Laurence H. Beck MD
ACUTE RENAL FAILURE
ESSENTIALS OF DIAGNOSIS
Acute renal failure (ARF) is more common in the elderly than in younger individuals with similar precipitating factors. Serum creatinine rises 1.0–1.5 mg/dL/day in typical ARF. Recovery of renal function is less complete and mortality is higher in the elderly. Because glomerular filtration rate (GFR) normally falls progressively with aging, the aged kidney has less functional reserve, so that fluid and electrolyte complications occur earlier in the course of ARF. From a management standpoint, it is crucial to distinguish among prerenal, intrinsic renal, and postrenal failure.
Avoidance of volume depletion and judicious use of potentially nephrotoxic drugs are the mainstays of prevention, particularly in acutely ill or hospitalized elderly patients.
Symptoms of early ARF are nonspecific and usually reflect the underlying etiological condition (Table 25-1). In hypovolemic ARF, postural dizziness or hypotension is common. Conversely, signs of congestive heart failure (CHF) may predominate. Later in the course of ARF, uremic symptoms, including nausea, vomiting, clouded sensorium, and asterixis, may develop. Because of platelet dysfunction, bleeding or oozing occurs more readily at sites of trauma. Rhythm disturbances may occur if electrolyte abnormalities (especially hyperkalemia) develop. Tachypnea and abdominal pain may be the result of metabolic acidosis. Oliguria (< 500 mL urine/24 h) is common in hypotensive or septic ARF. With nephrotoxins, nonoliguric renal failure is more common.
Stepwise increases in blood urea nitrogen (BUN) and serum creatinine concentration are typical. In prerenal and postrenal states, the BUN is increased disproportional to the creatinine, so that the BUN-creatinine ratio is usually > 20:1. Because of the decreased concentrating ability and sodium reabsorptive capacity of the aged kidney, urinary indexes (such as the urinary sodium concentration [UNa], urinary osmolality [UOsm], and fractional excretion of sodium [FENa]) are less useful in the elderly in distinguishing between a prerenal state and intrinsic renal failure.
Hyperkalemia is common, especially in the oliguric patient. If ARF lasts more than 2–3 days, metabolic acidosis, with low plasma bicarbonate concentration, is the rule. Early on, it is usually a hyperchloremic acidosis, but in later stages an anion gap metabolic acidosis ensues.
Urinalysis shows little abnormality in prerenal azotemia. In typical ATN, the sediment contains “dirty-brown” granular casts. If significant proteinuria is present in ARF, suspect acute glomerulonephritis (GN; see later discussion).
The most important diagnostic decision is to determine whether the ARF is prerenal, postrenal, or intrinsic renal failure. The most useful diagnostic tools are the physical examination and the renal sonogram. Physical examination should determine whether there are signs of hypovolemia (postural hypotension, tachycardia, dry mucous membranes, poor skin turgor) or heart failure, the principal causes of prerenal azotemia. If hypovolemia is present, a volume challenge with intravenous normal saline solution should be administered to look for reversal of oliguria and azotemia. If the patient is normovolemic at onset, a renal sonogram must be done to rule out urinary tract obstruction. The finding of hydronephrosis in the presence of ARF demands urgent
decompression with a Foley catheter or a nephrostomy. When these tests indicate intrinsic ARF and the urinalysis does not show significant proteinuria, ATN is the most likely diagnosis. One must then carefully review the history and medical record to determine the likely cause, of which there are many (see Table 25-1).
Table 25-1. Causes of acute renal failure.
ATN occurs as a result of prolonged renal ischemia or exposure to nephrotoxins. Ischemia can occur with true volume depletion (bleeding, diarrhea, diuretic-induced hypovolemia) or from decreased cardiac output (CHF, myocardial infarction, sepsis). The postsurgical setting is a common milieu for ATN in the elderly as a result of intraoperative hypotension, myocardial ischemia or arrhythmia, or intraoperative fluid loss.
Nephrotoxic drugs, especially aminoglycoside antibiotics, are more likely to produce ATN in the elderly because of decreased rate of clearance, resulting in toxic levels. Other medications implicated in ARF in the elderly are angiotensin-converting enzyme (ACE) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs). These cause functional ARF as a result of alterations in renal blood flow, especially in elderly individuals with poor underlying renal perfusion. This latter form of ARF is reversible if the drug is withdrawn.
Radioiodinated contrast-induced ATN is an important cause of ARF in the elderly. Risk factors include advanced age, diabetes mellitus, high or repeated dye loads, and preexisting renal insufficiency (with serum creatinine > 2.0 mg/dL). Volume expansion with saline solution and pretreatment with acetyl cysteine (Mucomyst) reduce the incidence of contrast-induced ATN.
Volume depletion causes a disproportionate increase in BUN compared with creatinine (BUN-creatinine ratio > 20:1). The same is true of CHF. Correction of the hemodynamic instability will restore renal perfusion and correct the azotemia. However, if the hypovolemia or CHF is left untreated, ischemic ATN may result.
If there is any possibility of urinary tract obstruction as a cause of ARF, a catheter should be inserted into the urinary bladder (to relieve outlet obstruction) and a renal ultrasonogram obtained to look for hydronephrosis. About 10–15% of cases of ARF in the elderly are due to obstruction. Oliguria or anuria is common, but some patients with postrenal failure have normal or increased urinary output resulting from nephrogenic diabetes insipidus caused by the elevated hydrostatic pressure from the obstruction.
Hyperkalemia is most likely in oliguric patients who are postsurgical or have deep tissue infections, with resultant release of large amounts of intracellular potassium into the circulation.
Volume overload can be prevented by meticulous attention to daily fluid intake and output, so that intake volume should not exceed the sum of urinary and gastrointestinal
output (plus 500–700 mL/day insensible loss), unless hypovolemia is present.
Rapid accumulation of nitrogenous waste can cause mental confusion, lethargy, and coma, especially in the elderly individual with underlying central nervous system (CNS) disease. Asterixis is an early sign of impending encephalopathy and is usually an indicator for dialysis.
Mortality in ATN remains about 50%, as it has for decades. Risk factors for survival include younger age, a cause other than ischemia or sepsis, and nonoliguric ATN. In surviving patients, recovery of renal function may not be complete, particularly in elderly patients with underlying vascular disease. Diabetic patients with dye-induced ATN who are oliguric and whose serum creatinine rises to 5 mg/dL or higher rarely recover function and usually progress to end-stage renal disease (ESRD).
Clark B: Biology of renal aging in humans. Adv Renal Repl Ther 2000;7:11. [PMID: 10672914]
ESSENTIALS OF DIAGNOSIS
Glomerular disease in the elderly usually presents as a nephritic syndrome, often with progressive renal failure, or as nephrotic syndrome. The nephritic patient has an abrupt onset of hypertension, hematuria, decreased GFR, and fluid retention. The nephrotic patient usually has a more gradual onset, with development of peripheral edema and hypoalbuminemia.
The causes of these conditions are generally unknown, except in certain systemic diseases, such as diabetic nephropathy. Renal complications, including proteinuria, nephrotic syndrome, and renal insufficiency, can be prevented or delayed by tight control of plasma glucose and of hypertension.
In the elderly, the onset of nephritic syndrome is often heralded by a sudden increase in blood pressure, development of edema, or symptoms of CHF. Oliguria is common in the nephritic syndrome.
The nephritic patient may have “smoky” urine or gross hematuria. Proteinuria is present, and the urinary sediment shows red blood cell casts. BUN and creatinine concentrations increase progressively, often in a pattern similar to ATN. In nephrotic syndrome, urinalysis shows heavy proteinuria, 24-h urinary protein excretion is > 3.5 g, and hypoalbuminemia and hypercholesterolemia are present. Urinalysis is often “bland,” with few cellular elements. Fat-laden tubular cells, which produce characteristic “Maltese crosses” under polarized light microscopy, are often seen in the urinary sediment.
Most patients with a nephritic or nephrotic syndrome should be referred to a nephrologist for consultation and comanagement.
Postinfectious GN is less common in elderly than in younger patients. The presentation is similar to poststreptococcal GN in younger individuals, although signs of fluid overload and CHF are more common. The most common clinicopathological diagnosis in elderly patients with a nephritic presentation is rapidly progressive GN (RPGN). Renal biopsy of such patients shows extensive epithelia crescent formation. About 50% of these patients are positive for antineutrophil cytoplasmic antibodies (ANCAs). The pattern of staining can distinguish between “pauci-immune” RPGN (perinuclear pattern: p-ANCA) or Wegener's granulomatosis (cytoplasmic pattern: c-ANCA). A smaller proportion of patients have serum antiglomerular basement membrane antibodies typical of Goodpasture's syndrome. Another cause of RPGN in the elderly is hepatitis C-associated cryoglobulinemia. These patients often have cutaneous vasculitis; serum complement is usually depressed.
The incidence of nephrotic syndrome does not change with aging, but the underlying diagnoses are skewed toward
certain diseases. The most common diagnoses from biopsy series of elderly patients are membranous GN (35–40%), amyloidosis (10–12%), and minimal change disease (11%). Underrepresented in biopsy series is diabetic glomerulosclerosis, because this diagnosis is often presumed, without biopsy, in the patient with long-standing diabetes and clinical evidence of nephropathy. There is little to differentiate clinically between the different types of primary glomerular diseases. Unless there are serious contraindications, renal biopsy should be sought in the elderly patient with nephrotic syndrome because treatment protocols differ for the various diseases.
The principal complications in elderly patients with nephritic presentation are hemodynamic: hypertension, volume overload, and CHF. Patients with RPGN may experience uremic symptoms within weeks or months of onset. Nephrotic patients virtually always have peripheral edema, but some have anasarca, with ascites or pleural effusions. Hypercoagulability results from loss of antithrombin III and other proteins in the urine. The incidence of deep venous thrombosis and of renal vein thrombosis is markedly increased as a consequence.
Treatment of primary glomerulopathies should be coordinated with a nephrologist. Management of the most common diagnosis, membranous GN, is controversial. Prednisone with or without chlorambucil has shown some benefit in populations other than the elderly. However, the potential complications of immunosuppressive therapy are increased in the elderly patient. There is no specific therapy for amyloidosis.
Nonspecific management is important. Hypertension should be treated aggressively to slow progression of renal insufficiency. Diuretics must be used with caution, particularly in nephrotic patients, who are susceptible to intravascular volume depletion and ARF.
Most elderly patients with RPGN and diabetic GN progress inexorably to ESRD. Membranous GN is characterized by occasional spontaneous remission, and immunosuppressive treatment may result in stabilization or reversal.
Madaio MP, Harrington JT: The diagnosis of glomerular diseases. Acute glomerulonephritis and the nephrotic syndrome. Arch Intern Med 2001;161:25. [PMID: 11146695]
ESSENTIALS OF DIAGNOSIS
Renovascular disease increases in prevalence with increasing age. Risk factors include a history of atherosclerosis, diabetes mellitus, tobacco use, and hypertension. Atherosclerotic narrowing of 1 or both renal arteries can present with hypertension and progressive renal insufficiency or without clinical manifestation. Clues to the diagnosis include onset of hypertension after age 50, refractory hypertension in the elderly, and progressive renal insufficiency in the presence of other signs of peripheral vascular disease. However, the mere presence of renal artery narrowing does not predict clinical disease. Autopsy studies in patients older than 70 demonstrate a prevalence of severe renovascular disease in up to 60–65%. Angiographic studies have indicated a similar incidence of ~70% in elders with hypertension and 35% in those who are normotensive.
There is reason to believe that smoking cessation, tight control of diabetes, lowering of elevated cholesterol, and control of hypertension itself will decrease the incidence or progression of atherosclerotic renal disease.
In renovascular hypertension (RVH), symptoms are similar to those of other forms of hypertension, ultimately resulting in CHF, atrial fibrillation, stroke, and myocardial infarction. Patients with RVH frequently are refractory to standard treatment, have abrupt onset of hypertension after age 50, and may have a unilateral abdominal bruit on the affected side. In atherosclerotic renovascular insufficiency, the symptoms and signs are no different from those of other forms of progressive renal failure.
Urinalysis in renovascular disease usually shows mild proteinuria, with a “bland” urinary sediment consisting of hyaline and granular casts. In unilateral renal artery stenosis (RAS), BUN and creatinine are usually normal. However, the use of ACE inhibitors in such patients frequently leads to a reversible azotemia, often accompanied by hyperkalemia. This development should strongly suggest the diagnosis and lead to further testing.
Abdominal ultrasonography shows unilateral or bilateral shrunken kidneys. More useful is Doppler ultrasonography, which can estimate renal blood flow on each side. This test is quite sensitive (> 90%) for detection of clinically significant RAS. Angiography is the most definitive test for diagnosing RAS but is also most risky, with possible atheroembolic or dye-induced renal injury as complications. Carbon dioxide subtraction angiography avoids these risks, as does magnetic resonance angiography.
The most effective screening test for RVH is captopril renography, in which renal perfusion is measured before and after administering the ACE inhibitor captopril. The affected kidney shows a dramatic decrease in perfusion after captopril.
RAS accounts for only ~5% of hypertension in the United States, so the much more likely diagnosis in most cases is essential hypertension. Increased age, sudden onset, and an abdominal bruit increase the likelihood of RAS, as does development of azotemia after use of an ACE inhibitor. There is little to distinguish ischemic nephropathy from other forms of progressive renal failure. The prevalence is uncertain.
The optimal management of RVH is uncertain. Medical management may be effective. Correction of the stenosis, with angioplasty or surgical repair, although invasive, can occasionally cure and usually decrease the severity of the hypertension. Recent series of surgical revascularization report 50–70% improved; angioplasty outcomes are similar.
The management of ischemic nephropathy is even less clear because of the unpredictability of progression of the atherosclerotic narrowing. Treatment, therefore, should be individualized. In centers with excellent surgical or angioplasty technical skills, intervention may be considered, particularly in elders with few comorbidities.
Safian RD, Textor SC: Renal-artery stenosis. N Engl J Med 2001;344:431. [PMID: 11172181]
van Jaarsveld BC et al: The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis. N Engl J Med 2000;342:1007. [PMID: 10749962]
CHRONIC RENAL FAILURE
ESSENTIALS OF DIAGNOSIS
Elderly individuals make up the majority of new ESRD patients in the United States. The 1999 U.S. Renal Data System (USRDS) report indicated that, for 1997, of 79,000 new ESRD patients who began treatment, 51% were 65 years of age or older. Of the 300,000 patients receiving renal replacement therapy (RRT), 34% were age 65 or older. The most common causes of ESRD in elderly are diabetes and hypertension-induced nephrosclerosis.
Rigorous control of blood pressure in patients with hypertension can prevent onset of chronic renal failure (CRF). Target blood pressure should be normal (< 130/85). ACE inhibitors are the antihypertensive drug of choice because of their beneficial effects on the renal glomerular pressure. A similar preventive effect has been shown in diabetic patients who maintain tight sugar control. Protein restriction has been shown in experimental animals to slow progression of renal failure. However, the effect in humans is relatively minor. For most patients with CRF, protein intake should not exceed 1 g/kg/day.
With minor exceptions, the symptoms, signs, and laboratory findings are no different in elderly patients with CRF than in younger patients.
Most patients with progressive CRF experience nonspecific symptoms of fatigue and weakness. With worsening
of renal failure, buildup of nitrogenous wastes leads to gastrointestinal symptoms (nausea, anorexia, hiccups) and later to neurological symptoms (somnolence, confusion, irritability). Itching may become severe, particularly in those with secondary hyperparathyroidism. Urinary frequency and nocturia are common because of a loss of concentrating function. Physical examination may reveal pallor (resulting from anemia), a yellowish tint to the skin, signs of pruritus, and bruising. Hypertension is usually present. Asterixis is a late neurological sign. In untreated end-stage patients, uremic “frost” on the skin, pericardial friction rub, and seizures may occur.
Increased BUN and creatinine, progressive over time, is diagnostic. Because of decreased muscle mass (the site of creatinine production), an elderly patient with normal serum creatinine (< 1.0 mg/dL) implies a GFR that is only 50–60% of that of a young patient with the same serum creatinine. As a result, a serum creatinine of 3–4 mg/dL may represent ESRD in an octogenarian. To avoid the need for 24-h urine collection to measure creatinine clearance, one should estimate GFR, using the Cockcroft-Gault equation:
Anemia (resulting from decreased erythropoietin production) is common and is usually normochromic and normocytic. Hyperphosphatemia and hypocalcemia are common in untreated patients with CRF. Urinalysis usually shows granular casts, variable amount of protein, and isosthenuria (specific gravity 1.010–1.012).
Renal ultrasonography shows bilaterally shrunken kidneys in most patients with CRF. Exceptions include adult polycystic kidney disease (very large kidneys with myriad cysts), amyloidosis (normal- to large-sized kidneys), and chronic obstructive uropathy (large kidneys with dilated collecting systems).
Renal biopsy is used less frequently in elderly than in younger patients with undiagnosed renal failure because of concern about increased risks of complications. Patients with progressive renal failure in the setting of chronic hypertension or long-standing diabetes mellitus may have a presumptive diagnosis made without biopsy. However, presentation of a nephritic syndrome or nephrotic syndrome in the absence of diabetes warrants a serious consideration of renal biopsy to diagnose potentially treatable kidney disease.
Anemia, primarily resulting from decreased erythropoietin production, develops in most patients with CRF. The anemia is normochromic and normocytic, similar to other anemias of chronic disease.
Hyperkalemia rarely occurs spontaneously until late in CRF. The exception is diabetic glomerulosclerosis, caused by a condition of hyporeninemic hypoaldosteronism (often called Type IV renal tubular acidosis).
Cardiovascular complications, including hypertensive heart disease and CHF, are common in elderly patients with CRF. Pericarditis is a late complication of ESRD.
Unless serum phosphate and calcium concentrations are kept normal, most patients with CRF experience secondary hyperparathyroidism, characterized by bones showing osteitis fibrosis cystica. Many also have a component of osteomalacia caused by deficiency of 1,25-dihydroxyvitamin D, which is normally produced by the kidney.
Management of CRF in the elderly does not differ importantly from that for younger patients. Treatment should be coordinated with a nephrologist in most cases by the time the serum creatinine concentration approaches 3 mg/dL.
Hypertension is common, and uncontrolled hypertension is a major contributor to progression of renal failure regardless of underlying cause. ACE inhibitors should generally be included in the drug regimen to preserve glomerular filtration. Because of associated coronary artery disease and valvular heart disease, CHF is common in the elderly CRF patient and should be aggressively treated to avoid a prerenal component contributing to the renal failure. Conversely, overdiuresis needs also to be avoided to prevent decreased perfusion to the already compromised kidney.
This is more common in ARF than in CRF. However, certain types of renal disease are more likely to have a potassium excretory defect: interstitial kidney diseases and diabetic patients (with hyporeninemic hypoaldosteronism). Acute severe hyperkalemia is managed in the usual way: intravenous calcium, glucose and insulin, or
bicarbonate infusion, with hemodialysis in extreme or refractory cases. Chronic hyperkalemia is best managed with a low-potassium diet and avoidance of ACE inhibitors, NSAIDs, and potassium-sparing diuretics (spironolactone, triamterene, amiloride).
Most patients with CRF have a defect in ammonia production (and thereby hydrogen ion excretion) when GFR falls to about 25% normal. The resultant metabolic acidosis has few symptoms but may contribute to chronic bone disease. More severe acidosis leads to anorexia, dyspnea, and abdominal pain. Patients whose serum bicarbonate concentration falls below 20 mmol/L should receive oral alkali (sodium bicarbonate or sodium citrate).
For patients with hemoglobin concentration < 10 g/dL, intravenous or subcutaneous erythropoietin should be begun once or twice weekly. Oral iron supplementation should be added if the serum ferritin is below 100 µg/mL.
Secondary hyperparathyroidism and hypovitaminosis D are usual concomitants of progressive renal failure and must be managed to prevent the serious consequences of metabolic bone disease (renal osteodystrophy). Dietary phosphorus restriction should begin when GFR decreases to 50% of normal. If serum phosphate concentration is elevated, intestinal phosphate binders, such as calcium carbonate or calcium acetate, should be begun. Aluminum hydroxide antacids also bind phosphate but should not be used chronically in the patient with CRF because of possible aluminum toxicity. Target serum calcium concentration should be 10 mg/dL. If hypocalcemia occurs despite phosphate control, oral vitamin D (or its active product 1,25-dihyroxyvitamin D) should be started.
In patients with CRF, it is important to modify drug doses for medications cleared primarily by the kidney. This is particularly true for drugs with serious dose-related toxicities (eg, aminoglycoside antibiotics, digoxin, amphotericin). Appropriate dose modifications can be found in published tables or the Physicians' Desk Reference.
Discussion and decision making about renal replacement therapy (RRT; peritoneal dialysis, hemodialysis, renal transplantation) should begin by consulting a nephrologist whenever an elderly patient without prohibitive comorbidities progresses toward ESRD. One can attempt a rough estimate of when RRT will be necessary by plotting 1/creatinine against time (usually a straight-line function) and projecting to the point where 1/creatinine reaches 0.10–0.13. The decision to initiate RRT in an elderly patient requires medical, ethical, and psychosocial considerations that are sometimes difficult to weigh. The decision is best made within a team approach, involving the primary physician, nephrologist, social worker, patient, and family.
Because of comorbidities (primarily cardiovascular disease), survival of elderly patients receiving hemodialysis or peritoneal dialysis is shorter than for younger ESRD patients. Although rates are improving, the most recent USRDS data indicate mortality rates that are 3 times as high for patients older than 75 compared to those patients aged 45–64 (46 deaths/100 patient years vs. 17.3).
Bennett WM et al: Drug prescribing in renal failure: dosing guidelines for adults. Am J Kidney Dis 1983;3:155. [PMID: 6356890]
Diabetes Control and Complications Research Group: Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. Kidney Int 1995;47:1703. [PMID: 7643540]
Levey AS et al: Dietary protein restriction and the progression of chronic renal disease: what have all of the results of the MDRD study shown% Modification of Diet in Renal Disease Study group. J Am Soc Nephrol 1999;10:2426. [PMID: 10541304]
McCarthy JR: A practical approach to the management of patients with chronic renal failure. Mayo Clin Proc 1999;74:269. [PMID: 10089997]
Ritz E, Orth SR: Nephropathy in patients with type 2 diabetes mellitus. N Engl J Med 1999;341:1127. [PMID: 10511612]
Stack AG, Messana JM: Renal replacement therapy in the elderly: medical ethical, and psychosocial considerations. Adv Renal Repl Ther 2000;7:52. [PMID: 10672917]
U.S. Renal Data System 1999 Annual Data Report: Executive summary. Am J Kidney Dis 1999;34:S9. [PMID: 10430999]
ESSENTIALS OF DIAGNOSIS
Hyponatremia is a common electrolyte disorder in the elderly, ranging from 7% in healthy ambulatory elders to as high as 15–20% in hospitalized individuals and those in chronic care facilities. In hospitalized patients, hyponatremia on admission is associated with a mortality of almost 10% compared with only 1% for those with a normal sodium concentration.
Sustained hyponatremia indicates an excess of total body water relative to total body solute, and it almost always indicates some impairment of free water excretion by the kidney. Hyponatremia indicates nothing about the state of total body sodium (TBNa); this determination requires a clinical physical examination. Patients with hyponatremia must be classified as having increased TBNa (the edema states), decreased TBNa (hypovolemia), or normal TBNa(euvolemia). The mechanism of hyponatremia differs in each of these states (Table 25-2).
Table 25-2. Causes of hyponatremia.
In CHF and cirrhosis, there is decreased effective intravascular volume, leading to volume-stimulated enhancement of salt and water reabsorption by the kidney. Furthermore, antidiuretic hormone (ADH) levels are increased, leading to inappropriate concentration of the urine, preventing water excretion and correction of the hyponatremia.
Examples are gastrointestinal losses (vomiting, diarrhea), bleeding, or diuretic-induced hypovolemia. As in CHF, there are volume-stimulated increases in renal salt and water reabsorption and volume-induced ADH release, causing a concentrated urine and preventing excretion of free water. The result is hyponatremia.
Most patients with hyponatremia in this clinical category have the syndrome of inappropriate ADH secretion (SIADH) as a result of medical disease, pain syndromes, postsurgical state, or medications (Table 25-3).
Principal symptoms of hyponatremia, if any, relate to the CNS. Change of mental status, in the form of lethargy, forgetfulness, cognitive decline, stupor, and rarely coma, usually occur as the PNa falls to ≤ 125 mmol/L. Rapid lowering of sodium concentration is more likely to produce symptoms than a gradual change to the same level. Few physical signs relate to the hyponatremia per se aside from demonstrable neuropsychological changes. Patients with hypervolemic hyponatremia usually have peripheral edema, ascites, or both and may have other typical signs of CHF. Hypovolemic hyponatremia is characterized by low blood pressure, often with significant postural drop; tachycardia; and dry mucous membranes.
Hyponatremia (PNa < 130 mmol/L), hypochloremia (< 90 mmol/L), and hypo-osmolality (usually < 270 mOsm/kg) are present. Plasma osmolality (POsm) can be estimated by the formula:
Table 25-3. Causes of SIADH.
Hyperglycemia can lead to hyponatremia by osmotically attracting water out of the intracellular space, diluting the serum sodium concentration. The expected change in PNa is a decrease of 1.6 mmol/L for every 100 mg/dL increase in blood glucose concentration.
Serum uric acid concentration is usually increased (> 7 mg/dL) in hypovolemic and hypervolemic hyponatremic patients. Conversely, in SIADH, serum uric acid concentration is typically reduced (< 4 mg/dL) as a result of increased uric acid renal clearance.
Restriction of water intake (< 500 mL/day) should be instituted in all cases. If hypovolemia is present, give IV normal saline (or blood or plasma if bleeding is the cause of the hypovolemia). If an edema state is present, treat the underlying condition (CHF, cirrhosis). In most cases, sodium restriction (to < 1 g sodium/day) is appropriate. Limit the rate of correction of hyponatremia to 1–2 mmol/L/h. More rapid correction can lead to a serious CNS complication, central pontine myelinolysis (CPM). For individuals with severe neurological symptoms (seizure, coma), infuse a small volume of 3% sodium chloride solution intravenously to produce a rapid initial rise in serum sodium concentration and reverse some of the brain edema. A useful formula for calculating the effect of any sodium-containing infusate is as follows:
In a 70-kg patient with a starting PNa of 112 mmol/L, 500 mL of 3% NaCl solution will raise the PNa to 121 mmol/L. In such an emergency, the target for this initial treatment should be 120 mmol/L, at which point the guidelines just presented should be followed.
The outcome is determined primarily by the underlying illness rather than the hyponatremia per se, unless severe neurological complications have occurred, such as seizure, coma, or CPM.
Adrogue HJ, Madias NE: Hyponatremia. N Engl J Med 2000; 342:1581. [PMID: 10824078]
Beck LH: Fluid and electrolyte balance in the elderly. Geriatr Nephrol Urol 1999;9:11. [PMID:10435222]
ESSENTIALS OF DIAGNOSIS
Hypernatremia is common in sick elderly patients. In nursing home patients requiring hospitalization, the prevalence of hypernatremia is 30% and is associated with a mortality rate of 42%.
It is reasonable to administer regular feedings of water, either orally or via nasogastric administration, to frail nursing home patients or other individuals who are dependent on others for their water requirements.
The symptoms of hypernatremia are similar to those of hyponatremia: Mental status changes predominate and are to be expected when the PNa is > 155 mmol/L. The hypernatremic patient may have no subjective symptoms. Physical findings include the neuropsychological abnormalities associated with depressed mental status, often accompanied by poor skin turgor and dryness of mucous membranes.
See Essentials of Diagnosis. Hypernatremic patients usually have elevated BUN and creatinine concentration, usually in a prerenal pattern (BUN-creatinine ratio > 20:1).
Electrolyte-free water must be administered to reduce PNa and plasma osmolality toward normal. Water can be given by mouth or nasogastric tube in the awake patient; more often, it should be infused intravenously (as dextrose and water solution). Hypotonic sodium solutions (eg, half-normal saline solution) can be given if there are concomitant signs of hypovolemia or if it is known that the preceding fluid losses consisted of sodium-containing hypotonic fluids (as in vomiting or diarrhea). The minimal volume of free water required to restore PNa to normal can be estimated from the formula: Water deficit = total body water × (1 — [140/PNa]) (total body water can be estimated as weight [in kg] × 60%).
Care must be taken not to correct the hypernatremia too rapidly, particularly if the abnormality has been developing over several days or more. Because of adaptive changes in brain electrolytes and other solutes, rapid correction of hypernatremia can lead to cerebral edema. A rule of thumb is to correct half of the deficit in the first 24 h, with the remaining correction taking place over the next 24–48 h.
Adrogue HJ: Hypernatremia. N Engl J Med 2000;342:1493. [PMID: 10816188]