Acute kidney injury overview: From basic findings to new prevention and therapy strategies

Gonsalez, Sabrina R.; Cortes, Aline L.; Silva, Raquel Costa da; Lowe, Jennifer; Prieto, Minolfa C.; Lara, Lucienne S.

doi:10.1016/j.pharmthera.2019.04.001

Cited by 111 publications

(75 citation statements)

References 143 publications

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“…Acute kidney injury (AKI), a clinical syndrome characterized by an abrupt loss of kidney function within hours, is a worldwide health problem with high mortality 1 . Although tremendous effort has been made by the nephrologist during the past decades, the therapeutic strategy for AKI patients is mainly supportive in nature up to date 2 . Therefore, deciphering the underlying mechanisms of AKI and pursuing efficient strategy for preventing and treating AKI in patients is necessary.…”

Section: Introductionmentioning

confidence: 99%

Rheb1 protects against cisplatin-induced tubular cell death and acute kidney injury via maintaining mitochondrial homeostasis

Wang

Gui

et al. 2020

Cell Death Dis

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Ras homolog enriched in brain (Rheb1), a small GTPase, plays a crucial role in regulating cell growth, differentiation, and survival. However, the role and mechanisms for Rheb1 in tubular cell survival and acute kidney injury (AKI) remain unexplored. Here we found that Rheb1 signaling was activated in kidney tubule of AKI patients and cisplatin-treated mice. A mouse model of tubule-specific deletion of Rheb1 (Tubule-Rheb1 −/−) was generated. Compared to control littermates, Tubule-Rheb1 −/− mice were phenotypically normal within 2 months after birth but developed more severe kidney dysfunction, tubular cell death including apoptosis, necroptosis and ferroptosis, mitochondrial defect and less PGC-1α expression after cisplatin injection. In primary cultured tubular cells, Rheb1 ablation exacerbated cisplatin-induced cell death and mitochondrial defect. Furthermore, haploinsufficiency for Tsc1 in tubular cells led to Rheb1 activation and mitigated cisplatin-induced cell death, mitochondrial defect and AKI. Together, this study uncovers that Rheb1 may protect against cisplatin-induced tubular cell death and AKI through maintaining mitochondrial homeostasis.

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Section: Introductionmentioning

confidence: 99%

Rheb1 protects against cisplatin-induced tubular cell death and acute kidney injury via maintaining mitochondrial homeostasis

Wang

Gui

et al. 2020

Cell Death Dis

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“…Acute kidney injury (AKI) is a nephrotic syndrome with a rapid decline in glomerular filtration, which may mostly induced by sepsis, ischemia–reperfusion injury, and nephrotoxic drugs (Song, Thaiss, & Guo, ). In recent years, the morbidity and mortality of AKI are increasing year by year (Hoste et al, ), among which the incidence rates of AKI are 21.6% in adults and 33.7% in children, and the mortality rates are 23.9% in adults and 13.8% in children (Susantitaphong et al, ), affecting public health costs worldwide (Gonsalez et al, ). Therefore, studying the cellular and molecular mechanisms underlying the occurrence and development of AKI and developing corresponding therapeutic methods and approaches will help in reducing the incidence and mortality of AKI.…”

Section: Introductionmentioning

confidence: 99%

Quercetin protects against cisplatin‐induced acute kidney injury by inhibiting Mincle/Syk/NF‐κB signaling maintained macrophage inflammation

Tan

Wang

Deng

et al. 2019

Phytotherapy Research

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Acute kidney injury (AKI) with high incidence and mortality is the main cause of chronic kidney disease. Previous studies have indicated that quercetin, an abundant flavonoid in plants, exhibited renoprotective role in AKI. However, the underlying mechanism is largely unknown. In this study, we try to explore whether quercetin protects against AKI by inhibiting macrophage inflammation via regulation of Mincle/Syk/NF‐κB signaling. The results demonstrated that quercetin can significantly inhibit expression and secretion of IL‐1β, IL‐6, and TNF‐α in LPS‐induced bone marrow‐derived macrophages (BMDMs) and reduce activity of Mincle/Syk/NF‐κB signaling in vitro. We also found that quercetin can strongly reduce the concentration of serum creatinine, BUN, IL‐1β, IL‐6, and TNF‐α in cisplatin‐induced AKI model. Furthermore, quercetin down‐regulated protein levels of Mincle, phosphorylated Syk and NF‐κB in kidney macrophages of AKI, as well as inhibited M1, up‐regulated M2 macrophage activity. Notably, the down‐regulation of LPS‐induced inflammation by quercetin was reversed after adding TDB (an agonist of Mincle) in BMDMs, suggesting that quercetin suppresses macrophage inflammation may mainly through inhibiting Mincle and its downstream signaling. In summary, these findings clarified a new mechanism of quercetin improving AKI‐induced kidney inflammation and injury, which provides a new drug option for the clinical treatment of AKI.

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“…These molecules express themselves primarily in distal and proximal epithelial tubular cells, respectively [2,6]. When there is sustained hypoxia, there are changes in renal blood low, changes in the GFR, and the supply of sodium towards the renal tubules, producing a disequilibrium in between the production and the demand of oxygen nutrients, damaging tubular epithelial cells and leading towards oxidative stress [9,14].…”

Section: Pathophysiology Of Akimentioning

confidence: 99%

“…During an ischemic event, all the segments of the nephrons are potentially affected, but the proximal tubular cells are the most commonly damaged [3]. The damaged endothelium in the small renal arterioles of the vasa recta in the ischemic kidney suffers vasoconstriction due to an increase in endothelin-1, angiotensin II, thromboxane A2, prostaglandin H2, leukotriene C4, and D4, as well an increase in the sympathetic nervous system activity [14].…”

Section: Pathophysiology Of Akimentioning

confidence: 99%

Biomarkers in acute kidney injury

Pájaro-Galvis¹

2020

J Clini Nephrol

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Acute kidney injury is a common condition associated with high morbidity and short-term mortality. Its pathophysiology varies according to the numerous conditions associated with its genesis. Biomarkers allow detecting changes at the level of kidney function; therefore, they play an important role in the prevention, early diagnosis, therapeutic response and prognosis of acute kidney injury. The search for biomarkers for acute kidney injury began over 15 years ago; initially, only serum creatinine was available for diagnosis. However, throughout history, great advances have been made in research, which have allowed the fi nding of new biomarkers in order to improve the health and quality of life of patients. A narrative review of the literature is carried out on the basis of available scientifi c evidence to clarify the role and importance of biomarkers in the context of acute renal injury. serum creatinine (sCr), knowing that a signi icant reduction in the glomerular iltration rate will increase the sCr [1]. Until the year 2002, there was no standardized de inition More Information

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Acute kidney injury overview: From basic findings to new prevention and therapy strategies

Cited by 111 publications

References 143 publications

Rheb1 protects against cisplatin-induced tubular cell death and acute kidney injury via maintaining mitochondrial homeostasis

Rheb1 protects against cisplatin-induced tubular cell death and acute kidney injury via maintaining mitochondrial homeostasis

Quercetin protects against cisplatin‐induced acute kidney injury by inhibiting Mincle/Syk/NF‐κB signaling maintained macrophage inflammation

Biomarkers in acute kidney injury

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