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Recent Aspects of Renal Pathophysiology in the Elderly
Abstract
The aging kidney is characterized by both anatomical and functional changes. However, renal modifications that are currently observed in the elderly are often due not only to the physiological renal senescence but also to the overlapping of various pathological conditions that may be subclinical or unrecognized. Therefore the present chapter will deal with the consequences of physiological aging of the kidney and the reasons will be examined why these modifications in the elderly are capable of conditioning a different reaction in the presence of a stressful or pathological situation in respect to the young.
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This chapter discusses changes in renal morphology that accompany aging, for the most part with those changes that affect the nephron and the renal vessels. There are evidences that the aging nephron degenerates as a unit. The micro-angiographic examinations strongly suggest that the long-looped juxtamedullary nephrons degenerate earlier than shorter-looped nephrons more peripherally situated. Microdissection has also revealed distal tubular ectasia and, with organisms, diverticula, which may account for an association between impaired concentrating capacity and bacteriuria. The aging nephron may be able to hypertrophy as its numbers decline. At the very least, there is evidence that the aging kidney retains a capacity to enlarge after nephrectomy. By histopathological studies based on a lifetime of scrupulous observation, vascular changes that are the result of aging have, in large degree, been carefully unraveled from those due to hypertension. The sclerosis of arterioles appears to be primarily an event of aging, although hypertension may make it worse.
• Various nephrotoxicity syndromes are seen with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The most common is reversible, hemodynamically mediated renal insufficiency. The role of prostaglandin inhibition by NSAIDs is discussed in the context of renal prostaglandin physiology. Potential differences among NSAIDs are reviewed. The "renal sparing" effect of sulindac may be attributable to the relative preservation of renal prostaglandin synthesis. Salsalate, although anti-inflammatory, demonstrates weak prostaglandin inhibition at therapeutic doses. A framework is developed for the clinical application of these considerations. Along a continuum of increasing risk factors for NSAID nephrotoxicity, or increasing NSAID dose, there likely exists a therapeutic window where differences among NSAIDs are most relevant.
(Arch Intern Med. 1990;150:268-270)
The new culture-free intelligence test, described in a former article (see XIV: 4768), is shown to be as valid as the Terman-Merrill, and as culture-free as the Arthur; it is the only test that combines both of these advantages. These findings were demonstrated by an experimental design that made possible the isolation of the influence on intelligence test scores of cultural familiarity with the test medium. Comparisons were made between Terman-Merrill, Arthur, A. C. E., Ferguson, and the culture-free tests. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The relative amount of interstitial cortical tissue was measured by the point count method in kidney tissue from human individuals without renal disease. One series (54 kidneys) consisted of kidneys intended for transplantation and removed immediately after death from persons who died suddenly. The other series (69 kidneys) was obtained by autopsy. In both groups, the percentage of interstitial tissue was dependent on age and followed the equations of regression (1) y=12.45+0.11 x (donor series) and (2) y=23.8+0,10 x (autopsy series). The autopsy values were significantly greater than the donor-kidney-values. There was no difference due to sex. The relative number of sclerotic, obsolescent glomeruli was very small (0–1%) until the age of 40. Thereafter it increased, most markedly in the autopsy series, until it reached values of about 30% in persons more than 80 years old.
Alterations in urine concentrating ability with age were examined in 98 active community-dwelling volunteers (aged 20-79 years) who were free from evidence of diseases known to adversely affect renal function. There was a significant decrease in urine osmolality reached after 12 h dehydration with advancing age, which could not be correlated with the age-related decline in creatinine clearance. A significant age-related diminution in the ability to conserve solute was also observed. This inability to conserve solute may result in diminished medullary tonicity and impaired urinary concentrating ability.
Standard true 24-hour creatinine clearance determinations were performed on 884 subjects of the Baltimore Longitudinal Study. On the basis of clinical data, subjects were placed in categories indicating the presence of specific diseases or medications which might alter glomerular filtration rate. Subjects not included in these categories were considered normal (N=548). In the normals, cross-sectional analysis by 10-year age groups showed a progressive linear decline in clearance from 140 ml/min/1.73m2 at age 30 to 97 at age 80. Three or more serial clearances were obtained at 12- to 18-mo. intervals on 293 normal subjects. These longitudinal data showed an acceleration of the rate of decline in creatinine clearance with advancing age. The decrease in creatinine clearance with age seen in this study represents true renal aging and is not secondary to diseases which become increasingly prevalent in the elderly. A nomogram constructed from these data provides normative age-corrected standards for creatinine clearance.
Age modifies a number of factors which determine renal sodium handling including the rate of glomerular filtration, renal hemodynamics, and the responsiveness of the renin-angiotensin-aldosterone system. This study was carried out, therefore, to examine the effects of age on the capacity of the normal human kidney to respond to restriction of sodium intake. Renal conservation of sodium and response to dietary sodium restriction was assessed in 89 healthy subjects who were free of cardiovascular, renal, or adrenal disease. The daily reduction in urine sodium which followed restriction of intake to 10 mEq. of sodium and 100 mEq. of potassium per day conformed well to an exponential function, defined by an unweighted least-squares fit. The half-time for the reduction in renal sodium excretion in subjects under 30 years was -17.6 +/- 0.7 hours, significantly faster than for subjects aged 30 to 59, who had a relatively constant half-time (23.4 +/- 1.1 hours). In subjects over 60 years of age the half-time was prolonged to 30.9 +/- 2.8 hours, significantly greater than that of the younger age group. These observations indicate that age significantly influences the kidney's capacity to conserve sodium. Age-related change must be considered in the assessment of this function in human disease.
1. The aim of this investigation was to study the role of prostaglandins in the impaired Na+ conservation of the ageing kidney.
2. We measured the urinary excretion of thromboxane B2, 6-keto-prostaglandin F1α and prostaglandin E2 in young (3–4 months) and old (20–21 months) rats after 12, 24 and 36 h of Na+ deprivation. In a separate protocol, we measured prostanoid synthesis by isolated glomeruli, cortical homogenates, medullary slices and papillary slices from young and old rats in basal conditions and after 15 days of dietary Na+ deprivation.
3. In the acute study, urinary excretion of 6-ketoprostaglandin F1α and prostaglandin E2 decreased in young but not in old rats. Urinary excretion of prostaglandin E2 was lower in old rats, but did not vary significantly with Na+ deprivation.
4. In old rats, thromboxane B2 synthesis was increased in all the portions of the kidney except the medulla. Production of 6-keto-prostaglandin F1α was elevated in glomeruli and tended to increase in the cortex. Prostaglandin E2 synthesis was also elevated in the cortex. Thromboxane B2 synthesis tended to increase in the medulla and was enhanced in the papilla. After Na+ deprivation, only glomerular prostaglandin E2 synthesis increased in young rats. In old rats, cortical and papillary synthesis of 6-ketoprostaglandin F1α increased, whereas prostaglandin E2 synthesis did not change.
5. The results suggest increased thromboxane synthesis in the ageing kidney. Increased prostacyclin and prostaglandin E2 synthesis may be an attempt to counteract enhanced thromboxane production. Blunting of this tendency in medulla and papilla could contribute to the conservation of medullary solute concentration, whereas inappropriate stimulation of prostacyclin synthesis during Na+ deprivation could impair Na+ conservation.
To determine the effects of age on the responses of renin, aldosterone (PA), sodium excretion, and renal function to provocative maneuvers, we performed volume expansion and contraction in 390 normotensive and 212 hypertensive subjects in the second to seventh decades of life. The subjects were classified as Na-sensitive if their mean blood pressure was 10 mm Hg or more higher after volume expansion than volume contraction. Sodium sensitivity was associated with hypertension and increasing age. Plasma renin activity decreased with age under basal, stimulated, and suppressed conditions; the decrease was greater in hypertensives than in normotensive persons. The PA values were greater in hypertensives than in normal subjects after volume expansion. There was an age-related decrease in PA values after volume contraction in normal, but not in hypertensive, persons. With volume expansion, hypertensive persons exhibited "exaggerated natriuresis." There was an age-related increase in natriuresis in both groups; the increase was greater in hypertensives than normal subjects. Creatinine clearance decreased with age; however, the rate of decrease in this cross-sectional study was not different in hypertensive and normotensive subjects. These observations may have a bearing on why NaCl affects the blood pressures of older individuals more than younger persons.