Dual and Pediatric En-Bloc Compared to Living Donor Kidney Transplant: A Single Center Retrospective Review

: Safely expanding the use of extended-criteria organ donors is critical to increase access to kidney transplantation and reduce wait list mortality. We performed a retrospective analysis of 24 pediatric en-bloc (PEB) compared to 13 dual-kidney transplantations (DKT) and 39 living donor kidney transplants (LDKT) at the University of Virginia hospital, performed between 2011 and 2019. All living donor kidney transplants were performed in 2017. This year was chosen so that 5-year outcomes data would be available. Primary outcomes were glomerular filtration rate and serum creatinine at 12 and 24 months postoperatively. Secondary outcomes were patient and graft survival. The 1-year creatinine levels (mL/min/1.73 m 2 ) were lower in the PEB group (median 0.9, IQR 0.8–1.4) when compared to the DKT (median 1.4, IQR 1.2–1.5) and LDKT (median 1.3, IQR 1.1–1.5) groups ( p < 0.001). The 2-year creatinine levels (mL/min/1.73 m 2 ) were also lower in the PEB group (median 0.8, IQR 0.7–1.08) compared to the DKT (median 1.3, IQR 1.1–1.5) and LDKT (median 1.3, IQR 1.0–1.5) groups ( p < 0.001). The glomerular filtration rates demonstrated similar results. Graft survival at 1, 3, and 5 years was 100/100/90, 100/92/69, and 96/96/91 for LDKT, DKT, and PEB, respectively ( p = 0.27). Patient survival at 1, 3, and 5 years was 100/100/90, 100/100/88 and 100/100/95 for LDKT, DKT, and PEB, respectively ( p = 0.78). Dual KT and PEB transplantation are two alternative techniques to safely expand the donor pool. PEB kidney transplantation, though technically more demanding, provides the best long-term graft function.


Introduction
The demand for organ transplantation exceeds the availability of donated organs.From 2006 to 2014, the kidney transplant wait list in the US increased from approximately 68,000 to over 100,000 patients, and subsequently stabilized [1].This number saw a decline due to the COVID-19 pandemic; however, this has since rebounded, and the number of waitlisted patients exceeded 139,000 in 2021.Despite the high demand for kidneys, one in four donated kidneys is not utilized, and fewer patients are willing to accept high-kidney donor profile index (KDPI) kidneys [2].
The aim of this study was to provide modern data on PEB, with the new addition of the use of infants below 10 kg and a newly initiated DKT program for high-KDPI kidneys to understand its value in safely increasing organ utilization.

Study Design
We performed a retrospective chart review of all DKT and PEB transplants performed at the University of Virginia from 2011 to 2019.This was performed under approval by the institutional review board (IRB).In total, 24 PEB and 13 DKT were performed during the study period.Out of the 24 PEB donors, 9 were ≤10 kg.Data from a control group of 39 patients who underwent LDKT were collected (all transplants occurred in 2017).This year was chosen so that 5-year outcomes data would be available for these recipients.Primary outcomes were glomerular filtration rate (GFR) and serum creatinine at 1 and 2 years postoperatively.Secondary outcomes were patient and graft survival.We compared recipient and donor baseline characteristics, as well as length of stay (LOS), dialysis duration, freedom from dialysis post-transplant, and readmissions in the first year in the recipients.

Selection Criteria
Selection criteria for PEB included donor weight ≤ 10 kg and donor age ≤ 3 years.The recipient criteria for PEB were BMI < 25 kg/m 2 and mild or no arterial calcifications, although the BMI was flexible based on recipient body habitus and weight distribution.Selection criteria for DKT were KDPI > 85%, grafts with suitable arterial anatomy to safely perform an anastomosis, donor age > 60 years, allograft biopsy demonstrating glomerulosclerosis > 15%, and donor hypertension and diabetes mellitus.Exclusion criteria were recipients with severe vascular calcifications and/or BMI > 31 kg/m 2 .All recipients consented appropriately.

Operative Procedure
For DKT, the surgical approach may consist of bilateral Gibson incisions with an allograft on each side, unilateral Gibson incision with placement of both allografts in the same iliac fossa, or a midline intraperitoneal approach.The vessels are anastomosed end-to-side, preferentially to the external iliac vessels of the recipient.Extra-vesical uretero-neocystostomy is performed individually for each ureter according to the Lich-Gregoir technique.
For PEB, the kidneys are recovered en-bloc at the donor center.The kidneys are prepared for implantation on the backtable, with care taken to ligate the small aortic and inferior vena cava lumbar branches.The supra-renal aorta and vena cava are closed individually with 5-0 or 6-0 Prolene.Implantation proceeds via standard Gibson incision, preferentially on the right side.The caudal ends of the aorta and vena cava are anastomosed to the iliac vessels using 6-0 or 7-0 Prolene.The ureters are either sutured together using 6-0 polydioxanone suture and then transplanted into the urinary bladder by use of an extra-vesicular method, or individually sutured to the bladder using the Lich-Gregoir technique.Here, the bladder patch technique was not used.The kidneys are carefully positioned to prevent torsion or kinking of the vessels.

Immunosuppression
All patients received a single dose of pre-operative antibiotic prophylaxis, methylprednisolone, and thymoglobulin for induction (3-6 mg/kg).Immunosuppression was administered based on our center's protocol with maintenance immunosuppression consisting of tacrolimus, mycophenolate mofetil, and prednisone, with dose adjustment to achieve therapeutic effects on an individual basis.

Statistical Analysis
Continuous variables are presented as median (interquartile range) or mean (SD) based on the distribution of the data.Categorical data are presented as count (percentages).Continuous variables were compared using the independent two-sample t-test, Mann-Whitney U-test or one-way analysis of variance (ANOVA) according to the normality of the data distribution and number of groups to compare.Post-hoc tests were conducted using Bonferroni correction and Tukey's HSD test procedures, as appropriate, to perform pairwise comparisons between groups when the p-value was ≤0.05.For categorical data, the Pearson Chi-Square test or Fisher's exact test were used as appropriate.The Kaplan-Meier method was used to analyze the actuarial graft and patient survival between study groups, and the groups were compared using a log-rank test.Event (yes/no) for graft survival was defined as per OPTN definition (time between transplant and any of the following events: a recipient's transplanted organ is removed, a recipient dies, a recipient is placed on chronic allograft support system).For all analyses, two-tailed p-values ≤ 0.05 were considered statistically significant.All analyses were performed using IBM SPSS Statistics Version 28.

Complications
The post-operative complications are summarized in Table 4.These were based on the Clavien-Dindo classification [28].The majority of complications w nor (grade 1 and 2).The DKT group experienced the highest proportion of grade above complications.No grafts were lost in the LD group.The reasons for graf the DKT group included one case of chronic allograft nephropathy and one chronic rejection.In the PEB group, reasons for graft loss included one case of v thrombosis on post-operative day 1 and one patient with chronic interstitial fibr tubular atrophy.In the LD group, four patients died with a functioning graft; in t group, this was one patient, and in the PEB group it was two patients, with ano tient in the PEB group dying without a functioning graft.

Complications
The post-operative complications are summarized in Table 4.These were graded based on the Clavien-Dindo classification [28].The majority of complications were minor (grade 1 and 2).The DKT group experienced the highest proportion of grade 3a and above complications.No grafts were lost in the LD group.The reasons for graft loss in the DKT group included one case of chronic allograft nephropathy and one case of chronic rejection.In the PEB group, reasons for graft loss included one case of vascular thrombosis on postoperative day 1 and one patient with chronic interstitial fibrosis and tubular atrophy.In the LD group, four patients died with a functioning graft; in the DKT group, this was one patient, and in the PEB group it was two patients, with another patient in the PEB group dying without a functioning graft.

Discussion
The demand for kidneys far outpaces the available organs in the deceased donor pool.The 5-year life expectancy on dialysis is approximately 50%, whereas with transplant it is well over 80% [29].Kidney transplantation is extending the life expectancy of patients with end-stage renal disease.As such, it is important to limit organ non-utilization, and we demonstrate here that PEB and DKT show results comparable to those of LDKT.
Overall, PEB transplants show significantly better 1-and 2-year serum creatinine and GFR compared to LDKT and DKT, which is consistent and comparable to already-published data [3,9,12,17].While no statistical difference in graft survival is noted in our series, this is a low-powered study, and the results highlight the expectedly higher quality of living donor kidneys (numerically improved graft survival), while also indicating lower graft survival for high-KDPI kidneys.The technical pitfalls of accepting PEB kidneys are illustrated in our series, as the graft loss experienced by one of the recipients was the result of venous thrombosis and outflow obstruction, a well-described complication of this operation.PEB has a higher rate of graft failure reported in the literature (mostly early), with surgical complication and early graft thrombosis accounting for this result [17,[21][22][23][24].We consider the initiation of early anticoagulation (it is our center's practice to use low-dose intravenous heparin infusion for the first several days, typically 300-500 units/hour).These allografts require a technical expertise: the backtable preparation is typically an hours-long process, and requires meticulous dissection and careful preservation of the tiny renal veins and arteries during ligation of the lumbar arteries and veins, and the oversewing of the aorta and vena cava.We also typically lay the allografts so that the vessels lie parallel to the external iliac vessels.It is crucial to individualize the approach to best suit the recipient.Given prior published data indicating that PEB have graft survival compared to ideal (e.g., living donors) donors, these grafts should preferentially be utilized in younger recipients with higher expected post-transplant survival (EPTS) [19].We prefer to implant these into leaner recipients, to limit the technical difficulty of implantation in an otherwise highly technical procedure.
For elderly and borderline frail patients in particular, a longer time on the waitlist correlates with a higher rate of mortality and morbidity [12,27].It has been estimated that 46% of the waitlisted patients over 60 years may die waiting for a transplant [30].It is imperative to provide a pathway to transplant these patients in a timely fashion.One such pathway is to use extended-criteria kidneys, including from donors with >85% KDPI.A high KDPI can correlate with reduced nephron mass, high immunogenicity and reduced repair capacity [12].Some high-KDPI kidneys show inferior graft survival when compared to standard criteria donors with lower KDPI, but well-selected high-KDPI kidneys can have similar outcomes [31].KDPI interpretation in DKT is difficult.In fact, past investigations have shown that high-KDPI DKT transplantations have lower overall allograft failure rates and better patient survival rates than ECD single-kidney transplants [32][33][34].Still, kidneys with a KDPI > 90% still have much higher discard rates than those with a KDPI < 80%, even though they could be used for DKT [32].There is room for improvement to decrease the rate of non-utilization in these kidneys.
Our analysis demonstrates that DKT allows for a shorter time on the waitlist, especially in the elderly (the median age at transplant for DKT recipients in our series was 65 years).Our practice with marginal kidneys (criteria described above) is to decline a single kidney, but accept if the organ procurement organization is willing to allocate both kidneys.We will oftentimes advocate for open offers and find the next suitable candidate from our waitlist that meets the previously described criteria.This can be labor-intensive, but careful recipient selection can still lead to a good transplant outcome with favorable outcomes when compared to remaining on dialysis.By transplanting two marginal-quality kidneys in DKT, comparable 5-year graft outcomes can be achieved.
Overall, both procedures increase the kidney donor pool and decrease not only waiting time, but also the number of patients on the waitlist, which again lowers mortality and morbidity in ESRD patients.However, each approach has its limitations.Efforts should be focused on limiting technical complications and adhering to defined graft and recipient selection criteria.
Our study has several limitations.Retrospective data analysis is non-randomized, and therefore subject to inherent bias.The sample size of our population limits the statistical analysis in many ways; however, statistical significance was demonstrated in several instances.The length of time across the study may contribute to bias, as well as differences in technique between the surgeons performing the implantation (four surgeons performed the transplants).We had a large proportion of white male LDKT recipients (80%) and white female living kidney donors (74%), and as such our results may not be generalizable to more diverse populations.This exposes the larger problem of poor access to transplantation among minorities, and we have focused our efforts over the last several years on improving this situation at our center.In addition, we prefer to place DKTs on pump; however, only 6 of the 13 (46.2) DKTs performed during the study period were pumped.We did not control for this, and therefore this confounds some of the results of the DKT group.