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The Promise of Single Kidney Transplants from Small Pediatric Donors

Foster, Bethany J. MD, MSCE1,2,3

doi: 10.1097/TP.0000000000002619
Commentaries
Free

1 Department of Pediatrics, Division of Nephrology, Montreal Children’s Hospital of the McGill University Health Centre, Montreal, QC, Canada.

2 Department of Pediatrics, McGill University, Montreal, QC, Canada.

3 Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada.

Received 28 December 2018. Revision received 4 January 2019.

Accepted 8 January 2019.

Correspondence: Bethany J. Foster, MD, MSCE, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada. (bethany.foster@mcgill.ca).

As the population of people with end-stage renal disease expands, the gap between demand and supply of suitable kidneys for transplantation widens. Older donors or those with important comorbidities—previously, expanded criteria donors (ECDs), and now high kidney donor profile index (KDPI) donors—have proved valuable in helping to meet the need for donor kidneys. Small kidneys from young pediatric donors have been suggested as another potential source of kidneys for transplantation.1-6 However, controversy remains regarding the best approach in using kidneys from small pediatric donors. Some advocate transplantation of single pediatric kidneys to adult recipients, citing outcomes similar or superior to those of ECD kidneys.2,3 Others favor en bloc transplantation of both pediatric donor kidneys to the same recipient. Single kidney transplant offers double the number of transplants compared with en bloc, but may carry a higher risk of vascular or urologic complications and of hyperfiltration injury. While several studies showed better outcomes with en bloc compared with single kidney transplants from small pediatric donors,2,5 others showed comparable, or even superior, outcomes for single kidney transplant than en bloc when the single kidney donor was >14 kg or the donor kidneys were ≥6 to 7 cm in length.1,4 Very small pediatric donors will have a higher KDPI than an ideal donor. However, the accuracy of the KDPI in predicting outcomes with very small donors is not known, and may differ depending on center volume.

Two large registry-based studies compared the outcomes of single kidney transplants from pediatric donors of different sizes.3,5 Both of these showed poorer outcomes with smaller compared with larger pediatric donors. However, when analyses were stratified on center volume, the outcomes of recipients of pediatric donors transplanted at high-volume centers varied little by donor size.5 At high-volume centers, even very small pediatric single kidney transplants showed excellent 1-year graft survival, superior to the outcome of ECD kidneys. Registry-based studies provide the advantage of large numbers, with adequate power to detect relatively small differences in graft outcomes, but lack the rich, detailed data available in single-center studies.

In this issue of Transplantation, Zhu et al7 compare the outcomes of 46 transplants from donors 8 to 36 months old (small kidney group [SKG]: median donor weight 10 kg; median kidney length 6.5 cm) with those of 56 transplants from donors 3 to 12 years old (big kidney group [BKG]: median donor weight 19 kg; median kidney length 8.0 cm). Not only do they compare the rates of delayed graft function, death-censored graft survival, and patient survival between the groups but also they provide detailed information on surgical complications and serial measurements of graft size and function posttransplant. The results are striking. Delayed graft function was less frequent in the SKG than the BKG, and the SKG had 100% death-censored graft survival over a median 30 months of follow-up compared with 98% in the BKG. These excellent outcomes are particularly striking when one considers the fact that 28% in the SKG and 16% in the BKG were donations after circulatory death, and 52% in the SKG and 59% in the BKG were donations after brain death followed by circulatory death (DBCD). Excellent graft outcomes despite the high prevalence of donations after circulatory death and donations after brain death followed by circulatory death likely reflect a greater resilience of pediatric than older donors to ischemia-reperfusion injury.

There were no transplants with primary nonfunction and no graft thromboses. Thrombosis is one of the most feared complications of transplants from pediatric donors.8 Other studies suggested that thrombosis risk is greatly reduced when the graft is recovered and transplanted on an aortic patch.2,9 This study provides additional evidence that experienced hands and meticulous surgical technique using a Carrell aortic patch and an inferior vena cava cuff may eliminate the high thrombosis risk observed in past studies of pediatric donors.

A serial ultrasound assessment of the grafts revealed a steady increase in graft size in both groups; by 12 months, the average graft measured 10 cm, with no difference in size between the groups. Similarly, the estimated glomerular filtration rate increased over time, reaching ~85mL/min/1.73 m2 by 1 year in both the groups. These findings are encouraging and consistent with the prior observation of graft hypertrophy during the first year.9 However, follow-up was relatively short, with a median of only about 2.5 years; this interval may have been inadequate for hyperfiltration injury to manifest. The high prevalence of proteinuria in the first month after transplant among those in both the groups suggests some elements of kidney injury. Resolution of proteinuria by 1 year is intriguing because ongoing hyperfiltration injury should result in more, not less, proteinuria. This finding requires further investigation over longer follow-up.

The 1-year mortality rate among recipients in the SKG was substantially higher than usually reported for adult kidney transplant recipients, at 10.9% (95% confidence interval, 3.6% to 23.6%). Although none of these deaths could be directly linked to the smaller kidney size, the authors note that severe, antibiotic-related acute kidney injury contributed to the deaths of two patients. They speculate that immature pediatric kidneys may have been less capable of clearing medications, resulting in acute kidney injury. This hypothesis needs to be confirmed. Nevertheless, it is reasonable to advise caution when treating recipients of small pediatric kidneys with potentially nephrotoxic medications; at very least dosing should be appropriately adjusted for renal function.

It is also worth noting that the recipients in the SKG were carefully selected, with a median weight of only 46.5 kg. Even recipients in the BKG, who had a median weight of 55 kg, were smaller than most North American recipients. Larger recipients may not be fare as well with such small kidney donors. The question of whether such small kidneys may be appropriate for pediatric recipients also comes to mind. Given the high risk of graft thrombosis previously observed in pediatric recipients of small pediatric kidneys,8 more data are needed before this could be recommended.

Despite its limitations, the study of Zhu et al7 provides important evidence that single kidneys from small pediatric donors may offer excellent graft function to selected adult recipients. Careful attention to surgical technique and an experienced team appear to be important factors in avoiding the surgical complications that have been previously reported with pediatric donors.

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