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Kidney Week

Abstract: TH-PO1119

Urinary Mitochondrial DNA Level as a Biomarker of Tissue Injury in Non-Diabetic CKD

Session Information

Category: CKD (Non-Dialysis)

  • 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Wei, Zhongping, The Chinese University of Hong Kong, Sha Tin, Hong kong, China
  • Szeto, Cheuk-Chun, The Chinese University of Hong Kong, Sha Tin, Hong kong, China
Background

Chronic kidney disease (CKD) is a global public health issue and an important economic burden to the health care system. However, the underlying mechanism of progressive renal function loss in CKD, it still remains incompletely understood. Emerging evidence shows that mitochondrial dysfunction plays an important role in the pathogenesis and progression of chronic kidney disease (CKD). We study the relation between urinary mitochondrial DNA (mtDNA) levels and renal dysfunction in non-diabetic CKD.

Methods

We recruited 102 non-diabetic CKD patients, 43 of them had kidney biopsy that showed non-specific nephrosclerosis. Urinary mtDNA level was measured by digital polymerase chain reaction, and compared to baseline clinical, biochemical, histological parameters as well as renal function decline in the subsequent 48.3 ± 31.8 months.

Results

Urinary mtDNA was easily detectable. The median urinary mtDNA level was 1519.4 (501.61 – 3131.23) million copy/mmol creatinine. There were modest but statistically significant positive correlations between urinary mtDNA level and baseline estimated glomerular filtration rate (GFR) (r = 0.427, p < 0.001) and proteinuria (r = 0.376, p < 0.001). For patients with kidney biopsy, urinary mtDNA level also inversely correlated with the severity of glomerulosclerosis (r = -0.537, p < 0.001), tubulointerstitial fibrosis (r = -0.309, p = 0.029). Urinary mtDNA level predicts renal event-free survival by univariate analysis (unadjusted hazard ratio [HR] 0.685, p = 0.033), but the predictive value of urinary mtDNA level fell short of statistical significance ((adjusted hazard ratio [HR] 0.808, 95%CI 0.331 – 1.968, p = 0.638) after adjusting for confounding factors.

Conclusion

Urinary mtDNA levels correlate with baseline renal function, proteinuria, and the severity of histological damage in non-diabetic CKD. Our result suggests that urinary mtDNA level may be a surrogate marker of the degree of permanent renal parenchymal damage in non-diabetic CKD.

Funding

  • Government Support - Non-U.S.