Objectives: Kidneys from expanded criteria donors with diagnosis of brain death have become a part of the organ transplant program, which have thus increased the number of transplants.
Materials and Methods: In this retrospective analysis, we identified the expanded criteria donors in a group of 156 kidney donors at our center. Basic parameters of the donors before kidney recovery were collected. Graft function, graft survival, and patient survival at 1, 3, and 5 years posttransplant were compared in expanded criteria versus standard criteria donors.
Results: Expanded criteria donors were significantly older than standard criteria donors (P < .001), had higher body mass index (P = .006), and had more frequent arterial hypertension (P < .001) and diabetes mellitus (P = .004) in their histories. When we considered the estimated glomerular filtration rate, graft function in the first 6 months after transplant was significantly worse in kidneys from expanded criteria donors (P = .011). In addition, recipients of grafts from expanded criteria donors had significantly worse survival in the first year posttransplant (P = .023); however, no differences in graft survival were observed.
Conclusions: From the long-term aspect, graft function and graft and patient survival in cases of kidneys from expanded criteria donors were comparable to results with kidneys from standard criteria donors. Expanded use of organs available for transplant is important due to the constantly increasing demands versus limited offers of organs.
Key words : Donor after brain death, Kidney transplantation, Older donors, Renal transplantation
Kidney transplant is the best choice for patients with terminal failure of kidneys. Both quality of life and patient survival are significantly better in patients after kidney transplant versus patients on wait lists.1 After kidney transplant, 75% of patients are able to return to work and approximately 1 in 50 women of fertile age become pregnant. The lack of available organs from deceased donors and the constantly increasing number of patients on wait lists have resulted in certain compensating and alternative strategies. Today, kidneys from expanded criteria donors (ECDs) after diagnoses of brain death are included in kidney transplant programs, thus increasing the number of transplant procedures.2
The Organ Procurement and Transplantation Network instituted a formalized definition of marginal kidneys in 2002 with the advent of ECD.3 Kidneys from ECDs are those from either a brain-dead donor ≥ 60 years of age or a donor 50 to 59 years of age with at least 2 of the following features: history of hypertension, terminal serum creatinine > 1.5 mg/dL (133 mmol/L), or cerebrovascular cause of death.4 These criteria for the definition of ECD were based on the presence of variables that increased the risk of graft failure by 70% (relative hazard ratio 1.70) versus that shown with standard criteria donor (SCD) kidneys. Kidney transplants from donors after cardiac death are not included in this definition. An SCD is defined as a donor who does not meet the criteria for donors after cardiac death or ECD.5
Kidneys transplanted from ECDs have (based on many large retrospective database analyses) higher delayed graft function rates, more acute rejection episodes, and decreased long-term graft function. An ECD kidney transplant recipient has a projected average added life-years of 5.1 years versus 10 years for a kidney recipient from an SCD.6,7 Despite these inferior results, patients who receive ECD transplants still have a survival advantage over dialysis patients who remain on transplant wait lists.7
Materials and Methods
All procedures performed in this study involving human participants were approved under the ethical standards of the institution and/or national research committee and complied with the 1964 Helsinki Declaration, as amended, or the comparable ethical standards.
In the group of 156 kidney donors seen at the Transplant Center Martin (Martin, Slovakia), we retrospectively identified ECD donors according to the Organ Procurement and Transplantation Network criteria. We recorded donor age and sex, cause of donor death, donor comorbidities (diabetes mellitus, arterial hypertension), and donor laboratory parameters before organ recovery, which included the estimated glomerular filtration rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration formula, creatinine levels, proteinuria, and serum sodium, calcium, and chloride levels. We compared the individual parameters in the ECD versus SCD groups. Furthermore, we also recorded graft function using eGFR at 1 month, 3 months, and 6 months after transplant, as well as at 1 year, 3 years, and 5 years after transplant. Within the evaluation of graft function, we also considered type of applied induction (basiliximab, antithymocyte globulin, or no induction), type of immunosuppression (tacrolimus, cyclosporine), and duration of cold ischemia (in minutes). We evaluated the onset of graft function (primary or delayed onset of the function, indicated by requirement for dialysis in the posttransplant period) and occurrence of acute rejection in the 12-month period after transplant. We also monitored development of surgical complications during the 30-day period posttransplant (bleeding, stricture of ureter, or lymphocele). The given parameters were compared between recipients of ECD grafts versus recipients of SCD grafts. Finally, we also compared patient and graft survival of ECD versus SCD kidneys 12 months and 5 years after transplant.
We used the certified statistical program MedCalc version 13.1.2 (MedCalc Software, Mariakerke, Belgium) for statistical evaluation with application of the following statistical analyses: t test, chi-square test, and Kaplan-Meier survival curves. We considered P < .05 to be statistically significant.
In our group of 156 donors (average age of 46 ± 16 years), we identified 50 ECD donors and 107 SCD donors. Table 1 shows the characteristics of each group.
We found that the ECDs were significantly older and had a higher body mass index, with hemorrhagic brain accident representing a significantly more frequent cause of death. In addition, ECDs had significantly higher occurrence of diabetes mellitus in their histories.
Table 2 shows characteristics of recipients of ECD and SCD grafts. Recipients of ECD grafts were significantly older, significantly more often received induction with antithymocyte globulin induction, and had higher creatinine levels during all monitored periods. However, graft function (as shown by eGFR) was only lower during the first year after transplant. After 1 year, no statistically significant differences in graft function were observed. Creatinine and eGFR levels over time are shown in Figure 1 and Figure 2. The use of an ECD had no effect on development of graft function and no effect on development of graft rejection over the 12-month follow-up period. Occurrences of posttransplant complications were not observed.
In our 12-month survival analysis of patients with organs from ECDs versus SCDs (Figure 3), we observed significantly worse survival in patients with ECD grafts versus SCD grafts (93.6% vs 99.3%; P = .023). However, no statistically significant differences in 12-month graft survival were shown in ECDs versus SCDs (95.5% vs 96.1%; P = .887) (Figure 4). Survival of recipients of ECD grafts 5 years after transplant was 96% versus 97% in recipients of SCD grafts (P = .772). At 5 years after transplant, ECD and SCD graft survival rates were not significantly different (91.9% vs 92%, P = .884) (Figure 5 and Figure 6).
In our retrospective analysis, we focused on several aspects regarding use of kidneys from ECDs. A lack of available organs and the high demand have led to an increased number of kidney transplants from ECDs. Most studies have shown that grafts from ECDs have worse survival and worse function than SCD grafts; however, survival of recipients of ECD grafts is obviously better than survival of patients on wait lists. The results of ECD kidney transplant procedures are certainly related to the recipient, namely, the recipient’s comorbidities.6 Studies have shown that, for younger patients, it is generally worth waiting for a higher-quality kidney. For older patients, prolonged wait time for an SCD kidney is not in their best interest.8,9. In our group, we confirmed that recipients of kidneys from ECDs were significantly older than recipients of kidneys from SCDs. We also observed a significantly more often use of antithymocyte globulin induction with ECD kidneys. Patients who received ECD kidneys were more likely to experience delayed graft function and diminished allograft function, resulting in increased medical resource use and higher risk of graft loss.10 However, regarding induction therapy, no higher occurrence of rejection and no delayed onset of graft function were shown in ECD recipients. The goal of any immunosuppression protocol should be to achieve an adequate immunosuppression level that offers minimum risk of infection without increasing the risk of rejection. However, older patients and recipients of ECD kidneys are often excluded from transplant trials; therefore, the optimum induction and maintenance regimens for these patients are unknown. Approaches are largely center specific and based on expert opinion.7,11
During the first 6 months posttransplant, we found that function of ECD grafts was significantly worse than shown for SCD grafts; however, function in both groups after 6 months was comparable. In a 2008 meta-analysis, Pascual and associates confirmed that ECD kidneys had worse long-term survival than SCD kidneys. The optimum ECD kidney for donation depends on adequate glomerular filtration rate and acceptable donor kidney histologic characteristics, although the usefulness of biopsy is debated.6 In a retrospective analysis, the Portuguese authors Ferrer and associates again confirmed that renal transplants with grafts from ECDs have significantly worse outcomes, showing higher rates of delayed graft function and acute rejection, worse graft function, and lower graft survival.12 Survival of grafts from ECDs and SCDs in our group were comparable at 5 years after transplant. Although survival of recipients of ECD grafts at 1 year after transplant was significantly worse versus survival of recipients of SCD grafts, we believe that this was related to the higher age of recipients of ECD kidneys (with assumed comorbidities in those patients). A conclusion similar to ours was made by Kim and associates, who retrospectively evaluated results of transplants from ECDs. They found that survival of ECD kidneys was comparable to that of SCD kidneys. The group observed that donor factors before organ recovery were not risk factors for graft failure.13
Graft function of ECD kidneys and patient and graft survival after ECD kidney transplant were comparable over the long term compared with results shown in SCD kidneys. The use of such organs for transplant is important because of the current situation of increasing demand with limited organs available.14,15 Appropriate selection of ECD kidney transplant recipients and close perioperative and postoperative follow-up are of prime importance to maximize the benefits associated with the increasingly widespread use of ECD kidney allografts.
Volume : 17
Issue : 1
Pages : 6 - 10
DOI : 10.6002/ect.2017.0188
From the 1Surgery Clinic and Transplant Center and the 2Department of
Anaesthesiology and Intensive Medicine, University Hospital, Martin and
Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Ivana Dedinská, Surgery Clinic and Transplant Center University Hospital Martin, Kollárova 2, 036 01 Martin, Slovak Republic
Phone: +421 43 4203 246
Figure 1. Creatinine Levels (μmol/L) at Time of Transplant in Recipients of Standard Criteria Donor Versus Expanded Criteria Donor Kidneys
Figure 2. Graft Function Based on Estimated Glomerular Filtration Rate at Time of Transplant in Recipients of Standard Criteria Donor Versus Expanded Criteria Donor Kidneys
Figure 3. Twelve-Month Survival of Recipients With Organs From Standard Criteria Donors and Expanded Criteria Donors
Figure 4. 12-Month Survival of Grafts From Standard Criteria Donors and Expanded Criteria Donors
Figure 5. Five-Year Survival of Patients With Organs From Standard Criteria Donors and Expanded Criteria Donors
Figure 6. Five-Year Survival of Grafts From Standard Criteria Donors and Expanded Criteria Donors
Table 1. Characteristics of Expanded Criteria Donors and Standard Criteria Donors
Table 2. Characteristics of Recipients of Kidneys from Expanded Versus Standard Criteria Donors