Hypoxia and chronic kidney disease: Possible mechanisms, therapeutic targets, and relevance to cats

Spencer, Sarah; Wheeler‐Jones, Caroline P.D.; Elliott, Jonathan

doi:10.1016/j.tvjl.2021.105714

Cited by 8 publications

(17 citation statements)

References 153 publications

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“…Therefore, studies to better understand its pathophysiology and identify prospective target for therapeutic intervention are needed. Furthermore, insights into this heterogeneous population of patients with naturally-occurring disease have translational potential for aging human kidney disease patients due to similarities in histopathologic lesions despite some differences in clinical characteristics [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Renal Senescence, Telomere Shortening and Nitrosative Stress in Feline Chronic Kidney Disease

Quimby

Erickson

McLeland

et al. 2021

Veterinary Sciences

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Kidney tissues from cats with naturally occurring chronic kidney disease (CKD) and adult and senior cats without CKD were assessed to determine whether telomere shortening and nitrosative stress are associated with senescence in feline CKD. The histopathologic assessment of percent global glomerulosclerosis, inflammatory infiltrate, and fibrosis was performed. Senescence and nitrosative stress were evaluated utilizing p16 and iNOS immunohistochemistry, respectively. Renal telomere length was evaluated using telomere fluorescent in situ hybridization combined with immunohistochemistry. CKD cats were found to have significantly increased p16 staining in both the renal cortex and corticomedullary junction compared to adult and senior cats. Senior cats had significantly increased p16 staining in the corticomedullary junction compared to adult cats. p16 staining in both the renal cortex and corticomedullary junction were found to be significantly correlated with percent global glomerulosclerosis, cortical inflammatory infiltrate, and fibrosis scores. p16 staining also correlated with age in non-CKD cats. Average telomere length was significantly decreased in CKD cats compared to adult and senior cats. CKD cats had significantly increased iNOS staining compared to adult cats. Our results demonstrate increased renal senescence, telomere shortening, and nitrosative stress in feline CKD, identifying these patients as potential candidates for senolytic therapy with translational potential.

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Section: Introductionmentioning

confidence: 99%

Renal Senescence, Telomere Shortening and Nitrosative Stress in Feline Chronic Kidney Disease

Quimby

Erickson

McLeland

et al. 2021

Veterinary Sciences

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“…Hypoxemia is caused by many factors, including airway obstruction ( Wilson and Shih, 2015 ). Though it can affect many organs such as the kidney, eyes, and brain damage caused by hypoxic encephalopathy is very common and can result in a coma ( Duncalf and Weitzner, 1963 ; Schmiedt et al , 2016 ; Brown et al , 2019 ; Dunn and Isaacs, 2020 ; Spencer et al , 2021 ). Fortunately, no neurological symptoms were observed after recovery from anesthesia in this case.…”

Section: Discussionmentioning

confidence: 99%

Use of a gum elastic bougie in a cat with severe upper airway stenosis

Kato¹,

Itami²,

Torisu³

et al. 2023

Open Vet J

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Background: Gum elastic bougie (GEB) is an airway management device for patients who are difficult to intubate and their use has been reported in human medicine. However, to our knowledge, no reports in veterinary medicine have described oxygenation using GEB. We describe a case in which GEB was used to maintain oxygenation in a cat with severe upper airway stenosis. Case Description: A 10-year-old neutered male domestic shorthair cat was diagnosed with a laryngeal tumour with severe upper airway stenosis. During anaesthesia induction, normal laryngeal structure could not be confirmed; orotracheal intubation was difficult, resulting in a “cannot intubate, cannot oxygenate” status. The GEB was inserted, making it possible to oxygenate the cat until a permanent tracheostoma could be created, but hypoventilation was noted. Conclusion: Although gum elastic bougies are not useful for proper ventilation, they can be useful for temporary oxygenation in veterinary medicine when airway management is difficult.

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“…Peritubular capillary rarefaction refers to microvessel loss and decreased microvascular density and is considered an important histologic feature of chronic kidney disease (CKD) in both humans and experimental animal models of kidney injury. 1 , 2 , 3 , 4 Capillary rarefaction is positively correlated with decreasing kidney function and fibrosis and is considered a major contributor to hypoxia and progression of disease. 1 , 2 , 3 , 4 The mechanisms by which it occurs are complex and likely involve some combination of pericyte damage and detachment, endothelial cell apoptosis, downregulation of vascular endothelial growth factor (VEGF), upregulation of antiangiogenic factors, and incompetence of endothelial progenitor cells.…”

Section: Introductionmentioning

confidence: 99%

“… 1 , 2 , 3 , 4 Capillary rarefaction is positively correlated with decreasing kidney function and fibrosis and is considered a major contributor to hypoxia and progression of disease. 1 , 2 , 3 , 4 The mechanisms by which it occurs are complex and likely involve some combination of pericyte damage and detachment, endothelial cell apoptosis, downregulation of vascular endothelial growth factor (VEGF), upregulation of antiangiogenic factors, and incompetence of endothelial progenitor cells. 1 , 2 These processes are likely initiated by damage to tubular epithelial cells and pericytes that result in apoptosis or transdifferentiation into extracellular matrix‐producing myofibroblasts.…”

Section: Introductionmentioning

confidence: 99%

Assessment of peritubular capillary rarefaction in kidneys of cats with chronic kidney disease

Paschall

Quimby

Cianciolo

et al. 2023

Veterinary Internal Medicne

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Background Hypoxia is a key driver of fibrosis and is associated with capillary rarefaction in humans. Objectives Characterize capillary rarefaction in cats with chronic kidney disease (CKD). Animals Archival kidney tissue from 58 cats with CKD, 20 unaffected cats. Methods Cross‐sectional study of paraffin‐embedded kidney tissue utilizing CD31 immunohistochemistry to highlight vascular structures. Consecutive high‐power fields from the cortex (10) and corticomedullary junction (5) were digitally photographed. An observer counted and colored the capillary area. Image analysis was used to determine the capillary number, average capillary size, and average percent capillary area in the cortex and corticomedullary junction. Histologic scoring was performed by a pathologist masked to clinical data. Results Percent capillary area (cortex) was significantly lower in CKD (median 3.2, range, 0.8‐5.6) compared to unaffected cats (4.4, 1.8‐7.0; P = <.001) and was negatively correlated with serum creatinine concentrations ( r = −.36, P = .0013), glomerulosclerosis ( r = −0.39, P = <.001), inflammation ( r = −.30, P = .009), and fibrosis ( r = −.30, P = .007). Capillary size (cortex) was significantly lower in CKD cats (2591 pixels, 1184‐7289) compared to unaffected cats (4523 pixels, 1801‐7618; P = <.001) and was negatively correlated with serum creatinine concentrations ( r = −.40, P = <.001), glomerulosclerosis ( r = −.44, P < .001), inflammation ( r = −.42, P = <.001), and fibrosis ( r = −.38, P = <.001). Conclusions and Clinical Importance Capillary rarefaction (decrease in capillary size and percent capillary area) is present in kidneys of cats with CKD and is positively correlated with renal dysfunction and histopathologic lesions.

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Hypoxia and chronic kidney disease: Possible mechanisms, therapeutic targets, and relevance to cats

Cited by 8 publications

References 153 publications

Renal Senescence, Telomere Shortening and Nitrosative Stress in Feline Chronic Kidney Disease

Renal Senescence, Telomere Shortening and Nitrosative Stress in Feline Chronic Kidney Disease

Use of a gum elastic bougie in a cat with severe upper airway stenosis

Assessment of peritubular capillary rarefaction in kidneys of cats with chronic kidney disease

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