Journal of Gerontological Nursing

Effects of Drug Therapy on Renal Function of Healthy Older Adults

Dorothy M Knox, EDD, RN; Mary T Martof, EDD, RN

Abstract

The two most common causes of renal insufficiency are decreased perfusion and nephrotoxins (McCance & Huelher, 1990), problems for which the older person is particularly susceptible. Although fluid balance in the older adult is not well understood (Rolls & Phillips, 1990), it is known that the total body water decreases with age (Spencer, Nichols, Lipkin, Henderson, & West, 1993). As one ages, normal physiological changes occurring in the body can affect the ability of the older person to maintain fluid balance. At the same time, there is a decrease in the thirst drive (McCance & Huether, 1990). These factors can affect the kidney's reabsorption, excretion, and filtration processes in an older person and may lead to decreased perfusion or drug toxicity. While reviewing the drug history of older persons for the potential inclusion in a research study, the authors became aware of the number of drugs these individuals were using that could influence the development of renal insufficiency.

THE STUDY

A 3-month drug history of 44 older persons (aged 57 to 81) was performed to determine eligibility for inclusion in a research study involving fluid balance. They had been screened earlier for known liver, heart, and kidney disorders. It had been previously determined that individuals would not be included in the study if they were using drugs that had major influences on fluid balance. The drug history revealed that nearly all of the individuals were taking or had taken drugs that could affect fluid balance. Twenty-eight different prescription drugs and 22 different nonsteroidal anti-inflammatory drugs (NSAIDs) were identified. Of the prescription drugs, diuretics, antihypertensives, and hormones were used most frequently. Aspirin and aspirin-containing products were the most common non-prescription drugs followed by acetaminophen.

Diuretic usage was the major reason for eliminating persons from the study with thiazide diuretics being the most commonly used. Thiazide diuretics promote the excretion of sodium, chloride, and water by inhibiting their re-absorption in the early distal tubules (McKenry & Salerno, 1992; Swonger & Matejski, 1991).

These diuretics increase the delivery rate of tubular fluid and electrolytes to the distal tubular sites where hydrogen and potassium ions are secreted. When an increased sodium load is delivered to the distal tubules, there is a corresponding increase in potassium excretion (Swonger & Matejski, 1991). Meanwhile, the decreased circulating blood volume, due to the fluid loss that was caused by the diuretic, stimulates aldosterone production (Drug Information far the Health Care Professional, 1991). This leads to further potassium loss (Swonger & Matejski, 1991). The increased tubular fluid delivery along with the increased aldosterone levels promotes sodium re-absorption at the distal tubules (rebound effect) with increasing excretion of potassium and hydrogen ions (Drug Information for the Health Care Professional, 1991; Swonger & Matejski, 1991).

Hyperuricemia also can occur because thiazides decrease tubular secretion of uric acid (McKenry & Salerno, 1992; Swonger & Matejski, 1991), which can precipitate gout in susceptible persons (Spencer et al., 1993). When the serum uric acid becomes too high, uric acid then can crystallize in the glomeruli causing renal damage (McCance & Huether, 1990). In the aging kidney, the tubular basement membrane surrounding Bowman's capsule and the small arteries within the parenchyma thicken with a concomitant decrease in the length of the proximal tubules (Rebenson-Piano, 1989). All thickening affects the active transport system of the proximal tubules, allowing a large amount of filtrate to enter the distal tubules Spencer et al., 1993). The large amount of sodium in the filtrate stimulates aldosterone production, which promotes the excretion of potassium (Swonger & Matejski, 1991). Thus, the older person is at risk for hypokalemia prior to use of…

The two most common causes of renal insufficiency are decreased perfusion and nephrotoxins (McCance & Huelher, 1990), problems for which the older person is particularly susceptible. Although fluid balance in the older adult is not well understood (Rolls & Phillips, 1990), it is known that the total body water decreases with age (Spencer, Nichols, Lipkin, Henderson, & West, 1993). As one ages, normal physiological changes occurring in the body can affect the ability of the older person to maintain fluid balance. At the same time, there is a decrease in the thirst drive (McCance & Huether, 1990). These factors can affect the kidney's reabsorption, excretion, and filtration processes in an older person and may lead to decreased perfusion or drug toxicity. While reviewing the drug history of older persons for the potential inclusion in a research study, the authors became aware of the number of drugs these individuals were using that could influence the development of renal insufficiency.

THE STUDY

A 3-month drug history of 44 older persons (aged 57 to 81) was performed to determine eligibility for inclusion in a research study involving fluid balance. They had been screened earlier for known liver, heart, and kidney disorders. It had been previously determined that individuals would not be included in the study if they were using drugs that had major influences on fluid balance. The drug history revealed that nearly all of the individuals were taking or had taken drugs that could affect fluid balance. Twenty-eight different prescription drugs and 22 different nonsteroidal anti-inflammatory drugs (NSAIDs) were identified. Of the prescription drugs, diuretics, antihypertensives, and hormones were used most frequently. Aspirin and aspirin-containing products were the most common non-prescription drugs followed by acetaminophen.

Diuretic usage was the major reason for eliminating persons from the study with thiazide diuretics being the most commonly used. Thiazide diuretics promote the excretion of sodium, chloride, and water by inhibiting their re-absorption in the early distal tubules (McKenry & Salerno, 1992; Swonger & Matejski, 1991).

These diuretics increase the delivery rate of tubular fluid and electrolytes to the distal tubular sites where hydrogen and potassium ions are secreted. When an increased sodium load is delivered to the distal tubules, there is a corresponding increase in potassium excretion (Swonger & Matejski, 1991). Meanwhile, the decreased circulating blood volume, due to the fluid loss that was caused by the diuretic, stimulates aldosterone production (Drug Information far the Health Care Professional, 1991). This leads to further potassium loss (Swonger & Matejski, 1991). The increased tubular fluid delivery along with the increased aldosterone levels promotes sodium re-absorption at the distal tubules (rebound effect) with increasing excretion of potassium and hydrogen ions (Drug Information for the Health Care Professional, 1991; Swonger & Matejski, 1991).

Hyperuricemia also can occur because thiazides decrease tubular secretion of uric acid (McKenry & Salerno, 1992; Swonger & Matejski, 1991), which can precipitate gout in susceptible persons (Spencer et al., 1993). When the serum uric acid becomes too high, uric acid then can crystallize in the glomeruli causing renal damage (McCance & Huether, 1990). In the aging kidney, the tubular basement membrane surrounding Bowman's capsule and the small arteries within the parenchyma thicken with a concomitant decrease in the length of the proximal tubules (Rebenson-Piano, 1989). All thickening affects the active transport system of the proximal tubules, allowing a large amount of filtrate to enter the distal tubules Spencer et al., 1993). The large amount of sodium in the filtrate stimulates aldosterone production, which promotes the excretion of potassium (Swonger & Matejski, 1991). Thus, the older person is at risk for hypokalemia prior to use of diuretics.

Several of the potential study subjects were on loop diuretics. The loop diuretics produce their action on the loop of Henle, but have physiological and pharmacological effects similar to the thiazide-type diuretics (Swonger & Matejski, 1991).

A variety of anti-hypertensive 4 drugs were used by the potential subjects. No single drug was dominant. Although various classes of antihypertensives are based on distinct action sites, all reduce peripheral resistance, either directly or indirectly ^ (Spencer et al., 1993). Reduction of blood pressure can decrease renal blood flow (RBF) with a concomitant decrease in glomerular filtration rate (GFR) due to the reduction of filtration pressure (McCance & Huether, 1990), which can trigger sodium and water retention causing edema and weight gain (McKenry & Salerno, 1992).

Normal physiological changes are intensified when anti-hypertensive ^ drugs are given to the elderly. Because the cardiac output drops by 25% between the ages of 25 and 65 Mathieson, 1986), blood flow to the kidneys and the GFR are decreased markedly in the aged, leading to diminished kidney function. Reduction in blood pressure activates the baroreceptor reflexes and stimulates sodium and water retention (McCance & Huether, 1990).

The common hormone used by the potential subjects was estrogen. This was not surprising because the majority of potential subjects were female and estrogen is thought to delay or prevent osteoporosis and to alleviate severe symptoms of menopause. Because estrogen increases lev- ? els of renin and angiotensin, it can induce sodium and water retention causing tissue edema (Spencer et al., 1993). The renin-angiotensin system acts as a powerful vasoconstrictor and triggers the release of aldosterone, which increases sodium and water re-absorption in the distal tubules (McCance & Huether, 1990).

Twenty-six (59%) of the individuals indicated use of NSAIDs either on a daily basis or as needed. NSAIDs are major nephrotoxic agents (Garfinkel, Porter, & Whelton, 1988) through their inhibiting effects on prostaglandin synthesis. Renal prostaglandins help maintain fluid and electrolyte homeostasis, renin release, and RBF, all of which are affected by NSAIDs and can lead to renal toxicity (Sager & Bennett, 1992). Renal prostaglandins maintain fluid and electrolyte homeostasis by inhibiting tubular reabsorption of sodium and chloride and by inhibiting tubular responsiveness to vasopressin (anti-diuretic hormone), thereby favoring free water excretion (Sager & Bennett, 1992; Stillman & Schlesinger, 1990). When this function is blocked by NSAIDs, sodium retention can occur in susceptible individuals causing peripheral edema (Sager & Bennett, 1992).

The inhibition of prostaglandin synthesis by NSAIDs decreases secretion of potassium by limiting the amount of sodium delivered (and thus available for exchange) to the distal tubule (Sager & Bennett, 1992). The blunting of renin activity by NSAIDs leads to decreased renin production, which causes a decreased aldosterone production that also contributes to hyperkalemia (Stillman & Schlesinger, 1990). Thus, symptoms of edema, hyponatremia, and hyperkalemia may occur.

Renal prostaglandins are potent renal circulation vasodilators (McCance & Huether, 1990); therefore, when their production is inhibited, vasoconstriction occurs. This can result in a decrease of both RBF and GFR manifested as an increase in serum urea nitrogen and creatinine (Stillman & Schlesinger, 1990). The effects of NSAIDs on kidney function can lead to glomerular damage, interstitial nephritis, or acute tubular necrosis (Garfinkel et al., 1988), one of the most common causes of renal insufficiency (McCance & Huether, 1990).

The decrease in RBF and GFR allows a higher concentration of nephrotoxins in the glomerular filtrate, which causes a hypersensitivity reaction in the interstitium. The interstitium reaction causes abnormally high levels of protein to be excreted (Garfinkel et al., 1988) making less protein available to bind with the drug and allowing more free drug to be available (Spencer et al., 1993) to circulate and eventually accumulate in the glomeruli.

Older persons already are at risk for NSAID nephrotoxicity because of an age-related decline in renal mass and GFR (Sager & Bennett, 1992). The number and size of nephrons decreases, leading to a 20% decrease in kidney weight between the ages of 40 and 80 (Rebenson-Piano, 1989) with approximately half of the kidney's original nephrons no longer functioning (Ebersole & Hess, 1990; Palmieri, 1991). The glomerulus, that portion of the nephron responsible for filtering the blood, undergoes vascular changes beginning at age 40 and becoming sclerosed by age 80 (Ebersole & Hess, 1990).

These sclerotic changes are thought to contribute to decreased renal perfusion. Consequently, the effects of prostaglandin inhibition on the hemodynamics and excretory function of the kidneys can lead to either acute or chronic renal insufficiency Stillman & Schlesinger, 1990). Adverse kidney function from NSAIDs can occur with the approved nonprescription dosage and can occur in as little as a week's time ("How safe," 1991).

Salicylates, particularly aspirin, which is the prototype for NSAIDs, has been around since the late 180Os and is one of the most common overthe-counter (OTC) drugs used today. Americans spend an estimated $2 billion annually on aspirin (Matuschak, 1991). Although popular, aspirin is one of the top five drugs that causes drug-induced fatalities (McKenry & Salerno, 1992). The danger of aspirin toxicity has been recognized in children, but salicylates also can cause problems for the elderly. Less than 2 g of salicylates per day can increase serum uric acid levels (Swonger & Matejski, 1991). Salicylic acid (SA), the substance that is responsible for the anti-inflammatory and toxic effects of aspirin-like drugs, is dependent upon renal function for excretion, liver function for metabolism, and protein binding to prevent toxicity (Vivian & Goldberg, 1982). The reduced renal function that occurs with aging may decrease SA elimination and increase blood levels. Reduced liver blood flow and metabolism in the elderly contributes to a longer half-life and increased plasma levels of aspirin-like drugs in the elderly, compared with younger persons. Some elderly people have less albumin and other serum proteins for SA to bind with, resulting in a higher level of free SA (the pharmacologically active ingrethent), which also may contribute to toxicity (Vivian & Goldberg, 1982).

Vivian and Goldberg (1982) describe the various mechanisms that contribute to fluid and electrolyte loss due to salicylate toxicity. Salicylates stimulate the respiratory center causing hyperventilation resulting in CO2 and water loss by exhalation. They also inhibit the Krebs cycle so that glucose metabolism is impaired and the production of lactic and pyruvic acid is increased. Salicylate toxicity induces a hypermetabolic state that is manifested by sweating, which leads to sodium and water loss through the skin. The hypermetabolic state increases the demand for glucose. Increased gluconeogenesis and lipid metabolism occur as the body attempts to compensate for impaired glucose metabolism. As excess glucose and ketones accumulate in the body, they are excreted through the kidney carrying with them water, sodium, and potassium that could result in hyperglycemia, glucosuria, and ketonuria. In addition, salicylates often cause gastrointestinal irritation that can result in nausea and vomiting, leading to further fluid and electrolyte losses. All of these mechanisms contribute to dehydration, which decreases RBR.

Although acetaminophen does not contain aspirin, cases of acute renal failure due to unintentional overdose (Curry, Robinson, & Sughrue, 1982; Jeffrey & Lafferty, 1981) have been reported. Because older people are subject to acute or chronic pain associated with rheumatic and nonrheumatic conditions, they may ingest salicylates or acetaminophen more frequently than recommended in an attempt to control the pain - not recognizing the consequences that can occur. Likewise, they may be taking several medications that contain salicylates or acetaminophen without knowing it.

POTENTIAL DRUG INTERACTIONS

Drug-drug interactions have been recognized as a problem and drugs taken by the potential subjects interviewed for the research study were no exception. People aged 60 and older are considered at increased risk for nephrotoxicity due to the decline of GFR with age (Stillman & Schlesinger, 1990). Renal problems are intensified with the concurrent use of NSAIDs, diuretics, anti-hypertensives, and estiogen therapy.

NSAIDs compete directly with diuretics (thiazides, furosemide, and potassium-sparing), which are transported via the secretory system of the proximal tubules (McGiff & Quilley, 1988). This system serves as the major source of elimination for NSAIDs, but it also serves as the major route of access for diuretics to their active sites within the renal tubules. When this route is blocked by NSAIDs, diminished effectiveness of the diuretic agent may occur (McGiff & Quilley, 1988). Concomitant thiazide diuretic and estrogen therapy increases the client's vulnerability to potassium loss (Spencer et al., 1993), because both drugs contribute to sodium and water retention and potassium excretion. Thiazides also can enhance the antihypertensive action of other antihypertensive drugs (McKenry & Salerno, 1992).

NSAIDs, including aspirin, reduce the effectiveness of virtually all antihypertensive drugs (Dunn, 1988) through their sodium retention effects, which blunt the action of the anti-hypertensive drugs (McGiff & Quilley, 1988). Elimination of the vasodilatory effects of prostaglandin results in a substantial decline in RBF and GFR (McGiff & Quilley, 1988), which could reduce the desired effects of anti-hypertension drugs or their rate of excretion.

When two or more NSAIDs are taken concurrently, the side effects of the drugs are potentiated (Swonger & Matejski, 1991). Nurses who are aware of these interactive effects can contribute to the reduction or prevention of renal dysfunction.

NURSING IMPLICATIONS

The most significant action nurses can implement to prevent renal insufficiency in older adults is to encourage an increase in fluid intake. A minimum of 1500 mL to 2500 mL of water per day has been recommended if no contradicting conditions are present (Kee, 1992). Maintenance of an intake and output record on hospitalized patients will indicate early whether an imbalance or inadequacy is occurring. The subjects in our fluid balance study kept an intake and output record and many became aware of the inadequacy of their fluid intake.

Another step in preventing renal insufficiency in the older person is a thorough assessment of drug usage for at least the previous 3 months. Older persons may or may not know the names of prescribed drugs, but generally know why they are taking them. For example, "It's for my high blood pressure." By getting the person to describe the size and color of the pill, determination of the drug often can be made through the Physician's Desk Reference product display.

Careful assessment of OTC medication is needed to determine the specific drug, as well as its frequency of use. Because of the availability of OTCs without prescription, many people do not perceive these as "medicines" and do not volunteer the information when asked about drug therapy. It has been estimated that for every prescription drug, two OTC drugs are used by the elderly and that drug reactions are twice that of adults age 30 to 40 (Wade & Bowling, 1986). In addition to the NSAIDs, laxatives and antihistamines are used commonly by the elderly. Laxatives combined with diuretics or decreased fluid intake potentiate the risk of electrolyte imbalance or drug toxicity (Spencer et al., 1993). AntUiistamines can cause urinary retention, especially in males, through their anticholinergic effects (Swonger & Matejski, 1991).

Physical assessment of the individual may not reveal any pertinent fluid problems, therefore careful questioning is needed to ascertain early signs and symptoms of renal dysfunction. Questions should be asked about alterations in urinary patterns, such as polyuria or oliguria, headaches, dyspnea, vague flank pain (Garfinkel et al., 1988), orthostatic hypotension, edema, hypothermia, and fatigue or general slowdown (Parrel, 1990). All of these symptoms can occur as a result of fluid imbalance and the accumulation of waste products.

SUMMARY

Older people are at particular risk for renal insufficiency because of the natural changes that occur in the body as a result of aging. Drugs - both prescription and OTC - used to treat common conditions or symptoms in the elderly can increase this risk because of their effects on the kidneys. Nurses should encourage older persons to increase their fluid intake. Through the use of both health history and drug history, nurses are in a position to detect early symptoms of kidney changes. In addition, nurses can do much to teach patients about the potential hazards associated with OTC drug usage.

REFERENCES

  • Curry, R-, Jr., Robinson, J., & Sughrue, M. (1982). Acute renal failure after acetaminophen ingestion. The fournal of the American Medical Association, 247, 1012-1014.
  • Drug information for the health care professional (Vol. IA, llth ed.). Rockford, MD: U.S. Pharmacopeial Convention Inc., 1991.
  • Dunn, MJ. (1988). Interaction of nonsteroidal anti-inflammatory drugs and anti-hypertensives. The Journal of the American Medical Association, 260, 851.
  • Ebeisole, P., & Hess, P. (1990). Toward healthy aging: Human needs and nursing response. St Louis, MO: C.V. Mosby.
  • Farrel, J. (1990). Nursing care of the older person. Philadelphia: J.B. Lippincort.
  • Garfinkel, H-, Porter, G.A., & Whelton A. (1988). Renal failure: Are drugs the cause? Patient Care, 22, 71-87.
  • How safe is ibuprofen? (1991). Patient Care, 25, 138-139.
  • Jeffrey, W., & Lafferty, W. (1981). Acute renal failure after acetaminophen overdose: Report of two cases. American journal of Hospital Pharmacy, 38, 1355-1358.
  • Kee, C.C. (1992). Age-related changes in the renal system: Causes, consequences, and nursing implications. Geriatric Nursing, 13, 80-83.
  • Mathieson, A. (1986). Old people and drugs. Nursing Times, 82, 22-24.
  • Matuschak, G.M. (1991). Pseudosepsis syndrome, multiple-system organ failure and chronic salicylate intoxication. Chest, 100, 1188-1189.
  • McCance, K.L., & Huether, S.E. (1990). Pathophysiology: The biologic basis for disease in adults and children. St. Louis, MO: C.V. Mosby.
  • McGiff, J.C., & Quilley, CR (1988). Interactions of nonsteroid anti-inflammatory drugs and anti-hypertensives. The Journal of the American Medical Association, 260, 850-851.
  • McKenry, L.M., & Salerno, E. (1992). Mostn/'s pharmacology in nursing (18th ed.). St Louis, MO: C.V. Mosby.
  • Palmieri, D.T. (1991). Clearing up the confusion: Adverse effects of medications in the elderly. Journal of Gerontological Nursing, 17, 32-35.
  • Rebenson-Piano, M. (1989). The physiologic changes that occur with aging. Critical Care in Nursing Quarterly, 12, 1-14.
  • Rolls, B.J., & Phillips, P.A. (1990). Aging and disturbances of thirst balance. Nutrition Reviews, 48, 379-381.
  • Sager, B.S., & Bennett, R.M. (1992). Individualizing the risk/benefit ratio of NSAIDs in older patients. Gerialrics, 47, 24-31.
  • Spencer, R.T., Nichols, L. W., Lipkin, G.B., Henderson, H.S., & West, EM. (1993). Clinical pharmacology and nursing management (4th ed). Philadelphia: J.B. Lippincott.
  • Stillman, M.T., & Schlesinger, P.A. (1990). Nonsteroidal anti-inflammatory drug nephrotoxicity. Archives of Internal Medicine, 150, 268-270.
  • Swonger, A.K., & Matejski, M.P. (1991). Nursing pharmacology: An integrated approach to drug therapy and nursing practice (2nd ed.). Philadelphia: J.B. Lippincott.
  • Vivian, A.S., & Goldberg, LB. (1982). Recognizing chronic salicylate intoxication in the elderly. Geriatrics, 37, 91-97.
  • Wade, B., & Bowling, A. (1986). Appropriate use of drugs by elderly people. Journal of Advances in Nursing, 11, 47-55.

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