NDT Advance Access originally published online on July 22, 2006
Nephrology Dialysis Transplantation 2006 21(9):2596-2600; doi:10.1093/ndt/gfl119
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Dialysis and Transplantation
Superior long-term graft function and better growth of grafts in children receiving kidneys from paediatric compared with adult donors
1 Department of Pediatric Nephrology and 2 Department of General, Visceral and Transplant Surgery, Medical School of Hannover, Germany
Correspondence and offprint requests to: PD Dr med. L. Pape, Department of Pediatric Nephrology, Medical School of Hannover, D-30623 Hannover, Germany. Email: larspape{at}t-online.de
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Abstract |
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Background. Organs from paediatric donors are often not accepted for paediatric recipients because previous reports suggested inferior graft function for small kidneys transplanted in children. On the other hand, studies have shown that kidneys of adult donors transplanted into children down-regulate filtration after transplantation and may not increase their function to the need of the growing child.
Methods. We assessed 64 male and 35 female (total n = 99) white children aged <10 years (male: mean 5.1 years, SD 2.8; female: mean 5.8 years, SD 3.4) who had received cadaveric kidney transplants at our centre between 1990 and 2005. Mean observation time was 5.9 years, SD 4.0. The children were divided into two groups depending on the kidney donor age: 63 children (mean age 5.0 years, SD 2.9) received an organ of an adult, and 39 (mean age 6.4 years, SD 3.4) of a paediatric donor. Immunosuppression was performed with prednisolone, cyclosporin A microemulsion±mycophenolate mofetil.
Results. Three to five years after transplantation the calculated glomerular filtration rate corrected to body surface was significantly higher in recipients of paediatric organs. The size of paediatric grafts doubled in the first years after transplantation while adult grafts had a stable size. Graft survival was comparable in both groups during observation time.
Conclusions. We conclude that paediatric donor kidneys should be given preferentially to paediatric recipients due to better long-term function.
Keywords: children; glomerular filtration rate; kidney transplantation; long-term survival; paediatric
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Introduction |
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It has been shown that adult donor kidneys in paediatric recipients down-regulate glomerular filtration rate (GFR) in the early stages and lack an increase in GFR with the growth of the child [1]. It was speculated that graft survival and graft function of paediatric grafts implanted into paediatric donors may be superior to that of grafts derived from adult donors [1]. In the first year after transplantation, no difference in GFR and graft survival was demonstrated in children receiving grafts from adult or paediatric donors [2]. Looking at GFR up to 6 years after transplantation, Gellert et al. [2] described that adult-sized grafts adapted to paediatric recipients during the first months post-transplantation but graft function then did not improve along with the increase in body size of the recipient. The absolute GFR of children receiving paediatric grafts increased along with body growth leading to a stable relative GFR up to 6 years post-transplantation [3]. With a few exceptions [4], graft survival of single renal transplants from donors <5 years have been inferior to those from older paediatric donors. Astonishingly, kidneys from paediatric donors of all ages are often not primarily allocated to paediatric recipients, i.e. in the Eurotransplant allocation system. It has recently been shown that 1-year graft survival and graft function of paediatric organs in adult recipients are comparable with grafts from older donors even in adult recipients [5]. However, no data have been published comparing long-term graft survival and kidney function of adult with paediatric grafts in paediatric recipients.
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Patients and method |
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TopAbstractIntroductionPatients and methodResultsDiscussionReferences |
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We assessed 64 male and 35 female (total n = 99) Caucasian children aged <10 years (male: mean 5.1 years, SD 2.8; female: mean 5.8 years, SD 3.4) receiving a first cadaveric kidney transplantation at our centre between 1990 and 2005. Mean observation time was 5.9 years, SD 4.0. The children were divided into two groups, depending on kidney donor age: 60 children (mean age 5.0 years, SD 2.9) received an organ of an adult (age 17–48 years) and 39 (mean age 6.4 years, SD 3.4) of a paediatric donor (age <16 years). Within the paediatric donor group, one donor was aged 2 years, two donors were 4 years old and the other donors had an age above 5 years. Immunosuppression was performed with prednisolone and cyclosporin A microemulsion±mycophenolate mofetil (all patients from 1998 onwards). Cyclosporin A was started 8 h after transplantation with target trough levels of 200–250 ng/ml in the first months after transplantation and 150–200 ng/ml thereafter. There was no difference in patient management when kidneys of donors <5 years were transplanted. Three patients in the adult donor group and one in the paediatric group were changed to tacrolimus. In each group, one patient stopped taking a calcineurin-inhibitor and started sirolimus in the first 5 years after transplantation. No en bloc grafts were used. Anticoagluation was performed with heparin 200 IE/kg/day over 2 weeks.
We recorded time and reason of graft loss for every patient as well as yearly weight, height, creatinine, blood urea nitrogen and kidney volume measured by ultrasound. The relative GFR corrected to body surface was calculated for the first 5 years after transplantation from serum creatinine and body height, according to Schwartz et al. [6]. Although the Schwartz formula tends to overestimate the true GFR and is not an exact measure, the systematic error allows an acceptable accuracy for GFR determination. The formula GFR = kL/Pcr was used with a k of 38 in all children as all were aged between 1 and 10 years. We have shown that there has been an acceptable correlation of approximated GFR after the Schwartz formula and the GFR measured by insulin-clearance in our centre [7] previously. The number of HLA-mismatches in HLA-A, HLA-B and HLA-DR was documented in each patient and the mean values of HLA mismatches have been calculated in the paediatric donor group with 2.5 SD 1.1 and in the adult donor group with 2.6 SD 1.2.
The unpaired t-test and analysis of covariance (ANOVA) were employed for statistical analysis by SPSS 13.0 for Windows software package. ANOVA was performed as a univariate analysis of variances with tests of between-subject factors in a saturated mode. P<0.05 was judged to be significant. In the figures, mean values and standard deviation are given. In the analysis of GFR, only patients with a 5-year follow-up were included, whereas survival analyses were performed for all patients.
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Results |
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Mean donor age was 36 years, SD 13 in the adult donor group and 9 years, SD 4 in the paediatric donors. No donor was older than 50 years. Graft survival was comparable in both groups during the first 15 years (Figure 1). None of these three grafts of young donors below 5 years was lost within the first 10 years after transplantation. No graft was lost due to graft thrombosis or other vascular complications. The main reasons for graft loss were severe infections, transplant nephropathy, steroid resistant acute rejection and hypoperfusion of grafts due to low blood pressure.
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The GFR was significantly higher in the paediatric recipient group in years 3–5 (Figure 2, Table 1). Covariance analysis (Table 2) and means (Table 3) when compared proved that this difference in GFR was independent of time on dialysis, recipient age, use of mycophenolate mofetil, number of acute rejections, HLA-match, pre-emptive transplantation or cold ischaemia time (Table 2).
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The volume of the transplanted kidneys from paediatric donors was significantly lower than that of adult kidneys at the time of transplantation. In the first 3 years after transplantation, the size increased reaching values similar to the adult donor kidneys (Figure 3). The mean graft volume in children receiving paediatric organs who had not experienced episodes of acute rejection was 62 ml, SD 17 (Tx), 104 ml, SD 52 (1 year after Tx), 112 ml, SD 38 (2 years after Tx), 108 ml, SD 35 (3 years after Tx), 100 ml, SD 22 (4 years after Tx) and 122 ml, SD 23 (5 years after Tx). In those children with acute rejection episodes, the mean volume of the Tx-kidney was 55 ml, SD 24 (Tx), 117 ml, SD 45 (1 year after Tx), 109 ml, SD 24 (2 years after Tx), 127 ml, SD 45 (3 years after Tx), 108 ml, SD 20 (4 years after Tx) and 118 ml, SD 25 (5 years after Tx). There was no significant difference (ANOVA, P>0.05) between recipients of paediatric organs with and without acute rejection in the development of kidney size.
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Discussion |
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TopAbstractIntroductionPatients and methodResultsDiscussionReferences |
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Our data show that kidneys from younger donors had a better long-term function in paediatric recipients compared with those of older donors. For the first 5 years after transplantation, GFR—known as the best predictor for the development of chronic allograft nephropathy (CAN)—was better in children transplanted with paediatric organs than with adult organs [8]. Graft survival was comparable in both groups. There was no difference between the two groups in recipient age, time of dialysis, number of rejections, pre-emptive transplantation, HLA-match, cold ischaemia time or immunosuppression.
In the past, the argument against the acceptance of paediatric donors for children was justified by a decreased graft survival rate compared with organs from adult donors. Older reports showed worse survival for kidneys of young paediatric donors due to infections and technical problems [9]. Bresnahan et al. [10] described decreased graft survival in children with paediatric donor grafts because of a high rate of complications with organs from paediatric donors <5 years of age. When eliminating this group, survival of paediatric (5–18 years) and adult grafts was comparable between paediatric and adult donors in this large United Network for Organ Sharing (UNOS) analysis. The North American Pediatric Renal transplant cooperative study (NAPRTCS) report 2005 demonstrates that graft survival after 5 years was 52% in recipients of organs from cadaveric donors below 5 years of age, 64% of organs from donors of 5–10 years and 68% of kidneys from older donors in paediatric kidney recipients in the US. The worse outcome of very young donors was completely based on the donors aged 1–2 years. Unfortunately, differences in long-term GFR depending on donor age were not evaluated in the annual NAPRTCS report (http://spitfire.emmes.com/study/ped/resources/annlrept2005.pdf). In our centre, graft survival after 5 years was higher than 80% in children receiving grafts from both paediatric and adult donors.
Until now, only graft survival in the first year but not long-term graft function was the fundamental argument for deciding whether paediatric grafts should be primarily used in paediatric recipients. However, we were able to show that at present there is no difference any more in graft survival between organs from donors of different ages when they are transplanted in a specialized centre. On the other hand, there are significant differences in long-term graft function with a higher GFR 5 years after transplantation for children receiving paediatric organs. We show in our study that paediatric grafts are able to grow with the growing recipient in the first 3 years after transplantation, independent of the appearance of acute rejection episodes, while adult grafts lose their capacity after initial down-regulation when adapting the renal function to the recipient's need. We speculated that children having a better GFR after 5 years will also have a better graft function 10 or 20 years after transplantation, thus leading to a better long-term graft survival. A multicentre study showed that graft function did not improve with the increase in body size of the recipient when adult donor kidneys were transplanted in children, whereas the absolute GFR of children receiving paediatric grafts increased with body growth [3,11]. These findings were supported by a matched-pairs analysis performed by our centre together with Eurotransplant showing the superiority of paediatric kidney allografts [1]. Melk et al. [12] have shown that due to senescence kidneys from older compared with younger donors led to a faster progression of chronic allograft nephropathy.
Therefore, we conclude that renal allografts from younger donors above 2 years of age should preferentially be given to paediatric recipients, a strategy that is practiced in several European countries that are not members of Eurotransplant like France [13]. We recommend an age-matched allocation system where a paediatric kidney is allocated to a child with a similar age and body size as the donor. This strategy may prolong the time till terminal graft failure and thereby may decrease the time on the waiting list for adult patients in the future. Long-term analyses from the past are biased by the increase in surgical expertise and the development of more effective immunosuppressive medications. As an age-matched allocation system might result in a worse HLA-match in individual cases, the transplant centre may decide whether they accept an age-matched organ with a worse HLA-match or not. Due to the small numbers of donor kidneys from children, there is also the need to accept kidneys from adult donors for paediatric recipients. In our opinion, a ‘young for young’ donor programme should be established in Eurotransplant and other allocation systems. Kidneys from young donors should be allocated primarily to paediatric recipients before entering the normal organ distribution programme.
Conflict of interest statement. None declared.
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References |
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Accepted in revised form: 24. 2.06
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