12.4: Age Changes in Kidneys

Aging causes the kidneys to gradually decrease in length, volume, and weight. The decline in size may begin as early as age 20, and the resulting changes are evident by age 50. Shrinkage of the kidneys continues thereafter. (Suggestion 258.01.03)

Blood Vessels

The loss of kidney mass seems to result primarily from declining blood flow through the kidneys caused by degenerative changes in the smaller arteries and glomeruli. The smaller arteries, including arterioles attached to glomeruli, become irregular and twisted. Glomeruli can be injured by *FRs, glycation of proteins, imbalances between substances causing vasodilation and vasoconstriction, and by excess cell formation. Functional glomeruli are lost gradually, beginning before age 40. By age 80, 40 percent of the glomeruli may stop functioning. From 20 to 30 percent of glomeruli that stop functioning become solidified, and this stops all blood flow through them. Increasing numbers of other glomeruli have their capillaries replaced by one or a few arterioles that permit blood flow while preventing filtration. These shunts develop predominantly in glomeruli close to the medulla. Many remaining glomeruli become smoother and have thicker and declining surface area. These latter changes reduce their filtration rates.

Renal Blood Flow

The amount of blood flowing through kidney vessels is called renal blood flow (RBF), and age changes in kidney vessels significantly decrease RBF. The decline may begin as early as age 20 and is apparent in most individuals during the fifth decade. The average decline in RBF is 10 percent per decade, though many individuals have more rapid decreases with age. There is a greater decline in blood flow through peripheral cortical nephrons than through glomeruli close to the medulla (juxtamedullary nephrons) and the medulla itself.

This decline seems to be the main reason for most reductions in the functional capacity of the kidney, including filtration, reabsorption, and secretion. In addition, age changes seem to reduce the ability of kidney vessels to dilate and constrict and therefore to adjust kidney blood flow. This change reduces both the speed of kidney functioning and the extent to which it may increase or decrease to meet alterations in body conditions. The greater decline in blood flow in the cortical region compared with the medulla also seems to contribute to the decline in the ability of the kidneys to reduce water loss. This change reduces the ability to compensate for high osmotic pressure.

Some older individuals are at risk for even greater reductions in RBF and kidney functioning because certain abnormal or disease conditions cause less blood to pass through the kidneys. Examples include dehydration, atherosclerosis of kidney arteries, weak heart function, and edema from protein malnutrition or cirrhosis. Renal blood flow is also reduced by certain pain-relieving medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), which lead to vasoconstriction of kidney arterioles.

Glomerular Filtration Rate

One main effect of age changes in glomeruli and a declining RBF is a declining rate of filtration through the glomeruli [glomerular filtration rate (GFR)]. The GFR usually begins to drop between ages 30 and 35. However, both the age at which GFR begins to drop and the rate of decline vary greatly among individuals. In some older individuals GFR may remain steady or improve for years before declining again.

A decline in GFR is important because it reduces the elimination rate of many undesirable substances by filtration and secretion. Examples include acids, urea, uric acid, creatinine, toxins, and certain antibiotics, NSAIDs, and other drugs. Therefore, these substances may accumulate in the body and reach hazardous levels. Reductions in GFR also limit the ability of tubules to adjust the retention or elimination of materials such as water, sodium, and potassium.

Normal individual variability in the changes in GFR, together with difficulties in accurately measuring GFR, increases the possibility of making errors in establishing GFRs for older individuals. Such errors can lead to other errors in making dietary recommendations or prescribing drug doses.

Tubules and Collecting Ducts

Age changes in blood vessels are accompanied by age changes in tubules. The tubules become thicker, shorter, and more irregular as their cell numbers decrease. These changes seem to have little effect on the functioning of individual tubules. However, the total capacity for reabsorption and secretion by kidney tubules is reduced because of the decrease in GFR, which supplies filtrate to the tubules, and because whole nephrons stop functioning, shrink, and are lost. The loss of nephrons whose glomeruli are close to the medulla exceeds the loss of more peripheral nephrons.

Little information about age changes in collecting ducts is available, suggesting that these ducts undergo few age changes. There are conflicting views about whether there is an age-related decline in the responsiveness of the collecting ducts to hormones that promote water reabsorption.

Other Changes

Renin

One way by which the kidneys regulate blood pressure is by adjusting the production of renin. The kidneys also produce renin when osmotic pressure or sodium concentrations are abnormal. Renin indirectly causes tubules to reabsorb more sodium and secrete more potassium. Therefore, adjusting renin production helps regulate blood pressure, along with osmotic pressure and concentrations of sodium and potassium.

Aging causes a gradual decrease in renin production by the kidneys, and the kidneys become less sensitive to messages initiated by renin. These changes decrease further the ability of the kidneys to maintain homeostasis of osmotic pressure, sodium and potassium concentrations, and blood pressure.

Vitamin D Activation

Aging causes a decline in vitamin D activation by the kidneys, especially after age 65. Lower vitamin D activation promotes calcium deficiencies, bone fractures, and osteoporosis.

Women experience dramatic decreases in vitamin D activation before age 65 because estrogen, which stimulates vitamin D activation, drops precipitously at menopause (approximately age 50). In women, the combination of aging of the kidneys and hormonal changes results in a greatly reduced vitamin D supply and is a major reason for the higher incidence of osteoporosis among postmenopausal women.

Consequences

In summary, there is an age-related decline in the reserve capacity of the kidneys for maintaining homeostasis of osmotic pressure, concentrations of sodium and potassium, acid/base balance, and blood pressure. Elimination of wastes and toxins becomes slower, and less vitamin D is activated. As with age changes in other parts of the body, these changes begin at different times and progress at different rates. The ability to produce erythropoietin to regulate oxygen levels declines, which increases the risk of anemia. Age changes in the ability to regulate substances such as calcium and magnesium have not been well studied.

In spite of the gradual decline in many kidney functions, healthy people enter adulthood with enough kidney reserve capacity so that under favorable living conditions there is ample functioning to maintain homeostasis regardless of age. However, the declining kidney capacity results in a narrowing of the range of conditions over which the kidneys can provide compensatory adjustments. This narrowing in range, together with certain age changes and many age-related abnormal and disease changes, increases the chances that excessive demands will be placed on the kidneys. Therefore, as people get older, there is a greater likelihood that the frequency, extent, and duration of excursions outside the urinary system's adaptive capacity and beyond the bounds of homeostasis will occur. This necessitates greater conscious effort to prevent such excursions and, when they occur, to correct the conditions causing them.

The relationships between the kidneys and medications change in several ways as age increases. Age changes in the kidneys reduce their ability to destroy some drugs (e.g., morphine) and to eliminate others in the urine (e.g., aspirin, NSAIDs, antibiotics). The effects of these age changes may be enhanced or reduced by diseases (e.g., circulatory diseases, cirrhosis, urinary tract infections, kidney diseases), by some medications (e.g., NSAIDs, diuretics), and by age-related decreases in total body water and increases in percent body fat. Therefore, as age increases, types and doses of all medications should be selected in a more individualized and careful manner to provide effective therapy while minimizing the risks of complications.