Association of Primary Kidney Disease Type and Donor Relatedness With Live Donor Kidney Transplant Outcomes: An Analysis of ANZDATA

Dong Yu, Eva Malacova, Cameron Hurst, Monica Suet Ying Ng, Andrew John Mallett

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Abstract

Rationale & Objective: There is limited information about the association between primary kidney disease and donor relatedness with transplant outcomes. This study addresses this gap by evaluating clinical outcomes after kidney transplantation in recipients of living donor kidneys as a function of primary kidney disease type and donor relatedness in Australia and New Zealand. Study Design: Retrospective observational study. Setting & Participants: Kidney transplant recipients who received allografts from living donors between January 1, 1998, and December 31, 2018, as recorded in the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). Exposures: Primary kidney disease type categorized as majority monogenic, minority monogenic, or other primary kidney disease based on disease heritability as well as donor relatedness. Outcome: Primary kidney disease recurrence, graft failure. Analytical Approach: Kaplan-Meier analysis and Cox proportion hazards regression to generate hazard ratios for primary kidney disease recurrence, allograft failure, and mortality. Partial likelihood ratio test was used to examine possible interactions between primary kidney disease type and donor relatedness for both study outcomes. Results: Among 5,500 live donor kidney transplant recipients, majority monogenic (adjusted HR, 0.58, P < 0.001) and minority monogenic primary kidney diseases (adjusted HR, 0.64, P < 0.001) were associated with reduced primary kidney disease recurrence compared with other primary kidney diseases. Majority monogenic primary kidney disease was also associated with reduced allograft failure (adjusted HR, 0.86, P = 0.04) compared with other primary kidney diseases. Donor relatedness was not associated with primary kidney disease recurrence nor graft failure. No interaction was detected between primary kidney disease type and donor relatedness for either study outcome. Limitations: Potential misclassification of primary kidney disease type, incomplete ascertainment of primary kidney disease recurrence, unmeasured confounding. Conclusions: Monogenic primary kidney disease is associated with lower rates of primary kidney disease recurrence and allograft failure. Donor relatedness was not associated with allograft outcomes. These results may inform pretransplant counseling and live donor selection. Plain-Language Summary: There are theoretical concerns that live-donor kidney transplants may be associated with increased risks of kidney disease recurrence and transplant failure due to unmeasurable shared genetic factors between the donor and the recipient. This study analyzed data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry and showed that, although disease type was associated with the risk of disease recurrence and transplant failure, donor relatedness did not impact transplant outcomes. These findings may inform pretransplant counseling and live donor selection.

Original languageEnglish
Pages (from-to)569-580.e1
Number of pages13
JournalAmerican Journal of Kidney Diseases
Volume82
Issue number5
Early online date2023
DOIs
Publication statusPublished - Nov 2023

Bibliographical note

Funding Information:
Dong Yu, MD, Eva Malacova, PhD, Cameron Hurst, PhD, Monica Suet Ying Ng, PhD, and Andrew John Mallett, PhD. Research idea and study design: MSYN, EM, CH, AJM; data acquisition: DY, MSYN, AJM; data management/processing: EM, CH, MSYN; statistical analyses: EM, CH; mentorship: MSYN, AJM. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. Dr Ng is supported by the Robert and Janelle Bird Postdoctoral Research Fellowship 2020. Dr Mallett is supported by a Queensland Health Advancing Clinical Research Fellowship. The funders did not have any role in study design, data collection, analysis, reporting, or decision to submit for publication. The authors declare that they have no relevant financial interests. The authors are grateful for the significant contributions of the Australian and New Zealand kidney medicine community (physicians, surgeons, database managers, nurses, and patients) in providing information for and maintaining the ANZDATA Registry. The analyses and interpretation presented are those of the authors, not ANZDATA. Received July 21, 2022. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form April 21, 2023.

Publisher Copyright:
© 2023 The Authors

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