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Transplantology, Volume 6, Issue 3 (September 2025) – 1 article

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17 pages, 965 KiB  
Article
Urinary Mitochondrial DNA Is Related to Allograft Function in Living Donor Kidney Transplantation—An Observational Study of the VAPOR-1 Cohort
by Lucas Gartzke, Julia Huisman, Nora Spraakman, Fernanda Lira Chavez, Michel Struys, Henri Leuvenink, Robert Henning and Gertrude Nieuwenhuijs-Moeke
Transplantology 2025, 6(3), 20; https://doi.org/10.3390/transplantology6030020 - 26 Jun 2025
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Abstract
Background: Ischemia–reperfusion injury (IRI) is a key contributor to graft dysfunction in kidney transplantation. Cell-free mitochondrial DNA (mtDNA) is increasingly recognized as a damage-associated molecular pattern (DAMP) and biomarker in IRI, but its prognostic role in living donor kidney transplantation (LDKT) remains [...] Read more.
Background: Ischemia–reperfusion injury (IRI) is a key contributor to graft dysfunction in kidney transplantation. Cell-free mitochondrial DNA (mtDNA) is increasingly recognized as a damage-associated molecular pattern (DAMP) and biomarker in IRI, but its prognostic role in living donor kidney transplantation (LDKT) remains unclear. Methods: This post hoc analysis of the VAPOR-1 study evaluated urinary mtDNA (UmtDNA) in 57 LDKT recipients. MtDNA levels (ND1, ND6, and D-loop) were measured at five early timepoints post-transplantation using qPCR. Associations between early UmtDNA and long-term graft function, defined by estimated glomerular filtration rate (eGFR) at 1, 12, and 24 months, were analyzed. Results: Higher UmtDNA levels in the first urine after reperfusion were significantly associated with improved eGFR at 12 months and a positive change in eGFR between month 1 and 24. These associations were not attributable to urine creatinine levels or mitochondrial copy number. Conclusions: In this LDKT cohort, elevated early UmtDNA may reflect a well-functioning graft capable of clearing systemic mtDNA rather than ongoing tubular injury. These findings suggest that the biological interpretation of mtDNA as a biomarker is context-dependent and call for careful reconsideration of its role in early transplant monitoring. Full article
(This article belongs to the Section Organ and Tissue Donation and Preservation)
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