Immunological Risk Factors in Paediatric Kidney Transplantation

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Abstract

Purpose

The aim of this study was to identify factors impacting recipient sensitization rates and paediatric renal transplant patient outcomes.

Patients and Methods

For this purpose, a retrospective analysis of 143 paediatric renal transplants was carried out. This included the evaluation of patient’s and donor’s demographic data, HLA mismatches, immunosuppressive therapy, rejection episodes, panel reactive antibody (PRA) and post-transplant lymphoproliferative disease (PTLD).

Results

The mean patient age at the point of transplant receival was 11.5 years with a mean follow up time of 9.33±5.05 years. It was noted that graft survival rates for donors over 59 years had the worst outcome. HLA match did not show statistically significant influence on graft outcome. Graft survival for more than one biopsy-proven rejection was also significantly shorter (p=0.008). PRA were found in 28% of the recipient’s post-transplantation and showed association with lower graft survival rates (p<0.001). In the present study, 22.7% (5/22) of the patients with EBV infections presented a PTLD.

Conclusion

In conclusion, good graft survival with reduced sensitization for future transplantations and minimize the risk of PTLD, can be ensured through a balance between donor age, HLA match and condition of the recipient should be sought. Furthermore, paediatric patients should preferably receive organs from donors between the age of 10 and 59. EBV infection could be a relevant factor for developing PTLD.

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Most cited references 20

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Long-term survival of children with end-stage renal disease.

Allen S. Craig, Michael P. McDonald, (2004)

Although renal-replacement therapy for children with end-stage renal disease has been used for several decades, data on patients' long-term survival are sparse. We examined the long-term survival of all children and adolescents who were under 20 years of age when renal-replacement therapy commenced (study period, April 1963 through March 2002), using data from the Australia and New Zealand Dialysis and Transplant Registry. Survival was analyzed with the use of Kaplan-Meier methods and age-standardized mortality rates. Risk factors for death were analyzed with the use of Cox regression analysis with time-dependent covariates. A total of 1634 children and adolescents were followed for a median of 9.7 years. The long-term survival rate among children requiring renal-replacement therapy was 79 percent at 10 years and 66 percent at 20 years. Mortality rates were 30 times as high as for children without end-stage renal disease. Risk factors for death were a young age at the time renal-replacement therapy was initiated (especially for children under 1 year of age, among whom the risk was four times as high as for children 15 to 19 years of age) and treatment with dialysis (which was associated with a risk more than four times as high as for renal transplantation). Overall, a trend toward improved survival was observed over the four decades of the study. Despite improvement in long-term survival, mortality rates among children requiring renal-replacement therapy remain substantially higher than those among children without end-stage renal disease. Increasing the proportion of children treated with renal transplantation rather than with dialysis can improve survival further. Copyright 2004 Massachusetts Medical Society

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Rates and determinants of progression to graft failure in kidney allograft recipients with de novo donor-specific antibody.

C. R. Wiebe, I W Gibson, T Blydt-Hansen … (2015)

Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor-specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with dnDSA) was studied. Recipients (n = 388) without dnDSA or dysfunction had an eGFR decline of -0.65 mL/min/1.73 m(2) /year. In recipients with dnDSA, the rate eGFR decline was significantly increased prior to dnDSA onset (-2.89 vs. -0.65 mL/min/1.73 m(2) /year, p < 0.0001) and accelerated post-dnDSA (-3.63 vs. -2.89 mL/min/1.73 m(2) /year, p < 0.0001), suggesting that dnDSA is both a marker and contributor to ongoing alloimmunity. Time to 50% post-dnDSA graft loss was longer in recipients with subclinical versus a clinical dnDSA phenotype (8.3 vs. 3.3 years, p < 0.0001). Analysis of 1091 allograft biopsies found that dnDSA and time independently predicted chronic glomerulopathy (cg), but not interstitial fibrosis and tubular atrophy (IFTA). Early T cell-mediated rejection, nonadherence, and time were multivariate predictors of IFTA. Independent risk factors for post-dnDSA graft survival available prior to, or at the time of, dnDSA detection were delayed graft function, nonadherence, dnDSA mean fluorescence intensity sum score, tubulitis, and cg. Ultimately, dnDSA is part of a continuum of mixed alloimmune-mediated injury, which requires solutions targeting T and B cells.

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Pediatric kidney transplant practice patterns and outcome benchmarks, 1987-2010: a report of the North American Pediatric Renal Trials and Collaborative Studies.

Jodi M Smith, Karen Martz, Tom D. Blydt-Hansen (2013)

The NAPRTCS transplant registry has collected clinical information on children undergoing kidney transplantation since 1987 and now includes information on 11 603 kidney transplants in 10 632 patients. Since the first data analysis in 1989, NAPRTCS reports have documented marked improvements in outcome after kidney transplantation in addition to identifying factors associated with both favorable and poor outcomes. Patient demographics have changed over the course of the registry with a decrease in the percentage of white recipients from a high of 72% in 1987 to less than 43% in 2007. The percentage of living donors decreased to its lowest point in 2007 at 37%. Acute rejection rates continue to decline with improvements in short- and long-term graft survival. Recently, NAPRTCS data have been used as a source of benchmark data for pediatric kidney transplant centers.

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Author and article information

Journal

Journal ID (nlm-ta): Res Rep Urol

Journal ID (iso-abbrev): Res Rep Urol

Journal ID (publisher-id): rru

Journal ID (pmc): rru

Title: Research and Reports in Urology

Publisher: Dove

ISSN (Electronic): 2253-2447

Publication date (Electronic): 23 February 2021

Publication date Collection: 2021

Volume: 13

Pages: 87-95

Affiliations

[1 ]Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany

[2 ]Berlin Institute of Health, Clinic of Urology and Paediatric Urology , Berlin, Germany

[3 ]Berlin Institute of Health , Department of Paediatric Gastroenterology, Nephrology and Metabolic Disorders, Berlin, Germany

[4 ]Berlin Institute of Health, Institute of Transfusion Medicine , Berlin, Germany

[5 ]Charité – Department of Anesthesiology and Operative Intensive Care Medicine, Campus Charité Mitte, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin , Berlin, Germany

[6 ]Berlin Institute of Health , Berlin, Germany

Author notes

Correspondence: Frank Friedersdorff Charité – Universitätsmedizin Berlin , Charitéplatz 1, Berlin, 10117, GermanyTel +4930450615219 Email frank.friedersdorff@charite.de

[*]

These authors contributed equally to this work

Author information

Anna Bichmann http://orcid.org/0000-0002-4611-9301

Article

Publisher ID: 289853

DOI: 10.2147/RRU.S289853

PMC ID: 7914070

SO-VID: 1dcffbdc-5290-498c-80e5-5055f12841d9

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 01 November 2020

Date accepted : 11 January 2021

Page count

Figures: 1, Tables: 10, References: 21, Pages: 9

Immunological Risk Factors in Paediatric Kidney Transplantation

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Abstract

Purpose

Patients and Methods

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IUCN Red List of Ecosystems

Most cited references 20

Long-term survival of children with end-stage renal disease.

Rates and determinants of progression to graft failure in kidney allograft recipients with de novo donor-specific antibody.

Pediatric kidney transplant practice patterns and outcome benchmarks, 1987-2010: a report of the North American Pediatric Renal Trials and Collaborative Studies.

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