Aging and Physiological Changes of the Kidneys Including Changes in Glomerular Filtration Rate

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. Copyright © 2011 S. Karger AG, Basel Published online: August 10, 2011 Dr. Carlos Guido Musso 14 de julio 246 Temperley, BA 1834 (Argentina) E-Mail [email protected] © 2011 S. Karger AG, Basel 1660–2137/11/1195–0001$38.00/0 Accessible online at: www.karger.com/nep D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /2 3/ 20 17 7 :0 8: 59 P M Musso /Oreopoulos Nephron Physiol 2011;119(suppl 1):p1–p5 p2 ( table 2 ). Renal tubules undergo fatty degeneration and irregular thickening of their basal membrane with increasing zones of tubular atrophy and fibrosis [1, 2] . In a recent study, Rule at al. [3] have shown that the prevalence of glomerulosclerosis in healthy people (kidney donors) was 2.7, 16, 44, 58, and 73% for those very young, young, adult, old and very old, respectively. These authors found that neither kidney function nor chronic kidney disease (CKD) risk factors could explain the strong association between age and glomerulosclerosis in healthy adults. As a result of the above anatomical changes, there is a decrease in the glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF); the latter decreases disproportionally more than GFR – 10% per decade from 600 ml/min/1.73 m 2 in youth to 300 ml/min/1.73 m 2 by the age of 80. Therefore, the filtration fraction, which is the ratio of GFR/ERPF, usually increases in the elderly since the denominator (ERPF) is disproportionately lower than the numerator (GFR) [1, 2, 4] . Measurement of the GFR with 51 Cr-EDTA confirms that healthy elderly individuals have a lower GFR than young subjects. At the third decade of life, GFR peaks at approximately 140 ml/min/1.73 m 2 , and from then on, progressively declines to an approximate rate of 8 ml/ min/1.73 m 2 per decade. This fall in creatinine clearance (Ccr) is accompanied by a decrease in creatinine production (senile sarcopenia), and consequently serum creatinine does not increase with the progressive decrease in GFR [5] . It may be better if GFR is expressed after correcting its value for body surface area, especially in the elderly in whom body surface area is usually reduced compared with the young [4] . After Kimmel et al. [34] demonstrated that old people who were on a high-protein diet maintained normal GFR, it has been hypothesized that ‘normal’ GFR observed in some elderly could be the consequence of increased protein intake that is followed by glomerular hyperfiltration [5, 6] . It has been reported that in approximately one third of old people the GFR does not decrease with age [6] , but this observation has not been confirmed by subsequent publications. Twenty-four-hour urinary sodium output and fractional excretion of sodium are significantly greater in old people because thick ascending loop of Henle sodium reabsorption and basal plasma concentrations of renin and aldosterone, and the response to their stimuli are diminished in old age. As GFR declines with age and the amount of filtered sodium is lower than in young subjects, a salt load given to an aged person takes longer to eliminate. Additionally, since there is medullary hypotonicity in old subjects, they exhibit an inability to maximally concentrate the urine. Moreover, urinary dilution capability is also decreased in aged people. Regarding the senile renal tubular handling of potassium and urea, potassium secretion and urea reabsorption are both reduced in this aged group ( table 3 ) [7, 8] . Senile Decrease in GFR Differs from That in Chronic