Urinary active transforming growth factor β in feline chronic kidney disease

Lawson, Jack; Syme, H M; Wheeler‐Jones, Caroline P.D.; Elliott, Jonathan

doi:10.1016/j.tvjl.2016.02.004

Cited by 25 publications

(38 citation statements)

References 36 publications

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“…However, according to our results, concentrations of established markers of CKD, such as creatinine or SDMA, did not differ between normalweight and overweight cats. In regard to the potential biomarkers assessed in this study, uaTGFb has been proposed as an important mediator of diabetic nephropathy in animal models, one of which showed that urinary aTGFb1:Cr ratio precedes the onset of azotemia by six months (Lawson et al 2016). In relation to RBP, its urine concentration might increase when tubular damage occurs, and higher levels of urinary RBP:Cr in cats with CKD compared to healthy cats have been reported (van Hoek et al 2008).…”

Section: Discussionmentioning

confidence: 90%

“…Those urine samples collected by the owner were preserved under refrigeration until the analysis was done; and those collected by cystocentesis were analyzed at the moment. Urine samples were aliquoted and frozen for later measurement of UPC by colorimetry (Animal Lab, Gran Canaria, Spain), and of the potential markers of renal disease: urinary free active transforming beta growth factor-creatinine ratio (uaTGFb1:Cr) [Human Free Active TGF-b1 (BioLegend, San Diego, USA)] (Lawson et al 2016)…”

Section: Analytical Proceduresmentioning

confidence: 99%

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Kidney function and glucose metabolism in overweight and obese cats

Pérez-López

Boronat

Melián

et al. 2020

Veterinary Quarterly

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Background: In people, obesity and prediabetes mellitus might predispose to chronic kidney disease (CKD). Aims: To assess the association of overweight [Body condition score (BCS) >5] and glucose metabolism alterations, with established or potential markers of CKD. In addition, fructosamine and fasted blood glucose were compared as predictors of early abnormal glucose metabolism. Methods: 54 clinically healthy cats were included in a cross-sectional study comprising 25 neutered males and 29 (28 neutered) females aged 7.2 (5.5-9.4) years. Two potential markers of CKD, namely urinary free active transforming growth factor-b1-creatinine ratio and urinary retinol binding protein-creatinine ratio were measured along with other parameters to assess CKD. A receiver operating curve was used to identify the best sensitivity and specificity of fructosamine to identify cats with fasting glucose >6.5 mmol/L. Results: No association was found between BCS and markers of CKD. Fructosamine was greater in cats with fasting glucose >6.5 mmol/L compared to those with fasting glucose 6.5 mmol/L. A fructosamine concentration !250 mmol/L was able to detect cats with hyperglycemia with a sensitivity of 77% and a specificity of 65%. Furthermore, fructosamine was more strongly correlated with fasting glucose than albumin-corrected fructosamine (r ¼ 0.43, p ¼ 0.002 vs r ¼ 0.32, p ¼ 0.026). Cats with higher fructosamine had lower serum symmetric dimethylarginine concentrations. Conclusion: The present study does not suggest an effect of obesity on renal function in domestic cats. Clinical relevance: Fructosamine might be of value for the diagnosis of prediabetes mellitus in cats.

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Section: Discussionmentioning

confidence: 90%

Section: Analytical Proceduresmentioning

confidence: 99%

Kidney function and glucose metabolism in overweight and obese cats

Pérez-López

Boronat

Melián

et al. 2020

Veterinary Quarterly

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“…However, there was a trend towards increasing active urinary TGF-β in cats that developed azotemia and were monitored longitudinally. 109 A study by Habenicht and colleagues investigated urinary concentrations of IL8 and MCP-1 as ratios to urine creatinine as potential markers of renal inflammation and injury. No significant difference in MCP-1:creatinine ratio could be detected although IL8: creatinine ratio were significantly higher in cats with CKD than control cats.…”

Section: Evidence Of Fibrosis In Feline Chronic Kidney Diseasementioning

confidence: 99%

Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats

Jepson

2016

Veterinary Clinics of North America: Small Animal Practice

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Abstract:In cats with chronic kidney disease (CKD), the most common histopathological finding is tubulointerstitial inflammation and fibrosis. However, these changes reflect a non-specific response of the kidney to any inciting injury. The risk of development of CKD in a patient is likely to reflect genetic predispositions, ageing, environmental and individual factors that influence decline in renal function over the course of a cat's life. However, there is still relatively little information about exactly which risk factors predispose a cat to develop CKD and these will be explored. Whilst many cats diagnosed with CKD have stable disease for many years, some cats show overtly progressive disease.

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“…TGF-β1 directly stimulates transcription of ECM, as well as mediating effects via downstream activation of the matricellular protein connective tissue growth factor (CTGF) [ 18 , 19 ]. Increased urinary TGF-β1 excretion is associated with interstitial fibrosis in cats [ 20 ], suggesting this cytokine may play a causative role in the development of fibrosis as in other species. However, whether TGF-β1 has analogous effects on feline renal fibroblasts at a cellular level is unknown.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor β1

et al. 2018

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BackgroundChronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1.ResultsCortical fibroblast cultures were successfully established from the kidney tissue of cats with normal kidney function (FCF) and cats with chronic kidney disease (CKD-FCF). Both cell types expressed the mesenchymal markers vimentin, CD44 and CD29, and were negative for the epithelial marker cytokeratin, mesangial cell marker desmin and endothelial cell marker vWF. Only CKD-FCF expressed VCAM-1, a cell marker associated with inflammation. Incubation with TGF-β1 (0–10 ng/ml) induced a concentration dependent change in cell morphology, and upregulation of myofibroblast marker gene α-SMA expression alongside collagen 1α1, fibronectin, TGF-β1 and CTGF mRNA. These changes were blocked by the TGF-β1 receptor 1 antagonist SB431542 (5 μM).ConclusionsFCF and CKD-FCF can be cultured via a simple method and represent a model for the investigation of the progression of fibrosis in feline CKD. The findings of this study suggest TGF-β1 may be involved in fibroblast-myofibroblast transition in feline CKD, as in other species.

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Urinary active transforming growth factor β in feline chronic kidney disease

Cited by 25 publications

References 36 publications

Kidney function and glucose metabolism in overweight and obese cats

Kidney function and glucose metabolism in overweight and obese cats

Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats

Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor β1

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