Urinary mitochondrial deoxyribonucleic acid: A novel biomarker of coronavirus disease 2019-associated acute kidney injury in renal transplant recipients

Abstract

Background: Acute kidney injury (AKI) is one of the common manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. An early identification of AKI is of paramount importance to modulate the management of AKI, limiting the severity, avoiding nephrotoxic medicines, and modifying the drug dose depending on renal function. Aim: To determine the utility of urinary mitochondrial deoxyribonucleic acid (umt-DNA) and neutrophil gelatinase-associated lipocalin (NGAL) in predicting coronavirus disease 2019 (COVID-19)-associated AKI and mitochondrial stress. Materials and Methods: Live-related renal transplant recipients (RTRs) (n = 66), who acquired SARS-CoV-2 infection and were admitted to a COVID hospital were included and subclassified into AKI (n = 19) with > 1.5-fold rise in serum creatinine level from the pre-COVID-19 serum creatinine level, and non-AKI (n = 47) whose serum creatinine value remained stable, or a rise of <1.5-fold of the baseline values of pre-COVID-19. A 50 mL urine sample was collected and urinary mt-DNA and NGAL was determined by the reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assays methods. Results: Both the urinary mitochondrial gene NADH dehydrogenase (ND-1) and NGAL level were significantly higher in the AKI group compared to non-AKI. The mean ND-1 gene Ct in the AKI group was (19.44 ± 2.58 a.u) compared to non-AKI (21.77 ± 3.60; P = 0.013). The normalized ND-1 gene cycle of threshold (Ct) in AKI was 0.79 ± 0.11 a.u compared to non-AKI (0.89 ± 0.14; P = 0.007). The median urinary NGAL level in AKI group was (453.53; range, 320.22–725.02, 95% confidence interval [CI]) ng/mL compared to non-AKI (212.78; range, 219.80–383.06, 95% CI; P = 0.015). The median urine creatinine normalized uNGAL was 4.78 (0.58–70.39) ng/mg in the AKI group compared to 11.26 ng/mg (0.41–329.71) in the non-AKI group. The area under curve of ND-1 gene Ct was 0.725, normalized ND-1 Ct was 0.713, uNGAL was 0.663, and normalized uNGAL was 0.667 for detecting the AKI and mitochondrial stress. Conclusions: Urinary mt-DNA quantification can detect the post-COVID mitochondrial distress with higher sensitivity than uNGAL in RTRs.

Keywords

• acute kidney injury
• mitochondrial deoxyribonucleic acid
• neutrophil gelatinase-associated lipocalin
• renal transplant recipient
• toll-like receptor
• urinary