scholarly journals The Benefit of Anti-Inflammatory and Renal-Protective Dietary Ingredients on the Biological Processes of Aging in the Kidney

Biology ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 45 ◽  
Author(s):  
Kiran Panickar ◽  
Dennis Jewell
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Kidney Function ◽  
Structural Changes ◽  
Dietary Intervention ◽  
Interstitial Fibrosis ◽  
Tubular Atrophy ◽  
Functional Changes ◽  
General Decline ◽  
Organ Systems

One of the significant organ systems which decline in aging is the kidney. While the causes of age-associated decline in renal function are likely multifactorial, oxidative stress and inflammation are hypothesized to play important roles in the structural and functional changes of the kidney. During aging there is a general decline in the glomerular filtration rate (GFR), a primary measurement used to assess kidney function. Inflammation and oxidative stress have been hypothesized to have a significant detrimental effect on renal function in aging and this may be attenuated by renal protective dietary ingredients. These dietary ingredients may affect renal function directly or through a microbiome-mediated secondary product. Likewise, structural changes including renal tubular atrophy, interstitial fibrosis, and glomerulosclerosis have all been described in aging. Such detrimental changes may benefit from dietary ingredients that may delay or attenuate the occurrence of such changes. This review will describe the physiology and pathophysiology of aging in renal function with an emphasis on dogs and cats that develop a decline in kidney function naturally. In addition, the varying biomarkers of health and renal dysfunction will be discussed. Finally, we will evaluate the aid in the management of this normal decline through dietary intervention in animal models.

scholarly journals Chronic Renal Changes After a Single Ischemic Event in an Experimental Model of Feline Chronic Kidney Disease

2019 ◽  
Vol 56 (4) ◽  
pp. 536-543 ◽  
Author(s):  
Cathy A. Brown ◽  
Daniel R. Rissi ◽  
Vanna M. Dickerson ◽  
Anastacia M. Davis ◽  
Scott A. Brown ◽  
...  
Keyword(s):  
Renal Function ◽  
Structural Changes ◽  
Interstitial Fibrosis ◽  
Renal Ischemia ◽  
Loss Of Function ◽  
Tubular Atrophy ◽  
Ischemic Event ◽  
Tubulointerstitial Lesions ◽  
Atubular Glomeruli

Previous work demonstrated renal fibrosis 70 days after a single unilateral in vivo renal ischemic event, but changes associated with a single episode of renal ischemia past this time are unknown. In this study, we evaluated renal function and structural changes 6 months after a 90-minute in vivo unilateral renal ischemic event. Six adult female cats underwent unilateral renal ischemia and renal function was followed for 6 months, at which time the kidneys were evaluated by histology and histomorphometry. Over time, there was a significant reduction in the glomerular filtration rate and an elevation of serum creatinine of 31% and 42%, respectively. All cats had tubulointerstitial lesions characterized by segmental interstitial inflammation, tubular atrophy, and interstitial fibrosis. Unlike short-term studies, ischemic kidneys had variable numbers of obsolescent glomeruli, consistent with the development of atubular glomeruli and subsequent ischemic glomerulosclerosis. Chronic changes associated with acute renal ischemia may include loss of function and glomerulosclerosis.

scholarly journals Structural and functional changes in the kidneys and their effect on cardiovascular risk in elderly patients

2020 ◽  
Vol 43 (4) ◽  
pp. 539-548
Author(s):  
Natalya I. Golovina ◽  
◽  
Yury A. Lykov ◽  
Keyword(s):  
Chronic Kidney Disease ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Structural Changes ◽  
Interstitial Fibrosis ◽  
The Elderly ◽  
Functional Changes ◽  
Age Related ◽  
Organ Systems

Like other organ systems, the kidneys also go through process of normal senescence, including both anatomical and physiological changes. Normal physiological aging is characterized by the expected age-related changes in the kidneys. With age, the kidneys are subject to structural changes, for example, there is a decrease in the number of functional glomeruli due to an increase in the prevalence of nephrosclerosis (atherosclerosis, glomerulosclerosis, atrophy of the tubules with interstitial fibrosis) and to some extent compensatory hypertrophy of the remaining nephrons. Older age is also associated with reduced cortical volume, increased medullary, and larger and more numerous renal cysts. Changes in normal aging are important in clinical practice. Against the background of suppression of reparative capabilities, the elderly are more prone to acute damage and chronic kidney disease, aggravation of the course of chronic kidney disease. The elderly have less renal functional reserve when they do actually develop chronic kidney disease and they are also at higher risk for acute kidney injury. Cardiovascular disease is a leading cause of death and a common comorbidity among patients with kidney disease. In this review, we have identified the most characteristic structural and functional changes in the kidneys in elderly patients and their impact on cardiovascular risk.

scholarly journals Kidney aging.Geriatric view

2021 ◽  
pp. 76-81
Author(s):  
L. I. Merkusheva ◽  
N. K. Runikhina ◽  
O. N. Tkacheva
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Structural Changes ◽  
Water Soluble ◽  
Older Age ◽  
Sodium Reabsorption ◽  
Tubular Atrophy ◽  
Age Related ◽  
Population Demographic

Individuals age >65 years old are the fastest expanding population demographic throughout the developed world. Consequently, more aged patients than before are receiving diagnoses of impaired renal function and nephrosclerosis. In this review, we examine these features of the aged kidney and explore the various validated and putative pathways contributing to the changes observed with aging. Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to chronic kidney disease (CKD) in some individuals. The microanatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitialfibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume. There is reason to be concerned that the elderly are being misdiagnosed with CKD. In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water -soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease.

scholarly journals Fenofibrate Improved Interstitial Fibrosis of Renal Allograft through Inhibited Epithelial-Mesenchymal Transition Induced by Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yishu Wang ◽  
Lei Pang ◽  
Yanghe Zhang ◽  
Jiahui Lin ◽  
Honglan Zhou
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Renal Allograft ◽  
Epithelial Mesenchymal Transition ◽  
Interstitial Fibrosis ◽  
Peroxisome Proliferator ◽  
Tubular Atrophy ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mesenchymal Transition ◽  
Stage Renal Disease

The best treatment for end-stage renal disease is renal transplantation. However, it is often difficult to maintain a renal allograft healthy for a long time following transplantation. Interstitial fibrosis and tubular atrophy (IF/TA) are significant histopathologic characteristics of a compromised renal allograft. There is no effective therapy to improve renal allograft function once IF/TA sets in. Although there are many underlying factors that can induce IF/TA, the pathogenesis of IF/TA has not been fully elucidated. It has been found that epithelial-mesenchymal transition (EMT) significantly contributes to the development of IF/TA. Oxidative stress is one of the main causes that induce EMT in renal allografts. In this study, we have used H2O2 to induce oxidative stress in renal tubular epithelial cells (NRK-52e) of rats. We also pretreated NRK-52e cells with an antioxidant (N-acetyl L-cysteine (NAC)) 1 h prior to the treatment with H2O2. Furthermore, we used fenofibrate (a peroxisome proliferator-activated receptor α agonist) to treat NRK-52e cells and a renal transplant rat model. Our results reveal that oxidative stress induces EMT in NRK-52e cells, and pretreatment with NAC can suppress EMT in these cells. Moreover, fenofibrate suppresses fibrosis by ameliorating oxidative stress-induced EMT in a rat model. Thus, fenofibrate may effectively prevent the development of fibrosis in renal allograft and improve the outcome.

Oxidative stress as a common pathway to chronic tubulointerstitial injury in kidney allografts

2007 ◽  
Vol 293 (2) ◽  
pp. F445-F455 ◽  
Author(s):  
Arjang Djamali
Keyword(s):  
Oxidative Stress ◽  
Interstitial Fibrosis ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Common Mechanism ◽  
Placebo Control ◽  
Tubulointerstitial Injury ◽  
Tubular Atrophy ◽  
Mesenchymal Transition

A major challenge for kidney transplantation is to dissect out the identifiable causes of chronic allograft tubulointerstitial fibrosis and to develop cause-specific treatment strategies. There has been a recent interest in the role of oxidative stress (OS) as a mediator of injury in chronic allograft tubular atrophy (TA) and interstitial fibrosis (IF). A review of the literature and data from my laboratory studying chronic allograft TA/IF in rat, rhesus monkey, and human kidneys suggests that OS is increased in graft-infiltrating macrophages, activated myofibroblasts, interstitium, and areas of tubular injury. Chronic allograft OS may be induced by inflammation, abnormal tissue oxygenation, immunosuppressant drugs, and comorbid clinical conditions including diabetes, hypertension, proteinuria, anemia, and dyslipidemia. Moreover, OS-induced chronic TA/IF is associated with signaling pathways including inflammation, apoptosis, hypoxia, and epithelial-to-mesenchymal transition. Most of these injury pathways participate in a self-perpetuating cycle with OS. In conclusion, evidence suggests that OS is a common mechanism of injury in chronic allograft TA/IF. However, most available data demonstrate a correlation and no causal relationship. Furthermore, the extent to which TA/IF is dependent on OS is unknown. These questions may be answered by prospective randomized placebo-control trials examining the role of select antioxidants in the prevention of chronic allograft TA/IF.

scholarly journals Identification, Confirmation, and Replication of Novel Urinary MicroRNA Biomarkers in Lupus Nephritis and Diabetic Nephropathy

2017 ◽  
Vol 63 (9) ◽  
pp. 1515-1526 ◽  
Author(s):  
Mariana Cardenas-Gonzalez ◽  
Anand Srivastava ◽  
Mira Pavkovic ◽  
Vanesa Bijol ◽  
Helmut G Rennke ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Lupus Nephritis ◽  
Kidney Function ◽  
Lupus Erythematosus ◽  
Interstitial Fibrosis ◽  
Functional Markers ◽  
Tubular Atrophy ◽  
Patients With Diabetes ◽  
Noninvasive Biomarkers ◽  
N 93

Abstract BACKGROUND The prevalence of chronic kidney disease (CKD) is increasing, leading to significant morbidity and mortality. Kidney biopsy remains the gold standard for diagnosing the underlying etiology of CKD, but the procedure carries complication risks. The aim of this study was to identify novel noninvasive biomarkers correlating with kidney function and histopathology in biopsy-proven CKD patients. METHODS We profiled 2402 urinary microRNAs (miRNAs) to identify and confirm differentially expressed miRNAs associated with kidney function and histopathology in patients with diabetic nephropathy (n = 58) or lupus nephritis (n = 89), important etiologies of CKD, compared with healthy controls (n = 93 and 119, respectively). Top performing miRNAs were then measured in 2 independent multi-institutional cohorts of patients with diabetes mellitus with (n = 74) or without nephropathy (n = 71) and systemic lupus erythematosus with (n = 86) or without (n = 37) nephritis. RESULTS In patients with diabetic nephropathy, miR-2861, miR-1915-3p, and miR-4532 were down-regulated (>10-fold, P < 0.0001) and were associated with estimated glomerular filtration rate (P < 0.01) and interstitial fibrosis/tubular atrophy (P < 0.05). The c-statistics for miR-2861, miR-1915-3p, and miR-4532 were 0.91, 0.86, and 0.85, respectively. In lupus nephritis patients, miR-3201 and miR-1273e were down-regulated (>3-fold, P < 0.0001) and associated with endocapillary glomerular inflammation (P < 0.01), with c-statistics of 0.97 and 0.91, respectively. CONCLUSIONS We have identified novel miRNAs that correlate with histopathological lesions and functional markers of kidney damage to facilitate sensitive, specific, and noninvasive detection of diabetic nephropathy and lupus nephritis.

scholarly journals The protective effect of trimetazidine against cisplatin-induced nephrotoxicity in rats

2016 ◽  
Vol 94 (7) ◽  
pp. 745-751 ◽  
Author(s):  
Nagla A. El-Sherbeeny ◽  
Ghalia M. Attia
Keyword(s):  
Oxidative Stress ◽  
Dna Binding ◽  
Protective Effect ◽  
Kidney Function ◽  
Structural Changes ◽  
Binding Activity ◽  
Significant Deterioration ◽  
Necrosis Factor Alpha ◽  
Dna Binding Activity ◽  
Tnf Α

Nephrotoxicity is a dose-limiting side effect of cisplatin (CSP). The study investigated the possible protective role of trimetazidine (TMZ) against CSP-induced nephrotoxicity in rats. Rats were divided into four groups; control, TMZ, CSP, and CSP + TMZ. The CSP group showed significant deterioration in kidney function with structural changes in the form of interstitial hemorrhage, glomeruli shrinkage and peritublar capillary congestion, tubular cells vacuolation, pyknosis, shedding and necrosis, and inflammatory cell infiltrates, all indicating renal damage. CSP also caused a significant increase in the lipid peroxidation marker malondialdehyde (MDA) levels, renal nuclear factor kappa B (NF-κB) DNA-binding activity and protein expression, and tumor necrosis factor alpha (TNF-α) and IL-6 levels. Treatment with TMZ before and after CSP injection produced significant improvement of kidney function and histopathology. TMZ treatment also significantly attenuated CSP-induced oxidative stress and suppressed elevated levels of TNF-α and IL-6 and NF-κB expression and its DNA-binding activity caused by CSP administration. TMZ has a protective effect against CSP-induced nephrotoxicity mediated by reduction of oxidative stress and attenuation of CSP-induced inflammation.

scholarly journals Alpha-Lipoic Acid Attenuates Renal Injury in Rats with Obstructive Nephropathy

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Orawan Wongmekiat ◽  
Dolrawee Leelarungrayub ◽  
Kamthorn Thamprasert
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Lipoic Acid ◽  
Renal Injury ◽  
Ureteral Obstruction ◽  
Structural Changes ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Obstructive Nephropathy ◽  
Alpha Lipoic Acid

This study was established to determine the possible protective effects of alpha-lipoic acid (ALA), a powerful antioxidant, on renal injury in obstructive nephropathy. Male Sprague-Dawley rats were assigned into sham-operated unilateral ureteral obstruction (UUO) and UUO treated with ALA groups. ALA 60 mg/kg was injected intraperitoneally 2 days before UUO induction and continued afterward for 7 days. Renal function, oxidative stress markers, nitric oxide, transforming growth factor-1 (TGF-β1), and histological changes were evaluated at the end of the experiment. Obstruction of the ureter resulted in renal dysfunction as indicated by significant increases in blood urea nitrogen and serum creatinine. Nonobstructed contralateral kidneys in all groups examined did not show any morphological or biochemical alterations. In untreated UUO group, the obstructed kidney developed marked hydronephrosis, leukocyte infiltration, and severe interstitial fibrosis. These functional and structural changes were associated with significant increases in tissue levels of malondialdehyde, nitric oxide, and TGF-β1 but decreases in reduced glutathione and total antioxidant capacity. Pretreatment with ALA significantly minimized all the changes elicited by ureteral obstruction. These findings demonstrate that ALA supplementation attenuates renal injury in rats with obstructive nephropathy and further suggest that oxidative stress inhibition is likely to be involved in the beneficial effects of this compound.

scholarly journals Tocilizumab in the Treatment of Chronic Antibody-Mediated Rejection Post Kidney Transplantation: Clinical and Histological Monitoring

2021 ◽  
Vol 8 ◽  
Author(s):  
Johan Noble ◽  
Diane Giovannini ◽  
Reda Laamech ◽  
Farida Imerzoukene ◽  
Bénédicte Janbon ◽  
...  
Keyword(s):  
Renal Function ◽  
Statistical Difference ◽  
Interstitial Fibrosis ◽  
Therapeutic Option ◽  
Single Center ◽  
Tubular Atrophy ◽  
Antibody Mediated Rejection ◽  
Peritubular Capillaritis ◽  
Over Time

Introduction: Chronic antibody-mediated rejection (cAMR) has very few effective therapeutic options. Interleukin-6 is an attractive target because it is involved in inflammation and humoral immunity. Therefore, the use of tocilizumab (anti-IL6 receptor, TCZ) is a potential valuable therapeutic option to treat cABMR in kidney-transplant (KT) recipients.Materials and Methods: This single-center retrospective study included all KT recipients that received monthly TCZ infusions in the setting of cABMR, between August 2018 and July 2021. We assessed 12-month renal function and KT histology during follow-up.Results: Forty patients were included. At 12-months, eGFR was not significantly different, 41.6 ± 17 vs. 43 ± 17 mL/min/1.73 m2 (p = 0.102) in patients with functional graft. Six patients (15%) lost their graft: their condition was clinically more severe at the time of first TCZ infusion. Histological follow-up showed no statistical difference in the scores of glomerulitis, peritubular capillaritis, and interstitial fibrosis/tubular atrophy (IFTA). Chronic glomerulopathy score however, increased significantly over time; conversely arteritis and inflammation in IFTA ares improved in follow-up biopsies.Conclusion: In our study, the addition of TCZ prevented clinical and histological worsening of cABMR in KT recipients, except for more severely ill patients. Randomized studies are needed to clarify the risk/benefit of TCZ in cABMR.

Renal Histologic Analysis Provides Complementary Information to Kidney Function Measurement for Patients with Early Diabetic or Hypertensive Disease

2021 ◽  
pp. ASN.2021010044
Author(s):  
Ghazal Quinn ◽  
Amin Abedini ◽  
Hongbo Liu ◽  
Ziyuan Ma ◽  
Andrew Cucchiara ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Kidney Function ◽  
Structural Damage ◽  
Interstitial Fibrosis ◽  
Early Disease ◽  
Tubular Atrophy ◽  
Histologic Analysis ◽  
Complementary Method ◽  
Disease Stages

Background: Patients with diabetic or hypertensive kidney disease rarely undergo kidney biopsy because nephrologists commonly believe that biopsy-related risk outweighs potential benefits of obtaining histologic information to guide clinical decisions. Although kidney function is acutely regulated, histologic changes such as interstitial fibrosis, tubular atrophy, and glomerulosclerosis may represent chronic kidney damage, and thus might provide additional information about disease severity. However, whether histologic analysis provides information complementary to clinically used kidney function measurements, such as estimated glomerular filtration rate (eGFR) and proteinuria, is unclear. Methods: We performed a standardized semiquantitative histologic analysis of 859 nephrectomies obtained from individuals with or without diabetes mellitus or hypertension and varying degrees of kidney dysfunction. Changes in glomeruli, tubules, interstitium, and the vasculature were scored using 17 descriptive parameters in a standardized manner. We used multivariable linear and logistic regression analyses and unbiased, hierarchical clustering to assess associations between histologic alterations and clinical variables. Results: At chronic kidney disease (CKD) stages 3-5, eGFR estimated reasonably well the degree of glomerulosclerosis and interstitial fibrosis and tubular atrophy (IFTA). In patients with CKD stages 1-2, the degree of histologic damage was highly variable and eGFR poorly estimated the degree of such damage. Individuals with diabetes mellitus, hypertension, or Black race had significantly more glomerulosclerosis, IFTA, or both at the same eGFR level. Inclusion of glomerulosclerosis improved the kidney function decline estimation even at early disease stages. Conclusions: Histologic analysis is an important complementary method for kidney disease evaluation, especially at early disease stages. Some individuals present with relatively severe structural damage despite preserved eGFR.

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