Renal disease in the elderly

Distinctive disorders, tailored treatments

Hassan Ali, MD
VOL 100 / NO 6 / DECEMBER 1996 / POSTGRADUATE MEDICINE

This is the first of three articles on renal problems

Preview: Many 40-year-olds would be surprised to learn that, as far as their kidneys are
concerned, the aging process is already under way. The decreased blood flow and
diminished regulatory capacity that come with age are not necessarily problems.
However, when another factor is added (eg, fluid loss from diarrhea, depressed thirst
mechanism from sedative use), serious fluid and electrolyte imbalances can result. Dr Ali
discusses renal disorders for which older people are at risk, and he provides safety tips on
drug choices and doses.

Elderly patients, commonly defined as those aged 65 and older, make up a large portion
of many practices, especially primary care practices. Age has many effects on the basic
structure and function of the kidneys, which may contribute to fluid and electrolyte
problems and glomerular disease. All these age-related changes must be considered in
prescribing drugs to elderly patients, who receive 30% of prescriptions and consume 40%
of over-the-counter drugs (1).

Age and the kidney

A progressive loss of nephron units with age has been well documented; between ages 40
and 80, the kidney loses about 20% of its mass. This natural involutionary process is
represented histologically by a decrease in the renal vasculature (especially in the renal
cortex), an increase in the number of obsolescent glomeruli, tubular atrophy and
dilatation, and interstitial scarring. In spite of compensatory hyperfiltration and
hyperfunction by the remaining nephron units, the glomerular filtration rate (GFR)
declines with age, beginning about age 35 to 40 (2). A yearly decline of about 0.8 to 1
mL/min continues thereafter. However, the serum creatinine level (an index of skeletal
muscle mass) remains within the normal range because of decreased muscle mass with
age.
Creatinine clearance (in mL/min) in men may be determined by using the following
Cockcroft-Gault formula; in women, multiply the result by 0.85 (3):

(140 - age) x body weight (kg)

____________________________
72 x serum creatinine (mg/dL)

As can be seen, a serum creatinine level of 1.5 mg/dL in two men who both weigh 81 kg
(180 lb) represents creatinine clearance of about 45 mL/min if the man is 80 years old but
90 mL/min if the man is 20 years old.
In general, tubular function is also altered in elderly persons (4): The kidney's ability to
maximally concentrate urine after water deprivation is decreased, and its ability to
excrete maximally diluted urine after water loading is lost. This tubular dysfunction is
accentuated during the night, which helps explain the common symptom of nocturnal
polyuria. Because they are closely linked to water disorders, sodium disorders are
common in the elderly (5). Also, aging kidneys have problems with distal tubular
acidification, which contributes to acid-base disturbances in elderly patients.

Sodium and water disorders

At least 10% to 25% of electrolyte disturbances in institutionalized elderly patients are
caused by hyponatremia and hypernatremia (which, simply put, reflect water excess and
relative water deficit) (6). Volume status is difficult to determine in elderly persons
because of altered skin turgor, decreased baroreceptor reflexes, and mouth dryness due to
mouth breathing and anticholinergic use. Also, volume status is both directly and
indirectly related to water metabolism. As mentioned, in older patients, the kidneys'
ability to achieve maximal urine dilution and concentration is lost, so hyponatremia or
hypernatremia may result from water loading or deprivation. These changes in dilution
and concentration are due mainly to relative insensitivity of antidiuretic hormone (ADH)
in the cortical collecting ducts.
Hyponatremia is usually categorized according to volume status as hypervolemic,
euvolemic, or hypovolemic. Hypervolemic hyponatremia is usually caused by an increase
in total body water level and is found mainly in three conditions: congestive heart failure,
nephrotic syndrome, and hepatic cirrhosis. In these conditions, levels of nonosmotically
secreted ADH are increased, which results in increased thirst and decreased water loss in
the distal tubule and cortical collecting duct. Euvolemic hyponatremia is often found in
the syndrome of inappropriate antidiuretic hormone, which may accompany pneumonia,
small-cell lung cancer, or head injury. It is also found in patients with polydipsia, which
may have an organic cause (eg, use of certain drugs, such as haloperidol [Haldol]) or a
psychogenic cause. Hypovolemic hyponatremia is due to a relative decrease in total body
sodium level and is found with diuretic use, presence of interstitial nephritis, and
excessive sweating.
Hypernatremia in the elderly is usually due to water losses (table 1) (7), rarely to
excessive sodium intake. Older patients often have a poorly functioning thirst mechanism
(8), or they may be bedridden and unable to get to a water source.

Table 1. Causes of hypernatremia in elderly patients

Increased fluid loss
Burns
Excessive sweating (eg, from lack of air conditioning during heat wave)
Excessive urinary loss (diabetes mellitus, diabetes insipidus, use of
diuretic or lithium, hypercalcemia, Addison's disease, postobstructive
diuresis)
Gastrointestinal loss (vomiting, diarrhea, use of laxatives or bowel
preparations, colon surgery, hypertonic enteral feeding)
Infection (especially one producing febrile illness)
Decreased fluid intake
Altered mental status (effects of drug, stroke, hospitalization)
Altered thirst mechanism
Fluid restriction (eg, preceding surgical procedure)
Gastrointestinal disorder (dysphagia, ischemic bowel)
Limited access to water (eg, patient bedridden or restrained)

Management of dysnatremia depends on the causative processes involved. Detailed

history taking (eg, recent use of diuretics or laxatives), thorough physical examination in
a well-lit room, and completion of pertinent laboratory tests (eg, serum and urine
osmolality, urine electrolytes) are essential to proper management (9). The following tips
may serve as guidelines:

Establish whether the serum sodium level is too low (< 130 mEq/L) or too high (>
145 mEq/L).
Determine whether the condition developed suddenly or insidiously.
Consider whether the patient has a "reset" osmostat (ie, osmoreceptors can
"sense" osmolality and turn off ADH secretion at a level lower than 285 to 288
mOsm/kg).
Note whether the patient has symptoms.
Carefully assess effective arterial blood volume, using hemodynamic monitors if
necessary.
Remember that total body water level decreases with age and is usually 40% to
50% of total body weight in patients over age 65.
Correct dysnatremia slowly; it is safer to undercorrect than overcorrect.

Measure serum electrolyte levels often (eg, every 6 hours) until the desired goal is
achieved (10). Formulas for assessing water excess and deficit serve as guidelines
only.

Potassium disorders
Total body potassium level declines with age, more so in women than in men. The
decline is thought to be due to the decrease in muscle mass that accompanies aging (11).
Surprisingly, hyperkalemia (table 2) is more common than hypokalemia in elderly
persons, due mainly to decreased GFR, increased use of drugs that alter potassium
metabolism, renal acidification defects, and hyporeninemic hypoaldosteronism.
Hypokalemia (table 3) is most often due to the three Ds: drugs (beta agonists, insulin),
diuretics (loop, thiazide), and diarrhea (laxative use, organic causes).
Table 2. Causes of hyperkalemia in elderly patients
Effect of drugs
Angiotensin-converting enzyme inhibitors
Beta blockers
Cyclosporin (Neoral, Sandimmune)
Heparin
Nonsteroidal anti-inflammatory drugs
Potassium chloride
Potassium-sparing diuretics
Gastrointestinal bleeding
Hyporeninemic hypoaldosteronism
Potassium shift
Hyperglycemia
Metabolic acidosis
Pseudohyperkalemia
Leukocytosis
Thrombocytosis
Renal failure

Management of dyskalemia in elderly patients is similar to that in younger adults.

However, particular attention must be paid to the following factors:

Use of offending drugs (eg, diuretics)

Gastrointestinal bleeding (a possible cause of hyperkalemia)
Acid-base balance
Magnesium level

Potassium losses
Serum electrolyte levels

Table 3. Causes of hypokalemia in elderly patients

Potassium depletion
Diarrhea
Diuretic use
Magnesium deficiency
Nasogastric drainage
Renal tubular acidosis
Vomiting
Potassium shift
Alkalemia
Beta-agonist use
Hypothermia
Insulin therapy
Treatment of megaloblastic anemia
Pseudohypokalemia
Other
Postobstructive diuresis
Recovery phase of acute tubular necrosis

Other electrolyte disturbances

Hypercalcemia is found in 2% to 3% of institutionalized elderly patients (12). Causes are
multifactorial and include malignant tumor, hyperparathyroidism, immobilization, and
thiazide diuretic use. Although clinical manifestations of hypercalcemia are similar in
elderly and younger patients, the elderly experience more neuromuscular disturbances
and neuropsychiatric dysfunction (eg, delirium, decreased tolerance to effort, weakness).
Hypocalcemia is less common than hypercalcemia and is seen mainly in patients with
chronic renal failure, chronic malabsorption, and severe malnutrition.
Hypomagnesemia may be present in as many as 7% to 10% of elderly patients admitted
to the hospital (13). It is usually due to poor nutrition and diuretic and laxative use. Any
patient with hypokalemia and hypocalcemia should be evaluated for suspected
hypomagnesemia. Treatment is the same in younger and elderly patients and usually
involves intravenous magnesium replacement if the level is less than 1.1 mg/dL or oral
replacement if the level is between 1.2 and 1.6 mg/dL.
Hypermagnesemia is less common than hypomagnesemia and is found mainly in patients
who are taking antacids that contain magnesium or who have chronic renal failure.

Acid-base disturbances in the elderly are common because of reduced efficiency of

compensatory mechanisms, defects in distal tubular acidification, and increased
frequency of diseases that can cause such disturbances. Causes are similar to those found
in younger patients.

Glomerular disease
Glomerular disease in the elderly is not qualitatively different from the disease in younger
adult patients (14). Bolton and Vaughan (15) compared renal biopsy results in patients
aged 60 and older with results in younger patients, and they found little histologic
difference between the two groups. In elderly patients, renal biopsy is recommended if
unexplained rapid deterioration of renal function, nephrotic syndrome, or nephritic
syndrome (ie, hypertension, proteinuria, hematuria, and red blood cell casts) is present.
The incidence of certain glomerular diseases is higher in elderly persons than in younger
adults. Among such diseases are amyloidosis, multiple myeloma, crescentic
glomerulonephritis, and nephrotic syndrome.
Amyloidosis--In a review by Kyle and Bayrd (16) of 236 patients with amyloidosis, 148
(63%) were over 60 years of age. Most of the patients died within 3 years of diagnosis of
this progressive disease.
Multiple myeloma--Any elderly patient who presents with renal insufficiency,
hypercalcemia, and an elevated total protein level must be aggressively evaluated for
multiple myeloma. The urine dipstick test detects only the presence of albumin, so
sulfosalicylic acid testing of a urine specimen and serum and urine protein
electrophoresis must also be performed.
Crescentic glomerulonephritis--The pauci-immune (ie, no immune deposits) variety of
this disorder is far more common in patients over age 65 than in younger patients. Pauciimmune glomerulonephritis presents as vasculitis. About 80% of patients have serum
antineutrophil cytoplasm autoantibodies (ANCA); the two most common lesions are
Wegener's granulomatosis (mainly C-ANCA) and microscopic polyarteritis nodosa
(mainly P-ANCA) (17). The value of renal biopsy in diagnosis of this disorder in the
elderly cannot be overemphasized.
Nephrotic syndrome--The common causes of this glomerular disorder in the elderly are
membranous nephropathy and minimal change disease.
Membranous lesions are more common in elderly persons than in younger ones, and the
prognosis is worse in the elderly (18). The correlation between membranous nephropathy
and presence of malignant tumors in older patients is variable, ranging from 1.4% to
10.9%. Colon and lung tumors, and possibly lymphomas, are most common. Available
data do not suggest that an exhaustive search for a tumor is necessary, but a chest
roentgenogram, a stool guaiac test, and an air-contrast barium enema should be
performed as part of screening.

Minimal change disease occurs with similar frequency in elderly and younger patients,
although accompanying acute renal failure occurs more often in older patients. There is
an association between minimal change disease and lymphoproliferative disorders (19).
Patients do not present with the classic hypersensitivity syndrome (rash, fever,
eosinophiluria) that is seen with antibiotic-induced allergic interstitial nephritis (20).
Long-term use of nonsteroidal antiinflammatory drugs, some of the most commonly used
agents among the elderly, has been associated with minimal change disease. A less
common cause may be lithium use.

Other renal diseases

Among other renal diseases found more commonly in elderly patients than in their
younger counterparts are atheroembolic disease and nephrotoxicity.
Atheroembolic disease--The increased propensity for atheromatous plaques in elderly
patients accounts for the higher incidence of atheroembolic disease in older populations
(21). The disease can present in any of four scenarios, summarized in table 4:
renovascular disease, ischemic nephropathy, cholesterol embolization syndrome, or
radiocontrast nephropathy.
Table 4. Presentations and features of renal atheroembolic disease in elderly patients
Renovascular disease
Abdominal bruit
Arteriosclerotic disease elsewhere
Flash pulmonary edema
Late-onset hypertension
Lesions amenable to angioplasty or revascularization
Tobacco use
Positive results on captopril (Capoten) test
Renal artery stenosis demonstrable on angiography
Renal failure with ACE inhibition
Ischemic nephropathy
Arteriosclerotic disease elsewhere
Bilateral renal artery stenosis
Bilateral small kidneys
Renal failure with ACE inhibition
Renal function possibly improved with angioplasty or revascularization
Cholesterol embolization syndrome
Accelerated hypertension
Acute renal failure after arteriography and use of warfarin sodium (Coumadin, Panwarfin,
Sofarin)
Back pain
Eosinophiluria
Fever
Irreversible renal failure

Livedo reticularis of lower extremities

Radiocontrast nephropathy
Early onset of acute renal failure (within 24-72 hr)
May be controllable with adequate hydration before and after study
May be preventable with use of dihydropyridine calcium channel blocker before study
Occurs most often in elderly with chronic renal insufficiency
ACE, angiotensin-converting enzyme.

Nephrotoxicity--Because of their decreased GFR and heightened sensitivity to

nephrotoxins, the elderly have a higher incidence of nephrotoxicity. Agents usually
associated with this renal insult are nonsteroidal anti-inflammatory drugs, angiotensinconverting enzyme inhibitors, aminoglycosides, and radiocontrast material.
Options for renal replacement therapy (ie, hemodialysis, peritoneal dialysis, renal
transplantation) are the same in the elderly as in younger patients (22), with hemodialysis
being the most common choice. Among new enrollees in end-stage renal disease
programs, 42% are aged 65 or older, and the most common causes of the renal failure are
diabetes and hypertension. Survival is markedly lower in elderly patients than in younger
ones receiving dialysis (23).

Prescribing in the elderly

The term "pharmacokinetics" refers to absorption, distribution, metabolism, and
elimination of drugs and their metabolites. Table 5 summarizes physiologic changes in
the elderly that affect these processes.
Table 5. Physiologic changes in the elderly that affect pharmacokinetics
Decreased
Creatinine clearance
Hepatic blood flow
Lean muscle mass
Renal blood flow
Serum albumin level
Total body water
Increased
Total body fat

The rate and extent of drug absorption are not severely affected by age (24). However,
some commonly prescribed drugs (eg, anticholinergics, laxatives, calcium channel
blockers, agents used to decrease gastric emptying) affect gastrointestinal motility. For

example, hepatic function is decreased in the elderly, so drugs that are mainly
transformed into active metabolites by the liver may have limited bioavailability after
absorption.
Drug distribution is also affected by the aging process (25). Total body water decreases
and total body fat levels increase with age. Thus, the volume of distribution is reduced for
water-soluble drugs (eg, digoxin [Lanoxicaps, Lanoxin], cimetidine [Tagamet], ethanol),
resulting in increased plasma concentrations. The volume of distribution is increased for
lipid-soluble drugs (eg, diazepam [Valium, Valrelease, Zetran], chlordiazepoxide
[Librium, Mitram]), resulting in a prolonged half-life. Serum albumin level is decreased
in the elderly, so for protein-bound drugs (eg, propranolol hydrochloride [Inderal]), the
unbound moiety is increased and drug action is prolonged and enhanced.
Hepatic metabolism and renal excretion are the main routes of drug removal from the
body. Agerelated decreases in renal function result in prolonged drug half-life, so doses
should be adjusted to the patient's renal function as determined by bedside assessment of
creatinine clearance.

Conclusion
Physicians who treat elderly patients must be aware of the declines in renal function that
accompany the aging process. Glomerular filtration rate decreases steadily, starting in
middle age. Muscle mass also decreases with age, so an apparently low serum creatinine
level may translate into creatinine clearance in the normal range in an elderly person.
Evaluation of elderly patients should include careful consideration of possible fluid and
electrolyte disturbances and of prescription and over-the-counter medications that may be
contributing to the disturbances. Physiologic changes of aging also affect
pharmacokinetic processes. Therefore, before a drug is prescribed, consideration must be
given to the available volume of distribution, metabolism and elimination capabilities,
and other functional factors that characterize elderly patients.

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