Nephrotoxicity

Ortíz, Alberto; Tejedor, Alberto; Caramelo, Carlos

doi:10.1002/9780470372531.ch10

Cited by 2 publications

(1 citation statement)

References 64 publications

(62 reference statements)

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“…There has been an emerging focus on mitochondria as key arbitrators of both acute kidney injury and chronic kidney diseases [ 59 , 60 , 61 ]. With regard to CNIT, the association between mitochondrial dysfunction and CNIs has been previously described by others [ 18 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. While it remains unknown whether the observed mitochondrial dysfunction is secondary to endothelial damage associated with ischemia (i.e., CNI vasculopathy) or direct tubular toxicity, the findings of our study support the assertion that mitochondrial oxidative phosphorylation defects play a role as one of the central mechanisms of CNIT development.…”

Section: Discussionmentioning

confidence: 81%

An Integrated Transcriptomic Approach to Identify Molecular Markers of Calcineurin Inhibitor Nephrotoxicity in Pediatric Kidney Transplant Recipients

Rhone

Bardhi

Bontha

et al. 2021

IJMS

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Calcineurin inhibitors are highly efficacious immunosuppressive agents used in pediatric kidney transplantation. However, calcineurin inhibitor nephrotoxicity (CNIT) has been associated with the development of chronic renal allograft dysfunction and decreased graft survival. This study evaluated 37 formalin-fixed paraffin-embedded biopsies from pediatric kidney transplant recipients using gene expression profiling. Normal allograft samples (n = 12) served as negative controls and were compared to biopsies exhibiting CNIT (n = 11). The remaining samples served as positive controls to validate CNIT marker specificity and were characterized by other common causes of graft failure such as acute rejection (n = 7) and interstitial fibrosis/tubular atrophy (n = 7). MiRNA profiles served as the platform for data integration. Oxidative phosphorylation and mitochondrial dysfunction were the top molecular pathways associated with overexpressed genes in CNIT samples. Decreased ATP synthesis was identified as a significant biological function in CNIT, while key toxicology pathways included NRF2-mediated oxidative stress response and increased permeability transition of mitochondria. An integrative analysis demonstrated a panel of 13 significant miRNAs and their 33 CNIT-specific gene targets involved with mitochondrial activity and function. We also identified a candidate panel of miRNAs/genes, which may serve as future molecular markers for CNIT diagnosis as well as potential therapeutic targets.

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Section: Discussionmentioning

confidence: 81%

An Integrated Transcriptomic Approach to Identify Molecular Markers of Calcineurin Inhibitor Nephrotoxicity in Pediatric Kidney Transplant Recipients

Rhone

Bardhi

Bontha

et al. 2021

IJMS

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Un nuevo paradigma en el fracaso renal agudo

Jorge

2019

Enferm Nefrol

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El fracaso renal agudo es una de las patologías con las que más ha avanzado el conocimiento médico y, sin embargo, menos se ha modificado el tratamiento o el pronóstico. Con un crecimiento anual de un 25%, el fracaso renal afecta a más de trece millones de personas en el mundo cada año. Cuando aparece en un paciente hospitalizado por otro motivo, aumenta la duración de la estancia media en casi cuatro días. La mortalidad por fracaso renal agudo es mayor que la mortalidad combinada por cáncer de mama, cáncer de próstata, insuficiencia cardíaca y diabetes. Varios factores pueden estar contribuyendo a esta epidemia mundial que afecta por igual, aunque por distintas causas, a los países del primer mundo tanto como a los subdesarrollados. - El envejecimiento de la población. - La aparición de gérmenes más agresivos y resistentes que requieren tratamientos más nefrotóxicos. - El aumento de la fragilidad en los pacientes seleccionados para tratamientos quirúrgicos, oncológicos y antibióticos cada vez más exigentes. - El aumento de prevalencia de enfermedades crónicas con un riesgo cardiovascular progresivamente mayor y proporcional al nivel de inflamación.

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Nephrotoxicity

Cited by 2 publications

References 64 publications

An Integrated Transcriptomic Approach to Identify Molecular Markers of Calcineurin Inhibitor Nephrotoxicity in Pediatric Kidney Transplant Recipients

An Integrated Transcriptomic Approach to Identify Molecular Markers of Calcineurin Inhibitor Nephrotoxicity in Pediatric Kidney Transplant Recipients

Un nuevo paradigma en el fracaso renal agudo

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