Chronic Kidney Disease

Goligorsky, Michael S.

doi:10.1016/j.ajpath.2020.01.016

Cited by 16 publications

(4 citation statements)

References 55 publications

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“…Increasing evidence indicates that there is a striking similarity between the manifestations of progressive CKD and aging kidney (Docherty et al, 2020;Goligorsky, 2020;Zhou et al, 2020). As such, CKD is often viewed as a form of premature and accelerated aging.…”

Section: Introductionmentioning

confidence: 99%

Cellular Senescence in Kidney Fibrosis: Pathologic Significance and Therapeutic Strategies

Zhou

Liu

2020

Front. Pharmacol.

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Age-related disorders such as chronic kidney disease (CKD) are increasingly prevalent globally and pose unprecedented challenges. In many aspects, CKD can be viewed as a state of accelerated and premature aging. Aging kidney and CKD share many common characteristic features with increased cellular senescence, a conserved program characterized by an irreversible cell cycle arrest with altered transcriptome and secretome. While developmental senescence and acute senescence may positively contribute to the fine-tuning of embryogenesis and injury repair, chronic senescence, when unresolved promptly, plays a crucial role in kidney fibrogenesis and CKD progression. Senescent cells elicit their fibrogenic actions primarily by secreting an assortment of inflammatory and profibrotic factors known as the senescence-associated secretory phenotype (SASP). Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. In this review, we discuss current understanding of the role and mechanism of cellular senescence in kidney fibrosis. We also highlight potential options of targeting senescent cells for the treatment of CKD.

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Section: Introductionmentioning

confidence: 99%

Cellular Senescence in Kidney Fibrosis: Pathologic Significance and Therapeutic Strategies

Zhou

Liu

2020

Front. Pharmacol.

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“…Unsurprisingly therefore, uremic inflammation resembles the systemic inflammation associated with aging effects on the immune system, termed “inflammageing” and similar pathogenic mechanisms have been observed in aging and CKD, specifically premature immunological aging ( 65 ). Associated with this is immunosenescence, which arises due to the chronic depletion of naïve T cells, B cells, and dendritic cells, an expansion of memory T cells, particularly pro-inflammatory CD4+CD28–T cells, along with impaired neutrophilic phagocytic capacity and the loss of reno-protective factors, including Klotho and bone-morphogenic proteins, vascular rarefaction, and increased oxidative stress ( 58 , 66 ). Reactive oxygen species (ROS) levels can also regulate signaling via the stress activated kinases, p38, and JNK.…”

Section: Why Klotho Is Important In Agingmentioning

confidence: 99%

Klotho, Aging, and the Failing Kidney

et al. 2020

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Klotho has been recognized as a gene involved in the aging process in mammals for over 30 years, where it regulates phosphate homeostasis and the activity of members of the fibroblast growth factor (FGF) family. The α-Klotho protein is the receptor for Fibroblast Growth Factor-23 (FGF23), regulating phosphate homeostasis and vitamin D metabolism. Phosphate toxicity is a hallmark of mammalian aging and correlates with diminution of Klotho levels with increasing age. As such, modulation of Klotho activity is an attractive target for therapeutic intervention in the diseasome of aging; in particular for chronic kidney disease (CKD), where Klotho has been implicated directly in the pathophysiology. A range of senotherapeutic strategies have been developed to directly or indirectly influence Klotho expression, with varying degrees of success. These include administration of exogenous Klotho, synthetic and natural Klotho agonists and indirect approaches, via modulation of the foodome and the gut microbiota. All these approaches have significant potential to mitigate loss of physiological function and resilience accompanying old age and to improve outcomes within the diseasome of aging.

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“…Finding correlations between NAG and other biomarkers can help for further differentiation and follow-up inspection of diseases . Senescence-associated β-GAL has been reported to be upregulated to varying degrees in several renal diseases according to the literature; there are also studies exploring the interactive correlation between kidney diseases and cell senescence, leading to progressive deterioration of renal function. , Certain differences in excretions of NAG and β-GAL in various stages of several different diseases, especially renal lesions, were enumerated in many articles as well. ,− Therefore, the simultaneous determination of NAG and β-GAL can be greatly meaningful, which contributes to ascertaining the duration and severity of lesions, discriminating between various kinds of kidney disorders, estimating the clinical outcome, and monitoring responses during the whole process from early detection to longitudinal tracking for later treatment.…”

Section: Introductionmentioning

confidence: 99%

Dual-Signal Triple-Mode Optical Sensing Platform for Assisting in the Diagnosis of Kidney Disorders

Gao

et al. 2023

Anal. Chem.

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As known biomarkers of kidney diseases, N-acetyl-β-d-glucosaminidase (NAG) and β-galactosidase (β-GAL) are of great importance for the diagnosis and treatment of diseases. The feasibility of using multiplex sensing methods to simultaneously report the outcome of the two enzymes in the same sample is even more alluring. Herein, we establish a simple sensing platform for the concurrent detection of NAG and β-GAL using silicon nanoparticles (SiNPs) as a fluorescent indicator synthesized by a one-pot hydrothermal route. p-Nitrophenol (PNP), as a common enzymatic hydrolysis product of the two enzymes, led to the attenuation of fluorometric signal caused by the inner filter effect on SiNPs, the enhancement of colorimetric signal due to the increase of intensity of the characteristic absorption peak at around 400 nm with increasing reaction time, and the changes of RGB values of images obtained through a color recognition application on a smartphone. The fluorometric/colorimetric approach combined with the smartphone-assisted RGB mode was able to detect NAG and β-GAL with good linear response. Applying this optical sensing platform to clinical urine samples, we found that the two indicators in healthy individuals and patients (glomerulonephritis) with kidney diseases were significantly different. By expanding to other renal lesion-related specimens, this tool may show great potentials in clinical diagnosis and visual inspection.

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Chronic Kidney Disease

Cited by 16 publications

References 55 publications

Cellular Senescence in Kidney Fibrosis: Pathologic Significance and Therapeutic Strategies

Cellular Senescence in Kidney Fibrosis: Pathologic Significance and Therapeutic Strategies

Klotho, Aging, and the Failing Kidney

Dual-Signal Triple-Mode Optical Sensing Platform for Assisting in the Diagnosis of Kidney Disorders

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