Abstract
Recent studies indicate that urinary mitochondrial DNA (mtDNA) is predictive of ischemic AKI and is related to delayed graft function (DGF) in renal transplantation. Nevertheless, the clinical implications and prognostic value of urinary mtDNA in kidney transplantation remain undetermined. Here, we aimed to evaluate the associations between cell-free mtDNA and clinical parameters, including pathological findings in allograft biopsy and post-transplant renal function. A total of 85 renal transplant recipients were enrolled, and blood and urine samples were collected at a median of 17 days after transplantation. Cell-free nuclear and mtDNA levels were measured by quantitative polymerase chain reaction for LPL and ND1 genes. Urinary cell-free mtDNA levels were significantly higher in patients with DGF (P < 0.001) and cases of deceased donor transplantation (P < 0.001). The subjects with acute rejection showed higher urinary mtDNA levels than those without abnormalities (P = 0.043). In addition, allograft functions at 9- and 12-month post-transplantation were significantly different between tertile groups of mtDNA independent of the presence of DGF or acute rejection, showing significantly better graft outcome in the lowest tertile group. Urinary cell-free mtDNA levels during the early post-transplant period are significantly associated with DGF, acute rejection in graft biopsy, and short-term post-transplant renal function.
Highlights
Recent studies indicate that urinary mitochondrial DNA is predictive of ischemic acute kidney injury (AKI) and is related to delayed graft function (DGF) in renal transplantation
We examined the associations of cell-free mitochondrial DNA (mtDNA) level with estimated glomerular filtration rate (eGFR) and neutrophil gelatinase-associated lipocalin (NGAL) at baseline; NGAL has been extensively studied as a biomarker of post-transplant allograft function[19]
We investigated the clinical implications of cell-free mtDNA quantified with qPCR from urine and plasma samples of 85 kidney transplant recipients during the early post-transplant period
Summary
Recent studies indicate that urinary mitochondrial DNA (mtDNA) is predictive of ischemic AKI and is related to delayed graft function (DGF) in renal transplantation. Urinary cell-free mtDNA levels during the early post-transplant period are significantly associated with DGF, acute rejection in graft biopsy, and short-term post-transplant renal function. Mitochondrial DAMPs have received considerable attention as an important mediator of tissue injury in various inflammatory conditions, including trauma, sepsis, cancer, hemodialysis, and transplantation[9,10,11,12,13,14] Of these mitochondrial DAMPs, cell-free mitochondrial DNA (mtDNA) has been reported to be a predictive biomarker of the progression of acute kidney injury (AKI)[15,16]. To date, there is limited www.nature.com/scientificreports research investigating the clinical implications of cell-free mtDNA in kidney transplantation It is uncertain whether the detected mtDNA is merely a consequence of mitochondrial damage from IRI or a causative factor for subsequent graft dysfunction, impacting as DAMP. We evaluated the clinical implication of cell-free mtDNA during the early post-transplant period on histological and clinical parameters and examined the association between cell-free mtDNA levels and short-term graft outcome in kidney transplantation
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