AKI: an increasingly recognized risk factor for CKD development and progression

Kurzhagen, Johanna T; Dellepiane, Sergio; Cantaluppi, Vincenzo; Rabb, Hamid

doi:10.1007/s40620-020-00793-2

Cited by 95 publications

(55 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The administration of exogenous Ang-(1-7) or other agonists of MasR seems logical in the management of hypertension [90]. The same might be said regarding slowing the progression of CKD, and perhaps even in the management of AKI, preventing its transformation to CKD [91], from the perspective of the vasodilatory, antioxidant, antiinflammatory, anti-apoptotic, and anti-fibrotic properties of this intervention. In fact, some of the renoprotective and blood-pressure-lowering effects of ARBs and ACEi have been attributed to the enhanced expression of ACE2 and the generation of Ang-(1-7) [70,92], and the same might be said to the impact of pregnancy on hypertension [93].…”

Section: Activating Renal Ace2/ang-(1-7)/asr: Plausible Therapeutic Interventions In Renal Diseasesmentioning

confidence: 99%

Angiotensin-(1-7)—A Potential Remedy for AKI: Insights Derived from the COVID-19 Pandemic

Heyman¹,

Walther

Abassi

2021

JCM

View full text Add to dashboard Cite

Membrane-bound angiotensin converting enzyme (ACE) 2 serves as a receptor for the Sars-CoV-2 spike protein, permitting viral attachment to target host cells. The COVID-19 pandemic brought into light ACE2, its principal product angiotensin (Ang) 1-7, and the G protein-coupled receptor for the heptapeptide (MasR), which together form a still under-recognized arm of the renin–angiotensin system (RAS). This axis counteracts vasoconstriction, inflammation and fibrosis, generated by the more familiar deleterious arm of RAS, including ACE, Ang II and the ang II type 1 receptor (AT1R). The COVID-19 disease is characterized by the depletion of ACE2 and Ang-(1-7), conceivably playing a central role in the devastating cytokine storm that characterizes this disorder. ACE2 repletion and the administration of Ang-(1-7) constitute the therapeutic options currently tested in the management of severe COVID-19 disease cases. Based on their beneficial effects, both ACE2 and Ang-(1-7) have also been suggested to slow the progression of experimental diabetic and hypertensive chronic kidney disease (CKD). Herein, we report a further step undertaken recently, utilizing this type of intervention in the management of evolving acute kidney injury (AKI), with the expectation of renal vasodilation and the attenuation of oxidative stress, inflammation, renal parenchymal damage and subsequent fibrosis. Most outcomes indicate that triggering the ACE2/Ang-(1-7)/MasR axis may be renoprotective in the setup of AKI. Yet, there is contradicting evidence that under certain conditions it may accelerate renal damage in CKD and AKI. The nature of these conflicting outcomes requires further elucidation.

show abstract

Section: Activating Renal Ace2/ang-(1-7)/asr: Plausible Therapeutic Interventions In Renal Diseasesmentioning

confidence: 99%

Angiotensin-(1-7)—A Potential Remedy for AKI: Insights Derived from the COVID-19 Pandemic

Heyman¹,

Walther

Abassi

2021

JCM

View full text Add to dashboard Cite

show abstract

“…Acute kidney injury (AKI) is also an increasing health burden with high morbidity and mortality rates worldwide. AKI is a risk factor for development of chronic kidney disease (CKD) and the progression to end stage renal disease (ESRD) (Kurzhagen et al 2020). Treatment for kidney disease largely involves renal replacement therapies, such as dialysis.…”

Section: Introductionmentioning

confidence: 99%

Human reconstructed kidney models

Kishi

Matsumoto

Ichimura

et al. 2021

In Vitro Cell.Dev.Biol.-Animal

View full text Add to dashboard Cite

The human kidney, which consists of up to 2 million nephrons, is critical for blood filtration, electrolyte balance, pH regulation, and fluid balance in the body. Animal experiments, particularly mice and rats, combined with advances in genetically modified technology have been the primary mechanism to study kidney injury in recent years. Mouse or rat kidneys, however, differ substantially from human kidneys at the anatomical, histological, and molecular levels. These differences combined with increased regulatory hurdles and shifting attitudes towards animal testing by non-specialists have led scientists to develop new and more relevant models of kidney injury. Although in vitro tissue culture studies are a valuable tool to study kidney injury and have yielded a great deal of insight, they are not a perfect model. Perhaps, the biggest limitation of tissue culture is that it cannot replicate the complex architecture, consisting of multiple cell types, of the kidney, and the interplay between these cells. Recent studies have found that pluripotent stem cells (PSCs), which are capable of differentiation into any cell type, can be used to generate kidney organoids. Organoids recapitulate the multicellular relationships and microenvironments of complex organs like kidney. Kidney organoids have been used to successfully model nephrotoxin-induced tubular and glomerular disease as well as complex diseases such as chronic kidney disease (CKD), which involves multiple cell types. In combination with genetic engineering techniques, such as CRISPR-Cas9, genetic diseases of the kidney can be reproduced in organoids. Thus, organoid models have the potential to predict drug toxicity and enhance drug discovery for human disease more accurately than animal models.

show abstract

“…The principal pathologic characteristics and central events of renal fibrosis are renal interstitial fibroblast activation and myofibroblast expansion in obstructive kidney disease and the anomalous and excessive deposition of the extracellular matrix, pathologies that give rise to the destruction of normal renal tubules and interstitial structures. Various stimuli and injuries (including: Ang II, high levels of glucose, hypoxia, ischemia, endo or exogenous nephrotoxins and immune molecules) can induce tissue cellular damage and the expression of relevant molecular products [1], which are considered to be crucial triggers for inflammation after acute kidney injury (AKI) [2]. Following injury, associated inflammatory cells are recruited to the injured site by the concentration gradients of chemotactic factors [3], including neutrophils, lymphocytes, monocytes/macrophages, dendritic cells, and mast cells.…”

Section: Introductionmentioning

confidence: 99%

“…Figure 2. Regulation of macrophage-to-myofibroblast transition (1). In response to kidney injury, the bone marrow increases the production and release of monocytes into the peripheral blood.…”

mentioning

confidence: 99%

The Mechanism of CD8+ T Cells for Reducing Myofibroblasts Accumulation during Renal Fibrosis

et al. 2021

View full text Add to dashboard Cite

Renal fibrosis is a hallmark of chronic kidney disease (CKD) and a common manifestation of end-stage renal disease that is associated with multiple types of renal insults and functional loss of the kidney. Unresolved renal inflammation triggers fibrotic processes by promoting the activation and expansion of extracellular matrix-producing fibroblasts and myofibroblasts. Growing evidence now indicates that diverse T cells and macrophage subpopulations play central roles in the inflammatory microenvironment and fibrotic process. The present review aims to elucidate the role of CD8+ T cells in renal fibrosis, and identify its possible mechanisms in the inflammatory microenvironment.

show abstract

AKI: an increasingly recognized risk factor for CKD development and progression

Cited by 95 publications

References 111 publications

Angiotensin-(1-7)—A Potential Remedy for AKI: Insights Derived from the COVID-19 Pandemic

Angiotensin-(1-7)—A Potential Remedy for AKI: Insights Derived from the COVID-19 Pandemic

Human reconstructed kidney models

The Mechanism of CD8+ T Cells for Reducing Myofibroblasts Accumulation during Renal Fibrosis

Contact Info

Product

Resources

About