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

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

doi:10.1186/s12882-019-1549-x

Abstract

IntroductionCell-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.MethodsOne 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.ResultsPatients 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.ConclusionsUrinary 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.

Highlights

Cell-free deoxyribonucleic acid DNA in urine is promising due to the advantage of urine as an obtained and non-invasive sample source over tissue and blood
To clarify the clinical application of cf-mtDNA and cell-free nuclear DNA (cf-nDNA) in chronic kidney disease (CKD), we studied the correlation between cf-mtDNA and cf-nDNA, both urine and plasma, and the stage of CKD or prognosis of renal outcomes
To the best of our knowledge, this study is the first to show the clinical significant correlation between urine cf-mtDNA, urine cf-nDNA and divergent renal outcome at 6 months. We propose that both urine protein-creatinine ratio (PCR) and albumin-creatinine ratio (ACR) could significantly predict urinary cf-nDNA and cfmtDNA levels

Summary

Introduction

Cell-free deoxyribonucleic acid DNA (cf-DNA) in urine is promising due to the advantage of urine as an obtained and non-invasive sample source over tissue and blood. It is important to identify non-invasive biomarkers of chronic kidney disease (CKD) in monitoring and surveillance of disease progression. Chronic kidney disease (CKD) is a global public health problem affecting up to 10% of the population worldwide [1], guidelines for the clinical staging of CKD have been established [2]. Proteinuria, caused by a primary insult to the kidney, induces oxidative stress in renal tubular cells and causes mitochondrial dysfunction [7, 8], which leads to cellular damage by. By the experimental models of CKD, preventing mitochondrial dysfunction inhibits renal tubular cell EMT and renal fibrosis [13]. Only a relatively small number of translational studies have shown the clinical relevance of these mechanisms between renal diseases and mitochondrial dysfunction in humans [6, 14, 15]

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