Anatomic and physiologic age changes in the kidney

Lindeman, Robert D.; Goldman, Ronald L.

doi:10.1016/0531-5565(86)90044-6

Cited by 163 publications

(81 citation statements)

References 123 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These changes include increased glomerulosclerosis, podocyte loss, GBM thickening, accumulation of abnormal mitochondria, and alteration in autophagy (Lindeman & Goldman, 1986; McKiernan et al ., 2007; Bolignano et al ., 2014). Most of these changes have been observed in our samples in all of the dietary groups, but especially in the CON animals.…”

Section: Discussionmentioning

confidence: 99%

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

et al. 2016

View full text Add to dashboard Cite

SummaryCalorie restriction (CR) has been repeatedly shown to prevent cancer, diabetes, hypertension, and other age‐related diseases in a wide range of animals, including non‐human primates and humans. In rodents, CR also increases lifespan and is a powerful tool for studying the aging process. Recently, it has been reported in mice that dietary fat plays an important role in determining lifespan extension with 40% CR. In these conditions, animals fed lard as dietary fat showed an increased longevity compared with mice fed soybean or fish oils. In this paper, we study the effect of these dietary fats on structural and physiological parameters of kidney from mice maintained on 40% CR for 6 and 18 months. Analyses were performed using quantitative electron microcopy techniques and protein expression in Western blots. CR mitigated most of the analyzed age‐related parameters in kidney, such as glomerular basement membrane thickness, mitochondrial mass in convoluted proximal tubules and autophagic markers in renal homogenates. The lard group showed improved preservation of several renal structures with aging when compared to the other CR diet groups. These results indicate that dietary fat modulates renal structure and function in CR mice and plays an essential role in the determination of health span in rodents.

show abstract

Section: Discussionmentioning

confidence: 99%

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Another example is obesity-associated hypertension, which is associated with SNS activation, 35 salt-sensitive hypertension, and renal damage with glomerulosclerosis and tubulointerstitial fibrosis. 36 Similarly, one might speculate that the routine but sometimes marked fluctuations in BP that occur daily in "normotensive" patients 37 and that are known to be triggered by the SNS 38 may be relevant to the age-related development of glomerulosclerosis and tubulointerstitial fibrosis, 39 the age-related decline in GFR, and the development of saltsensitive hypertension in this population. 40 Finally, one wonders whether a similar mechanism may be involved in the transition from labile to persistent hypertension that occurs in "white-coat" hypertension, 41 with sleep apnea, 42 or with exercise-induced hypertension, 43 all of which are SNS-driven responses.…”

Section: Discussionmentioning

confidence: 99%

Renal Injury and Salt-Sensitive Hypertension After Exposure to Catecholamines

et al. 1999

View full text Add to dashboard Cite

Abstract-We investigated whether chronic infusion of phenylephrine could induce structural and functional changes in the kidney of rats with the subsequent development of salt-sensitive hypertension. Rats were infused with phenylephrine (0.15 mmol/kg per day) by minipump, resulting in a moderate increase in systolic blood pressure (BP) (17 to 25 mm Hg) and a marked increase in BP variability as measured by an internal telemetry device. After 8 weeks, the phenylephrine infusion was stopped with the return of BP to normal, and a nephrectomy was performed for histological studies. Glomeruli were largely spared, but focal tubulointerstitial fibrosis was present, with the de novo expression of osteopontin by injured tubules, macrophage and "myofibroblast" accumulation, and focal increases in mRNA for transforming growth factor ␤ by in situ hybridization. Peritubular capillaries at sites of injury had distorted morphology with shrinkage, rounding, and focal rarefaction, and endothelial cell proliferation was also identified. Rats were randomized to a high (8% NaCl or 1.36 mol/kg) or low (0.1% NaCl or 17 mmol/kg) salt diet. After 4 to 8 weeks, phenylephrine-treated rats on a high salt diet developed marked hypertension, which was in contrast with phenylephrine-treated rats placed on a low salt diet or vehicle-treated rats given a high salt diet. Hypertension after phenylephrine exposure correlated with the initial mean systolic BP (r 2 ϭ0.99) and the degree of BP lability (r 2 ϭ0.99) during the phenylephrine infusion, the amount of osteopontin expressed in the initial biopsy/nephrectomy (r 2 ϭ0.74), and the final glomerular filtration rate (r 2 ϭ0.58). These studies provide a mechanism by which a markedly elevated sympathetic nervous system can induce salt-dependent hypertension even when the hyperactive sympathetic state is no longer engaged. (Hypertension. 1999;34:151-159.) Key Words: phenylephrine Ⅲ renal circulation Ⅲ hypertension, episodic Ⅲ sympathetic nervous system T here is ample evidence that a hyperactive sympathetic nervous system (SNS) is present in some forms of human hypertension, especially in early, borderline essential hypertension. 1 In addition to the acute effects of SNS activation to raise blood pressure (BP), adrenergic stimulation may induce target organ damage by both hemodynamic and nonhemodynamic mechanisms. 2 Adrenergic stimulation can be associated with left ventricular hypertrophy as well as hypertrophy and stiffening of large arteries. Adrenergic agents have also been shown to stimulate vascular smooth muscle cell proliferation and hypertrophy both in vivo and in vitro. 3,4 We have been interested in the potential role of the SNS as a mediator of renal injury. It is known that catecholamine infusions can induce acute elevations in glomerular hydrostatic pressure in association with intense renal vasoconstriction and a fall in renal blood flow (RBF). 5,6 Infusions of norepinephrine can also induce microalbuminuria in both normal and diabetic individuals. 7 A combination of intrarenal and i...

show abstract

“…3 The kidneys of men also undergo greater decline in renal function with age than do the kidneys of women. 4,5 This suggests that male sex hormones might play a role in mediating cardiovascular disease in men. However, the role that androgens play in the control of blood pressure and renal injury in men, especially with age, is not clear.…”

mentioning

confidence: 99%

Role of Androgens in Mediating Renal Injury in Aging SHR

et al. 2003

View full text Add to dashboard Cite

Abstract-Men have an increased risk of cardiovascular and renal diseases and develop greater renal injury despite similar levels of blood pressure when compared with women. The mechanisms responsible for this predisposition are unknown. Using the spontaneously hypertensive rat (SHR), we have found that androgens play an important role in the development of hypertension in young male SHR. However, the role that androgens play in age-related renal injury and dysfunction in SHR is unknown. Our hypothesis was that despite reductions in serum testosterone with age, androgens mediate renal injury and dysfunction in male SHR. Male SHR were castrated at 8 months of age, studied at 18 months of age, and compared with age-matched, intact males and young intact males (4 months). Serum testosterone was reduced by 30% in aging males compared with young SHR. With castration, blood pressure (mean arterial pressure [MAP]) was decreased by Ͼ20 mm Hg compared with old males, glomerular filtration rate (GFR) was increased by Ͼ35%, and renal vascular resistance (RVR) was reduced by Ͼ40%. MAP, GFR, and RVR in castrated, old males were similar to values in young males. With castration, glomerular sclerosis was reversed and proteinuria was also decreased by Ͼ80% when compared with old intact males. In addition, in castrated old males, plasma renin activity was decreased by 30% compared with old males and by 60% compared with young rats. The data support the hypothesis that despite a reduction in testosterone with age, androgens play an important role in age-related renal injury and dysfunction in SHR. Key Words: age Ⅲ aging Ⅲ androgens Ⅲ hypertension, renal Ⅲ renal disease C omparisons performed in age-matched groups show that men have higher blood pressures than women until old age, when blood pressures become similar. 1,2 Men also have a greater incidence of renal disease and proceed to end-stage renal failure faster than do women, even when exhibiting similar levels of blood pressure. 3 The kidneys of men also undergo greater decline in renal function with age than do the kidneys of women. 4,5 This suggests that male sex hormones might play a role in mediating cardiovascular disease in men. However, the role that androgens play in the control of blood pressure and renal injury in men, especially with age, is not clear.We have previously found that androgens play a role in the development of hypertension in young, spontaneously hypertensive rats (SHR), because castration at 5 to 7 weeks of age reduces blood pressure when measured at 4 months of age, and testosterone treatment of ovariectomized females increases blood pressure. 6,7 This difference in blood pressure between intact and castrated males is still present at 8 months of age, the oldest age we have studied thus far. 8 We also found that the renin-angiotensin system (RAS) plays an important role in the development of hypertension in young SHR, because blockade of the RAS with converting-enzyme inhibitors removed the sex difference in blood pressure, and testosterone treatmen...

show abstract

Anatomic and physiologic age changes in the kidney

Cited by 163 publications

References 123 publications

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

Renal Injury and Salt-Sensitive Hypertension After Exposure to Catecholamines

Role of Androgens in Mediating Renal Injury in Aging SHR

Contact Info

Product

Resources

About