Approach to the Patient with Acidemia
Approach to Acute Renal Failure
Approach to the Patient with Alkalemia
Approach to the Patient with Chronic Renal Failure
Approach to the Patient with Edema
Approach to the Patient with Hematuria
Approach to the Patient with Hyperkalemia
Approach to the Patient with Hypernatremia
Approach to the Patient with Hypokalemia
Approach to the Patient with Hyponatremia
Approach to the Patient with Nephrolithiasis
Approach to the Patient with Proteinuria and Nephrotic Syndrome
Renal Cell Carcinoma
Urinary Tract Infections
APPROACH TO THE PATIENT WITH ACIDEMIA
Arterial pH is determined by serum bicarbonate levels and arterial carbon dioxide tension (PaCO2). Acidemia is a systemic arterial pH less than 7.35.
Respiratory acidosis is an increase in respiratory acid measured with PaCO2 and caused by a reduction in alveolar ventilation. The basis may be severe pulmonary disease, a respiratory muscle disorder or fatigue, or depression of ventilatory control.
Metabolic acidosis is characterized by a decline in bicarbonate level. It is caused by a marked increase in endogenous production of acid, such as lactic acid and ketoacids, loss of bicarbonate stores (diarrhea or renal tubular acidosis [RTA]), or progressive accumulation of endogenous acids in renal insufficiency. The three main types of RTA reflect different defects in urine acidification. The hallmark finding in distal RTA (type I) is inability of the distal tubule to acidify the urine appropriately. Acid retention then decreases bicarbonate level. Although inherited forms of RTA exist, most patients with distal RTA have a systemic illness, such as an autoimmune disorder, hyperthyroidism, hypercalciuria, pyelonephritis, or obstructive uropathy, or a side-effect of a drug such as amphotericin B or lithium.
In proximal RTA (type II), the tubule fails to reabsorb the normal amount of filtered bicarbonate. Metabolic acidosis often occurs in association with Fanconi syndrome, which is generalized dysfunction of the proximal tubule manifested by glycosuria, aminoaciduria, and phosphaturia. Associated systemic conditions include multiple myeloma and Wilson’s disease. In both proximal and distal RTA, renal potassium excretion increases, and hypokalemia develops. Type IV RTA, which occurs among patients with diabetes mellitus and tubulointerstitial disease, is caused by a failure of the distal nephron to excrete normal amounts of acid and potassium. The cause usually is hypoaldosteronism or reduction in sensitivity to aldosterone. Unlike proximal and distal RTA, type IV RTA causes hyperkalemia.
Each form of acidosis provokes a compensatory response that tends to offset the change in pH. If the degree of compensation is either more or less than predicted (Table 149.2), an additional acid–base disturbance is present. In acute respiratory acidosis, an immediate compensatory increase in serum bicarbonate levels is caused by cellular buffering mechanisms. After 24 hours, an increase in renal bicarbonate reabsorption accomplishes an even greater increase in bicarbonate level. In metabolic acidosis, stimulation of medullary chemoreceptors increases ventilation and decreases PaCO2 so that acidosis is partially ameliorated.
Respiratory acidosis: A rapid increase in PaCO2 can cause a state of anxiety, dyspnea, confusion, psychosis, and hallucinations that can progress to coma. Lesser degrees of dysfunction in chronic hypercapnia include headaches, sleep disturbances, loss of memory, daytime somnolence, and personality changes.
Metabolic acidosis: Respiratory compensation triggers hyperventilation, which often is perceived by patients as dyspnea. Cardiac effects include reduced contractility and ventricular arrhythmia. Lethargy and coma may occur. RTA can cause symptoms and signs of intravascular volume loss and potassium imbalance. In distal RTA, chronic positive acid balance leads to calcium mobilization from bone, metabolic bone disease, hypercalciuria, urinary stone formation, and nephrocalcinosis. Proximal RTA is not associated with bone disease or nephrolithiasis, but acquired forms may have features of Fanconi syndrome.
DIFFERENTIAL DIAGNOSIS, LABORATORY STUDIES, AND DIAGNOSTIC TESTS
Respiratory acidosis: The differential diagnosis includes central causes (sedating drugs, stroke, central nervous system infection), airway obstruction (foreign body, bronchospasm), parenchymal disease (emphysema, chronic bronchitis, pneumoconiosis, adult respiratory distress syndrome), obesity, and neuromuscular disorders (muscular dystrophy, myositis, cord injuries, myasthenia gravis). Patients stimulated to hyperventilate by metabolic acidosis may experience respiratory fatigue if the metabolic abnormality is not controlled promptly. Pulmonary function testing, including measurement of lung volume and diffusing capacity, arterial oxygen levels, and neuromuscular studies, including electromyography, all may be useful.
Metabolic acidosis: The serum anion gap is used to differentiate high anion gap acidosis from hyperchloremic acidosis. The anion gap, defined as sodium ion concentration plus potassium ion concentration minus bicarbonate ion concentration, represents unmeasured anions normally present in plasma. When acid anions such as acetoacetate and lactate accumulate, the anion gap increases to higher than the normal range of 10 to 12 mEq per liter.
Disorders associated with an elevated anion gap include advanced renal failure, toxin ingestion (ethylene glycol, methanol, salicylates, and paraldehyde), ketoacidosis (alcoholic, diabetic, and starvation), and lactic acidosis. Measurement of serum levels of lactate and acetoacetate can be helpful. Other clinical features associated with high anion gap acidosis are listed in Table 2.
TABLE 2. HIGH ANION GAP METABOLIC ACIDOSIS
Hyperchloremic (normal anion gap) disorders include gastrointestinal bicarbonate loss (diarrhea, ureterosigmoidostomy), RTA types I, II, and IV, early renal insufficiency, rapid administration of saline solution, acid loads, and the posthypocapneic state. Laboratory evidence of distal RTA can be found by calculating the urinary net charge, Cl-u – (Na+ + K+)u, which becomes abnormally negative owing to a decline in urinary ammonium excretion. Proximal RTA can be diagnosed from an increased urine bicarbonate concentration response to administration of bicarbonate. Hyperkalemia suggests the existence of type IV RTA.
Respiratory acidosis: Treatment depends on severity and rate of onset. Acute respiratory acidosis can be life threatening and may necessitate mechanical ventilation if the underlying cause cannot be reversed quickly. Supplemental oxygen must be carefully titrated in the treatment of patients with severe chronic obstructive disease who retain carbon dioxide at baseline, because it may worsen the respiratory acidosis. Chronic respiratory acidosis often is difficult to control, but general measures, such as smoking cessation, use of bronchodilators, glucocorticoids, and diuretics, and physiotherapy, to manage underlying conditions may be helpful. Respiratory stimulants are used only in selected cases.
Metabolic acidosis: Table 149.9 outlines the therapy for the various forms of metabolic acidosis. Mild-to-moderate acidemia (pH greater than 7.20) often requires no specific therapy, especially if the underlying cause can be controlled. Proximal RTA is difficult to manage, because administered bicarbonate is rapidly filtered and lost. High doses therefore are necessary when treatment is needed. High doses of potassium supplements also are needed because of the kaliuresis induced by the high rate of distal delivery of bicarbonate.
APPROACH TO ACUTE RENAL FAILURE
Acute renal failure (ARF) is a clinical syndrome characterized by an abrupt decline in renal function.
ARF can have prerenal, intrarenal, and postrenal causes. Prerenal ARF is caused by a decrease in renal blood flow. Intrarenal ARF is caused by a sudden, severe renal parenchymal insult, which most often is due to acute tubular necrosis (ATN) from ischemia or exposure to a nephrotoxic agent. Postrenal ARF is caused by obstruction at a site along the urinary tract.
CLINICAL FEATURES, DIFFERENTIAL DIAGNOSIS, AND DIAGNOSTIC TESTS
Prerenal: The causes are outlined in Table 140.1; myocardial failure and intravascular volume depletion are most common. Important historical features and physical examination findings are presented in Table 140.4. The urinalysis is usually unremarkable, though the urine tends to be highly concentrated (more than 450 mOsm per kilogram) and low in sodium (fractional excretion of sodium [FENa] less than 1%). Reabsorption of blood urea nitrogen (BUN) with sodium raises the ratio of BUN to creatinine (often more than 20:1)
Intrarenal: The causes include ischemic ATN, nephrotoxic ATN (aminoglycosides, amphotericin B, heavy metals, cisplatin, radiocontrast agents, and endogenous toxins such as myoglobin, hemoglobin, and myeloma light chains), vascular processes (atheroembolic disease, renal artery occlusion, and vasculitis), acute glomerulonephritis, and acute tubulointerstitial nephritis. Distinguishing clinical features are presented in Table 140.4 and also include the following: (a) Hypertension, proteinuria, and hematuria, especially red blood cell casts, suggest acute glomerulonephritis. The urine has low sodium, low FENa, and is isotonic. (b) Skin rash, fever, eosinophilia, and eosinophiluria suggest acute interstitial nephritis when there is a history of exposure to a causative drug. Only biopsy provides enough information for a definitive diagnosis. (c) Anuria (less than 100 mL per 24 hours) can be caused by urinary tract obstruction or bilateral renal cortical necrosis, vascular occlusion, or overwhelming acute glomerulonephritis. (d) Myoglobinuric rhabdomyolytic ARF is associated with a high plasma level of creatine kinase and a urine dipstick test result positive for blood in the absence of red blood cells in the spun urinary sediment. Serum creatinine concentration often rises rapidly. Thus the BUN to creatinine ratio is often less than 10:1. Hyperkalemia often is severe. (e) Hemoglobinuric ATN is suggested when a hemolytic event is followed by excretion of dark urine; often with chills and hypotension.
Postrenal: Urine flow can be obstructed either in the kidney, as in crystal formation, methotrexate precipitation, and uric acid nephropathy after therapy for leukemia or lymphoma, or outside the kidney, as in ureteral compression or blockage. Acute ureteral obstruction typically causes severe colicky pain in the back and flank. Chronic obstruction can cause vague aching or no discomfort. Good urine output can be maintained in partial obstruction. A postvoid residual urine volume of more than 100 mL suggests infravesical obstruction. Renal ultrasonography reveals hydronephrosis and can also show polycystic or scarred kidneys but is less useful in showing the exact location and cause of obstruction. Computed tomography is useful in detecting extrinsic compression of the urinary tract. Intravenous pyelography remains the radiologic procedure of choice in the care of patients with normal renal function.
Figure 140.1 demonstrates the use of urinary indexes and findings in the diagnosis of ARF.
Prerenal: If ARF is caused by volume depletion, treatment involves saline and volume expanders. For patients in hemodynamically unstable condition, Swan-Ganz monitoring provides better measurement of effective intravascular volume. In hepatorenal syndrome, improvement depends on improved liver function.
Intrarenal: The underlying disease should be controlled, and nephrotoxic drugs should be discontinued. In ATN, fluid and electrolyte balance and adequate nutrition must be maintained, and infection should be managed. In early oliguric ARF, a trial of 80 to 400 mg intravenous furosemide or 12.5 to 25 mg mannitol may reduce the need for dialysis. Diuretics should be discontinued if urine flow does not improve. There are no clinical data to support the efficacy of low-dose dopamine. Uremic symptoms, volume overload, intractable acidosis, hyperkalemia, or oliguria with steadily rising creatinine concentration to 8 to 10 mg per deciliter are indications for dialysis.
Postrenal: The goals are to (a) decompress the urinary tract and (b) establish long-term drainage. Decompression may be followed by a large diuresis, hence hydration status and electrolytes must be monitored carefully. Uric acid nephropathy may be minimized by increasing urine pH with sodium bicarbonate infusion and acetazolamide. Patients receiving chemotherapy for leukemia should be pretreated with allopurinol for 1 to 3 days.
CLINICAL COURSE AND OUTCOME
Possible clinical problems include volume overload, hyponatremia, hyperkalemia, hyperphosphatemia, hypocalcemia, acidemia, and uremia (pericarditis, lethargy, vomiting, infection). Nonoliguric ATN has a better prognosis. Renal failure from ATN usually lasts 7 to 21 days; renal function then may return to baseline. The mortality rate for ATN after surgery or trauma is more than 40%. For nephrotoxic ATN, it is less than 10%.
APPROACH TO THE PATIENT WITH ALKALEMIA
Arterial pH is determined by the serum bicarbonate levels and arterial carbon dioxide tension (PaCO2). Alkalemia is a systemic arterial pH greater than 7.45.
Respiratory alkalosis is a decrease in respiratory acid reflected by a decreased serum PaCO2 level and caused by alveolar hyperventilation. Metabolic alkalosis is characterized by an increase in bicarbonate level; it is caused by bicarbonate administration, loss of acid from the upper gastrointestinal tract, or failure of the kidneys to eliminate bicarbonate in the usual manner. Accompanying hypovolemia may enhance reabsorption of bicarbonate in the proximal tubule. Each form of alkalosis provokes a compensatory response that tends to offset the change in pH. If the degree of compensation is either more or less than predicted (Table 149.2), an additional acid–base disturbance is present. In respiratory alkalosis, the kidney begins to respond within several hours by decreasing bicarbonate reabsorption and acid production. The consequent decline in bicarbonate levels tends to bring the pH toward normal. Full compensation may take several days and depends on normal volume status and renal function. In metabolic alkalosis, compensatory respiratory hypoventilation increases PaCO2 and lowers pH.
Respiratory alkalosis: Effects vary according to duration and severity but are generally those of the underlying condition. A rapid decline in PaCO2 can cause dizziness, confusion, and seizures as a consequence of reduced cerebral blood flow.
Metabolic alkalosis: Effects are generally those of the underlying condition.
DIFFERENTIAL DIAGNOSIS, LABORATORY STUDIES, AND DIAGNOSTIC TESTS
Respiratory alkalosis: The differential diagnosis includes various cardiopulmonary conditions, especially those associated with dyspnea, central nervous system lesions, pregnancy, endotoxemia, presence of salicylates, hepatic failure, hypoxemia, sepsis, anxiety, and pain.
Metabolic alkalosis: Diuretics and vomiting are the most common causes. Figure 149.2 shows the differential diagnosis and an approach based on urinary levels of chloride and potassium.
Respiratory alkalosis: Treatment is directed at alleviating the underlying disorder. Patients with hyperventilation syndrome may benefit from reassurance and paper bag rebreathing during attacks.
Metabolic alkalosis: Treatment is directed at removing the underlying stimulus for bicarbonate generation. Chloride-responsive alkalosis (Fig. 149.2) is associated with volume contraction and generally is corrected with administration of saline solution, which eliminates the hypovolemic stimulus for enhanced renal bicarbonate reabsorption. Management of underlying problems such as vomiting also is helpful. If the vomiting is refractory to therapy, proton-pump inhibitors can be used to decrease the gastric acid loss. Alkalosis unresponsive to chloride is managed by means of control of the underlying condition, such as an excess of mineralocorticoid. Ongoing diuretic use should be discontinued, if possible. Accelerated renal bicarbonate loss can be achieved with acetazolamide, a carbonic anhydrase inhibitor. Hemodialysis can be effective when renal function is impaired.
EPIDEMIOLOGY, ETIOLOGY, AND PATHOGENESIS
Bladder cancer accounts for more than 90% of malignant tumors of the urinary tract. The incidence increases with age and peaks during the seventh decade of life. The male-to-female ratio is about 4:1. Cigarette smoking is by far the leading risk factor. Others include occupational exposure to carcinogenic compounds in dyes, rubber, and paint; chronic infection of the lower urinary tract; history of external beam radiation to the pelvis; and use of cyclophosphamide. In the United States, about 90% of bladder cancers are transitional cell carcinoma (TCC); squamous cell carcinoma accounts for about 7%. In the Mediterranean basin, schistosomiasis is the main causative agent and is associated with squamous cell carcinoma.
Most bladder cancers manifest as painless, gross or microscopic hematuria, which can occur suddenly and intermittently. Urinary frequency and urgency can be caused by bladder wall irritation or volume loss. Invasive bladder cancer may extend into the prostate, rectum, uterus or vagina, and sacral vertebrae. It spreads through the lymphatic and blood vessels to distant lymph nodes, lungs, liver, and bones. About 5% to 20% of patients have symptoms caused by metastatic lesions. Constitutional symptoms can occur with disseminated disease, but paraneoplastic syndromes are rare.
Routine urinalysis almost invariably shows hematuria, the degree of which does not correlate with the extent of the lesion. Intravenous pyelography reveals an intravesical filling defect in 60% of cases. Ultrasonography sometimes is used to assess the bladder wall and to evaluate the kidneys and ureters. Urine cytologic examination has a sensitivity and specificity of 80% for grade III tumors but relatively low sensitivity for grade I and II tumors. Direct visualization and biopsy of the tumor usually are performed by means of cystoscopy. Staging should include a complete blood cell count, hepatic and renal chemical analysis, chest radiography, and abdominal and pelvic computed tomography.
PROGNOSIS AND MANAGEMENT
The most significant prognostic factor in transitional cell carcinoma is the depth of tumor invasion; tumor grade also is important. For superficial papillary blader cancer, the initial treatment is endoscopic resection. Intravesicular administration of Bacile Calmette Guerin (BCG) vaccine is adjuvant treatment of patients at high risk of recurrence. Patients with invasive cancer confined to the bladder organ usually are treated with radical cystectomy, which results in a 60% to 75% 5-year survival rate for T2 disease and a 20% to 40% survival rate with more invasive (T3 or T4) disease. Continent reservoirs such as the Koch pouch have been used to improve patient self-image after radical cystectomy. Postoperative combination chemotherapy has shown some promise. For patients with localized invasive disease who are not surgical candidates, radiation is alternative therapy. The role of neoadjuvant (first-line) systemic chemotherapy is being investigated. For patients with metastatic disease, combination chemotherapy is the treatment of choice, although therapy with even the best agents is associated with a median survival period of only 12.5 months.
APPROACH TO THE PATIENT WITH CHRONIC RENAL FAILURE
Chronic renal failure (CRF) is a slowly progressive and irreversible reduction in glomercular filtration rate (GFR). Chronic renal insufficiency is a term used to describe a mild to moderate reduction in GFR, usually less than 25 to 30 mL per minute, that has not reached the point at which symptoms of uremia appear.
A characteristic of most forms of CRF is progressive deterioration of renal function long after the initial insult. The pathogenesis has not been fully explained but likely involves mesangial cytokine production and the adverse effects of chronic proteinuria. The rate of loss of GFR varies with the type of renal disease but tends to be constant for any given patient. Two major mechanisms account for uremic syndrome—accumulation of ill-defined toxins normally eliminated by the kidney and defects in the function of specific organs.
The manifestations of CRF depend on severity and on the rapidity with which the reduction in GFR develops. In general, uremic symptoms develop when GFR decreases to less than 10 to 15 mL per minute. The initial symptoms may be so insidious that the patient is aware of them only in retrospect, after effective management has been implemented.
History: Uremia usually develops as the blood urea nitrogen (BUN) level exceeds 90 mg per deciliter. Generalized manifestations include fatigue and malaise. Gastrointestinal symptoms are common, including anorexia, nausea, vomiting, and hiccups. Cardiovascular symptoms consist of dyspnea, orthopnea, edema, and pericardial chest pain. Neuromuscular manifestations include impaired mentation and concentration, insomnia, irritability, headache, muscle cramps, restless legs, and twitching. Severe encephalopathy may develop and progress to confusion, stupor, seizures, and coma. Peripheral neuropathy may manifest initially as paresthesia with subsequent disturbances of motor function, including muscle weakness and atrophy. Autonomic neuropathy, especially among diabetic patients, may impair bowel and bladder function. Skin manifestations include itching and bruising. Genitourinary symptoms include nocturia, amenorrhea, and loss of libido.
Physical examination: The signs usually do not appear until late in the course. The patient may appear chronically ill with weight loss and muscle wasting. Dermal manifestations include pallor, yellow-brown discoloration, hyperpigmentation, ecchymosis, and petechiae. Inspection of the head may reveal hypertensive retinopathy or epistaxis. Cardiovascular findings include hypertension, cardiomegaly, edema, and in the preterminal stages, a pericardial friction rub. Kussmaul’s respirations reflect the severity of the underlying metabolic acidosis. Mental status findings include confusion, drowsiness, stupor, or coma. Myoclonic twitches and asterixis are typical of advanced uremia. Sensory abnormalities may include loss of vibratory and position sense. Loss of deep tendon reflexes and foot drop may occur. Severe renal osteodystrophy may give rise to bone tenderness and fractures.
The diagnosis is established with documentation of an elevation in BUN and creatinine levels, typically in a ratio of 10:1 to 15:1. The BUN level is disproportionately elevated with urinary obstruction, cardiac decompensation, high protein intake, gastrointestinal bleeding, and catabolism associated with sepsis or glucocorticoid therapy. The creatinine level is disproportionately elevated with liver disease or malnutrition. When the GFR falls to less than 25 to 30 mL per minute, other laboratory abnormalities may occur, including normocytic anemia, metabolic acidosis, hyperphosphatemia, hypocalcemia, and hyperuricemia. Hyperkalemia is a late manifestation.
A primary question in the evaluation of renal failure is whether it is acute or chronic. Chronic failure implies stability and thus presents a less immediate threat. The best evidence that renal failure is chronic is a prior documented elevation in BUN and creatinine levels. Also valuable are findings of long-standing renal failure, such as renal osteodystrophy or small kidneys at ultrasonography (although normal or even large kidneys may be associated with CRF caused by polycystic kidney disease, myeloma, amyloidosis, and diabetic nephropathy). Anemia, hyperphosphatemia, hypocalcemia, and acidosis are relatively poor indicators that renal failure is chronic; the presence of these disorders often correlates better with the severity of renal failure.
A second question is whether potentially reversible factors contribute to or aggravate the renal failure, such as hypovolemia, hypertension, reflux nephropathy, congestive heart failure, nephrotoxins, sepsis, hypercalcemia, pericarditis, or pericardial tamponade. Definitive diagnosis should then be attempted in which specific diseases that might be remediable are considered, such as malignant hypertension, renal artery stenosis, Wegener’s granulomatosis, systemic lupus erythematosus, multiple myeloma, obstruction, reflux, hypercalcemic nephropathy, interstitial nephritis, cholesterol emboli, and lead nephropathy.
CRF can have numerous causes (Table 141.1). The history and examination may reflect abnormalities of the underlying cause. The results of urinalysis typically are abnormal in most stages of renal failure and may show variable degrees of proteinuria, hematuria, pyuria, and casts. However, in many forms of CRF, such as hypertensive nephrosclerosis, obstructive uropathy, and polycystic kidney disease, urinalysis shows few abnormalities. Broad and waxy casts occur with CRF of almost any cause. The presence of heavy proteinuria or red blood cell casts suggests glomerulonephritis. Abnormal findings at serum and urine electrophoresis may occur with multiple myeloma. Serum and urine culture results may be positive in the presence of endocarditis or renal tuberculosis. Depressed serum complement levels and positive test results for antinuclear and anti-DNA antibodies are important clues to the presence of lupus nephritis. Antibodies for glomerular basement membrane are present in Goodpasture’s syndrome or antiglomerular basement membrane nephritis. The presence of antineutrophil cytoplasmic antibodies is helpful in the diagnosis of Wegener’s granulomatosis and other systemic types of vasculitis.
Renal ultrasonography provides valuable data about cystic disease, renal calculi, or a dilated pelvicalyceal system. Unfortunately, renal biopsy is of limited value in establishing the cause of renal failure, because the histologic findings may be too unspecific to disclose the cause of the original insult. Nevertheless, in some forms of renal failure associated with normal-sized kidneys, renal biopsy may be useful.
Even after causes of renal failure that can be treated are ruled out, many factors may still require intervention. Control of blood pressure (systolic less than 125 to 130 mm Hg, diastolic less than 80 mm Hg) is essential to limit progression of CRF and development of atherosclerosis. Another therapeutic goal is to maintain near-normal values of serum calcium, phosphate, and parathyroid hormone. This is accomplished by means of restricting phosphate intake (less than 0.8 g per day), prescribing phosphate binders such as calcium carbonate (long-term administration of aluminum hydroxide has detrimental side effects) when the serum phosphate level exceeds 5.0 to 5.5 mg per deciliter, and adding calcium and calcitriol supplements if the serum calcium level is less than 8.5 mg per deciliter despite normal phosphate levels.
Patient without symptoms should be instructed to follow a diet that contains 4 to 6 g per day of sodium; this should be reduced to 2 to 3 g per day in the presence of edema or hypertension and expanded if hypotension or an acute decline in GFR ensues. If hyperkalemia is present, patients should follow a low-potassium diet and avoid medications that increase serum potassium level, such as angiotensin-converting enzyme inhibitors and spironolactone. The potassium binder sodium polystyrene sulfonate (Kayexalate) may be necessary in refractory cases. Sodium bicarbonate or citrate may be given when the serum bicarbonate level falls to less than 18 to 20 mEq per liter. The dosages of medications that are excreted by the kidney, including digoxin, insulin, and many antibiotics, must be adjusted. Magnesium-containing compounds, nonsteroidal antiinflammatory drugs, and radiographic contrast materials are particularly dangerous and should be avoided altogether. A low-protein diet can reduce symptoms and retard progression of CRF, but care must be taken to avoid malnutrition. Recombinant erythropoietin and iron supplements are used to control anemia.
INDICATIONS FOR DIALYSIS
Objective findings that indicate the need for renal replacement therapy include progressive peripheral neuropathy, pericarditis, inadequate nutrition, congestive heart failure, severe hypertension, extreme and refractory hyperkalemia, metabolic acidosis, and general malaise and weakness that interfere with the ability to work. Long-term dialysis ideally should be started when there is an expectation that uremic symptoms soon will develop. A creatinine clearance of less than 10 mL per minute often is used as a guideline. Long-term options include hemodialysis, peritoneal dialysis, and renal transplantation.
APPROACH TO THE PATIENT WITH EDEMA
DEFINITION AND PATHOPHYSIOLOGY
Edema is the excessive accumulation of fluid within the interstitial space. Edema is caused by four primary abnormalities—increased mean capillary hydrostatic pressure, decreased capillary oncotic pressure, increased capillary permeability to protein, or obstruction of lymphatic flow. Most disorders associated with edema are initiated by an alteration in oncotic or hydrostatic forces and are perpetuated by renal sodium retention.
Common disorders associated with either generalized or localized edema are categorized according to primary pathophysiologic mechanism (Table 143.1). Some conditions, including primary aldosteronism, acute glomerulonephritis, and estrogen administration, appear to produce edema by causing inappropriate retention of sodium by the kidney independent of a primary alteration in Starling forces.
Sodium retention that causes a generalized edematous state may be associated with pulmonary edema, peripheral edema, or ascites. Patients with pulmonary edema often report dyspnea and orthopnea. Physical examination shows tachypnea and pulmonary crackles. The chest radiograph shows interstitial edema or alveolar fluid accumulation. Peripheral edema is associated with swollen legs or presacral accumulation of fluid in a patient at bed rest. Pitting edema is the persistence of a depression in the skin after 10 seconds of pressure applied with the fingers and usually occurs when at least 10 lb (4.5 kg) of fluid has accumulated. Patients with ascites have increased abdominal girth. The demonstration of shifting dullness or a fluid wave at physical examination suggests the presence of ascites. Ascites can be confirmed with abdominal ultrasonography.
Diuretics: Several classes are available. There are two groups of sulfonamide diuretics—the thiazides, such as hydrochlorothiazide, and the nonthiazides, such as chlorthalidone and metolazone. These agents act primarily at the distal tubule to inhibit the transport of sodium and chloride. Loop diuretics, such as furosemide, bumetanide, and ethacrynic acid, act at the thick ascending limb of the loop of Henle to inhibit the Na–K–2Cl transporter. These potent agents may increase urinary sodium excretion to more than 20% of the filtered sodium load. Potassium-sparing diuretics, such as spironolactone, triamterene, and amiloride, act in the distal tubule to induce natriuresis and to inhibit potassium excretion. If mild diuresis is needed, sulfonamide diuretics often are the agents of choice. They have poor efficacy in the setting of renal insufficiency. If more potent diuresis is needed, a loop diuretic is chosen. Loop diuretics bind to plasma proteins, and the effectiveness of these agents depends on the concentration of unbound drug. Therefore a single dose is more likely to be effective than the same amount administered in divided doses. Secondary hyperaldosteronism is common with cirrhosis. The diuretic of choice therefore is spitonolactone, a competitive antagonist of aldosterone.
Diuretics alone often cannot eliminate generalized edema because of secondary physiologic changes that they induce. They may cause intravascular volume depletion, cardiovascular compromise, and untoward metabolic effects such as hypokalemia (except for potassium-sparing agents), hyponatremia, and hyperglycemia.