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

2021 ◽  
Vol 8 (12) ◽  
pp. 314
Author(s):  
Jessica Quimby ◽  
Andrea Erickson ◽  
Shannon Mcleland ◽  
Rachel Cianciolo ◽  
David Maranon ◽  
...  

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.

2017 ◽  
Vol 34 (3) ◽  
pp. 208-212 ◽  
Author(s):  
Siheon Lee ◽  
Sungkyun Hong ◽  
Hyejin Kim ◽  
Dayoung Oh ◽  
Seungji Kim ◽  
...  

2013 ◽  
Vol 305 (3) ◽  
pp. F295-F303 ◽  
Author(s):  
Jessica M. Quimby ◽  
David G. Maranon ◽  
Christine L. R. Battaglia ◽  
Shannon M. McLeland ◽  
William T. Brock ◽  
...  

Telomeres are protective structures at the ends of chromosomes that have important implications for aging. To address the question of whether telomeres contribute to feline chronic kidney disease (CKD), we evaluated kidney, liver, and skin samples from 12 cats with naturally occurring CKD, 12 young normal cats, and 6 old normal cats. Telomere length was assessed using standard telomere fluorescent in situ hybridization (TEL-FISH) combined with immunohistochemistry (TELI-FISH) to identify proximal (PTEC) and distal tubular epithelial cells (DTEC), whereas senescence-associated β-galactosidase (SABG) staining was used to evaluate senescence. Results revealed statistically significant decreases in the average telomere fluorescence intensity (TFI) of PTEC in CKD cats compared with young and geriatric normal cats, and in the DTEC of CKD cats compared with young normal cats. When histograms of individual TFI were compared, statistically significant decreases in the PTEC and DTEC of CKD cats were observed compared with young and geriatric normal cats. Concomitantly, a statistically significant increase in SABG staining was seen in CKD kidney samples compared with young normal cats. CKD cats tended to have increased SABG staining in the kidney compared with normal geriatric cats, but this did not reach statistical significance. No significant telomere shortening in liver or skin from any group was observed. Real-time quantitative telomeric repeat amplification protocol assessment of renal telomerase activity revealed comparable low levels of telomerase activity in all groups. Our results suggest that shortened telomeres and increased senescence in the kidneys of CKD cats may represent novel targets for interventional therapy.


2021 ◽  
Vol 22 ◽  
Author(s):  
Andressa Keiko Matsumoto ◽  
Ana Paula Michelin ◽  
Laura de Oliveira Semeão ◽  
Walter Sepúlveda-Loyolaa ◽  
João Victor de Lima Pedrão ◽  
...  

Background: Increased generation of reactive oxygen and nitrogen species in chronic kidney disease (CKD) patients leads to increased oxidative stress. The antioxidant capacity of folic acid has been shown to scavenge radicals efficiently. Objective: The current study was carried out to examine the effects of folic acid treatment on biochemical and oxidative stress biomarkers in patients in different stages of CKD. Methods: This was a randomized, non-blinded, clinical trial that assessed the effects of 3 months of treatment with 5 mg of folic acid daily or no treatment in 113 outpatients within CKD stages 3a and 3b. At the end of the intervention, we analyzed the data of 66 patients treated with folic acid and 47 in the control group. Serum homocysteine levels and biochemical and oxidative/nitrosative stress biomarkers were analyzed in all patients. Results: In most patients, folic acid treatment normalized homocysteine levels and increased antioxidant enzyme activity (paraoxonase 1) and decreased sulfhydryl (SH) groups. In addition, oxidative biomarkers (products of nitric oxide and lipid hydroperoxide) were significantly lower post-treatment compared to baseline in the active intervention group. In the no active intervention group, no statistically significant effects were found on the oxidative and biochemical biomarkers. Conclusion: Folic acid treatment in stages 3a-4 CKD patients effectively ameliorated their hyperhomocysteinemia and increased the activity of antioxidant enzymes, as well as decreased the levels of pro-oxidant biomarkers in stage G3a and G3b CKD patients. Folic acid treatment attenuated oxidative/nitrosative stress and may be considered as a possible strategy to improve redox status and diminish the damages associated with oxidative/nitrosative stress in CKD patients. Further studies are needed to confirm these findings.


2020 ◽  
Vol 393 (8) ◽  
pp. 1427-1436 ◽  
Author(s):  
Badreldin H. Ali ◽  
Mohammed Al Za’abi ◽  
Yousuf Al Suleimani ◽  
Priyadarsini Manoj ◽  
Haytham Ali ◽  
...  

2018 ◽  
Vol 45 (6) ◽  
pp. 2293-2304 ◽  
Author(s):  
Mohammed Al Za’abi ◽  
Suhail Al Salam ◽  
Yousuf Al Suleimani ◽  
Priyadarsini Manoj ◽  
Abderrahim Nemmar ◽  
...  

Background/Aims: The effect of treatment with gum acacia (GA), a prebiotic shown previously to ameliorate chronic kidney disease (CKD), in diabetic and non – diabetic rats with adenine – induced CKD has been investigated using several conventional and novel physiological, biochemical, and histopathological parameters. Methods: Diabetes mellitus was induced in rats by a single injection of streptozotocin (STZ). Diabetic and non – diabetic rats were randomly divided into several groups, and given either normal food or food mixed with adenine (0.25% w/w, for five weeks) to induce CKD. Some of these groups were also concomitantly treated orally with GA in the drinking water (15% w/w). Results: Rats fed adenine alone exhibited physiological (decreased body weight, increased food and water intake and urine output), biochemical (increase in urinary albumin/creatinine ratio, plasma urea and, creatinine, indoxyl sulfate and phosphorus), inflammatory biomarkers (increased in neutrophil gelatinase-associated lipocalin, transforming growth factor beta -1, tumor necrosis factor alpha, adiponectin, cystatin C and interleukin-1β), oxidative biomarkers (8-isoprostane, 8 -hydroxy -2-deoxy guanosine), nitrosative stress biomarkers (nitrite and nitrate) and histopathological (increase in tubular necrosis and fibrosis) signs of CKD. STZ - induced diabetes alone worsened most of the renal function tests measured. Administration of adenine in STZ – diabetic rats further worsened the renal damage induced by adenine alone. GA significantly ameliorated the renal actions of adenine and STZ, given either singly or in combination, especially with regards to the histopathological damage. Conclusion: GA is a useful dietary agent in attenuating the progression of CKD in rats with streptozotocin-induced diabetes.


2019 ◽  
Vol 33 (5) ◽  
pp. 1921-1925 ◽  
Author(s):  
Laura Pérez‐López ◽  
Mauro Boronat ◽  
Carlos Melián ◽  
Pedro Saavedra ◽  
Yeray Brito‐Casillas ◽  
...  

2017 ◽  
Vol 49 (9) ◽  
pp. 1627-1635 ◽  
Author(s):  
Arkadiusz Lubas ◽  
Grzegorz Kade ◽  
Robert Ryczek ◽  
Piotr Banasiak ◽  
Przemysław Dyrla ◽  
...  

2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Catherine Anne McLeonard

<p>A comprehensive search of the available veterinary literature found three studies which assess whether feeding wet or dry maintenance diets place cats at an increased risk of chronic kidney disease (CKD) diagnosis. None of the three studies found any significant benefit of feeding either diet in reducing the risk of CKD. However, the criteria used to diagnose CKD was not standardised across any of the three studies. There is currently insufficient evidence that feeding a wet maintenance diet will help to reduce the risk of CKD but further studies are needed to assess whether diet can play some role in reducing the risk of CKD diagnosis.</p><p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/pr-icon.jpg" alt="Peer Reviewed" /></p>


2021 ◽  
pp. 1098612X2110391
Author(s):  
Hirosumi Miyakawa ◽  
Huai-Hsun Hsu ◽  
Mizuki Ogawa ◽  
Ryota Akabane ◽  
Yuichi Miyagawa ◽  
...  

Objectives The aim of this study was to investigate serum fibroblast growth factor (FGF)-23 concentrations in young and mature adult cats with chronic kidney disease (CKD). Methods The present study retrospectively investigated the serum samples and medical records of 1–8-year-old clinically healthy cats (control group, n = 7) and cats with CKD (n = 54). Cats with CKD were divided into four stages based on serum creatinine concentrations, according to the International Renal Interest Society (IRIS) CKD guidelines. Serum FGF-23 concentrations were compared between cats in the control group, IRIS stages 1, 2 and 3–4 CKD. Continuous variables were analysed using correlations and multiple linear regression. Results Serum FGF-23 concentrations were significantly higher in cats with IRIS stages 1, 2 and 3–4 CKD, compared with those in the control group ( P = 0.02, P = 0.002 and P = 0.002, respectively). Additionally, serum FGF-23 concentrations in cats with IRIS stages 3–4 CKD had higher serum FGF-23 concentrations than those with IRIS stages 1 and 2 CKD ( P = 0.04 and P = 0.02, respectively). In the multiple linear regression analysis, serum urea nitrogen concentration, serum phosphorus concentration and blood ionised calcium concentration were independent variables predicting serum FGF-23 concentration. Conclusions and relevance Serum FGF-23 concentrations in younger cats with CKD increased in early-stage CKD and were associated with mineral metabolic markers, as also occurs in geriatric cats.


2021 ◽  
pp. ASN.2021020267
Author(s):  
Luisa Ricaurte ◽  
Aleksandar Denic ◽  
Aidan Mullan ◽  
Ramya Narasimhan ◽  
Marija Bogojevic ◽  
...  

Background Chronic tubulointerstitial injury on kidney biopsy is usually quantified by the percentage of cortex with interstitial fibrosis/tubular atrophy (IF/TA). Whether other patterns of IF/TA or inflammation in the tubulointerstitium have prognostic importance beyond percentage IF/TA is unclear. Methods We obtained, stained, and digitally scanned full cortical thickness wedge sections of renal parenchyma from patients who underwent a radical nephrectomy for tumor in 2000 to 2015 and morphometrically analyzed the tubulointerstitium of the cortex for percentage IF/TA, IF/TA density (foci per mm2 cortex), percentage subcapsular IF/TA, striped IF/TA, percentage inflammation (both within and outside IF/TA regions), and percentage subcapsular inflammation. Patients were followed with visits every 6-12 months. Progressive chronic kidney disease (CKD) was defined as dialysis, kidney transplantation, or 40% decline from the postnephrectomy estimated glomerular filtration rate (eGFR). Cox models assessed risk of CKD or noncancer mortality with morphometric measures of tubulointerstitial injury after adjustment for percentage IF/TA and clinical characteristics. Results Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73m2), 117 progressive CKD events and 183 noncancer deaths occurred over a median 6.4 years. Higher IF/TA density predicted both progressive CKD and noncancer mortality after adjustment for percentage IF/TA and predicted progressive CKD after further adjustment for clinical characteristics. Independent of percentage IF/TA, age, and sex, higher IF/TA density correlated with lower eGFR, smaller nonsclerosed glomeruli, more global glomerulosclerosis, and smaller total cortical volume. Conclusions Higher density of IF/TA foci (a more scattered pattern with more and smaller foci) predicts higher risk of progressive CKD after radical nephrectomy compared with the same percentage of IF/TA but with fewer and larger foci.


Sign in / Sign up

Export Citation Format

Share Document