Abstract
ABSTRACT. The current organ shortage has led to the utilization of double kidney transplants from marginal adult donors, but outcomes data are limited. The United Network for Organ Sharing registry database was used to compare the outcomes of 403 dual adult kidney transplantations (DKT) and 11,033 single kidney transplantations (SKT) from 1997 to 2000. Graft and patient survival and the effect of multiple risk factors were evaluated. It was found that DKT patients were older, less sensitized, and received grafts from older, more mismatched donors with longer cold ischemia times. There was also a greater percentage of donors with a history of diabetes or hypertension and African-American recipients and donors in the DKT group. Graft survival was inferior in the DKT group, with a 7% lower graft survival rate at 1 yr. There was a higher incidence of primary nonfunction in the DKT group, although the incidence of delayed graft function, early rejection treatment, and graft thrombosis did not differ. Multivariate analysis was used to identify African-American recipient ethnicity and retransplant as risk factors for graft loss. Graft survival was comparable in DKT and SKT with donors over 55 yr of age. DKT resulted in inferior graft outcomes compared with SKT. When compared with SKT with donors over 55 yr of age, DKT resulted in similar graft outcomes. These otherwise discarded kidneys should be cautiously considered as a source of marginal donors. E-mail: mike.bunnapradist@cshs.org
Kidney transplantation has become the treatment of choice for end-stage renal disease patients (1). The demand for kidney transplants has increased dramatically in the last several years. This is evidenced by the current waiting list, which has increased to more than 50,000 patients in the United States. The annual death rate for patients on the wait list is 6.3% (2). Despite the increased demand, the number of cadaver donors has remained stable and is clearly insufficient to keep pace with the dramatically increasing demand. This has resulted in prolonged waiting times, with increased dialysis-related morbidity and mortality (1). These factors have made patients less acceptable candidates for transplantation and ultimately affected patient and graft survival once transplantation has been achieved (3).
The rapid increase in the number of patients awaiting transplantation has led many transplant centers to consider accepting older kidney donors with co-morbidities (4). Despite this, the number of organs retrieved but not transplanted has increased from 400 in 1990 to 1300 in 2000. Multiple innovative techniques have evolved in an attempt to utilize these wasted organs (5). One of these involves the utilization of double kidney transplants from extremely young or old donors to compensate for marginal allograft function (3). Recently, the University of Maryland and Stanford University have routinely accepted adult kidneys that have been discarded by other local centers and transplanted both kidneys into a single recipient (6). This practice has been adopted by multiple centers in the United States and worldwide (7–9 ⇓ ⇓). Although theoretical benefits exist, little data are available regarding long-term outcomes.
Here, we compare the outcomes of dual and single kidney transplants in the United States. We performed univariate and multivariate analyses to assess factors responsible for graft outcome using the United Network for Organ Sharing (UNOS) renal scientific registry database.
Materials and Methods
From January 1997 to December 2000, 403 dual kidney transplantations (DKT) from adult cadaver donors (age > 18 yr) from 70 transplant centers (range, 1 to 69 per center) were reported to UNOS. To evaluate the effectiveness of this approach, we compared the outcomes with those for 11,033 single kidney transplantations (SKT) performed at the same centers during the same period. Graft survival rates were estimated by the Kaplan-Meier product-limit method. In graft survival analyses, patient deaths were counted as graft failures regardless of the functional status of the graft at the time of death. To compare continuous variables, the Wilcoxon rank-sum test was used for comparison of the two groups. The χ2 test was used to compare categorical variables. The log-rank test was used to compare entire survival curves. In Table 2, we performed multivariate Cox regression analyses for the SKT and DKT groups separately because of the heterogeneous effects of risk factors on graft loss; for example, significant effects of donor age and race on graft survival were only seen in the DKT group. In multivariate analysis, continuous variables, such as age, duration of dialysis, percent peak panel reactive antibodies (PRA), cold ischemia time (CIT), and the number of HLA-A, B, DR mismatched antigens, were categorized, because their effects on the hazard function were nonlinear. The analysis included follow-up reports received at UNOS through September 2001. All reported P values were two-tailed.
Table 2. Comparison of risk factors for graft loss in SKT and DKT using multivariate Cox regression analysis
Results
Between 1997 and 2000, seventy US transplant centers reported 403 DKT procedures to UNOS. Figure 1 shows distributions of adult donor age according to single and dual kidney transplants performed between January 1997 and December 2000. The utilization of DKT showed an annual increase from 83 in 1997 to 102 in 2000. Recipient, donor, and graft characteristics of SKT and DKT groups are shown in Table 1. There were significant disparities for many characteristics between the two groups. DKT recipients were significantly older, less sensitized, and received grafts from older donors. DKT recipients also received grafts with longer CIT and a higher number of HLA-A, B, DR mismatched antigens compared with SKT patients. There was a larger number of African-American recipients, primary grafts, grafts from donors with stroke as cause of death, African-American donors, female donors, and donors with a history of diabetes or hypertension in the DKT group when compared with the SKT patients. Figure 2 shows that the 403 DKT patients experienced significantly inferior graft survival compared with the 11,033 SKT patients (P < 0.001), with a 7% lower graft survival rate at 1 yr posttransplant and a 15% lower graft survival at 3 yr in DKT patients compared with SKT patients. Incidences of anuria, delayed graft function (DGF), rejection treatment during the initial hospital stay, graft failure due to acute rejection, and graft thrombosis were not statistically different between the two groups. However, a significantly higher incidence of primary nonfunction of the allograft was noted in the DKT group compared with the SKT group (3% in the DKT group versus 1% in the SKT group; P = 0.004).
Figure 1. Distribution of donor age in single kidney transplantations (SKT) and double kidney transplantations (DKT).
Table 1. Characteristics of donors, recipients, and transplants
Figure 2. Overall graft survival of SKT and DKT.
An analysis of the risk factors adversely affecting allograft outcomes for the SKT and DKT groups using multivariate regression analysis of 13 potential risk factors is shown in Table 2. For SKT patients, donor age was the most influential factor influencing graft survival, followed by sensitization. However, significant risk factors affecting graft survival for the DKT patient group were quite different. Among DKT patients, retransplant was a significant risk factor, along with recipient age and African-American ethnicity. Factors such as donor age and race, cause of donor death, donor history of hypertension, duration of dialysis, sensitization measured by peak PRA, cold ischemia time, and degree of HLA mismatch had no significant influence on graft outcome in the DKT group.
To compare DKT with other marginal donors, we plotted the graft survival rates of DKT and SKT recipients with donors greater than 55 yr of age from the same centers (Figure 3). Although there was a trend toward lower graft survival in the DKT group, the result did not reach statistical significance.
Figure 3. Comparison of graft survival rates of SKT and DKT from donors over 55-yr-old.
We then compared the graft survival of SKT and DKT patients whose grafts received pretransplant biopsies. Among those grafts with pretransplant biopsies, graft survival of DKT patients (n = 87) was not significantly inferior to the SKT group (n = 1112), although a 4% lower graft survival rate developed in the first 3 mo and persisted thereafter. Seventy transplant centers that performed DKT reported a total of 1199 pretransplant kidney biopsies to UNOS during 1999 to 2000. The frequency of the percentage of glomerulosclerosis according to type of transplant is shown in Table 3. Two hundred ninety-nine biopsy results (10%) were reported to UNOS in 1999 and 897 (30%) were reported in the year 2000. Among those 1196 transplants, 118 had pretransplant biopsy results demonstrating greater than 20% glomerulosclerosis (97 SKT and 21 DKT). One-year graft survival of these 97 SKT patients was 82.8% compared with 90.5% of 21 DKT patients (log-rank P = 0.46).
Table 3. Number and percentage of glomerulosclerosis among performed kidney biopsies
Discussion
Multiple donor factors contribute to the outcome of kidney transplantation and are used as criteria to accept or reject organs. In the past decade, the demand for cadaveric organs has increased, resulting in the use of marginal organs for transplantation from what are termed expanded criteria donors (10). The transplant outcomes utilizing these expanded donors are often inferior to those achieved with ideal donors. Each transplant center has developed its own protocol for selecting donors and potential recipients (4). With this approach, a recent study reported significant survival advantages for those who received a marginal donor kidney transplant compared with those remaining on dialysis (11).
Recently, double kidney transplant techniques were developed to maximize the number of transplantable glomeruli from elderly donors (8). Various surgical techniques are described, including en bloc and split individual implantation (12). Alfrey et al. (13) from Stanford University Medical Center proposed the use of both kidneys to theoretically double nephron mass and compensate for inadequacies anticipated with SKT in this high-risk group. All DKT were kidneys that were rejected by other transplant centers in the organ sharing area. Their first report in 1996 suggested that the use of DKT provided satisfactory early function and allowed salvage of kidneys from older donors (14). Lee et al. (10) reported a series of satisfactory DKT based on estimated baseline creatinine clearances of < 50 ml/min. Preliminary data from these studies encouraged other centers to begin performing DKT. The Dual Kidney Transplant Registry was initiated and results were compared with SKT from donors over 54 yr of age reported to the UNOS database. An analysis of the dual registry patients concluded that DKT have a significantly decreased incidence of delayed graft function and lower serum creatinine up to 2 yr after transplant despite receiving kidneys from significantly older donors with poorer HLA matching (9). However, the registry did not include all the DKT performed in the United States. In October 1996, the Double Kidney Transplant Group (DKG) was established. Remuzzi et al. (7) reported a short-term follow-up of this prospective case-control multicenter study, comparing DKT with age- and gender-matched SKT, which showed comparable outcomes with a trend toward earlier renal function recovery in the DKT group.
Here, we evaluated transplant outcomes of DKT from all US centers utilizing the UNOS database. Like previous reports, DKT donor profiles are less favorable compared with SKT, with more HLA mismatches. Furthermore, these kidneys are more likely to be transplanted into older recipients, the fastest growing population of patients with end-stage renal disease (ESRD). This is likely due to recipient selection to match lower donor nephron mass with older recipients who are deemed to have lower metabolic demands and a lower likelihood of rejection (15,16 ⇓). We demonstrated that DKT results in inferior outcomes compared with SKT (Figure 2). DKT results in a 7% inferior graft survival at 1 yr, and the survival curves continue to diverge to 15% at 3 yr of follow up, indicating a higher rate of early graft failure and an increasing rate of graft failure with time. We confirmed earlier reports that DKT results in a similar 3-yr graft survival compared with SKT with donors older than 55 yr. Cadaveric donors over 55 yr of age were responsible for more than 15% of all donors. There was a significantly higher incidence of primary nonfunction observed in the DKT group compared with the SKT group. The known risk factors for primary nonfunction include prolonged cold ischemia time, significant underlying renal pathology, and irreversible acute tubular necrosis. Many of these factors presented more frequently in DKT. After primary nonfunction was censored, we found no differences between DKT and SKT in terms of graft survival.
Using multivariate analysis, we found that retransplant was the strongest risk factor for graft loss in the DKT group, with a relative risk of 2.37. This was followed by recipient age, graft from donors with diabetes, and African-American recipient ethnicity. The donor age, a profound risk factor in SKT, did not appear to be a significant risk factor in DKT. This may be due to an increase in nephron mass provided by DKT. Donor kidney biopsy has been shown to correlate with allograft dysfunction and delayed graft function in SKT (17,18 ⇓). Patients who underwent DKT from kidneys with more than 20% glomerulosclerosis had a tendency toward improved short-term graft survival, although the numbers were too small for statistical significance. The procurement renal biopsy by itself had no effect on outcome. However, this result needs to be interpreted with caution given the small number of biopsies performed.
Our study has some limitations. Even though this is currently the largest retrospective study on dual kidney transplant, the number of DKT may not have been large enough to detect some significant risk factors using multivariate analysis. These may include donor age, one of the most profound risk factors for graft loss in SKT. This is a study with 3-yr follow-up; therefore, the theoretical benefit of double nephron mass in DKT on long-term graft outcome could not be demonstrated. However, the slopes of the Kaplan-Meier graphs seem to be equivalent between DKT and SKT. African-American recipients and retransplant recipients have poorer graft outcomes, and DKT should probably be cautiously considered in these recipients.
In conclusion, transplantation of paired renal allografts from older or expanded cadaver donors resulted in inferior graft outcomes compared with SKT. DKT was associated with significantly higher risks of primary nonfunction and graft thrombosis. However, DKT resulted in a similar graft survival outcomes when compared with SKT with donor age over 55 yr. With this approach, the transplant community in the United States has expanded the donor pool by more than 400. Half of these grafts are still functioning at 3 yr. Recently, UNOS policy has been modified to promote the use of extended criteria donors by including the development of an alternate recipient list. When donors are considered unsuitable as single kidney transplant donors, DKT should be cautiously considered, at least for this subgroup of recipients. Because of the greater risk of primary nonfunction, DKT should be used in recipients with minimal risk of thrombosis. The use of anticoagulation should be considered.
Acknowledgments
Part of this work was presented at the 18th International Congress of the Transplantation Society 2000, Rome, Italy
- © 2003 American Society of Nephrology
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