Urinary cell-free mitochondrial and nuclear deoxyribonucleic acid correlates with the prognosis of chronic kidney diseases

Chia-Chu Chang, Ping-Fang Chiu, Chia-Lin Wu, Cheng-Ling Kuo, Ching-Shan Huang, Chin-San Liu, Ching-Hui Huang, Chia-Chu Chang, Ping-Fang Chiu, Chia-Lin Wu, Cheng-Ling Kuo, Ching-Shan Huang, Chin-San Liu, Ching-Hui Huang

Abstract

Introduction: Cell-free deoxyribonucleic acid DNA (cf-DNA) in urine is promising due to the advantage of urine as an easily obtained and non-invasive sample source over tissue and blood. In clinical practice, it is important to identify non-invasive biomarkers of chronic kidney disease (CKD) in monitoring and surveillance of disease progression. Information is limited, however, regarding the relationship between urine and plasma cf-DNA and the renal outcome in CKD patients.

Methods: One hundred and thirty-one CKD patients were enrolled between January 2016 and September 2018. Baseline urine and plasma cell-free mitochondrial DNA (cf-mtDNA) and cell-free nuclear DNA (cf-nDNA) were isolated using quantitative real-time PCR. Estimated glomerular filtration rate (eGFR) measurement was performed at baseline and 6-month follow-up. Favorable renal outcome was defined as eGFR at 6 months minus baseline eGFR> = 0. Receiver operator characteristics (ROC) curve analysis was performed to assess different samples of cf-DNA to predict favorable renal outcomes at 6 months. A multivariate linear regression model was used to evaluate independent associations between possible predictors and different samples of cf-DNA.

Results: Patients with an advanced stage of CKD has significantly low plasma cf-nDNA and high plasma neutrophil gelatinase-associated lipocalin (NGAL) levels. Low urine cf-mtDNA, cf-nDNA levels and low plasma NGAL were significantly correlated with favorable renal outcomes at 6 months. The urine albumin-creatinine ratio (ACR) or urine protein-creatinine ratio (PCR) level is a robust predictor of cf-mtDNA and cf-nDNA in CKD patients. Baseline urine levels of cf-mtDNA and cf-nDNA could predict renal outcomes at 6 months.

Conclusions: Urinary cf-mtDNA and cf-nDNA may provide novel prognostic biomarkers for renal outcome in CKD patients. The levels of plasma cf-nDNA and plasma NGAL are significantly correlated with the severity of CKD.

Keywords: Cell-free mitochondrial deoxyribonucleic acid; Cell-free nuclear deoxyribonucleic acid; Cf-mtDNA; Cf-nDNA; Chronic kidney disease; NGAL; Neutrophil gelatinase-associated lipocalin.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Evaluation of urinary cf-nDNA and urine cf-mtDNA as predictors of CKD patient outcomes after 6 months. The areas under the curves (AUC) were as follows: urine cf-mtDNA: 0.685 (0.586–0.784, P = 0.001*), and urine cf-nDNA: 0.730 (0.637–0.823, P < 0.001*)

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