20. Plasma mitochondrial DNA levels and damage correlate with post-transplant renal allograft function

M. Trefna, G. J. Nieuwenhuijs-Moeke, Z. Hijazi, M.A.J. Seelen, F.H. Hoogstra-Berends, R.H. Henning

Thursday 5 march 2020

0:00 - 0:00h at Toon Hermans Foyer

Parallel session: Postersessie 5 – Klinische en Verpleegkundige abstracts

Background: The definition of an organ’s transplantability and prediction of early graft dysfunction is hindered by the lack of sensible biomarkers. Mitochondrial DNA (mtDNA) in plasma was identified as a propagator of tissue injury in trauma and sepsis, and as a marker predicting progression of acute kidney injury progression. Here we explore the potential of plasma mtDNA level and damage as a marker in organ evaluation in a cohort of living donor kidney transplantations, a post-hoc analysis of VAPOR1.

Methods: Plasma was obtained from 57 donor-recipients undergoing living kidney donation and transplantation at various timepoints. MtDNA levels were measured in donors preoperatively (pre-op) and in recipients pre-, intra- and post-operatively, with intraoperative samples taken from both the renal vein and systemic arterial circulation, using polymerase chain reaction for D-loop, ND1 and ND6. MtDNA damage was determined using ND/Dloop ratios, under the assumption that D-loop is less prone to DNA damage than ND1 and ND6. MtDNA levels and damage were associated with recipient’s kidney function parameters and urinary kidney biomarkers KIM-1 and NAG.

Results: Pre-op mtDNA levels were higher in recipients than donors. Highest levels of mtDNA from the renal vein were highest directly upon reperfusion. Recipients showed increased mtDNA levels 9 days post-op compared to pre-op, those receiving a kidney from a related donor having higher mtDNA levels than those with unrelated donation. Recipient’s mtDNA levels at 2 hours post-op correlated with creatinine at 6 and 24 months. MtDNA levels at 9 days correlated with KIM-1 at day 9, creatinine at 6 and 24 months and glomerular filtration rate at 6 months. Pre-op mtDNA damage was comparable between donors and recipients, while it increased in recipients 9 days post-op. Recipients with high mtDNA damage directly after reperfusion of the kidney, both from the renal vein and systemic circulation, had significantly higher levels of KIM-1 at 1 and 9 days, but lower creatinine at 6 and 24 months post-op compared to recipients with low mtDNA damage. Conversely, patients with the highest mtDNA damage at 9 days post-op showed lower KIM-1 and NAG.

Conclusions: Levels and damage of plasma mtDNA obtained early after kidney transplantation are associated with momentuous kidney damage markers and a long-term accelerated decline in renal function markers. Measurement of post-op mtDNA levels may aid to the identification of patients at risk for accelerated kidney dysfunction.