Investigation of hallmarks of carbonyl stress and formation of end products in feline chronic kidney disease as markers of uraemic toxins

Valle, Emanuela; Prola, Liviana; Vergnano, Diana; Borghi, Roberta; Monacelli, Fiammetta; Traverso, Nicola; Bruni, Natascia; Bovero, Andrea; Schiavone, Achille; Nery, Joana; Bergero, Domenico; Odetti, Patrizio

doi:10.1177/1098612x18783858

Cited by 8 publications

(7 citation statements)

References 53 publications

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“…The generation of ROS is also promoted by hypoxia associated with fibrosis and capillary rarefaction, RAAS activation, anemia, hyperphosphatemia, and uremic toxins [5]. Evidence of oxidative stress has been demonstrated in feline CKD [49][50][51][52]. Cats with CKD display the activation of antioxidant defense mechanisms and lower antioxidant capacity than normal controls, consistent with imbalance between oxidative stress and antioxidant defense mechanisms [49].…”

Section: Discussionmentioning

confidence: 98%

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: Discussionmentioning

confidence: 98%

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

Quimby

Erickson

McLeland

et al. 2021

Veterinary Sciences

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“…In cats, oxidative stress is involved in different metabolic conditions such as diabetes mellitus, obesity, and chronic kidney disease 36‐38 . N ε ‐carboxymethyllysine, an advanced glycation end‐product produced during protein oxidation, has been detected in the renal tissue of humans affected by AA amyloidosis with kidney involvement 39,40 .…”

Section: Discussionmentioning

confidence: 99%

“…In cats, oxidative stress is involved in different metabolic conditions such as diabetes mellitus, obesity, and chronic kidney disease. 36 , 37 , 38 N ε ‐carboxymethyllysine, an advanced glycation end‐product produced during protein oxidation, has been detected in the renal tissue of humans affected by AA amyloidosis with kidney involvement. 39 , 40 In our case series, glutathione peroxidase, selenoprotein P, and selenoprotein M were excreted in urine of cats with renal AA amyloidosis in larger amounts, suggesting a link between oxidative damage and the protein misfolding disease.…”

Section: Discussionmentioning

confidence: 99%

Renal amyloid‐A amyloidosis in cats: Characterization of proteinuria and biomarker discovery, and associations with kidney histology

Palizzotto,

Ferri,

Callegari

et al. 2023

Veterinary Internal Medicne

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BackgroundAmyloid A (AA) amyloidosis is a protein misfolding disease arising from serum amyloid A (SAA). Systemic AA amyloidosis recently was shown to have a high prevalence in shelter cats in Italy and was associated with azotemia and proteinuria.ObjectivesInvestigate urine protein profiles and diagnostic biomarkers in cats with renal AA amyloidosis.AnimalsTwenty‐nine shelter cats.MethodsCase‐control study. Cats with renal proteinuria that died or were euthanized between 2018 and 2021 with available necropsy kidney, liver and spleen samples, and with surplus urine collected within 30 days before death, were included. Histology was used to characterize renal damage and amyloid amount and distribution; immunohistochemistry was used to confirm AA amyloidosis. Urine protein‐to‐creatinine (UPC) and urine amyloid A‐to‐creatinine (UAAC) ratios were calculated, and sodium dodecyl sulfate‐agarose gel electrophoresis (SDS‐AGE) and liquid chromatography‐mass spectrometry (LC‐MS) of proteins were performed.ResultsTwenty‐nine cats were included. Nineteen had AA amyloidosis with renal involvement. Cats with AA amyloidosis had a higher UPC (median, 3.9; range, 0.6‐12.7 vs 1.5; 0.6‐3.1; P = .03) and UAAC ratios (median, 7.18 × 10−3; range, 23 × 10−3‐21.29 × 10−3 vs 1.26 × 10−3; 0.21 × 10−3‐6.33 × 10−3; P = .04) than unaffected cats. The SDS‐AGE identified mixed‐type proteinuria in 89.4% of cats with AA amyloidosis and in 55.6% without AA amyloidosis (P = .57). The LC‐MS identified 63 potential biomarkers associated with AA amyloidosis (P < .05). Among these, urine apolipoprotein C‐III was higher in cats with AA amyloidosis (median, 1.38 × 107; range, 1.85 × 105‐5.29 × 107 vs 1.76 × 106; 0.0 × 100‐1.38 × 107; P = .01). In the kidney, AA‐amyloidosis was associated with glomerulosclerosis (P = .02) and interstitial fibrosis (P = .05).Conclusions and Clinical ImportanceRenal AA amyloidosis is associated with kidney lesions, increased proteinuria and increased urine excretion of SAA in shelter cats. Additional studies are needed to characterize the role of lipid transport proteins in the urine of affected cats.

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“…Hyperglycemia, redox imbalance, endothelial dysfunction, TGF-β activation, etc. (Figures 2B and 7D), lead to reduced production and availability of NO, which underlies the development and progression of diabetes [26][27][28]. In patients with diabetes and neuropathy, in addition to TNF-α, IL-6 production is increased (Figure 7A) [29].…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of Oxidative Stress in Diabetes Mellitus with Diabetic Nephropathy Complications

Goycheva,

Petkova-Parlapanska,

Georgieva

et al. 2023

IJMS

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The present study aimed to investigate and compare biomarkers of oxidative stress and the activity of antioxidant enzymes in the plasma of patients with different stages of diabetic nephropathy. For this purpose, we studied (1) the levels of reactive oxygen species and reactive nitrogen species as oxidative stress parameters, (2) lipid and protein oxidation, (3) the activity of antioxidant enzymes, and (4) cytokine production. Patients with type 2 diabetes mellitus were divided into three groups according to the loss of renal function: patients with compensated diabetes mellitus with normal renal function DMT2N0 measured as an estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2, a group with decompensated diabetes mellitus with complication diabetic nephropathy and mild-to-moderate loss of renal function DMT2N1 (eGFR < 60 mL/min/1.73 m2: 59–45 mL/min/1.73 m2), and a decompensated diabetes mellitus with diabetic nephropathy group with moderate-to-severe loss of renal function DMT2N2 (eGFR > 30 mL/min/1.73 m2: 30–44 mL/min/1.73 m2). All results were compared with healthy volunteers. The results showed that patients with diabetic nephropathy had significantly higher levels of ROS, cytokine production, and end products of lipid and protein oxidation compared to healthy volunteers. Furthermore, patients with diabetic nephropathy had depleted levels of nitric oxide (NO), an impaired NO synthase (NOS) system, and reduced antioxidant enzyme activity (p < 0.05). These findings suggest that patients with impaired renal function are unable to compensate for oxidative stress. The decreased levels of NO radicals in patients with advanced renal complications may be attributed to damage NO availability in plasma. The study highlights the compromised oxidative status as a contributing factor to impaired renal function in patients with decompensated type 2 diabetes mellitus. The findings of this study have implications for understanding the pathogenesis of diabetic nephropathy and the role of oxidative stress and chronic inflammation in its development. The assessment of oxidative stress levels and inflammatory biomarkers may aid in the early detection and prediction of diabetic complications.

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Investigation of hallmarks of carbonyl stress and formation of end products in feline chronic kidney disease as markers of uraemic toxins

Cited by 8 publications

References 53 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

Renal amyloid‐A amyloidosis in cats: Characterization of proteinuria and biomarker discovery, and associations with kidney histology

Biomarkers of Oxidative Stress in Diabetes Mellitus with Diabetic Nephropathy Complications

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