Abstract
BackgroundUrinary mitochondrial DNA (mtDNA) fragment level has been proposed as a biomarker of chronic kidney disease (CKD). In this study, we determine the relation between urinary mtDNA level and rate of renal function deterioration in non-diabetic CKD.MethodsWe recruited 102 non-diabetic CKD patients (43 with kidney biopsy that showed non-specific nephrosclerosis). Urinary mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 48.3 ± 31.8 months for renal events (need of dialysis or over 30% reduction in estimated glomerular filtration rate [eGFR]).ResultsThe median urinary mtDNA level was 1519.42 (inter-quartile range 511.81–3073.03) million copy/mmol creatinine. There were significant correlations between urinary mtDNA level and baseline eGFR (r = 0.429, p < 0.001), proteinuria (r = 0.368, p < 0.001), severity of glomerulosclerosis (r = − 0.537, p < 0.001), and tubulointerstitial fibrosis (r = − 0.374, p = 0.014). The overall rate of eGFR decline was − 2.18 ± 5.94 ml/min/1.73m2 per year. There was no significant correlation between the rate of eGFR decline and urinary mtDNA level. By univariate analysis, urinary mtDNA level predicts dialysis-free survival, but the result became insignificant after adjusting for clinical and histological confounding factors.ConclusionUrinary mtDNA levels have no significant association with the rate of renal function decline in non-diabetic CKD, although the levels correlate with baseline renal function, proteinuria, and the severity of histological damage. Urinary mtDNA level may be a surrogate marker of permanent renal damage in non-diabetic CKD.
Highlights
Urinary mitochondrial DNA fragment level has been proposed as a biomarker of chronic kidney disease (CKD)
The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease (MDRD) formula [23] and the stage of CKD was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria [24]
In another study on biopsy-proved hypertensive nephrosclerosis and IgA nephropathy, we found that urinary mitochondrial DNA (mtDNA) level correlates with the rate of renal function decline and predicts the risk of doubling of serum creatinine or need of dialysis [34]
Summary
Urinary mitochondrial DNA (mtDNA) fragment level has been proposed as a biomarker of chronic kidney disease (CKD). We determine the relation between urinary mtDNA level and rate of renal function deterioration in non-diabetic CKD. Chronic kidney disease (CKD) is a global public health issue [1]. The prevalence of CKD is estimated to be 8 to 16% worldwide [2]. A considerable proportion of CKD patients eventually progresses to dialysis-dependent end stage renal disease (ESRD), which is an important economic burden to the health care system [1]. CKD is characterized by progressive renal function loss irrespective to the primary cause of kidney damage [5]. The underlying mechanism of progressive renal function loss in CKD, it still remains incompletely understood.
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