Age‐Dependent Changes of Kidney Injury Biomarkers in Pediatrics

BackgroundMononuclear phagocytes (MPs), including macrophages, monocytes, and dendritic cells (DCs), are phagocytic cells with important roles in immunity. The developmental origin of kidney DCs has been highly debated because of the large phenotypic overlap between macrophages and DCs in this tissue.MethodsWe used fate mapping, RNA sequencing, flow cytometry, confocal microscopy, and histo-cytometry to assess the origin and phenotypic and functional properties of renal DCs in healthy kidney and of DCs after cisplatin and ischemia reperfusion–induced kidney injury.ResultsAdult kidney contains at least four subsets of MPs with prominent Clec9a-expression history indicating a DC origin. We demonstrate that these populations are phenotypically, functionally, and transcriptionally distinct from each other. We also show these kidney MPs exhibit unique age-dependent developmental heterogeneity. Kidneys from newborn mice contain a prominent population of embryonic-derived MHCIInegF4/80hiCD11blow macrophages that express T cell Ig and mucin domain containing 4 (TIM-4) and MER receptor tyrosine kinase (MERTK). These macrophages are replaced within a few weeks after birth by phenotypically similar cells that express MHCII but lack TIM-4 and MERTK. MHCII+F4/80hi cells exhibit prominent Clec9a-expression history in adulthood but not early life, indicating additional age-dependent developmental heterogeneity. In AKI, MHCIInegF4/80hi cells reappear in adult kidneys as a result of MHCII downregulation by resident MHCII+F4/80hi cells, possibly in response to prostaglandin E2 (PGE2). RNA sequencing further suggests MHCII+F4/80hi cells help coordinate the recruitment of inflammatory cells during renal injury.ConclusionsDistinct developmental programs contribute to renal DC and macrophage populations throughout life, which could have important implications for therapies targeting these cells.

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The role of the age-dependent loss of alpha(E)-catenin in increased acute kidney injury

10.32469/10355/57785 ◽

2015 ◽

Author(s):

◽

Xinhui Wang

Keyword(s):

Acute Kidney Injury ◽

Epithelial Cells ◽

Actin Cytoskeleton ◽

Kidney Injury ◽

Actin Binding ◽

Aged Patients ◽

Age Dependent ◽

Aging Kidney ◽

Aged Kidney

The aging kidney undergoes structural and functional alterations which make it more susceptible to acute kidney injury (AKI). Previous studies in our laboratory have shown that the aging kidney has a marked loss of alpha(E)-catenin in proximal tubular epithelium. alpha-Catenin, a key regulator of actin cytoskeleton, interacts with a variety of actin-binding proteins. Fascin 2 is an actin bundling protein that interacts with adhesion molecules and F-actin. In this work, we hypothesized that loss of alpha(E)-catenin leads to disruption of actin cytoskeleton which increases cisplatin-induced injury in aged kidney. A stable shRNA knock-down of alpha(E)-catenin was generated in NRK-52E cells (C2 cells); NT3 cells are the non-targeted control. We demonstrated that age-dependent loss of alpah(E)-catenin in renal tubule epithelial cells facilitates the Fas-mediated apoptotic signaling pathway in response to cisplatin-induced AKI injury. In addition, a cisplatin-induced loss of fascin 2 was observed in aged kidney. Overexpression of Fscn2 abolished increased cisplatin-induced apoptosis, mitochondrial dysfunction and oxidative stress in C2 cells compared with NT3 cells. In conclusion, this dissertation projects novel insight into understanding the increased incidence of AKI in aged kidney and identified a novel role of fascin 2 in renal epithelial cells, which depends on the functional interaction with alpha(E)-catenin and F-actin. These findings may lay the groundwork for new therapeutic approaches to AKI in aged patients in the future.

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Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent*

Critical Care Medicine ◽

10.1097/ccm.0b013e3182591ebe ◽

2012 ◽

Vol 40 (9) ◽

pp. 2638-2646 ◽

Cited By ~ 14

Author(s):

Bert Maddens ◽

Benjamin Vandendriessche ◽

Dieter Demon ◽

Raymond Vanholder ◽

Koen Chiers ◽

...

Keyword(s):

Acute Kidney Injury ◽

Mouse Model ◽

Kidney Injury ◽

Age Dependent

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Is acute kidney injury age-dependent in older adults: an observational study in two centers from North China

BMC Geriatrics ◽

10.1186/s12877-020-01906-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Libin Xu ◽

◽

Yanhua Wu ◽

Yuanhan Chen ◽

Ruiying Li ◽

...

Keyword(s):

Older Adults ◽

Acute Kidney Injury ◽

Hospital Admissions ◽

Multivariable Analysis ◽

Kidney Injury ◽

Adverse Outcomes ◽

Charlson Comorbidity Index Score ◽

Hospital Death ◽

Dependent Manner ◽

Age Dependent

Abstract Background Although aging increases susceptibility to acute kidney injury (AKI), whether the AKI risk and the association between AKI and adverse outcomes are age-dependent remain unclear in older adults. The current study aimed to identify whether AKI risk was age-dependent in older adults and to investigate whether the association between AKI and mortality increased with increasing age. Methods Medical records from 47,012 adult hospital admissions, including 30,194 older adults aged 60 or older, in two tertiary general hospitals were studied retrospectively. AKI was identified based on changes in blood creatinine levels according to the Kidney Disease: Improving Global Outcomes criteria. Results Among the total population and 30,194 older adult patients, the raw incidences of AKI were 8.2 and 8.3%, respectively. The curve of the age-grouped AKI incidence was “U-shaped”, which revealed a positive relationship between the AKI incidence and age among the older adults aged 75 years or older. This trend of the age-AKI relationship was supported by further multivariable analysis. After adjusting for the Charlson Comorbidity Index score, the AKI was associated with in-hospital mortality; however, the associations did not increase with increasing age. Conclusion The AKI risk does not increase with age in older adults, except for those aged 75 and above. The association between AKI and in-hospital death did not increase in an age-dependent manner in older adults. Trial registration This study was retrospectively registered at clinicaltrials.gov (NCT03054142) on February 13, 2017.

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Role of Age‐Dependent Changes in MMP Expression in Acute Kidney Injury

The FASEB Journal ◽

10.1096/fasebj.22.1_supplement.942.4 ◽

2008 ◽

Vol 22 (S1) ◽

Author(s):

Adebayo D. Akintola ◽

Gang Chen ◽

Jeffrey M. Catania ◽

Robert C. Burghardt ◽

Alan R. Parrish

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Age Dependent

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Effects of Hyperoxia on Lung Utrastructure

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100067121 ◽

1970 ◽

Vol 28 ◽

pp. 26-27

Author(s):

Gladys Harrison

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Light Microscopy ◽

Oxygen Effects ◽

Age Dependent ◽

The Central Nervous System ◽

The Subject ◽

Space Age ◽

Alveolar Septa ◽

Extensive Damage

With the advent of the space age and the need to determine the requirements for a space cabin atmosphere, oxygen effects came into increased importance, even though these effects have been the subject of continuous research for many years. In fact, Priestly initiated oxygen research when in 1775 he published his results of isolating oxygen and described the effects of breathing it on himself and two mice, the only creatures to have had the “privilege” of breathing this “pure air”.Early studies had demonstrated the central nervous system effects at pressures above one atmosphere. Light microscopy revealed extensive damage to the lungs at one atmosphere. These changes which included perivascular and peribronchial edema, focal hemorrhage, rupture of the alveolar septa, and widespread edema, resulted in death of the animal in less than one week. The severity of the symptoms differed between species and was age dependent, with young animals being more resistant.

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