KIDNEY, AGING

The kidneys sit, one on each side of the midline, high in the back of the abdomen—so high in fact that their top halves fall under the lower end of the rib cage. The chief roles of the kidneys are filtration of blood, reabsorption of key chemicals, excretion of fluid and waste metabolites, and the maintenance of acid/base balance, but they also have important glandular (endocrine) functions. The kidneys are particularly important in drug metabolism.

Usually, as people age, there are highly predictable changes in both the structure and the function of the kidneys, so that by age seventy-five the kidneys weigh about 15 to 20 percent less than they do at age twenty-five, due to loss of cells that make up the kidneys. Nevertheless, kidney function, in the absence of disease, remains adequate throughout life, even into extreme old age.

The cells that make up the kidney are complex, and are formed into special structures called nephrons. Blood enters the kidneys from the aorta (the major artery that leaves the heart) via the renal arteries, which branch to smaller and smaller structures known as arterioles. The blood flows into a filtration structure called a glomerulus. Filtered material passes through a complex membrane into tubules. The remainder of the blood, consisting of plasma, blood cells and certain large proteins passes into another arteriole. The tubule and arteriole are in close proximity, allowing water and other chemicals (chiefly sodium, chloride and potassium) to be reabsorbed back from the tubules into the blood in the arterioles. Reabsorption is affected both by local factors in the kidney and by hormones. In this way, the body is able to regulate the relative proportion of water and these chemicals very precisely in response to changes in other parts of the body, and thus to changes in the environment. While all these functions are preserved in old age, the mechanisms become increasingly susceptible to even small changes. Thus, for example, in response to stress such as injury or pain, regulation of sodium reabsorption can become impaired, leading to sodium levels that are relatively too low and body water levels that are relatively too high. This, in turn, can lead to serious consequences, such as delirium.

As the filtrate (now urine) travels through the tubules, it collects in larger structures until ultimately it passes through the ureters, which emerge at the center of the kidneys. The ureter provides the piping to the bladder, where urine is stored before being excreted through the urethra.

An important consequence of impaired kidney function is a decreased ability to excrete certain commonly used drugs, which thus can accumulate and give rise to adverse drug reactions. Drug metabolism and excretion by the kidney are complex, and depend on many characteristics of the drug, including the size and solubility of its molecules, and whether other drugs are being metabolized. Also of great importance are other characteristics, such as blood flow to the kidneys. The latter can be impaired by conditions that become more common as people age (diabetes, lipid disorders, high blood pressure). In general, blood flow to the kidney decreases by about 10 percent per decade after age thirty. It must be emphasized, however, that this is the average case: when individuals are followed over time, many (up to almost one-third) do not show a significant decrease in kidney function, even in the ninth decade of life.

Decline in blood flow to the kidney, accompanied by the loss of kidney cells, means that as people age, the kidneys are less able to filter blood. The lower filtration rate needs to be taken into account when prescribing drugs that are excreted through the kidneys. A standard formula allows ready calculation of the amount by which drug doses should be adjusted in the face of lower kidney function.

For the most part, poor kidney function does not give rise to symptoms, except when it results in kidney failure. As a consequence, physicians must rely on two blood tests (of urea and creatinine) to assess kidney function. As kidneys filter less, they are less able to excrete urea and creatinine, and in consequence the level of each rises. Unfortunately, these are insensitive tests, and especially in elderly people, up to 90 percent of kidney function can be lost before these tests indicate a problem.

Kidney failure in both older and younger people is traditionally divided into three types. Failure resulting from diminished blood flow to the kidneys is called prerenal failure. As noted, many factors result in vascular disease and thus low kidney blood flow becomes more common with age. Kidney failure arising from a problem intrinsic to the kidney itself is renal failure. Many diseases can impair kidney function by direct damage to the nephrons, with various parts of the nephron being particularly susceptible to particular types of disease. For example, the complex membrane across which water and certain proteins flow to the tubules can be the site of deposition of toxic substances, including complexes that arise in autoimmune disorders. The glomeruli are particularly susceptible to diseases associated with aging. Failure that arises from blockage of the flow of urine is called postrenal failure. For example, ureters can be obstructed by strictures, by kidney stones, and, in men, by enlargement of the prostate. In consequence, urine flow backs up so that ultimately glomerular filtration is disrupted.

The kidneys are not just filters, however; but also are the sites of action of several hormones. In addition to those which respond to water handling, important hormones include erythropoietin (necessary to produce red blood cells) and vitamin D (needed for bone integrity). Vitamin D undergoes an essential step in the kidney to become metabolically active.

In general, the rise of kidney disease, and especially kidney failure, has closely paralleled the aging of the population. It is not aging in and of itself, however, but the diseases associated with aging, that is resulting in kidney problems becoming more common. How to interpret the fact that many older people have near-normal kidney function is unclear, but many scientists see in this the hope that such successful aging might be extended to more people, so as to result in less disability in late life.

Kenneth Rockwood

BIBLIOGRAPHY

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