Acute tubular necrosis may be produced by a variety of factors that interfere with glomerular filtration or tubular reabsorption. The pathogenesis of acute tubular necrosis may be divided into an initiation period, a maintenance period, and a recovery period. Renal hypoperfusion or a nephrotoxic insult may initiate renal failure. Surgical patients with external and internal fluid losses or sepsis may have renal hypoperfusion. The initiating insult culminates in the development of one or more maintenance factors, such as decreased tubular function, tubular obstruction, and sustained reductions in renal blood flow and glomerular filtration. Urine flow and solute excretion are reduced. Once the maintenance period has begun, pharmacologic interventions to improve renal blood flow do not reverse the failure.

Prerenal oliguria is associated with physiologic mechanisms that conserve salt and water. In this case, urine has low sodium levels and high osmolality. Urine sodium levels are high, and osmolality is low. Renal damage is also associated with a progressive rise in serum urea, creatinine, uric acid, and polypeptide levels. Serum potassium levels may increase by 0.3 to 3 mEq/L/day, and a decrease occurs in the serum levels of sodium, calcium, and proteins such as albumin. The creatinine clearance remains the single most helpful test in defining renal status and predicting the prognosis in cases of severe renal dysfunction.

Prevention of renal failure can be based on the following generalizations:

A key strategy in reducing the incidence of renal failure is limiting the magnitude and duration of renal ischemia. Although a number of preventive strategies have been described, none apart from maintenance of normovolemia appears to be effective.

In the preoperative preparation of surgical patients, high-risk patients and procedures should be identified. Reversible renal dysfunction should be sought, and fluid losses and hypovolemia should be corrected by intravenous fluids. Perioperative ADH and renin-angiotensin-aldosterone secretion can be minimized with adequate hydration before anesthetic induction. Administration of saline rather than solutions low in sodium is helpful in prevention of aldosterone secretion, hyponatremia, and oliguria.

Oliguria often signals inadequate systemic perfusion, and prevention of acute renal failure requires its rapid recognition through adequate monitoring. In addition to standard monitors and a urinary catheter, monitors for patients with questionable cardiac and pulmonary function should include a direct arterial line for blood pressure monitoring and a central venous pressure or Swan-Ganz catheter, when appropriate, for assessment of cardiac function and volume status.

Use of a urinary catheter is the only means of monitoring renal function in the operating room. A fluid challenge is necessary if hourly urinary output decreases to below acceptable levels.

The use of diuretics in the face of inadequate urinary output must be carefully evaluated. While diuretics may not be effective during the initiation of failure, large doses of furosemide may convert oliguric renal failure into nonoliguric failure, which is easier to manage. In the maintenance phase, doses of furosemide in excess of 1 g may be required to convert oliguric failure to nonoliguric failure. Diuretic therapy must be associated with aggressive monitoring and intravascular volume expansion.

Although the mechanism is unknown, prophylactic administration of mannitol in well-hydrated patients protects renal function. Loop diuretics may also prevent acute renal failure. Mechanisms for protection include the inhibition of sodium reabsorption and the prevention of tubular obstruction through the maintenance of high flow and pressure within the tubules and the reversal of intrinsic renal vasoconstriction. Prophylactic use of diuretics may be of benefit in the case of jaundice in surgical patients, excessive exposure to contrast media, hyperuricemia, or the presence of pigment in the urine. Fenoldopam, a dopamine receptor agonist, also may be helpful.

Fenoldopam mesylate (Corlopam) is a selective DA ₁ receptor agonist. It causes both systemic and renal arteriolar vasodilation and has no impact on DA ₂, α-adrenergic, or β-adrenergic receptors. Unlike dopamine, which causes renal vasoconstriction at higher doses, fenoldopam at high dose produces even greater renal vasodilation. Fenoldopam is more than 6 times as potent as dopamine in increasing renal blood flow.

If acute renal failure develops, it progresses through four distinct phases: onset, the oliguric phase, the diuretic phase, and the recovery phase. Onset, or the initiation phase, precedes actual necrotic injury and correlates with a major alteration in renal hemodynamics. The oliguric phase reflects four pathophysiologic processes:

The diuretic phase signifies that tubular function is returning. It is marked by a large daily urinary output (more than 3 L) secondary to the osmotic diuretic effect produced by an elevated blood urea nitrogen (BUN) and impaired ability of tubules to conserve sodium and water. The recovery phase is characterized by gradual improvement of renal function over 3 months to 1 year.

After renal failure is established, the primary consideration in management is the maintenance of fluid and electrolyte balance. The early use of hemodialysis for the prevention of severe fluid and electrolyte imbalance is necessary during the oliguric and diuretic phases. The clinical management of oliguria is discussed in the following section.