Acute renal failure is an abrupt decline in kidney function resulting in an inability to clear and excrete metabolic waste and maintain proper fluid balance. There is not a universal laboratory or clinical definition for acute renal failure. Most commonly used definitions include the following:

Acute renal failure is marked by azotemia, an increase (>50% over baseline) in serum blood urea nitrogen (BUN) and other nitrogenous substances. Azotemia is associated with oliguria defined as urine output <400 mL per 24 hours and on occasion, anuria defined as urine output <100 mL per 24 hours.

Azotemia resulting from decreased renal perfusion without cellular injury is known as prerenal azotemia. The injured patient is subject to many factors that can lead to diminished renal blood flow including loss of intravascular volume, decreased effective intravascular volume, diminished cardiac output, or exposure to vasoconstrictive medications. Prerenal azotemia accounts for most of the azotemia found in trauma patients and can be usually remedied by addressing the primary etiology (e.g., correction of the volume deficit).

Azotemia related to obstruction of urinary out flow can be termed obstructive uropathy. Common trauma-related causes are urethral disruption associated with a pelvic fracture, ureteral or cystic compression from pelvic retroperitoneal hemorrhage, clotted blood within the genitourinary tract, neurogenic bladder associated with a spinal cord injury, or an obstructed urinary catheter. Timely sonographic assessment and correction or diversion of the obstruction is essential because duration of obstruction is inversely related to recovery of renal function.

Intrinsic causes for acute renal failure can be categorized according to the primary anatomic sites of injury. These are the renal interstitium, the glomeruli, and the renal tubules. The renal interstitium is subject to a diffuse inflammatory process known as interstitial nephritis. Interstitial nephritis is most often caused by an allergic reaction to medication. Other causes include autoimmune disease, malignancy, and/or infectious agents. Renal failure due to interstitial nephritis is often reversible after withdrawal of the offending agent. Corticosteroids may hasten the recovery of renal function; however, their role remains controversial in the absence of controlled clinical trials.

The glomeruli can also be affected and glomerulonephritis can present as a subacute or acute renal failure. Histopathologic examination of the kidney is often necessary to make a diagnosis of etiology. Prompt use of appropriate immunosuppressive agents and plasma exchange may be indicated to reduce the occurrence of end-stage renal failure.

Injury to the tubules, acute tubular necrosis (ATN), is the most common etiology of acute renal failure in the trauma patient. The cause of this injury is usually due to ischemic insult to the tubules. Prerenal azotemia is a common precursor to this ischemia. If renal perfusion is not corrected in a timely manner, ATN will arise. Nephrotoxins such as myoglobin, contrast media, aminoglycosides, or amphotericin can also play a role in the development of ATN.

The functional unit of the kidney is the nephron. It is estimated that the human kidney contains 1 to 1.5 × 10⁶ nephrons. The nephron consists of a glomerulus, a capillary complex with afferent and efferent arterioles, and the Bowman capsule that receives the filtrate from the glomerulus and a tubule. The nephron’s tubule consists of a proximal convoluted tubule, a loop of Henle, a thick ascending tubule, and a distal convoluted tubule which empties into the collecting duct. These collecting ducts coalesce into the calyces and pelvis of the kidney. The renal cortex contains the glomeruli and proximal and distal convoluted tubules, whereas the loop of Henle and thick ascending tubules extend into the renal medulla along with a distal capillary bed known as the vasa recta.

The major elements of renal function are glomerular filtration, and tubular excretion and reabsorption. The kidneys receive 20% of the cardiac output with the majority of that flow directed at the renal cortex to support glomerular filtration. Renal blood flow including glomerular blood flow is subject to autoregulation and is maintained within a narrow range (<10% variation) over a wide range of perfusion pressures (80 to 180 mm Hg). Renal blood flow autoregulation is governed by neural, hormonal, and local paracrine mediators.

The afferent arteriole of the glomerulus empties into a porous capillary bed contained within the Bowman capsule. Effluent glomerular blood empties into a highresistance efferent arteriole, which enters a peritubular capillary network (vasa recta). Virtually all plasma without proteins passes into the Bowman capsule due to the relatively high hydrostatic pressure to which the glomerulus is subjected. This proteinfree plasma ultrafiltrate is produced at a well-controlled rate known as the glomerular filtration rate (GFR). Naturally occurring substances such as creatinine can be utilized to measure GFR by the following equation:

This dilute ultrafiltrate enters the nephron’s tubule where it is concentrated by reabsorption of sodium and water. Within the renal medulla, the surrounding vasa recta allows for countercurrent exchange. Active reabsorption of sodium occurs at the water-impermeable thick ascending limb while water is extracted from the relatively solute impermeable loop of Henle. Glucose, potassium, chloride, and phosphate are also actively reabsorbed in the tubule. Urea is passively reabsorbed with the amount inversely proportional to tubular flow rate. During high flow, up to 70% of urea is excreted; urea excretion drops to only 10% to 20% in low flow situations. Hydrogen and ammonium ions are both secreted in the tubule in response to the surrounding pH.

Regardless of the inciting event, ATN arises from two major factors, renal ischemia and direct toxic insult to the nephron tubule. Renal ischemia occurs from diminished absolute effective circulating volume. This ischemia leads to renal vasoconstriction with reduction in renal blood flow and loss of autoregulation. The consequent reduction in glomerular blood flow decreases glomerular filtration. Furthermore, the medullary thick ascending tubule due to its high oxygen demands is exquisitely sensitive to an ischemic insult. This insult leads to early impairment of the countercurrent exchange mechanism and the loss of the concentration ability of the kidney. As decreased intrarenal blood flow persists, adherent neutrophils and platelets obstruct capillaries and cause persistence of the ischemia with collapse of normal feedback mechanisms.

In response to the ischemic insult, morphologic changes occur in tubule cells, including loss of their brush border, loss of polarity, and loss of integrity of the tight junctions between cells. Dead and dying cells along the tubule obstruct the lumen contributing to cast formation and increase intratubular pressure, further reducing GFR. Loss of these tubular epithelial cells and the tight junctions between viable cells lead to leakage of glomerular filtrate into the interstitial space causing medullary congestion. Nephrotoxins can harm tubular epithelial cells in a similar manner and cause ATN despite the presence of adequate circulating renal blood volume.

Following ischemic or toxic injury, the renal tubule cells can progress onto apoptosis, necrosis, or dedifferentiation and proliferation. With timely and adequate supportive measures, the latter response predominates and leads to recovery of tubular function. The kidney can completely regenerate normal structure and restore full function after injury.

The most common cause of traumatic ATN is due to prolonged volume deficit without sufficient resuscitation. However, a variety of other conditions commonly experienced in the management of the injured patient significantly contribute to the development of ATN.