedings, 48, 1477e1481 (2016)
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JOZWIK, DOMAGALA, KIESZEK ET AL Table 1. Donor Characteristics
Table 2. Characteristics of Kidney Recipients
Kidney Donors 70 Years Old
Kidney Donors 69 Year Old
P Value
75 26.4 4.1 100 1.62
45 25.5 4.5 88 1.5
NS NS NS NS NS
Average age (y) Body mass index (m2/kg) Intensive care unit stay (d) Catecholamines (%) Serum creatinine (mg/dL) Abbreviation: NS, not significant.
1.5 mg/dL, or a history of hypertension [3]. In practice, there is no upper age limit for a potential kidney donor. There are many reports of good results for kidney transplantation when an organ is procured from an elderly donor. Many authors have reported that the mortality rate for dialysis patients is much higher than that for the transplant recipient group [4]. Patients undergoing hemodialysis have more than a 2-fold higher risk of death than patients after kidney transplantation when an organ is procured from a deceased donor who more than 65 years old [5]. Compared with chronological age, many parameters that can be defined before transplantation are more important in assessment of the suitability of an organ for transplantation. Among others, concentrations of serum creatinine and urea, glomerular filtration rate (GFR), histological evaluations of organ biopsies, and parameters that describe flow and resistance during storage of a kidney by hypothermic machine perfusion can be used for evaluation of a kidney prior to transplantation. This study aimed to assess the results of transplantation procedures in which the kidney was procured from an older donor. MATERIALS AND METHODS A total of 27 kidneys procured from donors who died at age 70 years or older were transplanted between January 1, 2010, and April 25,
Average age (y) Sex, male/female HCV(þ) (%) Body mass index (m2/kg) Hypertension (%) Human leukocyte antigen mismatch Induction therapy (%)
Kidney Donors 70 Years Old
Kidney Donors 69 Year Old
P Value
65 56/44 7.4 (n ¼ 2) 24.9 93 4.3
48 63/37 0.95 (n ¼ 6) 24.4 90 3.5
NS NS NS NS NS NS
64
2015. This represented 4.1% of the total number of 657 kidneys that were transplanted from deceased donors during this period at the same center. There were 16 (67%) kidneys in the study group that were stored by hypothermic machine perfusion; the remaining 9 (33%) kidneys were maintained in cold storage. A total of 10 of the transplanted kidneys (37%) were derived from donors age 70 to 74 years, 14 kidneys (52%) were from donors age 75 to 79 years, and the 3 (11%) other kidneys were from donors who were at least 80 years old. The mean donor age was 75 years old. In this cohort, 2 kidneys procured from a hepatitis C viruse infected donor were transplanted into recipients who were also infected with this virus. Additionally, during the study period, 5 kidneys taken from donors who were at least 70 years old were disqualified from transplantation because of unsatisfactory performance during organ storage by hypothermic machine perfusion in 4 cases and a cold ischemia time that was too long in 1 case. The control group included 630 kidneys taken from donors who were up to 69 years old. The average donor age in this group was 45.5 years, 458 (72.7%) of these kidneys were stored under hypothermic machine perfusion, and the remainder were maintained in cold storage. Additionally, 6 kidneys procured from a hepatitis C viruseinfected donor in the control group were transplanted into recipients who were also infected with this virus (Table 1).
90.00% 80.00% 70.00% 60.00% 46.10%
40.00%
32.70%
30.00% 20.00% 10.00% 0.00% Kidney recipients from donor ≥ 70 years old
NS
Abbreviation: NS, not significant.
100.00%
50.00%
56
Kidney recipients from donor ≤ 69 years old
Fig 1. Delayed graft function of transplanted kidneys.
TRANSPLANTATION USING OLDER KIDNEYS 100% 90%
92% 85%
1479
89%
88% 82%
80%
80% 70% 60% 50% 40% 30% 20% 10% 0% Annual kidney gra survival
3-years kidney gra survival
Kidneys from donors ≥ 70 years old
Kidneys from donors ≤ 69 years old
Na onal data (acording to "Poltransplant")
Fig 2. Kidney graft survival. In the study group, 56% (15 individuals) recipients were male and the average recipient age was 65 years old. However, in the control group, 63% of recipients were male and the mean age was 48 years old. No demographic parameters were found to be significantly different between groups (Table 2). All calculations were made using Microsoft Excel (MS Office 2010).
RESULTS
Delayed graft function (DGF) occurred in 46.1% of recipients of a kidney procured from a donor who was more than 70 years old, and in 32.7% of the control group patients (taken from donors younger than 69 years old; P ¼ NS; Fig 1). The annual and 3-year survival rates of kidneys in the study group were 85% and 80%, respectively, compared with 92.5% and 88.6% in the control group (P ¼ NS). The annual overall survival rate of a transplanted kidney in Poland is currently 89%, whereas the 3-year survival rate is 82% according to Poltransplant (Fig 2). The average serum creatinine concentration showed a
nonsignificant trend to be higher in recipients of kidneys procured from elderly donors compared with the control group tested at 6, 12, 24, and 36 months posttransplantation (Fig 3). Accordingly the average estimated GFR calculated with the Modification of Diet in Renal Disease formula showed a nonsignificant trend to be lower in recipients of kidneys procured from elderly donors compared with the control group (Fig 4). Multivariable analysis showed that donor age and donor creatinine were associated with DGF (Table 3).
DISCUSSION
In this current era of a shortage of organs for transplantation and a growing number of patients awaiting a kidney, identifying an additional pool of donor kidneys that is suitable for transplantation is urgently needed. In this study, we found that the transplantation of kidneys procured from donors who were at least 70 years old performed
2.5 2.18
2.18 1.92
2 1.65
1.69
6 months a er Tx
12 months a er Tx
1.81
1.9 1.66
1.5
1
0.5
0
Kidneys from donors ≥ 70 years old
24 months a er Tx
36 months a er Tx
Kidneys from donors ≤ 69 years old
Fig 3. Mean serum creatinine concentration after transplantation.
1480
JOZWIK, DOMAGALA, KIESZEK ET AL 60 50.91
50.8
53.85
55.42
50 40
33.53
30.61
30.24 26.19
30 20 10
Fig 4. Mean glomerular filtration rate according to Modification of Diet in Renal Disease formula.
0 6 months a er Tx
Kidneys from donors ≥ 70 years old
similarly to organs obtained from younger donors. The rate of DGF was slightly higher in the study group compared with the control group; however, this difference did not Table 3. Multivariable Analysis for Risk Evaluation of DFG DGF
Donor age (y) Donor sex (male/female) Donor body mass index (kg/m2) Donor creatinine (mg/dL) Donor cardiac arrest (yes/no) Donor vasoactive drugs use (yes/no) Donor hypertension (yes/no) Donor diabetes (yes/no) Male donoremale recipient (yes/no) Male donorefemale recipient (yes/no) Female donoremale recipient (yes/no) Female donorefemale recipient (yes/no) Recipient age (y) Recipient sex (male/female) Recipient body mass index (kg/m2) Time on dialysis (mo) Recipient hypertension (yes/no) Panel reactive antibodies (%) Human leukocyte antigen mismatches (n) Induction therapy (yes/no)
12 months a er Tx
Univariable
Multivariable
P
Odds Ratio (95% Confidence Interval), P
<.05 NS NS <.05
1.014 (1.004e1.026), P < .05 NS NS
NS NS
1.435 (1.287e1.935), P < .05 NS NS
NS NS NS
NS NS NS
NS
NS
NS
NS
NS
NS
NS NS NS
NS NS NS
NS NS
NS NS
NS NS
NS NS
NS
NS
Abbreviations: DGF, delayed graft function; NS, not significant.
24 months a er Tx
36 months a er Tx
Kidneys from donors ≤ 69 years old
meet our threshold for statistical significance. Interestingly, we observed a slightly higher annual and 3-year survival rate of kidneys in the control group compared with national data, whereas our observed 3-year kidney survival rate was similar to that of the entire population of Polish kidney transplant recipients. Renal function was assessed based on serum creatinine levels and estimated GFR according to Modification of Diet in Renal Disease formula measured at 6, 12, 24, and 36 months posttransplantation and was found to be slightly worse in the study group, although within the acceptable range, and this difference was not found to be significantly different compared with the control group. Probably the small number of cases in the study group is the answer for nonsignificant but observable differences in the estimated GFR between groups. Other researchers have arrived at similar conclusions in descriptions of the results of kidney transplantation procedures using organs procured from older donors [6e10]. Kute et al. reported that the results of renal transplantation procedures obtained from donors older than 70 years old were good, and were comparable to the results of renal transplantation in the recipients of younger kidneys; however, this study highlighted the importance of a preoperative biopsy to evaluate the organ prior to transplantation [6]. Collini et al. found that the survival of transplanted kidneys, rate of complications, and function of transplanted kidneys were slightly worse, but remained acceptable in patients who received an organ from a donor who was more than 75 years old [11]. In a study that was conducted in Italy, Pierobon et al. described a careful allocation system used for kidneys obtained from donors more than 60 years old that included a clinical evaluation of the donor and histological changes in the kidney. They found that such an allocation system based on an evaluation of the organ prior to transplantation helped to achieve good results from transplantation procedures [12]. The upper limit of kidney donor age was also increased in cases of live kidney donors. Tekin et al. reported the results of kidney transplantation from living donors younger than 65
TRANSPLANTATION USING OLDER KIDNEYS
years of age who were compared to those from a living donor who was at least 65 years old. The findings of Tekin et al. were comparable between groups as assessed by recipient survival and the lifetime of the transplanted organ [13]. At some centers that used expanded donor criteria, both kidneys obtained from a single donor were transplanted into the same recipient. The good results of such experiences have been described by Andrés and Lee, among others [14,15]. In this study, multivariate analysis showed that donor age and donor creatinine were independent risk factors for DGF. The results are similar to those from other papers [16]. CONCLUSIONS
The early and long-term results of transplantation when a kidney was collected from elderly donors were comparable to those from the transplantation of kidneys procured from younger donors. In this current era of a shortage of donor organs, kidneys obtained from elderly donors should be used for transplantation. An appropriate evaluation should be carried out before transplantation of a kidney from an elderly donor. The most valuable assessments are histological examinations of biopsy tissues obtained prior to transplantation, along with perfusion parameters during the storage of kidneys under hypothermic machine perfusion. We would argue that all kidneys taken from donors age 70 years or older should be stored under hypothermic machine perfusion. An evaluation of the current allocation system in Poland and adapting these criteria to the changing pool of donors and recipients will also be necessary. REFERENCES [1] Poltransplant. Biuletyn informacyjny. Available at: http:// www.poltransplant.org.pl/biuletyn_2015.html. Accessed January 23, 2015. [2] Medin C, Elinder CG, Hylander B, Blom B, Wilczek H. Survival of patients who have been on a waiting list for renal transplantation. Nephrol Dial Transplant 2000;15:701e4. [3] Domagala P, Kwiatkowski A, Wszola M, Czerwinski J, Cybula K, Trzebicki J, et al. Complication of transplantation of
1481 kidneys from expanded-criteria donors. Transplant Proc 2009;41: 2970e1. [4] Rabbat CG, Thorpe KE, Russell JD, Churchill DN. Comparison of mortality risk for dialysis patients and cadaveric first renal transplant recipients in Ontario, Canada. J Am Soc Nephrol 2000;11:917e22. [5] Lloveras J, Arcos E, Comas J, Crespo M, Pascual J. A paired survival analysis comparing hemodialysis and kidney transplantation from deceased elderly donors older than 65 years. Transplantation 2015;99:991e6. [6] Kute VB, Trivedi HL, Vanikar AV, Shah PR, Gumber MR, Patel HV, et al. Deceased donor renal transplantation from older donors to increase the donor pool. Int J Artif Organs 2012;35: 663e70. [7] Thornton SR, Hamilton N, Evans D, Fleming T, Clarke E, Morgan J, et al. Outcome of kidney transplantation from elderly donors after cardiac death. Transplant Proc 2011;43:3686e9. [8] Foss A, Heldal K, Scott H, Foss S, Leivestad T, Jørgensen PF, et al. Kidneys from deceased donors more than 75 years perform acceptably after transplantation. Transplantation 2009;87:1437e41. [9] Remuzzi G, Cravedi P, Perna A, Dimitrov BD, Turturro M, Locatelli G, et al. Long-term outcome of renal transplantation from older donors. N Engl J Med 2006;354:343e52. [10] Machado S, Figueiredo N, Neves M, Macário F, Alves R, Mota A, et al. Kidney transplantation using donors over 70 years old: are the criteria for organ allocation too expanded? Transplant Proc 2012;44:2289e92. [11] Collini A, Kalmar P, Dhamo A, Ruggieri G, Carmellini M. Renal transplant from very old donors: how far can we go? Transplantation 2009;87:1830e6. [12] Pierobon ES, Sandrini S, De Fazio N, Rossini G, Fontana I, Boschiero L, et al. Optimizing utilization of kidneys from deceased donors over 60 years: Five-year outcomes after implementation of a combined clinical and histological allocation algorithm. Transpl Int 2013;26:833e41. [13] Tekin S, Yavuz HA, Yuksel Y, Yucetin L, Ates¸ I, Tuncer M, et al. Kidney transplantation from elderly donor. Transplant Proc 2015;47:1309e11. [14] Andrés A, Morales JM, Herrero JC, Praga M, Morales E, Hernández E, et al. Double versus single renal allografts from age donors. Transplantation 2000;69:2060e6. [15] Lee CM, Carter JT, Weinstein RJ, Pease HM, Scandling JD, Pavalakis M, et al. Dual kidney transplantation: older donors for older recipients. J Am Coll Surg 1999;189:82e91, discussion 91e2. [16] de Sandes-Freitas TV, Felipe CR, Aguiar WF, Cristelli MP, Tedesco-Silva H, Medina-Pestana JO. Prolonged delayed graft function is associated with inferior patient and kidney allograft survivals. PLoS One 2015;10:1e13.