a condition in which a previously normal serum creatinine rises by 0.5 mg/dL, or an absolute increase in serum creatinine of >1 mg/dL in a patient with previous chronic kidney disease (CKD).
In the clinical setting, ARF is classified in a variety of ways. Classifying ARF by daily urine output can be useful. Anuria is defined as a urine output of <50 mL/d, oliguria is when the daily urine output is 50 to 450 mL/d, and nonoliguria occurs when the patient can make >450 mL of urine per day.
ARF is a common condition in the general population, with an annual incidence of approximately 200 cases per million population per year.2 The incidence rate is higher in hospitalized patients, 5% of whom may require RRT (Table 42–1).7 The highest incidence of ARF is in hospitalized patients in the intensive care unit. Depending on the definition used, ARF develops in 2% to 25% of patients in intensive care units.8−10 Many patient-specific factors cause a predisposition to the development of ARF. In nonhospitalized patients, ARF is often druginduced. Common causes of drug-induced ARF include nonprescription
nonsteroidal anti-inflammatory drugs (NSAIDs), prompting the FDA to convene an advisory committee to re-examine labeling
of these products.11 This drug class alone may be responsible for 500,000 to 2,500,000 cases of nephrotoxicity in the United States per year.
The development of ARF is one of the most serious events that can happen to a hospitalized patient, regardless of the reason for hospitalization. In patients admitted for cardiac surgery, the mortality risk is seven- to eightfold higher if the patient develops ARF.19 Patients who develop ARF following administration of intravenous radiocontrast dye and requiring dialysis have twice the mortality rate of similar patients receiving radiocontrast dye who do not experience an increase in their serum creatinine values.13 The outcome of a patient with ARF predominantly depends on the cause of the condition. In general, higher mortality rates are seen in conditions that result in hypoxia to the kidney causing acute tubular necrosis (ATN; 60%) or cortical necrosis (100%) compared to the lower mortality associated with autoimmune ARF causes like glomerulonephritis (9% to 25%), vasculitis (45%), or interstitial nephritis (13%).2 Similarly, postrenal causes like obstructive ARF tend to have lower mortality rates (27%), ostensibly because these obstructions can be surgically repaired before permanent damage can be done to the kidney. Other patient factors influence ARF outcomes. Understandably, those patients with higher severity of illness have higher mortality rates than those who do not.18 Critically ill patients with ARF due to sepsis have mortality rates that are significantly
higher than those of patients who develop ARF for other reasons (74% vs. 45%).
Prerenal renal failure
Functional acute renal failure
Acute intrinsic renal failure
Postrenal renal failure
Isolated renal hypoperfusion
Acute tubular necrosis
Acute interstitial nephritis
Bladder outlet obstruction
Ureteral (bilateral or unilateral with
solitary functioning kidney)
Renal pelvis or tubules
Intravascular volume depletion
Bilateral renal artery stenosis (unilateral renal
artery stenosis in solitary kidney)
Thrombotic thrombocytopenic purpura
Hemolytic uremic syndrome
Systemic lupus erythematosus
Antiglomerular basement membrane disease
Drugs (amphotericin B, aminoglycosides, etc.)
Improperly placed bladder catheter
Tumor lysis syndrome
A basic knowledge of renal function facilitates the understanding of how ARF manifests itself clinically. The most logical approach to understanding renal function is to divide the kidney into its four basic component parts: the vasculature, the glomeruli, the tubules, and the interstitium surrounding the other three component parts.
The kidney is a highly vascular organ with blood vessels ranging from the very large (renal arteries) to the very small capillaries providing blood to each individual glomerulus. Obstruction of the renal artery will result in an increase in serum creatinine, hematuria, and proteinuria, but obstruction of smaller vessels will only cause infarction of the downstream parenchyma. If this area is small, no change in serum creatinine will occur. Smaller vessels may be obstructed with cholesterol emboli, vascular
lesions, or platelet plugs, all of which will present as isolated decreased perfusion of the glomeruli. The serum creatinine frequently is increased since the lesions are usually diffuse. However, the urinalysis most commonly will be normal since the kidney itself is not ischemic and the glomeruli are not involved. The urinary indices suggest prerenal azotemia (i.e., a low urine sodium concentration and a low fractional excretion of sodium) in the absence of systemic hypotension or a decrease in effective blood volume. The urine volume may or may not be diminished. However, the onset of oliguria secondary to diffuse arterial lesions within the kidney, such as that which occurs with hemolytic uremia syndrome, denotes a poor chance for salvage of renal function.
The glomerulus consists of an enlargement of the proximal end of the renal tubule to incorporate a vascular tuft connecting the afferent and efferent arterioles (Fig. 42–1). The production of glomerular ultrafiltrate is predominantly dependent on the transcapillary hydrostatic pressure (dictated by the afferent and efferent arteriolar resistance) and the glomerular surface area. Afferent arteriolar tone is determined primarily by the local levels of angiotensin II (which induces vasoconstriction)
and prostaglandins (which induce vasodilation). Efferent arteriolar tone is predominantly determined by the local concentration
of angiotensin II. Pathophysiologic processes and medications that result in alterations of the afferent and efferent arteriolar tone (i.e., systemic hypotension, hypercalcemia, or use of ACEIs, angiotensin II receptor blockers, or NSAIDs) reduce glomerular ultrafiltrate production as a result of a decrease in glomerular hydrostatic pressure. Under these conditions, the serum creatinine will rise, the urine sediment will be normal, and the urine indices will suggest prerenal azotemia. However, the urinary solutes may or may not be maximally concentrated, depending on the circulating level of antidiuretic hormone
that is necessary to maximally concentrate the urine. Damage to the glomerular capillary tuft (e.g., acute glomerulonephritis) results in a decline in the production of glomerular ultrafiltrate as a result of a decrease in glomerular capillary surface area. Under these conditions the serum creatinine rises and the urinalysis is significant for hematuria and proteinuria because of the increased permeability of the damaged glomerular capillaries. Proteinuria exceeding 3 g/day is often referred to as nephrotic range proteinuria. Prolonged heavy proteinuria secondary to glomerular damage may result in the nephritic syndrome.
Under normal conditions, approximately 180 L of glomerular ultrafiltrate are produced per day, the vast majority of which must be reabsorbed by the renal tubules to maintain homeostasis. Clinically, the renal tubule can be divided into three major sections: the proximal tubule, Henle’s loop, and the distal nephron, which includes the distal tubule, the cortical collecting tubule, and the medullary collecting ducts. In the proximal tubule, approximately 60% to 70% of the filtered load of water and solute is isovolemically reabsorbed, as is the vast majority of filtered amino acids, glucose, and bicarbonate. In addition to its other functions, Henle’s loop is responsible for a significant portion of the total reabsorption of potassium, calcium, and magnesium, as well as for generating the osmotic gradient within the kidney that is necessary for the concentration of urinary solutes. Damage
to this portion of the nephron results in wasting of potassium and magnesium by the kidney and an inability of the kidney to concentrate the urine. The medullary portions of Henle’s loop are very sensitive to ischemia secondary to hypoperfusion. Consequently, in severe prerenal azotemia with renal hypoperfusion, there may be a loss of urinary concentrating ability despite the continued presence of a low urinary sodium concentration and a low fractional excretion of sodium. Major functions of the distal nephron include the regeneration of bicarbonate, the excretion of acid (hydrogen ion), the secretion of
potassium, and the reabsorption of water. Damage to this portion of the nephron may present as significant acidemia and either hypoor hyperkalemia, depending on the mechanism of injury.
The interstitium of the kidney provides the structural support for the kidney and serves to provide the environment in which concentrating gradients can be established. In addition, the interstitium of the kidney plays a major role in urinary ammonia handling. To facilitate the regeneration of bicarbonate and the excretion of acid by the distal nephron, the kidney utilizes ammonia as a urinary buffer. When the interstitium of the kidney is damaged (e.g., in acute allergic interstitial nephritis), the concentrating gradient within the kidney may be dissipated and ammonia handling disrupted. Consequently, patients presenting with acute interstitial nephritis frequently are unable to concentrate the urinary solutes. The urinalysis may show mild proteinuria
and hematuria. However, the striking finding on microscopic examination of the sediment is the presence of numerous WBCs and WBC casts.
C L I N I C A L PRESENTATION OF ACUTE RENAL FA I L U R E
Outpatients often are not in acute distress; hospitalized patients may develop ARF after a catastrophic event
Outpatient: Change in urinary habits, weight gain, or flank pain
Inpatient: Typically ARF is noticed by clinicians before it is noticed by the patient
Patient may have edema; urine may be colored or foamy.
Vital signs may indicate orthostatic hypotension in volumedepleted patients
Urine and blood chemistries may determine prerenal cause complete blood cell count (CBC) and differential rules out
infectious causes Urine microscopy may reveal casts, WBCs, RBCs, and eosinophils
OTHER DIAGNOSTIC TESTS
Renal ultrasound or cystoscopy may be needed to rule out obstruction; renal biopsy reserved for difficult diagnoses
In situations in which administration of a nephrotoxin cannot be avoided, such as when radiocontrast dye is to be administered, nonpharmacologic therapies can be employed to prevent ARF. The key to nonpharmacologic ARF prevention is the elimination of the patient’s risk factors to the degree that is possible. The best-studied examples of this are the interventions used to maximize renal perfusion when radiocontrast dye is administered. Adequate hydration and sodium loading prior to radiocontrast dye administration have been shown to be beneficial therapies. A trial comparing infusions of 0.9% NaCl or 5% dextrose with 0.45% NaCl administered prior to radiocontrast dye infusion conclusively demonstrated that the normal saline was superior in preventing ARF.26 The intravenous solution infusion rate used in this study was 1 mL/kg per hour beginning the morning that
the radiocontrast dye was going to be given, and all subjects were encouraged to drink fluids liberally as well. The benefits of 0.9% NaCl infusions have been found in similar studies,27 suggesting this regimen should be used in all at-risk patients who can tolerate the sodium and fluid load.
HYDARTION, MANNITOL, LOOP DIURETIC, DOPAMINE, CCBs, THEOPHYLLINE, ACETYLCYSTEINE, FENOLDOPAM, INSULIN.