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Keywords:

  • Center experience;
  • graft survival;
  • kidney transplantation;
  • pediatric donor

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

The optimal balance between maximizing the number versus the outcome of transplantation utilizing kidneys from small (≤20 kg) pediatric donors remains unclear, complicated by the choice of single versus en bloc transplantation with their attendant technical risks. Using the Organ Procurement and Transplantation Network (OPTN) database, we examined kidney recovery and utilization patterns, and 1-year transplant outcomes by single kilogram weight strata. Between January 1, 2005 and June 30, 2010, 2352 kidneys from ≤20 kg donors were transplanted into 1531 recipients, 710 single kidney transplants (SKTs) and 821 en bloc kidney transplants (EBKTs). Increased donor weight was associated with higher rates of recovery, transplantation and SKT. Low donor weight (linear p < 0.001; quadratic p = 0.003), SKT versus EBKT (p = 0.008), increased cold ischemia time (p = 0.003), local versus nonlocal donor (p = 0.0044), low versus high volume center (p = 0.003) and the interaction term between center volume and donor weight (p = 0.0024) were associated with graft failure. Notably, lower donor weight exacerbated the negative impact of low center volume but did not worsen the negative impact of SKT on outcomes. Our data show that EBKT offers superior 1-year survival at the expense of accomplishing one rather than two transplants. However, SKTs yield excellent outcomes when performed at experienced centers.


Abbreviations
BMI

body mass index

cPRA

calculated panel reactive antibody

DDKT

deceased donor kidney transplantation

EBKT

en bloc or sequential double kidney transplantation

ECD

extended criteria donor

ESRD

end-stage renal disease

GFR

glomerular filtration rate

HR

hazard ratio

LDKT

living donor kidney transplantation

SCD

standard criteria donor

SKT

single kidney transplantation

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

Renal transplantation confers benefit by extending survival for patients with end-stage renal disease (ESRD) compared to dialysis [1]. Furthermore, the duration of time on dialysis is an independent predictor of long–term posttransplant prognosis [2]. The waitlist has grown exponentially in the last decades, motivating the transplant community to expand the donor pool. Expanded criteria donor (ECD) kidneys are increasingly used for transplantation as an approach to alleviate the organ shortage. Transplantation of ECD kidneys yields inferior outcomes when compared to transplantation of standard criteria donors (SCD) but superior outcomes compared to ongoing dialysis [3, 4]. Although the formal definition of ECD kidneys includes only kidneys from older donors, kidneys from younger or pediatric donors fit the spirit of an ECD organ. Reluctance to transplant small pediatric deceased donor kidneys into adults stems from both short- and long–term considerations. In the short term, the increased incidence of vascular and urinary complications represents a strong deterrent [5-10]. Another concern is that insufficient nephron dose will lead to hyperfiltration injury and accelerate graft failure [11-14]. A surgical approach that addresses both risks is to transplant two kidneys from the same donor using an en bloc technique. The vascular anastomoses are performed using aortic and vena caval conduits rather than the diminutive renal vessels. Moreover, the nephron mass is doubled. Recent reports have shown that the graft survival rate for en bloc kidney transplantation (EBKT) is comparable to either adult deceased donor kidney transplantation (DDKT) or living donor kidney transplantation (LDKT) [4, 15, 16]. Pediatric kidneys transplanted en bloc into adults grow to normal adult renal size within the first few months after transplantation and exhibit a longitudinal increase in glomerular filtration rate (GFR) for as many as 5 years after transplantation [6, 7, 9, 12, 15-21]. However, while EBKT may mitigate technical risk in the short term and functional risk in the long term, transplantation of two young and healthy kidneys into a single patient is resource intensive and fails to maximize transplant opportunities.

Currently, there are scarce data to indicate and therefore no consensus in the community as to the optimal use of kidneys from small pediatric donors. We therefore undertook a study to carefully examine, by single kilogram donor weight strata, kidney recovery, discard and 1-year transplant outcomes. Our aim was to identify strategies that might alleviate the risk associated with SKT and/or EBKT and thereby maximize the individual as well as the communal benefit provided by this important but challenging source of deceased donor kidneys in the United States.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

Organ procurement organizations submit data on all deceased donors in the United States to the Organ Procurement and Transplantation Network (OPTN). An organ donor is defined as any human being from whom at least one organ was recovered for the purpose of transplantation. Transplant programs are required to submit data to the OPTN on all transplant recipients. These data include demographic as well as follow-up (graft and patient survival) information. The data included in this report are based on all small pediatric deceased donors, defined as a donor weighing 20 kg or less, recovered in the United States between January 1, 2005 and June 30, 2010, and the recipients of these donor organs.

Assessment of organ utilization practices included kidneys transplanted in conjunction with other organs, including kidney–pancreas or other multi-organ transplants. All other analyses were based on kidney-alone transplants. For graft survival estimates, a patient death is considered to be a graft failure regardless of the reported graft status at time of death. Cox proportional hazards models were used to analyze time to graft failure 1 year after transplantation. Subjects alive with functioning grafts at 1 year were right censored. One-year survival estimates and hazard ratios (HRs) were examined to show outcome profiles for kidney transplants spanning values of donor weight ≤20 kg. Models included donor and recipient demographic characteristics of age, gender, ethnicity, and BMI, donor height and weight, number of previous kidney transplants, HLA mismatch, cold ischemia time, transplant procedure type (single vs. en bloc) and kidney origin (local or imported). Transplant center volume was tested as both a categorical and a continuous variable. Categorical stratification by quartiles, tertiles and the median for separating volume groups was examined with final selection of the median. Small centers performed the median number of small pediatric donor transplants or fewer during the study period (≤5 transplants), while large centers performed more than the median number of these transplants during the study period (>5 transplants). Backwards selection was used with a retention p-value of 0.10 to select model terms or covariates that significantly predict graft failure. Nonlinear relationships between donor weight and graft survival were fit with polynomial terms up to the third order. We also determined whether differences in single and en bloc transplants changed based on donor weight or transplant center volume by testing for the inclusion of interaction terms. The HRs are directly calculated from the parameter estimates by the exponential function. If the model lends a negative parameter estimate for a covariate, then that variable is said to be negatively associated with graft failure (i.e. higher values for that variable tend toward lower chance of graft failure). Positive parameter estimates indicate that the corresponding variable is associated with higher chance of graft failure as it increases in value. Survival rates were calculated using the estimated parameters from the model, holding nonspecific covariates at their means. The survival rates were then estimated for small, large and average-sized centers at varying donor weights (Table 4). The estimated survival rates for average-sized centers were then used to forecast the hypothetical effect on the number of individuals with a functioning graft 1 year after transplant if all kidneys were transplanted singly, in contrast to the number of individuals with a functioning graft 1 year after transplant if kidneys were transplanted both singly and en bloc in proportions based on actual transplants (Table 5). SAS PROC PHREG in version 9.3 was used to fit these models (SAS Institute, Cary, NC).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

Recovery and utilization patterns for kidneys from small (≤20 kg) pediatric donors

Utilizing the OPTN database, data from 1757 small, defined as ≤20 kg, pediatric organ donors between January 2005 and June 2010 were analyzed. No kidneys were transplanted from 554 (36%) donors while 1203 (68%) had at least one kidney transplanted and are termed kidney donors. The frequency with which at least one kidney was transplanted increases steeply as donor weight increases, as demonstrated by the increasing percentage of donors who were kidney donors (Table 1).

Table 1. Numbers of small (≤20 kg) pediatric organ donors, kidney donors and kidney transplants (single and en bloc)
Donors1KidneysTransplants2
Weight (kg)NKidney donors,3 N (%)Recovered, NDiscarded,4 N (%)Transplanted,4 N (%)Not transplanted,5 NSingle,6 N (%)En bloc,6 N (%)
  • 1

    Donors: defined as someone who donates at least one solid organ for transplantation.

  • 2

    Includes solitary and multi-organ kidney transplants (either single or en bloc).

  • 3

    The number signifies the number of donors who had at least one kidney transplanted. The percentage is calculated using the total number of donors as the denominator. For donors <8 kg, there were 312 donors (431–119) for whom no kidneys were transplanted; 119 of 431 donors = 28% were kidney donors.

  • 4

    The percentage is calculated using the number of recovered kidneys as the denominator. For donors <8 kg, the discarded percentage is 145/382 = 38%; the transplanted percentage is 237/382 = 62%.

  • 5

    Sum of kidneys not recovered and kidneys discarded after recovery. For donors <8 kg, there are 862 available kidneys (431 × 2); 480 were not recovered (862–382 recovered kidneys = 480) and 145 discarded kidneys to total 625 kidneys that were not transplanted.

  • 6

    The percentage is calculated using the total number of kidney transplants as the denominator. For donors <8 kg, the total number of transplants performed was 129; 21/129 = 16% single kidney transplants and 108/129 = 84% en bloc transplants.

<8431119 (28)382145 (38)237 (62)62521 (16)108 (84)
811066 (60)14921 (14)128 (86)9214 (20)57 (80)
99261 (66)15030 (20)120 (80)6416 (24)52 (76)
10176131 (74)29438 (13)256 (87)9644 (29)106 (71)
118967 (75)15825 (16)133 (84)4521 (28)56 (72)
12139114 (82)24725 (10)222 (90)5654 (39)84 (61)
13123103 (84)22926 (11)203 (89)4371 (52)66 (48)
1411498 (86)21623 (16)193 (84)3569 (52)62 (48)
15160145 (91)30724 (8)283 (92)3789 (48)97 (52)
167468 (92)1409 (6)131 (94)1759 (62)36 (38)
176154 (89)11812 (10)106 (90)1648 (63)29 (37)
186564 (99)1274 (3)123 (97)763 (68)30 (32)
193734 (92)724 (5)68 (94)640 (74)14 (26)
208679 (92)16415 (9)149 (91)23101 (81)24 (19)
Total17571203 (68)2753401 (15)2352 (85)1162710 (46)821 (54)

From the total of 2753 recovered kidneys from small pediatric donors, 2352 (85%) were transplanted into 1531 recipients; 710 recipients received a SKT (46%) and 821 recipients received an EBKTs (54%). The frequency of EBKT decreased steadily from 84% to 19% as donor weight increased from <8 to 20 kg. However, even considering donors weighing >14 kg, there were 230 EBKTs, accounting for 28% of all EBKTs performed utilizing kidneys from small pediatric donors.

Figure 1 shows the center volume distribution of transplants involving kidneys from small pediatric donors. Among the 255 centers that performed any DDKTs during the 5.5-year study period, 106 (42%) centers did not perform a single transplant utilizing kidney(s) from small pediatric donors. Among the 149 (58%) transplant centers that did perform at least one transplant, the median (range) of transplants per center was 5 (1–67), corresponding to less than one per year on average. Using the median of 5 as the threshold, there were 77 small-volume and 72 large-volume centers. The 77 small-volume centers together performed a comparable number of small pediatric donor kidney transplants as the three highest volume centers, 199 compared to 185, respectively.

image

Figure 1. Distribution of center volume of kidney transplants (single or en bloc) from small pediatric donors (≤20 kg) from January 1, 2005 through June 30, 2010.

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Donor, recipient and transplant characteristics of solitary kidney transplants utilizing kidneys from small (≤20 kg) pediatric donors

Donor, recipient and transplant characteristics for solitary kidney transplants from small (≤20 kg) pediatric donors are provided in Table 2. Donors (n = 1195) were predominantly male (56%), with a mean ± standard deviation age of 2.1 ± 1.9 years and weight of 12.8 ± 4.0 kg. Recipients (n = 1516) were approximately half male (51%), predominantly (91%) undergoing primary kidney transplant, with a mean ± standard deviation age of 45.2 ± 16.1 years, height of 164 ± 15.4 cm, weight of 67.8 ± 18.2 kg and body mass index (BMI) of 24.9 ± 5.1. EBKTs accounted for the majority (54%) of transplants; the mean ± standard deviation cold ischemia time was 19.7 ± 10 h. Approximately 45% of kidney grafts were imported into the recipient's donor service area.

Table 2. Continuous and categorical characteristics of small (≤20 kg) pediatric kidney donors, recipients and transplants
 NMeanSDMedianMinMax
Kidney donor characteristics1
Age (yrs)11952.11.92.00.013.0
Weight (kg)119512.84.013.03.320.0
Height (cm)119587.216.687.041.0133.0
Solitary kidney (single and en bloc) recipient characteristics1
Age (years)151645.216.147.00.081.0
Height (cm)1431164.215.4165.165.0210.8
Weight (kg)145167.818.266.75.5157.0
BMI (kg/m2)140824.95.124.410.151.3
Solitary kidney (single and en bloc) transplant characteristics1
HLA mismatch15164.31.55.00.06.0
Cold time (h)141719.710.318.10.579.0
 N%
  • 1

    The tables describe donors (N = 1195) and recipients (N = 1156) for solitary kidney transplants only, excluding donors and recipients of kidneys performed as part of multi-organ transplants.

Kidney donor characteristics1
Male gender66855.9
Ethnicity/race
White61251.2
Black27623.1
Hispanic231.9
Asian26422.1
Other201.7
Solitary kidney (single and en bloc) recipient characteristics1
Male gender77351.0
Ethnicity/race
White60039.7
Black41627.5
Hispanic18612.3
Asian30019.9
Other90.6
Primary kidney transplant138091.0
Solitary kidney (single and en bloc) transplant characteristics (N = 1516)
Local donor83655.1
Transplant type
Single70146.2
En bloc81553.8

Risk factors for 1-year graft failure for solitary kidney transplants (SKT and EBKT) utilizing kidneys from small pediatric donors

Table 3 shows the final Cox proportional hazards multivariable model for 1-year graft failure for solitary kidney transplants (excluding multi-organ transplants) utilizing grafts from small pediatric donors. Negative versus positive parameter estimates indicate that the corresponding variable is associated with a lower versus higher chance of graft failure as it increases in value. Among donor and recipient demographic factors, only lower donor weight (linear: estimate −0.52 per kg; p < 0.001; quadratic: estimate 0.01 per kg; p = 0.003), was significantly associated with graft failure. Donor age (estimate −0.17 per year; p = 0.055) and recipient BMI (estimate 0.028 per unit; p = 0.070) showed a trend toward association. Several transplant factors including EBKT relative to SKT (estimate −0.48; p = 0.008), increased cold ischemia time (estimate 0.02 per hour; p = 0.003), imported versus local status (estimate −0.38; p = 0.044), large versus small volume center (estimate −2.65; p = 0.003) and the interaction term of large-volume center X donor weight (estimate 0.14; p = 0.024) were significantly correlated with graft failure. The interaction term indicates that center experience favorably impacts the outcome of kidney transplants from low-weight donors more than high-weight donors. In contrast, the interaction term of transplant type and donor weight was not significant, indicating that the impact of transplant type did not vary with donor weight.

Table 3. Final Cox proportional hazards multivariable model for 1-year graft failure for kidneys from small (≤20 kg) pediatric donors
Model termEstimateSEp-ValueHazard ratio1
  • 1

    Hazard ratios displayed are indicative of the hazard for one-unit increases in the corresponding covariate, where applicable. Hazard ratios are dependent on the values of the interacting variables for interaction terms (thus quadratic terms).

Donor age (per year)−0.170.090.0550.846
Donor weight (per kg)−0.520.14<0.001 
Donor weight (per kg; quadratic)0.010.000.003 
Recipient BMI (per unit)0.0280.030.0701.01
En bloc transplant type (vs. single)−0.480.180.0080.617
Cold time (per hour)0.020.010.0031.024
Imported donor kidney (vs. local)−0.380.190.0440.76
Center volume > median−2.650.890.003 
Center volume > median × donor weight0.140.060.024 

The resulting parameter estimates enabled calculation of HRs for 1-year graft failure and 1-year graft survival for both SKT and EBKT by kg weight strata for the “average” center (Table 4; Figure 2); SKT utilizing a 20 kg donor kidney served as the reference group. For SKT, HRs started at 5.85 for 8 kg donor kidneys, decreasing steadily as donor weight increased. Calculated 1-year SKT graft survival started at 69.0% for 8 kg donor kidneys, rising to 81.4% for 11 kg donor kidneys, comparable to the 81.7% 1-year graft survival for ECD kidney transplants [4], and reaching 86.3% for 20 kg donor kidneys. For EBKTs, HRs started at 3.61 for 8 kg donor kidneys, dropping steeply as donor weight increased, and reaching a nadir of 0.62 for 19–20 kg donor kidneys (Table 4; Figure 3A). Notably, calculated 1-year EBKT graft survival started at 79.5% (slightly lower than ECD kidney transplants), rising to 89.6% for 12 kg donor kidneys, which is comparable to the 89.3% 1-year graft survival for SCD transplants [4].

Table 4. Hazard ratios for 1-year graft failure and calculated 1-year graft survival based on the final multivariable Cox model
Weight (kg)Hazard ratiosCalculated 1-year graft survival
The average centerLarge-volume center1Small-volume center2
SingleEn blocSingle (%)En bloc (%)Single (%)En bloc (%)Single (%)En bloc (%)
  • 1

    Large centers perform more than the median number of transplants during the study period (>5 transplants).

  • 2

    Small centers perform the median number of transplants or fewer during the study period (≤5 transplants).

85.853.6169.079.584.189.945.061.1
94.362.6974.383.386.291.355.169.3
103.332.0678.486.187.892.363.475.5
112.621.6281.488.188.993.069.980.2
122.111.3083.789.689.693.574.983.7
131.751.0885.490.790.193.878.786.3
141.490.9286.691.590.393.981.682.2
151.300.8187.392.090.293.983.789.6
161.170.7287.892.389.993.685.290.6
171.080.6787.992.389.393.386.891.3
181.030.6387.792.288.492.786.991.7
191.000.6287.291.987.191.887.291.9
20Ref0.6286.391.385.390.787.291.9
image

Figure 2. Hazard ratios for 1-year graft survival: single versus en bloc kidney transplants by donor weight for small (≤20 kg) pediatric donors. Reference group is single kidney transplant from a 20 kg donor.

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image

Figure 3. One-year graft survival for single and en bloc kidney transplants by donor weight and center volume for small (≤20 kg) pediatric donors. (A) Average-volume center. (B) Large (>5 transplants) and small (≤5 transplants) volume centers.

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Impact of center volume on outcomes of SKTs and EBKTs utilizing kidneys from small pediatric donors

Table 4 and Figure 3B display estimated 1-year graft survival rates for large-versus small-volume centers. For transplants utilizing kidneys from 8 kg donors, center experience was associated with estimated outcome differentials of 40% for SKT and 30% for EBKT. However, at the upper end of the weight spectrum, there are essentially no outcome differences based on center experience. At small-volume centers, SKTs compared to EBKTs fared disproportionately worse at low donor weights. In contrast, at large-volume centers, the outcome differential between SKT and EBKT remained fairly constant throughout the entire weight range studied.

Causes of graft failure

Graft thrombosis, either venous, arterial or both, was the dominant etiology of graft failure within 1 year of transplant, occurring in 67 of 1516 (4.4%) of transplants from small pediatric donors. Thrombosis rates were 6.0% (42 of 710) after SKT and 3.0% (25 of 821) after EBKT. Surgical/urologic complication was listed as the reason for graft failure in three additional transplants (one SKT; two EBKT). There were an additional 19 cases of “primary graft failure” (11 SKT; 8 EBKT), some of which may relate to technical complications. Patient death with functional graft accounted for 30 cases of graft failure.

Assessment of potential for additional transplant opportunities

Table 5 presents the potential positive and negative impacts of a hypothetical scenario whereby all transplants during the study period were performed as SKTs rather than a combination of SKTs and EBKTs. The potential positive impact is denoted by the increased number of transplants; the potential negative impact is denoted by the increased number of graft losses within 1 year of transplant. The overall potential for gain is derived from subtracting the number of additional graft losses from the number of additional transplants. Note that the analyses are limited solely to transplanted kidneys and do not include the 761 nonrecovered kidneys or the 401 recovered but discarded kidneys.

Table 5. Impact if all transplanted kidneys from small (≤20 kg) pediatric donors were transplanted singly compared to actual transplants (both single and en bloc): Additional patients with functioning grafts at 1 year, additional patients who suffer graft loss within 1 year, and overall gain
Donor weight (kg)Number of actual transplantsNumber of transplants if all transplanted kidneys were transplanted singly1Expected number with a functioning graft 1 year after transplantationComparison of actual transplants versus all single kidney transplants
SingleEn blocTotalBased on actual transplantsIf all transplanted kidneys were transplanted singlyAdditional patients with a functioning graft at 1 year2Additional patients who suffer graft loss within 1 year3Overall gain4
  • 1

    Calculated by adding the number of single kidney transplants and twice the number of en bloc kidney transplants; for donor weight 8 kg: 14 + (2 × 57) = 128.

  • 2

    Calculated by subtracting the estimated number of patients with functioning graft 1 year after transplant based on actual transplants from that based on all single kidney transplants; for donor weight 8 kg: 88–55 = 33.

  • 3

    Calculated by subtracting the expected number of graft losses within 1 year based on all single kidney transplants from that based on actual transplants: for donor weight 8 kg: (71–55)–(128–88) = 16–40 = −24.

  • 4

    Calculated by adding the number of additional patients with a functioning graft at 1 year and the number of additional patients who suffer graft loss within 1 year if only single kidney transplants were performed; for donor weight 8 kg: 33 + (−24) = 9.

81457711285588+33−24+9
91651671185488+34−17+17
1043105148253124198+74−31+43
1121557613166107+41−14+27
125484138222120186+66−18+48
137166137203120173+53−13+40
146862130192116166+50−12+38
158696182278165243+78−16+62
1659369513185115+30−6+28
174828761046891+23−5+18
1862278911680102+22−5+17
19391453674758+11−3+8
209624120144106124+18−6+12

As seen in Table 5, the hypothetical scenario yields only modest gains at the extremes of donor weight. At the lowest end (8–9 kg), since the majority of transplants were EBKTs, performing only SKTs results in a large increase of transplants. However, high failure rates associated with SKT nullify much of the gain. At the highest end (17–20 kg), since only a small proportion of transplants are EBKTs, performing only SKTs results in a modest increase in additional transplants that is minimally affected by graft losses. Clearly, the middle weight range presents the greatest opportunity. Exclusive SKT for all kidneys from >10 kg or >12 kg donors would result in 300 or 225 additional recipients with functioning grafts 1 year after transplantation, respectively.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

While the number of candidates on the deceased donor kidney waitlist has increased steeply, the availability of donors has increased more gradually by comparison. Aggressive efforts have been made to expand the donor pool, focusing predominantly on older donors, often with medical comorbidities, and donation after cardiac death donors. Our analyses corroborated previous reports that donor weight correlated better with both endpoints of interest than age or height [9, 18, 21, 22]. We decided to focus exclusively on 1-year outcomes and deliberately selected a highly contemporary cohort (January 2005 through June 2010), in sharp contrast to the previous single-center and registry studies that have typically included transplants dating back to the 1990s or even the 1980s [6, 9, 10, 12, 15, 17-21, 23-26]. Moreover, our study is unique in examining the impact on outcomes of SKT versus EBKT. Our aim was to present highly granular and up-to-date data to best inform decision-making by physicians and transplant centers with respect to the optimal use of these technically and functionally challenging grafts.

Although at first blush, our results appear to echo the previous reports, we believe that they provide novel insight into several dimensions. First, as expected, recovery rates and utilization rates of recovered kidneys increased steeply as donor weight increased [6, 22]. Among the 1757 ≤ 20 kg pediatric donors, 554 donors (32%) had no kidneys transplanted and 54 donors (3%) had only one of their two kidneys transplanted. In total, 2352 or 67% of available kidneys were transplanted, leaving 1162 (33%) unutilized kidneys over the 5.5-year study period. Interestingly, during the last two decades, overall utilization has fluctuated but remains essentially unchanged. Pelletier et al [6] identified 2886 ≤ 20 kg pediatric donors between 1993 and 2002. Of the 5772 potential kidneys, 3777 or 65% were transplanted. Kayler et al [22] identified 3341 ≤ 20 kg pediatric donors between 1997 and 2007. Of the 6682 potential kidneys, 3710 or 55% were transplanted. Previously reported risk factors for nonrecovery and/or discard after recovery include small donor size (age and weight), female gender, increased donor serum creatinine, single kidney (vs. en bloc) procurement and intestinal procurement [6, 22].It is provocative to consider whether the experience of the procurement team with small pediatric donors correlates with the recovery rate of transplantable kidneys and whether this varies with donor size. If such an association can be demonstrated, then strong consideration should be given to limiting multi-organ abdominal procurements for all or a subset of small pediatric donors to teams with a proven track record of procuring transplantable organs. Alternatively, the close proximity of vascular structures critical for liver and particularly intestinal procurement may be the true limiting factor.

Second, it is quite clear, as donor weight increases, the frequency of EBKT decreases from 84% at the lowest end of the spectrum to 20% at the highest end of the spectrum. This practice almost certainly reflects knowledge that EBKT outcomes are superior to SKT outcomes, particularly for kidneys procured from the smallest of small pediatric donors [6, 9, 10, 25]. Our analyses, however, extend previous findings. Surprisingly, we did not identify an interaction between transplant type (EBKT vs. SKT) and donor weight with respect to 1-year graft survival. Therefore, the increased relative risk of graft loss is relatively constant across the weight spectrum examined. While relative risk does not change with donor weight, the absolute outcome differential is larger and more striking at the low compared to the high weight strata. It is important, however, for physicians and patients to consider the absolute graft outcomes within the context of the outcomes for kidneys from ideal, average and expanded criteria donors [3, 4, 6, 9, 10].

Third, our analyses show that center experience with transplantation of kidneys from small pediatric donors exerts a profound impact on 1-year graft survival, particularly for SKT at low donor weight strata. For “high-volume” centers, there is essentially no decrement in 1-year SKT or EBKT graft survival as donor weight decreases. Moreover, although EBKT outcomes are superior to SKT outcomes across the entire spectrum of donor weight, the difference is modest and stable. For low-volume centers, outcomes are comparable to those of high-volume centers for the largest of these small pediatric donors (donor weight approaching 20 kg). However, as donor weight decreases, there is not only a steep decrement in 1-year graft survival for both SKT and EBKT but also a widening differential between the two transplant types. These data, in totality, strongly suggest that superior technical expertise at “high-volume” centers, rather than donor and/or recipient selection or posttransplant management protocols, mitigates the risk of 1-year graft loss for both SKT and EBKT. This was observed in spite of our very modest definition of “high volume”—more than one transplant per year, on average. It is certainly possible that, even within a transplant center, there is specialization such that only a subset of practicing surgeons performs transplants utilizing kidneys from small pediatric donors. Moreover, it is important to keep in mind that 42% or 106 of the 255 active kidney transplant centers did not perform any such transplants during the 5.5-year study period. There is substantial literature that center/surgeon volume and expertise are critical outcome determinants for many technically advanced technical surgical procedures [27-29].

Beyond the threat of technical complications that often lead to early devastating graft loss, utilization of kidneys from small pediatric donors is challenged by long-term concerns of inadequate nephron mass resulting in chronic hyperfiltration injury [11, 13, 14]. The level of concern is proportional to donor size and further exacerbated by SKT relative to EBKT. Unfortunately, markers of hyperfiltration injury—emergence of proteinuria and decreasing GFR—are problematic as they are highly nonspecific in the posttransplant population. Moreover, relevant data are not available in the OPTN database. We therefore focused solely on 1-year graft survival, a robust outcome for which our data is ideally suited.

While concern regarding inadequate nephron dosing resulting in gradual but inexorable functional deterioration may be intuitive, review of single-center reports with highly granular data over a protracted timeframe is nonconclusive [15, 16, 18, 21]. Borboroglu et al [21] reported that SKT recipients did not experience hyperfiltration injury if the donor's weight exceeded 14 kg and the kidney length exceeded 6 cm. Foss et al [18] reported on 16 recipients of kidneys from pediatric donors <5 years of age, 11 SKTs and 5 EBKTs, the latter technique employed when donors were <12 kg or ≤2 years old. After a median follow-up of 7 years, recipients' mean estimated GFR was 84 mL/min/1.73 m2. None had significant proteinuria. Sharma et al compared 20 EBKTs to 214 LDKTs and 249 SCD DDKTs [16]. Five years after transplantation, graft survival was highest (92 ± 7.7% EBKT vs. 88 ± 3.4% LDKT vs. 70 ± 4.3% SCD DDKT) and serum creatinine was lowest for EBKT recipients (1.0 ± 0.6 mg/dL EBKT vs. 1.7 ± 1.0 mg/dL LDKT vs. 2.2 ± 2.8 SCD DDKT). Sureshkumar et al [15] compared all EBKTs to all LDKTs performed at a single center between 1990 and 2001. Pediatric donors were 16.9 ± 11.2 months and weighed 10.7 ± 3.8 kg; EBKTs had cold ischemia time of 30.5 ± 9.8 h. Proteinuria was detected earlier after transplantation for LDKT compared to EBKT recipients (23.4 ± 16.3 months vs. 45.6 ± 33.6 months; p < 0.002). Compared to LDKT recipients, EBKT recipients had significantly higher MDRD GFR as early as 6 months after transplantation (56.6 ± 14.5 vs. 48.1 ± 14.7 mL/min/1.73 m2; p < 0.001). Between 6 months and 5 years after transplantation, GFR increased for EBKT but decreased for LDKT recipients such that the difference in mean GFR exceeded 25 mL/min/1.73 m2 (EBKT 70.7 ± 27.1 vs. 43.3 ± 16.9 mL/min/1.73 m2; p < 0.001). Taken together, these data indicate that, if the gauntlet of technical complications can be successfully negotiated, kidneys from small pediatric donors can bestow excellent long–term outcomes for selected recipients, very likely secondary to superior functional reserve [9, 17, 30]. Animal models have elegantly demonstrated that kidneys from young donors have greater capacity to withstand the stress and injury engendered by transplantation because they have more vigorous proliferative and repair mechanisms [31].

Ultimately, the issue of utilizing kidneys from small pediatric donors for transplantation and the choice of performing SKT versus EBKT requires consideration of the potential harm versus benefit afforded to not only individual patients but also the entire waitlist community. The first tier of opportunity would appear to be at the level of recovery, since a large number of kidneys (n = 761) from small pediatric donors are not recovered. Although risk factors for nonrecovery have been elucidated [6, 22], specific reasons are not well documented in the OPTN database and deserve further consideration, likely at the level of the organ procurement organization. The second tier of opportunity would appear to be at the level of utilization, since a large number of recovered kidneys (n = 401) are discarded. As previously reported, reasons for discard listed in the OPTN database are dominated by two noninformative categories (“missing” or “other”) accounting for approximately half of the cases. For the remaining cases, dominant concerns relate to organ anatomy/organ damage (30%), organ function/donor medical history (10%) and, finally, recipient issues (<10%). The third and final tier of opportunity would be more aggressive splitting of the transplanted kidneys. Since the risk-benefit considerations for SKT versus EBKT change with donor weight, we have presented data in single kg weight strata (Table 5). Moreover, we have accounted for the anticipated “cost” of performing SKTs, as reflected by the increased numbers of grafts that would be lost during the first year to arrive at an estimated net gain of functioning grafts 1 year after transplantation.

Therefore, in conclusion, using national registry data with the pros and cons previously delineated, we have dissected, by single kg weight strata, recovery, utilization and outcomes of SKTs and EBKTs involving kidneys from small pediatric donors. EBKT does offer superior 1-year graft survival compared to SKT. However, this incremental benefit to individual recipients comes at the substantial expense of accomplishing one rather than two transplants. We have provocatively shown that even SKTs with kidneys from the smallest of small donors, if performed at an experienced center, yield excellent 1-year outcomes comparable to nonideal SCD transplants and far superior to ECD transplants. Finally, we suspect that the experience of the procurement team may substantially impact the yield of transplantable kidneys—a concept deserving of further exploration. Fundamentally, kidneys from small pediatric donors are healthy and high-quality kidneys with great potential to serve in the long term and bestow the benefit of transplantation to many more ESRD patients. We encourage careful consideration of strategies to optimize procurement as well as allocation/distribution logistics that will increase the number and improve the outcomes of transplantation utilizing kidneys from small pediatric donors.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

This work was supported wholly or in part by Health Resources and Services Administration contract 234-2005-370011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government.

The work in this manuscript originated in UNOS/OPTN Organ Availability Committee (OAC). The authors would like to acknowledge Kim Johnson, the liaison to the OAC, for her tireless work in coordinating the efforts of this group.

Disclosure

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References