Roles of Mitochondrial DNA Damage in Kidney Diseases: A New Biomarker

Feng, Jun; Chen, Zhaowei; Liang, Wei; Wei, Zhongping; Ding, Guohua

doi:10.3390/ijms232315166

Cited by 15 publications

(13 citation statements)

References 139 publications

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“…In our population, RS was linked with a mitochondrial gene profile, distinguishing it from the profile of children with resolved APN and those without any kidney involvement in the first DMSA. The association of polymorphic mitochondrial genes with RS in children has not been previously demonstrated, but the clinical relevance is supported by research describing the role of mitochondria in acute kidney injury and in chronic kidney diseases such as focal segmental glomerulosclerosis and tubulopathy [33][34][35]. Since mitochondrial genes affect most organs, they play a role in the heterogeneity of disease phenotypes in children [36].…”

Section: Discussionmentioning

confidence: 99%

“…The mitochondrial role in immunity encompasses the production of reactive oxygen species (ROS) and other signaling molecules such as mitochondrial constituents and metabolic products in the progression of inflammatory disorders [37][38][39]. For example, the leakage of mtDNA is known to increase the levels of ROS, leading to hyperactivation of inflammatory responses resulting in kidney damage and pathology [33]. This is intriguing given previous studies showing that a distinctive genetic APN profile is related to hyperinflammation in combination with inhibited lymphocyte maturation (unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

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Genetic determinants of renal scarring in children with febrile UTI

Rosenblad,

Lindén,

Ambite

et al. 2024

Pediatr Nephrol

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Background Febrile urinary tract infections (UTIs) are among the most severe bacterial infections in infants, in which a subset of patients develops complications. Identifying infants at risk of recurrent infections or kidney damage based on clinical signs is challenging. Previous observations suggest that genetic factors influence UTI outcomes and could serve as predictors of disease severity. In this study, we conducted a nationwide survey of infant genotypes to develop a strategy for infection management based on individual genetic risk. Our aims were to identify genetic susceptibility variants for renal scarring (RS) and genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs. Methods To assess genetic susceptibility, we collected and analyzed DNA from blood using exome genotyping. Disease-associated genetic variants were identified through bioinformatics analysis, including allelic frequency tests and odds ratio calculations. Kidney involvement was defined using dimercaptosuccinic acid (DMSA) scintigraphy. Results In this investigation, a cohort comprising 1087 infants presenting with their first episode of febrile UTI was included. Among this cohort, a subset of 137 infants who underwent DMSA scanning was subjected to gene association analysis. Remarkable genetic distinctions were observed between patients with RS and those exhibiting resolved kidney involvement. Notably, the genetic signature indicative of renal scarring prominently featured mitochondrial genes. Conclusions In this nationwide study of genetic susceptibility to RS after febrile UTIs in infancy, we identified a profile dominated by mitochondrial polymorphisms. This profile can serve as a predictor of future complications, including RS and recurrent UTIs. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic determinants of renal scarring in children with febrile UTI

Rosenblad,

Lindén,

Ambite

et al. 2024

Pediatr Nephrol

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“…Elevated mtDNA levels may serve as surrogate biomarkers of mitochondrial dysfunction, kidney damage, and the progression and prognosis of kidney diseases [ 88 ]. Following ischemic AKI, considerable mitochondrial damage occurs in renal tubular cells and podocytes, resulting in the release of mtDNA into the extracellular space, and subsequently, in systemic circulation.…”

Section: Mitochondrial-related Biomarkers For Ischemia-induced Akimentioning

confidence: 99%

Mitochondrial metabolism and targeted treatment strategies in ischemic-induced acute kidney injury

Chen,

Li,

Zhang

et al. 2024

Cell Death Discov.

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Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI). The kidney is susceptible to IRI under several clinical conditions, including hypotension, sepsis, and surgical procedures, such as partial nephrectomy and kidney transplantation. Extensive research has been conducted on the mechanism and intervention strategies of renal IRI in past decades; however, the complex pathophysiology of IRI-induced AKI (IRI-AKI) is not fully understood, and there remains a lack of effective treatments for AKI. Renal IRI involves several processes, including reactive oxygen species (ROS) production, inflammation, and apoptosis. Mitochondria, the centers of energy metabolism, are increasingly recognized as substantial contributors to the early phases of IRI. Multiple mitochondrial lesions have been observed in the renal tubular epithelial cells (TECs) of IRI-AKI mice, and damaged or dysfunctional mitochondria are toxic to the cells because they produce ROS and release cell death factors, resulting in TEC apoptosis. In this review, we summarize the recent advances in the mitochondrial pathology in ischemic AKI and highlight promising therapeutic approaches targeting mitochondrial dysfunction to prevent or treat human ischemic AKI.

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“…In addition, mitochondrial DNA activates the cGAS-STING pathway and can act as a marker for AKI. 34 Mitochondrial DNA consumption can hinder cGAS-STING pathway. 11 Targeted Gasdermin D and mtDNA-related pathways are also potentially applied to the regimen of AKI.…”

Section: Future Perspectives and Potential Therapymentioning

confidence: 99%

The Activation of cGAS-STING in Acute Kidney Injury

Sun,

Shi,

Zhao

et al. 2023

JIR

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The activation of the cGAS-STING pathway is associated with many sterile inflammatory and inflammatory conditions, including acute kidney injury. As a cytoplasmic DNA sensor, sensitization of the cGAS-STING pathway can ignite the innate immune response in vivo and trigger a series of biological effects. In recent years, there is increasing evidence showing that the cGAS-STING pathway plays a vital role in acute kidney injury, a non-inflammatory disease induced by activation of innate immune cells, and closely related to intracellular reactive oxygen species, mitochondrial DNA, and the cGAS-STING pathway. This review provides a prospect of the cGAS-STING pathway and its relationship to acute kidney injury.

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Roles of Mitochondrial DNA Damage in Kidney Diseases: A New Biomarker

Cited by 15 publications

References 139 publications

Genetic determinants of renal scarring in children with febrile UTI

Genetic determinants of renal scarring in children with febrile UTI

Mitochondrial metabolism and targeted treatment strategies in ischemic-induced acute kidney injury

The Activation of cGAS-STING in Acute Kidney Injury

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