Sage Journals: Discover world-class research

Abstract

French

Background:

The use of small pediatric donors (age ≤ 5 years and body weight < 20kg) for adult transplant recipients is still regarded controversially in terms of early complications, long-term outcomes, and development of hyperfiltration injury due to body size mismatch.

Objective:

To investigate long-term outcomes of adult renal allograft recipients receiving a kidney from small pediatric donor (SPD) in terms of kidney function and early features of hyperfiltration injury such as histological changes and proteinuria.

Design:

Retrospective, single center study.

Settings:

Transplant center of the University Hospital of Basel, Switzerland.

Patients:

Adult renal allograft recipients receiving a kidney from a small pediatric donor at our center between 2005 and 2017.

Methods:

The outcome of 47 transplants from SPD were compared with 153 kidney transplants from deceased-standard criteria donors (SCD) occurring during the same time period. Incidence of clinical signs of hyperfiltration injury (eg, proteinuria) was investigated. According to our policy, surveillance biopsies were taken at 3 and 6 months post-transplant and were evaluated in terms of signs of hyperfiltration injury.

Results:

At a median follow-up of 2.3 years post-transplant, death-censored graft survival of SPD was comparable to transplants from SCD (94% vs 93%; P = .54). Furthermore, allograft function at last follow-up (estimated glomerular filtration rate–Modification of Diet in Renal Disease) was significantly higher in pediatric transplant (80 vs 55 ml/min/1.73 m², P = .002). We found histological signs of early hyperfiltration injury in 55% of SPD. There was an equally low proteinuria in both groups during follow-up.

Limitations:

It is a single center and retrospective observational study with small sample size. The outcomes were investigated in a well-selected population of recipients with low body mass index, low immunological risk, and well-controlled hypertension and was not compared with equal selected group of recipients.

Conclusions:

Early histological and clinical signs of hyperfiltration injury in SPD is frequent. Despite the hyperfiltration injury, there is an equal allograft survival and even superior allograft function in SPD compared with SCD during follow-up. This observation supports the concept of high adaptive capacity of pediatric donor kidneys.

Keywords

small pediatric kidney donor hyperfiltration injury allograft biopsy body size mismatch

Introduction

The growing number of patients on the deceased donor renal allograft waiting list has prompted efforts to expand the criteria for acceptable organs, on both ends of the age scale. Presently, kidneys from pediatric donors as single organ or en bloc are frequently used for adult recipients. However, the literature analyzing the outcomes in pediatric donor transplantation reveals inconsistent results: some studies describe an elevated risk of early complications (ie, vascular and ureteral problems) and the development of hyperfiltration injury (ie, focal segmental glomerulosclerosis), whereas some studies report promising results.^1,2 To overcome the risk of early surgical complications and early hyperfiltration injury, small pediatric kidneys donors (SPD) (defined as age < 5 years and body weight < 20 kg) were rather transplanted en bloc than as single kidneys. Single kidney transplantation were only performed well-defined recipients.^3,4 During the last decade, this strategy has been subject to change; today SPD are routinely transplanted as single kidneys if the donor body weight is at least above 10 kg.^5
-9 The selection of recipients in terms of body weight is crucial as there is a significant impact on graft survival and development of hyperfiltration injury, in cases of transplantation with a substantial body weight mismatch between donor and recipient.^10
-13 There are several reports describing an equal or even better the long-term outcome of en-bloc pediatric kidney transplantations compared with living-donor kidney transplantations,^7,14 or standard-criteria-deceased donor kidney transplantation (SCD).^15,16 Recently, register data showed similar long-term outcome of single kidney transplantation with small pediatric donors (weight < 20 kg) compared with SCD.⁵ Despite the comparable long-term outcome concerning glomerular filtration rate (GFR) in these recipients, there are scarce data about development of hyperfiltration injury in these small pediatric donors, especially focusing on proteinuria and histological changes.^17,18 Of note, surveillance biopsies were not performed routinely.

The aim of this retrospective study was to compare long-term outcomes of adult renal allograft recipients receiving a kidney from SPD (age < 5 years and body weight < 20 kg) to SCD. Special attention was paid to early features of hyperfiltration injury such as histological changes and proteinuria.

Materials and Methods

Patient Population

In this retrospective single center study, all pediatric kidney transplantations of donors age < 5 years performed between January 2004 and December 2016 were included. During this time period, a total of 438 deceased donor kidney transplantations were performed at our center. Of these, 47 were transplantation with SPD, 153 were SCD transplantations, and 238 were extended-criteria-deceased donors transplantations. If the donors body weight was < 10 kg, the kidneys were transplanted en bloc, otherwise they were transplanted as single kidney. In total, 9 patients were transplanted with en bloc pediatric kidneys. There was no pediatric donor whose kidneys were transplanted in 2 distinct adult recipients at our center.

To minimize the risk of early hyperfiltration injury in pediatric kidney transplantation, we very carefully selected recipients in terms of body weight and pre-existing hypertension. Only recipients with a body mass index (BMI) < 30 kg/m² and a body weight < 100 kg were allowed to be transplantation with SPD. If there were several recipients suitable for pediatric kidney transplantation, the recipient with the lower BMI was preferred. Only patients without a history of hypertensive nephropathy and on 2 or less antihypertensive medication were suitable for transplantation with SPD. Even if there is no evidence in literature showing an increased immunologic risks in SPD transplantation, only recipients with a low immunological risk (ie, no donor-specific HLA-antibodies detected by single flow-beads and first kidney allograft) were preferred to minimize additional harm for SPD transplantation. The outcome of SPD was compared with the outcome in patients who received a graft from SCD during the same time period. SCD was defined as age < 50 years or age 50 to 59 years with only 1 of the following conditions: cerebrovascular cause of death, creatinine > 132 µmol/l, or hypertension. The local ethics committee of the University of Basel performed this retrospective single center study, after providing approval.

Immunosuppressive Regimen

The immunosuppressive regimen included induction treatment with basiliximab (Simulect, Novartis Pharma Schweiz AG, Bern, Switzerland). Maintenance immunosuppressive therapy changed over time due to different ongoing protocols but consisted of a triple therapy including tacrolimus and prednisone, as well as azathioprine or mycophenolate mofetil (MMF) or an mTOR-inhibitor (everolimus or sirolimus). Tacrolimus was started the day of transplantation, whereas mTOR-inhibitors were started at day 4 after transplantation. Tacrolimus target trough levels were 8 to 12 ng/ml during the first 3 months. Surveillance biopsies were performed at 3 and 6 months. In the absence of subclinical rejection, steroids were withdrawn and patients maintained on a dual therapy, which consisted of either tacrolimus (through level 4-8 ng/ml) and MMF or azathioprine, or an mTOR-inhibitor (trough levels 6-8 ng/ml) and MMF.

Surgical Technique and Perioperative Management

There were no specific changes in standard surgical technique for SPD. All transplantations (SPD and SCD) were only performed by vascular surgeons including anastomosis of the ureter to the bladder. Prophylaxis for vascular thrombosis with heparin 10 000 U per day was started immediately after transplantation if there were no major bleedings. This was later switched to aspirin 100 mg per day for 3 months. Recipients of a SCD received weight adapted low-molecular weight heparin as general thrombosis prophylaxis day 1 after transplantation and until discharge from hospital.

Clinical Outcomes

Currently, there is no knowledge of which formula provides the best accuracy to calculate the estimated glomerular filtration rate (eGFR) in SPD transplantation. Therefore, the Modification of Diet in Renal Disease (MDRD) equation was used to calculate the eGFR as¹⁹ it provides at least a better accuracy of eGFR in adults to adults kidney transplant recipients than the Chronic Kidney Disease Epidemiology Collaboration equation.^20,21 Proteinuria was evaluated by measuring the protein/creatinine-ratio (normal range < 11 mg/mmol) at 6 months after transplantation and annually thereafter. Blood pressure was measured at every visit and was recorded at specified time points. Kidney size was measured immediately after transplantation and 12 months later by ultrasound.

Evaluation of Renal Biopsy

Surveillance biopsies as well as clinical indicated biopsies were evaluated in terms of early hyperfiltration injury defined as mesangial matrix expansion, mesangial hypercellularity, focal segmental glomerulosclerosis or irregular lamination and splintering of the glomerular basement membrane (GBM) on electronic microscopy (EM) picture.¹⁷ The pathological diagnosis of rejection of renal allograft was in accord with the most recent Banff criteria at the time of the study performance.^22,23 The evaluation was performed unblinded to donor type.

Statistical Analysis

Statistical analyses were performed using STATA/MP v.11.0 (Stata Corp, College Station, TX). Discrete variables were expressed as counts (percentage). Non-normally distributed continuous variables were expressed as median and range. For categorical data, we used Fisher exact or Pearson chi-square test. To test equality of median between 2 groups, we used the K-sample equality-of-medians test. Graft survival rates were estimated using Kaplan-Meier analysis, and statistical comparisons of survival curves were done by log-rank test. A 2-tailed P value of < 0.05 was considered statistically significant and confidence intervals (CI) are 95% CI.

Results

Outcomes after SPD (n = 47) were compared with those after SCD (n = 153). Donor and recipient characteristics of both groups are summarized in Table 1. The median recipient weight and BMI were significantly lower in the SPD group compared with the SCD group (weight: 61 kg vs 76 kg, P < 0.001; BMI 22 kg/m² vs 25 kg/m², P < 0.001). Median kidney length was significant less in SPD group compared with SCD group (7.0 cm vs 11.3 cm, P < 0.001). Median cold ischemia time (CIT) was significant longer in the SPD compared with the SCD group because most of these grafts came from other surrounding European countries, due to lack of a transplant program for SPD into adults in these countries (13.9 h vs 8.5 h, P < .001). We observed a similar incidence of delayed graft function between the SPD (23%) and SCD (24%) (P = .9). The median follow-up time was 2.3 (5 days-12.1 years) years.

Table 1.

Baseline Characteristics of the SCD and SPD Group.

	SCD group(n = 153)	SPD group(n = 47)	P value
Recipient
Gender, female, n (%)	54 (35)	23 (49)	.09
Age, years, median (range)	54 (16-75)	53 (20-74)	.50
Weight, kg, median (range)	76 (44-132)	61 (46-99)	<.001
Height, cm, median (range)	172 (152-196)	167 (152-182)	.003
BMI, median (range)	25 (17-41)	22 (17-30)	<.001
Donor
Age, years, median (range)	48 (18-60)	2 (0.5)
Weight, kg, median (range)	75 (45-120)	12 (7-20)
Height, cm, median (range)	173 (140-190)	88 (64-110)
D/R BSA	1.0 (0.6-1.5)	0.3 (0.2-0.4)	<.001
Kidney size in cm, median (range)	11.3 (8-14)	7 (5-9)
Cold ischemia in h, median (range)	8.5 (1.3-20.1)	13.9 (7.4-37)	<.001
Delayed graft function, n (%)	37 (24)	11 (23)	.9
cPRA ≥10%, n (%)	18 (12)	4 (8)	.2
Maintenance treatment
CNI-based, n (%)	152 (99)	46 (98)	.5
Follow-up time, d	760 (5-4418)	1225 (41-3559)	.7

Note. SCD = standard criteria donors; SPD = small pediatric donor; BMI, body mass index; D/R BSA = Donor/Recipient body surface area ratio; cPRA = calculated panel reactive antibodies; CNI = calcineurin inhibitor.

Overall, death-censored graft survival and patient survival were equal between the SPD and SCD group (P = .28 and P = .09, respectively). Compared with the SCD group, median graft function according to the MDRD formula at 1 year was numerically higher in the SPD group (eGFR of 69.7 versus 60.2 ml/min/1.73m², P = .15), and during follow-up (eGFR of 80 ml/min/1.73m² versus 55 ml/min/1.73m², P = .002) (Figure 1). In a subgroup analysis comparing recipients of SPD with recipients of SCD with the same selection criteria in terms of BMI < 30 kg/m² and at least 1 year follow-up, we still found a numerically higher median graft function in the SPD group at 1 year (eGFR of 69.9 versus 59.7 ml/min/1.73m², P = .053) and during follow-up (eGFR of 91 versus 57 ml/min/1.73m², P < .0001).

Figure 1.

Graft function defined by the MDRD formula at 1 year and end of follow-up within the 2 groups.

In an another subgroup analysis comparing SPD with recipients of SCD with an age <50 years (n = 98), we still found a higher eGFR at the end of follow-up (eGFR 80 ml/min/1.73 m² versus 63 ml/min/1.73 m², P = .005, respectively, data not shown).

Median proteinuria (protein/creatinine ratio) was equal between the SPD group (11 mg/mmol) and SCD group (13 mg/mmol) at the end of follow-up (P = .7) (Figure 2). In the SPD group, only 4 patients developed macroalbuminuria during follow-up. Two developed macroalbuminuria due to recurrence of native kidney disease, 1 patient revealed severe focal segmental glomuerlosclerosis (FSGS), and 1 patient suffered from poorly controlled hypertension. In total, we performed 105 renal biopsies in 42 of the SPD group (ie, 78 surveillance biopsies and 27 clinical indicated biopsies).

Figure 2.

The protein to creatinine ratio (mg/mmol) at the end of follow-up stratified by the 2 groups.

We found mesangial matrix expansion in 23/42 (55%) patients, mesangial hypercellularity in 13/42 (31%) patients, and FSGS in 3/42 (7%) patients. In patients with clinical suspicion of significant hyperfiltration injury whenever possible, EM was performed (n = 29). Eight of these (28%) showed splintering of GBM (Table 2). There were 4 patients with recurrence of native kidney disease (3 with an IgA nephritis and 1 with oxalosis due to short bowel disease). Other pathologies were de novo nephrocalcinosis (n = 5) and de novo thrombotic microangiopathy (n = 2). In summary, a total of 23 patients (55%) showed histological signs of early hyperfiltration injury.

Table 2.

Type and Incidence of Histological Signs of Hyperfiltration Injury in Allograft Biopsies in SPD.

	Mesangial matrix expansion	Mesangial hypercellularity	FSGS	EM with splintering of GBM
Clinical indicated biopsies <3 mo	1/8 (13%)	1/8 (13%)	0/8(0%)	0/0
Protocol biopsy at 3 mo	10/38 (26%)	3/38 (8%)	2/38 (5%)	0/2 (0%)
Protocol biopsy at 6 mo	19/40 (48%)	9/40 (23%)	2/40 (5%)	4/15 (27%)
Clinical indicated biopsies >6 mo	8/19 (42%)	7/19 (37%)	1/19 (5%)	4/12 (33%)
Total	38/105 (36%)	20/105 (18%)	5/105 (6%)	8/29 (28%)
Incidence per patient with allograft biopsy (n = 42)	23/42 (55%)	13/42 (31%)	3/42 (7%)	8/21 (38%)^a

Note. FSGS = focal segmental glomuerlosclerosis; EM = electronic-microscopy; GBM = glomerular basement membrane.

Incidence per patient with allograft biopsy and available.

In 135 of SCD patients with an allograft biopsy, 16 (12%) showed histological signs of early hyperfiltration injury, namely 6% (8/135) FSGS, 5% (7/135) mesangial matrix expansion, 3% (4/135) mesangial hypercellularity, and none splintering of GBM.

The median blood pressure was 127/74 mmHg at month 3, 131/78 mmHg at months 6, 132/75 mmHg at months 12, and 133/78 mmHg at last follow-up. The patients were on a median of 1.78 blood pressure medications (range: 0-5). There were 77% of patient on a RAAS-Inhibition. Only single agent was used for RAAS-Inhibition.

The overall risk of any clinical or subclinical rejection was equal between the SPD and SCD group (P = .15 and P = .85, respectively). Also the type of rejection episodes (antibody mediated rejection and T -cell mediated rejection) were equal (P = .37 and P = .23, respectively, data not shown). During follow-up, there was a continuing growth of kidney size observed in the SPD group with a median length growth by 28.6% from 7.0 cm up to 9.0 cm. We observed equal incidence of surgical complications within the first year postoperative (P = .94, data not shown).

Discussion

In our single center retrospective study, we found an equal graft function at 1 year with a steady rise of the GFR during follow-up leading to a significantly higher eGFR in the SPD group compared with the SCD group (eGFR of 80 ml/min/1.73 m² versus 55 ml/min/1.73 m², P = .002). This observation reinforces our strategy to use single kidney from pediatric donors for transplantation even in very small donors. In the past, there have been concerns about a reduced long-term allograft function caused by hyperfiltration injury in SPD, with possible low or insufficient nephron mass. To reduce the main risk factor for hyperfiltration injury namely, the donor recipients weight mismatch, we selected only recipients for SPD if the BMI was < 30 kg/m² and a maximum body weight of 100 kg. Consequently, the BMI in the SPD group was significant lower (22 kg/m² vs. 25 kg/m², P < .001). But even in the subgroup analysis with SCD with the same selection criteria in terms of BMI < 30 kg/m² and a follow-up of at least 1 year, we found a significantly higher eGFR in the SPD group compared with the SCD group at 1 year (eGFR of 69.9 versus 59.7 ml/min/1.73m², P = .053), and during follow-up (eGFR of 91 versus 57 ml/min/1.73m², P < .0001). In this subgroup analysis, despite the same selection criteria of BMI < 30 kg/m², BMI in the SPD group still remained significant lower (22.3 kg/m² vs 24.7 kg/m², P = .05). In addition, we also selected recipients without history of severe hypertension and on <2 antihypertensive medications. Nevertheless, we found histological signs of hyperfiltration injury in 55% of SPD. However, the presence of early histological signs of hyperfiltration injury was not leading to high incidence of proteinuria during follow-up. We found proteinuria in 14/47 (30%) of SPD, most of them were in the range of microalbuminuria (n = 10/14). Two out of the 4 patients with macroalbuminuria had recurrence of their native kidney disease. An important therapeutic intervention to prevent microalbuminuria was the rigorous control of the blood pressure in these patients. Zhang showed that early initiation of renin angiotensin aldosterone system (RAAS) inhibitors and aggressively treatment of blood pressure with a target of < 130/80 mmHg during the early post-transplant phase in recipients with SPD has a favorable impact of long-term graft survival.²⁴ In fact, 77% of our SPD recipients were on RAAS-inhibitor treatment, and 91% of the patients had at least 1 antihypertensive medication. The median blood pressure during the early post-transplant phase in these patients was 127/74 mmHg, perfectly in the target range. Whether in the future renal transplant recipients including recipients of SPD will benefit from a therapy with a sodium-glucose linked transporter 2 inhibitor for reduction of proteinuria and hyperfiltration injury is not yet known.

Allograft adaption with allograft hypertrophy is a well-known phenomenon in SPD. Basiri et al²⁵ showed that there is a substantial growth in kidney size during the first 12 months with a lower additional growth between months 12 to 18 in SPD. They observed a median kidney length growth of 37 mm during the first 12 months, with further rise to 43 mm until months 18. We found also an allograft hypertrophy in our SPD group, but the median kidney growth was slightly lower with 20 mm during the first 12 months. This hypertrophic adaption in single kidney transplantation has also seen in kidneys from adult donors but it is significant less in these patients and the adaption is seen only in the first few months after transplantation, whereas in pediatric donors the adaptive capacity is seen up to 6 years after transplantation.²⁶ In the literature, there are several data reporting poorer outcomes in transplantation with significant body weight mismatch.^10,11,27 This may not hold true in pediatric donors since the adaptive capacity is able to compensate the size mismatch.²⁸ In fact, the adaptive capacity of pediatric kidneys is most probably the main factor for the comparable results in recipient of SPD with even higher BMI (>30 kg/m²) or body weight > 100 kg.²⁹ The permitted upper limit of the recipient’s BMI or body weight is still not defined and requires further investigations.

CIT was significant longer in SPD group (13.9 h vs 8.5 h, P < .001). Kayler et al³⁰ found a very small but significant impact of CIT on graft survival in kidney transplant from small pediatric donors only if the CIT exceeded 18 hours with a HR of 1.37 (CI 1.04-1.81). Therefore, they suggested that ischemic injury is likely a reversible lesion especially in pediatric kidneys. In adult donors, the effect of CIT on the outcome in terms of graft survival and delayed graft function is more pronounced and starts already if CIT exceeds 14 hours.³¹ Similarly, Hansson et al³² observed an increase of 8% of graft failure per any hour of increase in CIT.

Pediatric kidney transplantation is associated with elevated risk of surgical complications due to small vessel and ureter size with the risk of thrombotic complications, renal artery stenosis and urinary leaks.^33,34 We found an equal low surgical complications rate in our SPD compared with SCD.

This study has some limitations. First, it is a single center and retrospective observational study with small sample size. Second, the good clinical outcome was achieved in a well-selected population of recipients with low BMI, low immunological risk, and well-controlled hypertension and was not compared with equal selected group of recipients, especially in terms of BMI. So, there is a uncertainty whether the observed equal death-censored graft survival and allograft function would be observed in a well-matched control group. Third, the transplantations were performed by dedicated vascular surgeons with improved knowledge and handling of technical complications. Fourth, the evaluation of the allograft biopsies was not blinded to donor type, so there is a risk of overdiagnosis of hyperfiltration injuries in these recipients. As we did not perform an allograft biopsy at the time of transplantation, there might be an overestimation of hyperfiltration injury in SCD as we could not rule out pre-existing hyperfiltration injury, whereas it is very unlikely in pediatric donors. Fifth, there might be a lower risk of rejection episodes leading to better allograft outcomes in SPD compared with SCD due to selection of low immunological risk in these recipients, although the SCD recipients happened to have the same low immunological risks (cPRA ≥ 10% was not different between the groups, P = .2).

Whether these good results could be achieved in an unselected population and not experience transplant team is unknown.

In conclusion, early clinical and histological signs of hyperfiltration injury is frequent in SPD, even in a well-selected recipient population. Despite the hyperfiltration injury, we observed an excellent long-term allograft survival and superior long-term allograft function in SPD compared with SCD. Our observation supports the concept of high adaptive capacity of pediatric kidneys and the importance of early rigorous blood pressure control in these patients.

Footnotes

List of Abbreviations

BMI, body mass index; CIT, cold ischemia time; eGFR, estimated glomerular filtration rate; EM, electronic microscopy picture; FSGS, focal segmental glomerular sclerosis; GBM, glomerular basement membrane; HLA, human leukocyte antigen system; MDRD, modification of diet in renal disease; MMF, mycophenolate mofetil; mTOR, mammalian target of rapamycin; RAAS, renin angiotensin aldosterone system; SCD, standard criteria deceased donor; SPD, small pediatric deceased donor.

Ethics Approval and Consent to Participate

This retrospective study was approved by the ethic committee of Northwestern and Central Switzerland (Project ID 2018_01571).

Consent for Publication

Not applicable.

Availability of Data and Materials

Data will be available upon request from the corresponding author.

Author Contributions

Participated in the research design: F.B., Y.H., S.S., and P.A. Participated in the writing of the paper: F.B., Y.H., and P.A. Participated in the performance of the paper: F.B., Y.H., A.G., C.W., P.H., G.H., H.H., L.G., J.S., S.S., and P.A. Participated in the data analysis: F.B., Y.H., and P.A.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Felix Burkhalter

References

Maluf

Carrico

Rosendale

Perez

Feng

Optimizing recovery, utilization and transplantation outcomes for kidneys from small, ≤20 kg, pediatric donors. Am J Transplant. 2013;13(10):2703-2712. doi:10.1111/ajt.12410.

Thomusch

Tittelbach-Helmrich

Meyer

Drognitz

Pisarski

Twenty-year graft survival and graft function analysis by a matched pair study between pediatric en bloc kidney and deceased adult donors grafts. Transplantation. 2009;88(7):920-925. doi:10.1097/TP.0b013e3181b74e84.

Dharnidharka

Stevens

Howard

RJ.

En-bloc kidney transplantation in the United States: an analysis of United Network of Organ Sharing (UNOS) data from 1987 to 2003. Am J Transplant. 2005;5(6):1513-1517. doi:10.1111/j.1600-6143.2005.00878.x.

Pelletier

Guidinger

Merion

, et al. Recovery and utilization of deceased donor kidneys from small pediatric donors. Am J Transplant. 2006;6(7):1646-1652. doi:10.1111/j.1600-6143.2006.01353.x.

Suneja

Kuppachi

Katz

Hunsicker

Small Split pediatric kidneys to expand the donor pool: an analysis of scientific registry of transplant recipients (SRTR) data. Transplantation. 2019;103(12):2549-2557. doi:10.1097/TP.0000000000002706.

Mohanka

Basu

Shapiro

Kayler

LK.

Single versus en bloc kidney transplantation from pediatric donors less than or equal to 15 kg. Transplantation. 2008;86(2):264-268. doi:10.1097/TP.0b013e318177894e.

Sureshkumar

Habbach

Tang

Chopra

Long-term Outcomes of pediatric en bloc compared to living donor kidney transplantation: a single-center experience with 25 years follow-up. Transplantation. 2018;102(5):e245-e248. doi:10.1097/TP.0000000000002104.

Gröschl

Wolff

Gürke

, et al. Intermediate-term outcome of single kidney grafts from pediatric donors weighing 10-14 kg in adult recipients. Clin Transplant. 2013;27(3):E302-E307. doi:10.1111/ctr.12115.

Fayek

Ali

Hasham

Herbert

Allam

Rofaiel

Expanding the envelope: favorable outcomes utilizing kidneys from small pediatric donors (≤ 15 kg). Transplant Proc. 2018;50(10):3204-3210. doi:10.1016/j.transproceed.2018.04.037.

10.

Dick

Mercer

Smith

McDonald

Young

Healey

PJ.

Donor and recipient size mismatch in adolescents undergoing living-donor renal transplantation affect long-term graft survival. Transplantation. 2013;96(6):555-559. doi:10.1097/TP.0b013e31829d672c.

11.

Miller

Kiberd

Alwayn

Odutayo

Tennankore

KK.

Donor-recipient weight and sex mismatch and the risk of graft loss in renal transplantation. Clin J Am Soc Nephrol. 2017;12(4):669-676. doi:10.2215/CJN.07660716.

12.

Zhu

Chen

, et al. Successful single-kidney transplantation in adult recipients using pediatric donors aged 8 to 36 months: comparable outcomes with those using pediatric donors aged >3 years. Transplantation. 2019;103(11):2388-2396. doi:10.1097/TP.0000000000002618.

13.

Goldberg

Smits

Wiseman

AC.

Long-term impact of donor-recipient size mismatching in deceased donor kidney transplantation and in expanded criteria donor recipients. Transplantation. 2010;90(8):867-874. doi:10.1097/TP.0b013e3181f24e75.

14.

Sharma

Fisher

Cotterell

King

Maluf

Posner

MP.

En bloc kidney transplantation from pediatric donors: comparable outcomes with living donor kidney transplantation. Transplantation. 2011;92(5):564-569. doi:10.1097/TP.0b013e3182279107.

15.

Kayler

Magliocca

Kim

Howard

Schold

JD.

Single kidney transplantation from young pediatric donors in the United States. Am J Transplant. 2009;9(12):2745-2751. doi:10.1111/j.1600-6143.2009.02809.x.

16.

Bhayana

Kuo

Madan

, et al. Pediatric en bloc kidney transplantation to adult recipients: more than suboptimal? Transplantation. 2010;90(3):248-254. doi:10.1097/TP.0b013e3181e641f8.

17.

Choung

Meleg-Smith

Glomerulopathy in adult recipients of pediatric kidneys. Ultrastruct Pathol. 2014;38(2):141-149. doi:10.3109/01913123.2014.888112.

18.

Jiang

Liang

Zhong

, et al. Pediatric donor glomerulopathy is a possible cause of proteinuria and/or hematuria in adults receiving small pediatric donor kidneys. Transplantation. 2020;104:S11-S103. doi:10.1097/tp.0000000000003038.

19.

Levey

Bosch

Lewis

, et al. Modification of diet in renal disease study group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130:461-470.

20.

Masson

Flamant

Maillard

, et al. MDRD versus CKD-EPI equation to estimate glomerular filtration rate in kidney transplant recipients. Transplantation. 2013;95(19):1211-1217.

21.

Utiel

Navarro

de la Rosa

, et al. Comparison of MDRD equations and the old equations CKD-EPI against new equations CKD-EPI in patients with kidney transplantation when used 51Cr-EDTA to measure glomerular filtration. Nefrologia. 2020;40(1):53-64.

22.

Haas

Sis

Racusen

, et al. Banff 2013 meeting report: inclusion of C4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014;14:272-283. doi:10.1111/ajt.12590.

23.

Sis

Mengel

Haas

, et al. Banff ’09 meeting report: antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant. 2010;10:464-471. doi:10.1111/j.1600-6143.2009.02987.x.

24.

Zhang

Laguardia

Paramesh

, et al. Early inhibition of the renin-angiotensin system improves the long-term graft survival of single pediatric donor kidneys transplanted in adult recipients. Transpl Int. 2013;26(6):601-607. doi:10.1111/tri.12087.

25.

Basiri

Zare

Simforoosh

Tabibi

Shakibi

MH.

Comparison of renal growth, proteinuria and graft survival between recipients of pediatric and adult cadaveric kidney transplants. Int J Organ Transplant Med. 2017;8(2):97-103. http://www.ncbi.nlm.nih.gov/pubmed/28828169. Accessed April 6, 2020.

26.

Dubourg

Cochat

Hadj-Aïssa

Tydén

Berg

UB.

Better long-term functional adaptation to the child’s size with pediatric compared with adult kidney donors. Kidney Int. 2002;62(4):1454-1460. doi:10.1111/j.1523-1755.2002.kid576.x.

27.

Giral

Foucher

Karam

, et al. Kidney and recipient weight incompatibility reduces long-term graft survival. J Am Soc Nephrol. 2010;21(6):1022-1029. http://www.ncbi.nlm.nih.gov/pubmed/20488949. Accessed April 6, 2020.

28.

Müller-Deile

Bräsen

Pollheimer

, et al. Graft growth and podocyte dedifferentiation in donor-recipient size mismatch kidney transplants. Transplant Direct. 2017;3(10):e210. doi:10.1097/txd.0000000000000728.

29.

Zhang

Paramesh

Florman

, et al. Long-term outcome of adults who undergo transplantation with single pediatric kidneys: how young is too young? Clin J Am Soc Nephrol. 2009;4(9):1500-1506. doi:10.2215/CJN.04610908.

30.

Kayler

Lubetzky

Friedmann

Influence of Cold ischemia time in kidney transplants from small pediatric donors. Transplant Direct. 2017;3(7):e184. doi:10.1097/txd.0000000000000668.

31.

Wong

Teixeira-Pinto

Chapman

, et al. The impact of total ischemic time, donor age and the pathway of donor death on graft outcomes after deceased donor kidney transplantation. Transplantation. 2017;101(6):1152-1158. doi:10.1097/TP.0000000000001351.

32.

Hansson

Mjörnstedt

Lindnér

The risk of graft loss 5 years after kidney transplantation is increased if cold ischemia time exceeds 14 hours. Clin Transplant. 2018;32(9):e13377. doi:10.1111/ctr.13377.

33.

Satterthwaite

Aswad

Sunga

, et al. Outcome of en bloc and single kidney transplantation from very young cadaveric donors. Transplantation. 1997;63(10):1405-1410. doi:10.1097/00007890-199705270-00006.

34.

Bresnahan

McBride

Cherikh

Hariharan

Risk factors for renal allograft survival from pediatric cadaver donors: an analysis of united network for organ sharing data. Transplantation. 2001;72(2):256-261. doi:10.1097/00007890-200107270-00016.

Excellent Clinical Long-Term Outcomes of Kidney Transplantation From Small Pediatric Donors (Age ≤ 5 Years) Despite Early Hyperfiltration Injury

Abstract

Background:

Objective:

Design:

Settings:

Patients:

Methods:

Results:

Limitations:

Conclusions:

Keywords

Introduction

Materials and Methods

Patient Population

Immunosuppressive Regimen

Surgical Technique and Perioperative Management

Clinical Outcomes

Evaluation of Renal Biopsy

Statistical Analysis

Results

Discussion

Footnotes

List of Abbreviations

Ethics Approval and Consent to Participate

Consent for Publication

Availability of Data and Materials

Author Contributions

Declaration of Conflicting Interests

Funding

ORCID iD

References