Renal disease in the elderly

Renal disease in the elderly

Distinctive disorders, tailored treatments

Hassan Ali, MDVOL 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 kidneyA 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 disordersAt 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 lossBurns

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 intakeAltered 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 disordersTotal 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 drugsAngiotensin-converting enzyme inhibitorsBeta blockersCyclosporin (Neoral, Sandimmune)HeparinNonsteroidal anti-inflammatory drugsPotassium chloridePotassium-sparing diuretics

Gastrointestinal bleedingHyporeninemic hypoaldosteronismPotassium shiftHyperglycemiaMetabolic acidosis

PseudohyperkalemiaLeukocytosisThrombocytosis

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 depletionDiarrheaDiuretic useMagnesium deficiencyNasogastric drainageRenal tubular acidosisVomiting

Potassium shiftAlkalemiaBeta-agonist useHypothermiaInsulin therapyTreatment of megaloblastic anemia

PseudohypokalemiaOtherPostobstructive diuresisRecovery phase of acute tubular necrosis

Other electrolyte disturbancesHypercalcemia 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 diseaseGlomerular 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. Pauci-immune 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 diseasesAmong 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 diseaseAbdominal bruitArteriosclerotic disease elsewhereFlash pulmonary edemaLate-onset hypertensionLesions amenable to angioplasty or revascularizationTobacco usePositive results on captopril (Capoten) testRenal artery stenosis demonstrable on angiographyRenal failure with ACE inhibition

Ischemic nephropathyArteriosclerotic disease elsewhereBilateral renal artery stenosisBilateral small kidneysRenal failure with ACE inhibitionRenal function possibly improved with angioplasty or revascularization

Cholesterol embolization syndromeAccelerated hypertensionAcute renal failure after arteriography and use of warfarin sodium (Coumadin, Panwarfin, Sofarin)Back painEosinophiluriaFeverIrreversible renal failureLivedo reticularis of lower extremities

Radiocontrast nephropathyEarly onset of acute renal failure (within 24-72 hr)May be controllable with adequate hydration before and after studyMay be preventable with use of dihydropyridine calcium channel blocker before studyOccurs 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, angiotensin-converting 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 elderlyThe 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

DecreasedCreatinine clearanceHepatic blood flowLean muscle massRenal blood flowSerum albumin levelTotal body water

IncreasedTotal 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.

ConclusionPhysicians 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.

References

1. Piraino AJ. Managing medication in the elderly. Hosp Pract (Off Ed) 1995;30(6):59-64

2. Lubran MM. Renal function in the elderly. Ann Clin Lab Sci 1995;25(2):122-33

3. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16(1):31-41

4. Wedr AB. The renally compromised older hypertensive: therapeutic considerations. Geriatrics 1991;46(2):36-46

5. Lindeman RD. Overview: renal physiology and pathophysiology of aging. Am J Kidney Dis 1990;16(4):275-82

6. Luft FC, Weinberger MH, Fineberg NS, et al. Effects of age on renal sodium homeostasis and its relevance to sodium sensitivity. Am J Med 1987;82(1B):9-15

7. Rowe JW, Shock NW, DeFronzo RA. The influence of age on the renal response to water deprivation in man. Nephron 1976;17(4):270-8

8. Miller PD, Krebs RA, Neal BJ, et al. Hypodipsia in geriatric patients. Am J Med 1982;73(3):354-6

9. Berl T. Treating hyponatremia: damned if we do and damned if we don't. (Clinical Conference) Kidney Int 1990;37(3):1006-18

10. Mimran A, Ribstein J, Jover B. Aging and sodium homeostasis. Kidney Int Suppl 1992;37:107-13S

11. Minaker KL, Rowe JW. Potassium homeostasis during hyperinsulinemia: effect of insulin level, beta-blockade, and age. Am J Physiol 1982;242(6):373-7E

12. Grero PS, Hodkinson HM. Hypercalcaemia in elderly hospital in-patients: value of discriminant analysis in differential diagnosis. Age Ageing 1977;6(1):14-20

13. Martin BJ, Black J, McLelland AS. Hypomagnesaemia in elderly hospital admissions: a study of clinical significance. Q J Med 1991;78(286):177-84

14. Ponticelli C, Passerini P, Como G, et al. Primary nephrotic syndrome in the elderly. Contrib Nephrol 1993;105:33-7

15. Bolton WK, Vaughan ED Jr. A comparative study of open surgical and percutaneous renal biopsies. J Urol 1977;117(6):696-8

16. Kyle R, Bayrd E. Amyloidosis: review of 236 cases. Medicine 1975;54:271-99

17. Falk RJ, Hogan S, Carey TS, et al. Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. Ann Intern Med 1990;113(9):656-63

18. Schieppati A, Mosconi L, Perna A, et al. Prognosis of untreated patients with idiopathic membranous nephropathy. N Engl J Med 1993;329(2):85-9

19. Korbet SM, Schwartz MM, Lewis EJ. Minimal-change glomerulopathy of adulthood. Am J Nephrol 1988;8(4):291-7

20. Bakris GL, Kern SR. Renal dysfunction resulting from NSAIDs. Am Fam Physician 1989;40(4):199-204

21. Tilley WS, Harston WE, Siami G, et al. Renal failure due to cholesterol emboli following PTCA. Am Heart J 1985;110(6):1301-2

22. Vivas CA, Hickey DP, Jordan ML, et al. Renal transplantation in patients 65 years old or older. J Urol 1992;147(4):990-3

23. Henrich WL. Dialysis considerations in the elderly patient. Am J Kidney Dis 1990;16(4):339-41

24. Williams L, Lowenthal DT. Drug therapy in the elderly. South Med J 1992;85(2):127-31

25. Bakris GL, Talbert R. Drug dosing in patients with renal insufficiency: a simplified approach. Postgrad Med 1993;94(8):153-64