Browsing by Subject "Acute renal injury"

Now showing 1 - 4 of 4
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    AKI and diastolic dysfunction: Opportunity for targeted intervention?
    (Karger, 2023) Soranno, Danielle E.; Gist, Katja M.; Pediatrics, School of Medicine
    Background/aims: Acute kidney injury (AKI) is common, results in nonrenal sequelae, and predisposes patients to long-term cardiovascular disease. The long-term systemic effects of AKI remain unclear. Sex is an important biological variable in ischemia-reperfusion AKI, and the protective role of estrogen has stymied the inclusion of both sexes in preclinical AKI studies. ITF2357 is a nonspecific histone deacetylase inhibitor that has been shown to improve cardiac outcomes in murine models of hypertension. Here, we review recent work that provides new insight into our understanding of cardiovascular sequelae following AKI. Methods: Adult male and female C57BL/6J mice underwent 25 min (males) and 34 min (females) of bilateral ischemia-reperfusion AKI or sham procedure. A male treatment arm received chow containing the nonspecific histone deacetylase inhibitor ITF2357 starting 3 days after AKI. Serial renal function, echocardiograms, and blood pressure assessments were performed throughout the 1-year study; renal histology and cardiac and plasma metabolomics were evaluated at 1 year. Results: Measured glomerular filtration rates throughout the 1-year study showed that the female model of AKI matched the male model. Untreated males developed depressed diastolic function after AKI, whereas females and males treated with ITF2357 maintained normal diastolic function. Both untreated males and females developed hypertension after AKI; males treated with ITF2357 remained normotensive. Conclusions: Ischemic AKI results in long-term cardiovascular sequelae with sex as an important biological variable in outcomes. Histone deacetylase inhibition affects cardiovascular outcomes after AKI.
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    The emerging role of cellular senescence in renal diseases
    (Wiley, 2020-02) Zhou, Bingru; Wan, Ying; Chen, Rong; Zhang, Chunmei; Li, Xuesen; Meng, Fanyin; Glaser, Shannon; Wu, Nan; Zhou, Tianhao; Li, Siwen; Francis, Heather; Alpini, Gianfranco; Zou, Ping; Medicine, School of Medicine
    Cellular senescence represents the state of irreversible cell cycle arrest during cell division. Cellular senescence not only plays a role in diverse biological events such as embryogenesis, tissue regeneration and repair, ageing and tumour occurrence prevention, but it is also involved in many cardiovascular, renal and liver diseases through the senescence-associated secretory phenotype (SASP). This review summarizes the molecular mechanisms underlying cellular senescence and its possible effects on a variety of renal diseases. We will also discuss the therapeutic approaches based on the regulation of senescent and SASP blockade, which is considered as a promising strategy for the management of renal diseases.
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    Orai1: A New Therapeutic Target for the Acute Kidney Injury-to-Chronic Kidney Disease Transition
    (Karger, 2022) Basile, David P.; Collett, Jason A.; Anatomy, Cell Biology and Physiology, School of Medicine
    This review focuses on the potential mediation in the acute kidney injury (AKI)-to-chronic kidney disease (CKD) transition by lymphocytes. We highlight evidence that lymphocytes, particularly Th17 cells, modulate the severity of both acute injury and chronic kidney disease. Th17 cells are strongly influenced by the activity of the store-operated Ca2+channel Orai1, which is upregulated on lymphocytes in animal models of AKI. Inhibition of this channel attenuates both acute and chronic kidney injury in rodent models. In addition, Oria1+ cells are increased in peripheral blood of patients with AKI. Similarly, peripheral blood cells manifest an early and sustained increase in Orai1 expression in a rat model of ischemia/reperfusion, suggesting that blood cell Orai1 may represent a marker informing potential Th17 activity in the setting of AKI or the AKI-to-CKD transition.
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    Renal Protection Phenomenon Observed in a Porcine Model After Electromagnetic Lithotripsy Using a Treatment Pause
    (Mary Ann Liebert, Inc., 2021) Connors, Bret A.; Gardner, Tony; Liu, Ziyue; Lingeman, James E.; Williams, James C., Jr.; Anatomy, Cell Biology and Physiology, School of Medicine
    Purpose: Pretreating the kidney with 100 low-energy shock waves (SWs) with a time pause before delivering a clinical dose of SWs (Dornier HM-3, 2000 SWs, 24 kV, and 120 SWs/min) has been shown to significantly reduce the size of the hemorrhagic lesion produced in that treated kidney, compared to a protocol without pretreatment. It has been assumed that a similar reduction in injury will occur with lithotripters other than the HM-3, but experiments to confirm this assumption are lacking. In this study, we sought to verify that the lesion protection phenomenon also occurs in a lithotripter using an electromagnetic shock source and dry-head coupling. Materials and Methods: Eleven female pigs were placed in a Dornier Compact S lithotripter where the left kidney of each animal was targeted for lithotripsy treatment. Some kidneys received 2500 SWs at power level (PL) = 5 (120 SWs/min) while some kidneys were pretreated with 100 SWs at PL = 1, with a 3-minute time pause, followed immediately by 2500 SWs at PL = 5 (120 SWs/min). Lesion size analysis was performed to assess the volume of hemorrhagic tissue injury created by each treatment regimen (% functional renal volume). Results: Lesion size fell by 85% (p = 0.01) in the 100 SW pretreatment group compared to the injury produced by a regimen without pretreatment. Conclusions: The results suggest that the treatment pause protection phenomenon occurs with a Dornier Compact S, a machine distinctly different from the Dornier HM-3. This result also suggests that this phenomenon may be observed generally in SW lithotripters.