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Advances in Chronic Kidney Disease Jan 2016Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The... (Review)
Review
Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all 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 interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous kidney cysts. Among carefully screened healthy kidney donors, glomerular filtration rate (GFR) declines at a rate of 6.3 mL/min/1.73 m(2) per decade. There is reason to be concerned that the elderly are being misdiagnosed with CKD. Besides this expected kidney function decline, the lowest risk of mortality is at a GFR of ≥75 mL/min/1.73 m(2) for age <55 years but at a lower GFR of 45 to 104 mL/min/1.73 m(2) for age ≥65 years. Changes with normal aging are still of clinical significance. The elderly have less kidney functional reserve when they do actually develop CKD, and they are at higher risk for acute kidney injury.
Topics: Aged; Aged, 80 and over; Aging; Glomerular Filtration Rate; Humans; Kidney; Renal Insufficiency
PubMed: 26709059
DOI: 10.1053/j.ackd.2015.08.004 -
Journal of the American Society of... Feb 2017Individuals age >65 years old are the fastest expanding population demographic throughout the developed world. Consequently, more aged patients than before are receiving... (Review)
Review
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-age-associated histologic changes in the kidneys. Recent studies have shown that the aged kidney undergoes a range of structural changes and has altered transcriptomic, hemodynamic, and physiologic behavior at rest and in response to renal insults. These changes impair the ability of the kidney to withstand and recover from injury, contributing to the high susceptibility of the aged population to AKI and their increased propensity to develop subsequent progressive CKD. 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 in both experimental animal models and humans. We also discuss the potential for additional study to increase understanding of the aged kidney and lead to novel therapeutic strategies.
Topics: Aging; Biomedical Research; Cell Cycle; Cell Hypoxia; Forecasting; Humans; Kidney; Male; Oxidative Stress; Renal Insufficiency, Chronic; Signal Transduction
PubMed: 28143966
DOI: 10.1681/ASN.2015121308 -
Journal of the American Society of... Oct 2017Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level,... (Review)
Review
Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction in measured whole-kidney GFR. However, single-nephron GFR remains relatively constant with healthy aging as does glomerular volume. Only when glomerulosclerosis and arteriosclerosis exceed that expected for age is there an increase in single-nephron GFR. In the absence of albuminuria, age-related reduction in GFR with the corresponding increase in CKD (defined by an eGFR<60 ml/min per 1.73 m) has been shown to associate with a very modest to no increase in age-standardized mortality risk or ESRD. These findings raise the question of whether disease labeling of an age-related decline in GFR is appropriate. These findings also emphasize the need for a different management approach for many elderly individuals considered to have CKD by current criteria.
Topics: Aging; Humans; Kidney
PubMed: 28790143
DOI: 10.1681/ASN.2017040421 -
Ageing Research Reviews Nov 2020As human life expectancy keeps increasing, ageing populations present a growing challenge for clinical practices. Human ageing is associated with molecular, structural,... (Review)
Review
As human life expectancy keeps increasing, ageing populations present a growing challenge for clinical practices. Human ageing is associated with molecular, structural, and functional changes in a variety of organ systems, including the kidney. During the ageing process, the kidney experiences progressive functional decline as well as macroscopic and microscopic histological alterations, which are accentuated by systemic comorbidities like hypertension and diabetes mellitus, or by preexisting or underlying kidney diseases. Although ageing per se does not cause kidney injury, physiologic changes associated with normal ageing processes are likely to impair the reparative capacity of the kidney and thus predispose older people to acute kidney disease, chronic kidney disease and other renal diseases. Mechanistically, cell senescence plays a key role in renal ageing, involving a number of cellular signaling mechanisms, many of which may be harnessed as international targets for slowing or even reversing kidney ageing. This review summarizes the clinical characteristics of renal ageing, highlights the latest progresses in deciphering the role of cell senescence in renal ageing, and envisages potential interventional strategies and novel therapeutic targets for preventing or improving renal ageing in the hope of maintaining long-term kidney health and function across the life course.
Topics: Aged; Aged, 80 and over; Aging; Cellular Senescence; Humans; Hypertension; Kidney
PubMed: 32835891
DOI: 10.1016/j.arr.2020.101151 -
Cells Nov 2021Hypertensive nephrosclerosis is the second most common cause of end-stage renal disease after diabetes. For years, hypertensive kidney disease has been focused on the... (Review)
Review
Hypertensive nephrosclerosis is the second most common cause of end-stage renal disease after diabetes. For years, hypertensive kidney disease has been focused on the afferent arterioles and glomeruli damage and the involvement of the renin angiotensin system (RAS). Nonetheless, in recent years, novel evidence has demonstrated that persistent high blood pressure injures tubular cells, leading to epithelial-mesenchymal transition (EMT) and tubulointerstitial fibrosis. Injury primarily determined at the glomerular level by hypertension causes changes in post-glomerular peritubular capillaries that in turn induce endothelial damage and hypoxia. Microvasculature dysfunction, by inducing hypoxic environment, triggers inflammation, EMT with epithelial cells dedifferentiation and fibrosis. Hypertensive kidney disease also includes podocyte effacement and loss, leading to disruption of the filtration barrier. This review highlights the molecular mechanisms and histologic aspects involved in the pathophysiology of hypertensive kidney disease incorporating knowledge about EMT and tubulointerstitial fibrosis. The role of the Hsp70 chaperone on the angiotensin II-induced EMT after angiotensin II type 1 receptor (ATR) blockage, as a possible molecular target for therapeutic strategy against hypertensive renal damage is discussed.
Topics: Animals; Epithelial-Mesenchymal Transition; HSP70 Heat-Shock Proteins; Humans; Hypertension, Renal; Kidney; Losartan; Nephritis; Protective Agents
PubMed: 34831368
DOI: 10.3390/cells10113146 -
Journal of the American Society of... Aug 2015The transition of AKI to CKD has major clinical significance. As reviewed here, recent studies show that a subpopulation of dedifferentiated, proliferating tubules... (Review)
Review
The transition of AKI to CKD has major clinical significance. As reviewed here, recent studies show that a subpopulation of dedifferentiated, proliferating tubules recovering from AKI undergo pathologic growth arrest, fail to redifferentiate, and become atrophic. These abnormal tubules exhibit persistent, unregulated, and progressively increasing profibrotic signaling along multiple pathways. Paracrine products derived therefrom perturb normal interactions between peritubular capillary endothelium and pericyte-like fibroblasts, leading to myofibroblast transformation, proliferation, and fibrosis as well as capillary disintegration and rarefaction. Although signals from injured endothelium and inflammatory/immune cells also contribute, tubule injury alone is sufficient to produce the interstitial pathology required for fibrosis. Localized hypoxia produced by microvascular pathology may also prevent tubule recovery. However, fibrosis is not intrinsically progressive, and microvascular pathology develops strictly around damaged tubules; thus, additional deterioration of kidney structure after the transition of AKI to CKD requires new acute injury or other mechanisms of progression. Indeed, experiments using an acute-on-chronic injury model suggest that additional loss of parenchyma caused by failed repair of AKI in kidneys with prior renal mass reduction triggers hemodynamically mediated processes that damage glomeruli to cause progression. Continued investigation of these pathologic mechanisms should reveal options for preventing renal disease progression after AKI.
Topics: Acute Kidney Injury; Capillaries; Disease Progression; Humans; Hypoxia; Kidney Tubules; Nephrosclerosis; Renal Circulation; Renal Insufficiency, Chronic; Vasoconstriction
PubMed: 25810494
DOI: 10.1681/ASN.2015010006 -
Journal of the American Heart... Apr 2023The incidence of heart failure and chronic kidney disease is increasing, and many patients develop both diseases. Angiotensin receptor-neprilysin inhibitor (ARNI) is a... (Review)
Review
The incidence of heart failure and chronic kidney disease is increasing, and many patients develop both diseases. Angiotensin receptor-neprilysin inhibitor (ARNI) is a promising therapeutic candidate for both diseases. ARNI has demonstrated superior cardioprotective effects compared with renin-angiotensin system inhibitors (RAS-Is) in large clinical trials such as the PARADIGM-HF (Prospective Comparison of ARNI With ACEI [Angiotensin-Converting Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. It has also been suggested that ARNI can provide renoprotective effects beyond those of RAS-Is in patients with HF. ARNI might have beneficial effects on the kidneys because of its ability to improve cardiac function in patients with heart failure and affect renal hemodynamics by enhancing the effects of hormones such as natriuretic peptide. In contrast, in the PARADIGM-HF trial, ARNI was associated with more albuminuria compared with RAS-I; thus, it is unclear whether long-term ARNI therapy has renoprotective effects. Additionally, ARNI did not provide renoprotective effects beyond RAS-I in patients with chronic kidney disease in the UK HARP-III (United Kingdom Heart and Renal Protection-III) trial. In other words, the patient population in which ARNI is more renoprotective than RAS-I might be limited. Collectively, ARNI may have renoprotective effects in addition to cardioprotective effects, but the evidence to date is applicable only to heart failure. Theoretically, given the molecular mechanism of ARNI, it could also be renoprotective in conditions such as nephrosclerosis, which has low risks of albuminuria and reduced kidney perfusion, but the evidence for such effects is lacking. Further research is needed to clarify whether ARNI therapy is an acceptable treatment strategy for renal protection.
Topics: Humans; Valsartan; Neprilysin; Tetrazoles; Receptors, Angiotensin; Albuminuria; Angiotensin Receptor Antagonists; Drug Combinations; Heart Failure; Antihypertensive Agents; Kidney; Enzyme Inhibitors; Renal Insufficiency, Chronic; Biphenyl Compounds; Stroke Volume
PubMed: 37066800
DOI: 10.1161/JAHA.122.029565 -
Jornal Brasileiro de Nefrologia Mar 2017Obesity has been pointed out as an important cause of kidney diseases. Due to its close association with diabetes and hypertension, excess weight and obesity are... (Review)
Review
Obesity has been pointed out as an important cause of kidney diseases. Due to its close association with diabetes and hypertension, excess weight and obesity are important risk factors for chronic kidney disease (CKD). Obesity influences CKD development, among other factors, because it predisposes to diabetic nephropathy, hypertensive nephrosclerosis and focal and segmental glomerulosclerosis. Excess weight and obesity are associated with hemodynamic, structural and histological renal changes, in addition to metabolic and biochemical alterations that lead to kidney disease. Adipose tissue is dynamic and it is involved in the production of "adipokines", such as leptin, adiponectin, tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β and angiotensin-II. A series of events is triggered by obesity, including insulin resistance, glucose intolerance, dyslipidemia, atherosclerosis and hypertension. There is evidence that obesity itself can lead to kidney disease development. Further studies are required to better understand the association between obesity and kidney disease.
Topics: Humans; Obesity; Renal Insufficiency, Chronic
PubMed: 28355395
DOI: 10.5935/0101-2800.20170011 -
International Journal of Molecular... Dec 2022The renal condition is one of the crucial predictors of longevity; therefore, early diagnosis of any dysfunction plays an important role. Kidneys are highly susceptible... (Review)
Review
The renal condition is one of the crucial predictors of longevity; therefore, early diagnosis of any dysfunction plays an important role. Kidneys are highly susceptible to the aging process. Unfavorable conditions may lead to a significant disturbance of the body's homeostasis. Apart from physiological changes, there are some conditions such as hypertension, diabetes or obesity which contribute to the acceleration of the aging process. A determination of macroscopic and microscopic changes is essential for assessing the progression of aging. With age, we observe a decrease in the volume of renal parenchyma and an increase in adipose tissue in the renal sinuses. Senescence may also be manifested by the roughness of the kidney surface or simple renal cysts. The main microscopic changes are a thickening of the glomerular basement membrane, nephrosclerosis, an accumulation of extracellular matrix, and mesangial widening. The principal aspect of stopping unfavorable changes is to maintain health. Studies have shown many useful ways to mitigate renal aging. This review is focused especially on medications such as renin-angiotensin-aldosterone system blockers or resveratrol, but even eating habits and lifestyle.
Topics: Humans; Kidney; Nephrosclerosis; Kidney Diseases; Aging; Hypertension; Glomerular Filtration Rate
PubMed: 36499760
DOI: 10.3390/ijms232315435 -
Nephron 2015For a century, nephrosclerosis was ascribed to nonmalignant hypertension and aging. However, it was intuitively perceived that hypertension may follow rather than... (Review)
Review
For a century, nephrosclerosis was ascribed to nonmalignant hypertension and aging. However, it was intuitively perceived that hypertension may follow rather than explain this nephrovasculopathy. Hypertensive nephrosclerosis was long considered a major cause of end-stage renal failure (ESRD). This is especially true in blacks of African descent but not in other ethnic populations. The term 'nephrosclerosis' is still an easy way out to classify a patient with renal insufficiency. This leads to neglect the possibility of an overlooked nephropathy complicated by hypertension and to believe that drastic blood pressure control may retard the progression to ESRD. Several clinical and experimental lines of evidence lead to the understanding that nephrosclerosis, especially in blacks, is a genetic renovasculopathy that precedes the rise in blood pressure. The identification of coding region variants in APOL1 encoding apolipoprotein L-1 in black but also white and Asians opens new lines of research on the genetics of nephroangiosclerosis and of FSGS. Metabolic derangements, such as obesity, oxidative stress, dyslipidemia and atherosclerosis may be considered confounding factors with regard to nephrosclerosis. Histomorphometric studies led to sorting out the lesions due to aging from those stemming from hypertension. They shed new light not only on glomerular lesions that comprise ischemic obsolescence but also on glomerulomegaly and focal-segmental sclerosis, the latter due to a loss of renal autoregulation. It appears that the control of hypertension is not credited with the expected benefit for slowing the decline of renal function. 'Nephrosclerosis' can be considered an umbrella term of poor significance that should be replaced by its pathologic description, that is, arterionephrosclerosis and incite to elucidate the various genetic and metabolic factors that lead to a lesion in quest of a specific disease.
Topics: Humans; Hypertension; Nephrosclerosis; Risk Factors; Terminology as Topic
PubMed: 25871843
DOI: 10.1159/000381195