2016
DOI: 10.1152/ajprenal.00125.2016
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Proteinuria causes dysfunctional autophagy in the proximal tubule

Abstract: Proteinuria is a major risk factor for chronic kidney disease progression. Furthermore, exposure of proximal tubular epithelial cells to excess albumin promotes tubular atrophy and fibrosis, key predictors of progressive organ dysfunction. However, the link between proteinuria and tubular damage is unclear. We propose that pathological albumin exposure impairs proximal tubular autophagy, an essential process for recycling damaged organelles and toxic intracellular macromolecules. In both mouse primary proximal… Show more

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Cited by 42 publications
(29 citation statements)
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“…Kidney nephrectomized from children with congenital nephrotic syndrome of the Finnish type, which is characterized by constant heavy proteinuria from birth, had interstitial inflammation and fibrosis . Proteinuria induced apoptosis in proximal tubular cells and dysfunctional autophagy in the proximal tubule, which resulted in the accumulation of intracellular proteins . Albuminuria impaired renal tubular tight junctions and induced a proinflammatory and profibrotic response in cortical collecting duct .…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Kidney nephrectomized from children with congenital nephrotic syndrome of the Finnish type, which is characterized by constant heavy proteinuria from birth, had interstitial inflammation and fibrosis . Proteinuria induced apoptosis in proximal tubular cells and dysfunctional autophagy in the proximal tubule, which resulted in the accumulation of intracellular proteins . Albuminuria impaired renal tubular tight junctions and induced a proinflammatory and profibrotic response in cortical collecting duct .…”
Section: Discussionmentioning
confidence: 99%
“…25 Proteinuria induced apoptosis in proximal tubular cells and dysfunctional autophagy in the proximal tubule, which resulted in the accumulation of intracellular proteins. 26,27 Albuminuria impaired renal tubular tight junctions and induced a proinflammatory and profibrotic response in cortical collecting duct. 28,29 In our study, the ability to predict ESRD for increase in proteinuria during an observation period of 1 year became higher for 2 years, with no further improvement by one more year prolongation to 3 years.…”
Section: Discussionmentioning
confidence: 99%
“…Sabe-se que a perda da integridade da BFG e do sistema tubular renal são determinantes para a proteinúria na DRC (VADEN; ELLIOTT, 2016). Em adição, o aumento da concentração de proteínas na urina induz atrofia e fibrose tubular, contribuindo para a progressão da DRC (NOLIN et al, 2016). Um estudo recente identificou que os cães com DRC e isostenúria (ou seja, densidade urinária entre 1,008 e 1,012, semelhante ao plasma) têm 2,5 vezes mais chance de desenvolverem a proteinúria, do que cães com a densidade urinária acima de 1,013, e que a isostenúria também predispõe o cão a bacteriúria assintomática e infecções do trato urinário (LAMOUREUX et al, 2019).…”
Section: Discussionunclassified
“…Este mecanismo compensatório, que a princípio será responsável pela manutenção da filtração glomerular e homeostase hídrica, trará consequências indesejadas, uma vez que a DRC é progressiva e irreversível, mantendo a perda funcional de néfrons e a ativação do SRAA, e resultando, cada vez mais, na elevação da pressão arterial e maior proteinúria (POLZIN; OSBORNE; ROSS, 2005). A exposição das células tubulares proximais ao excesso de albumina promove atrofia e fibrose tubular, contribuindo para a progressão da DRC (NOLIN et al, 2016). E, como foi discutido no item 2.3.5 desta revisão de literatura, a HAS pode ocasionar diversos prejuízos para a visão e os sistemas cardiovascular e nervoso.…”
Section: Tratamento Da Drc Em Cãesunclassified
“…Os mecanismos propostos para explicar a proteinúria mediando uma acelerada progressão da DRC são a toxicidade tubulointersticial e podocitária (19,20). Proteinúria induz apoptose em túbulo proximal, o que resulta em acúmulo de proteínas intracelulares (21,22). Além disso, a nível de ducto coletor, já foi demonstrado que a albuminúria prejudica as junções celulares e induz resposta pró-inflamatória e prófibrótica (23,24).…”
unclassified