Fibrotic Changes Mediating Acute Kidney Injury to Chronic Kidney Disease Transition

hAinmhire, Eoghainín Ó; Humphreys, Benjamin D.

doi:10.1159/000474960

Cited by 25 publications

(13 citation statements)

References 31 publications

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“…Induction and maintenance of AKI-CKD transition depends on inflammatory and fibrotic mediators expressed during initial stages of AKI [ 227 , 228 , 229 ]. AKI insults promote tissue damage and cell death, resulting in an early acute inflammatory response, and subsequent reparative and regenerative reactions in late phases of AKI to restore renal parenchyma [ 230 , 231 ].…”

Section: Aki To Ckd Transitionmentioning

confidence: 99%

Toll-Like Receptors in Acute Kidney Injury

Vázquez‐Carballo

Guerrero‐Hue

García‐Caballero

et al. 2021

IJMS

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Acute kidney injury (AKI) is an important health problem, affecting 13.3 million individuals/year. It is associated with increased mortality, mainly in low- and middle-income countries, where renal replacement therapy is limited. Moreover, survivors show adverse long-term outcomes, including increased risk of developing recurrent AKI bouts, cardiovascular events, and chronic kidney disease. However, there are no specific treatments to decrease the adverse consequences of AKI. Epidemiological and preclinical studies show the pathological role of inflammation in AKI, not only at the acute phase but also in the progression to chronic kidney disease. Toll-like receptors (TLRs) are key regulators of the inflammatory response and have been associated to many cellular processes activated during AKI. For that reason, a number of anti-inflammatory agents targeting TLRs have been analyzed in preclinical studies to decrease renal damage during AKI. In this review, we updated recent knowledge about the role of TLRs, mainly TLR4, in the initiation and development of AKI as well as novel compounds targeting these molecules to diminish kidney injury associated to this pathological condition.

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Section: Aki To Ckd Transitionmentioning

confidence: 99%

Toll-Like Receptors in Acute Kidney Injury

Vázquez‐Carballo

Guerrero‐Hue

García‐Caballero

et al. 2021

IJMS

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“…In this process, normal repair can restore tubular epithelial integrity and function; however, incomplete or maladaptive repair results in the development of chronic pathologies (e.g., interstitial fibrosis) and the progression to CKD (4,23,59,61). Emerging evidence suggests that after severe or episodic AKI, normal tubular epithelial cells undergo a phenotype change with persistent production and secretion of profibrotic factors, leading to atrophic proximal tubules and renal interstitial fibrosis (20,23,41,61,67). However, it is largely unclear how these cells become atrophic and assume a profibrotic phenotype.…”

Section: Introductionmentioning

confidence: 99%

Rodent models of AKI-CKD transition

Tang

Cai

et al. 2018

American Journal of Physiology-Renal Physiology

175

131

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Acute kidney injury (AKI) is a contributing factor in the development and progression of chronic kidney disease (CKD). Despite rapid progresses, the mechanism underlying AKI-CKD transition remains largely unclear. Animal models recapitulating this process are crucial to the research of the pathophysiology of AKI-CKD transition and the development of effective therapeutics. In this review, we present the commonly used rodent models of AKI-CKD transition, including bilateral ischemia-reperfusion injury (IRI), unilateral IRI, unilateral IRI with contralateral nephrectomy, multiple episodes of IRI, and repeated treatment of low-dose cisplatin, diphtheria toxin, aristolochic acid, or folic acid. The main merits and pitfalls of these models are also discussed. This review provides helpful information for establishing reliable and clinically relevant models for studying post-AKI development of chronic renal pathologies and the progression to CKD.

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“…For instance, to our knowledge a dose–response relation between the frequency and severity of heat-related AKI and the subsequent development of CKD has never been experimentally examined in rodent models nor explored in epidemiological studies. That said, in the absence of heat exposure, data from pre-clinical models indicate that AKI can result in renal tubular remodeling [40,41], which can lead to long-term impairments in kidney function, the defining characteristic of CKD [40,42,43,44,45,46]. More recently, these findings have been extended to instances of combined heat exposure and dehydration.…”

Section: Introductionmentioning

confidence: 99%

The Potential for Renal Injury Elicited by Physical Work in the Heat

et al. 2019

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An epidemic of chronic kidney disease (CKD) is occurring in laborers who undertake physical work in hot conditions. Rodent data indicate that heat exposure causes kidney injury, and when this injury is regularly repeated it can elicit CKD. Studies in humans demonstrate that a single bout of exercise in the heat increases biomarkers of acute kidney injury (AKI). Elevations in AKI biomarkers in this context likely reflect an increased susceptibility of the kidneys to AKI. Data largely derived from animal models indicate that the mechanism(s) by which exercise in the heat may increase the risk of AKI is multifactorial. For instance, heat-related reductions in renal blood flow may provoke heterogenous intrarenal blood flow. This can promote localized ischemia, hypoxemia and ATP depletion in renal tubular cells, which could be exacerbated by increased sodium reabsorption. Heightened fructokinase pathway activity likely exacerbates ATP depletion occurring secondary to intrarenal fructose production and hyperuricemia. Collectively, these responses can promote inflammation and oxidative stress, thereby increasing the risk of AKI. Equivalent mechanistic evidence in humans is lacking. Such an understanding could inform the development of countermeasures to safeguard the renal health of laborers who regularly engage in physical work in hot environments.

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Fibrotic Changes Mediating Acute Kidney Injury to Chronic Kidney Disease Transition

Cited by 25 publications

References 31 publications

Toll-Like Receptors in Acute Kidney Injury

Toll-Like Receptors in Acute Kidney Injury

Rodent models of AKI-CKD transition

The Potential for Renal Injury Elicited by Physical Work in the Heat

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