The risk of development of AKI in critically ill patients has been classified by a multinational group of nephrologists.10 The classification uses the acronym RIFLE (risk, injury, failure, loss, and end-stage kidney disease [ESKD]).¹¹ The RIFLE system classifies AKI into three categories of increasing severity (R, I, F) and two outcome criteria (L, E) based on GFR status reflected by the change in urine output or loss of kidney function¹¹ (Table 20-1). If AKI is superimposed on a kidney that is already compromised, the term chronic is added to the RIFLE criteria to denote the cause as acute-on-chronic kidney failure.¹¹

The Acute Kidney Injury Network (AKIN) criteria are listed in Box 20-1. These criteria are similar to those proposed by the RIFLE group, and both groups intend to make the point that in the acutely ill patient, small changes in the serum creatinine level and urine output may signal important declines in the GFR and kidney function. A conceptual model that combines the features of the RIFLE criteria and AKIN criteria are shown in Figure 20-1.¹¹

Any condition that decreases blood flow, blood pressure (BP), or kidney perfusion before arterial blood in the renal artery enters the kidney may be anatomically described as prerenal AKI. When arterial hypoperfusion due to low cardiac output, hemorrhage, vasodilation, thrombosis, or other cause reduces the blood flow to the kidney, glomerular filtration and, consequently, urine output decrease (see Box 20-2). This is a major reason that the critical care nurse monitors the urine output on an hourly basis. Initially, in prerenal states, the integrity of the kidney’s nephron structure and function may be preserved. If normal perfusion and cardiac output are restored quickly, the kidney will not suffer permanent injury. However, if the prerenal insult is not corrected, the GFR will decline, the blood urea nitrogen (BUN) concentration will rise (prerenal azotemia),⁹ oliguria will develop, and the patient will be at risk for significant kidney damage. Oliguria (urine output <400 mL/day) is a classic finding in AKI.⁵ Prerenal AKI is seen frequently in the critically ill. In a study of hospitalized older patients with kidney failure, prerenal AKI occurred in 58%.⁵ This compares with rates of 34% for intrarenal AKI and 8% for postrenal AKI in the same study.⁵

Any condition that produces an ischemic or toxic insult directly at the site of the nephron places the patient at risk for development of intrarenal AKI (see Box 20-2).

Ischemic damage to the kidney can also damage internal structures from prolonged hypotension or low cardiac output. In the multicenter study of critical care patients with AKI by Mehta and colleagues,⁴ 50% of the patients had ischemic injury, which was largely precipitated by hypotension (20%) and sepsis (19%).

Toxins that damage kidney tubular endothelium include medications that are administered to treat a coexisting condition¹² as well as radiopaque (contrast) dye administered during an interventional or diagnostic radiological study. Complications from the contrast dye cause AKI in 9% to 14% of patients.⁴ In affected patients, the serum creatinine levels typically begin to rise 48 to 72 hours after the study, peak at 3 to 5 days, and return to baseline within another 3 to 5 days.¹³ Kidney dysfunction can persist up to 3 weeks after the procedure. Although patients with normal kidney function are not considered to be at risk, those with elevated serum creatinine levels, diabetes, or microvascular disease are highly vulnerable.¹³

The term azotemia is used to describe an acute rise in the BUN level.9 Uremia is another term used to describe an elevated BUN value.

The oliguric or anuric phase, the second phase of AKI, lasts 5 to 8 days in the nonoliguric patient and 10 to 16 days in the oliguric patient.14 The accumulation of necrotic cellular debris in the tubular space blocks the flow of urine and causes damage to the tubular wall and basement membranes. Backleak occurs because damage in the tubular wall causes the glomerular filtrate to flow passively into the kidney tissue rather than to be passed out as urine through the ureters and bladder. Oliguria is encountered more often in ischemic damage and is a sign that the damage is extensive and severe. During the oliguric or anuric phase, the GFR is greatly reduced, leading to increased levels of BUN (azotemia), elevated serum creatinine values, electrolyte abnormalities (hyperkalemia, hyperphosphatemia, hypocalcemia), and metabolic acidosis.

Critically ill patients with AKI have a high mortality on long-term follow-up.15 Kidney function may return to normal, or near normal, with a GFR that is 70% to 80% of normal within 1 to 2 years.¹⁶ However, if significant kidney parenchymal damage has occurred, BUN and creatinine levels may never return to normal. Of the patients who survive AKI, approximately 62% eventually recover normal kidney function, 33% have residual kidney damage, and at least 5% require long-term hemodialysis.¹⁶

Acidosis (pH <7.35) is one of the trademarks of severe AKI.17 Metabolic acidosis occurs from accumulated metabolic waste products. The acid waste products consist of strong negative ions (anions), elevated serum phosphorus values (hyperphosphatemia), and other normally unmeasured ions (e.g., sulfate, urate, lactate) that decrease the serum pH.¹⁷ A low serum albumin concentration, which often occurs in AKI, has a slight alkalinizing effect, but it is not enough to offset the metabolic acidosis.¹⁷ Even respiratory compensation and mechanical ventilatory support are rarely sufficient to reverse the metabolic acidosis. Information on acidosis and arterial blood gas interpretation is found in Chapter 14. Anion gap measurement is discussed in Chapter 19.

The BUN level is not a reliable indicator of kidney damage.9,18 The BUN concentration is changed by protein intake, blood in the gastrointestinal (GI) tract, and cell catabolism, and it is diluted by fluid administration. An elevated BUN-to-creatinine ratio may signal early AKI. The BUN-to-creatinine ratio is most useful in diagnosing prerenal AKI (often described as prerenal azotemia), in which the BUN value is greatly elevated relative to the serum creatinine value.

Creatinine is a by-product of muscle metabolism that is formed from nonenzymatic dehydration of creatine in the liver18; 98% of creatine is in the muscles,¹⁸ and it is almost totally excreted by the kidney tubules. If the kidneys are not working, the serum creatinine level will increase. When the serum creatinine values doubles (e.g., from 0.75 to 1.5 mg/dL), the increase reflects a decrease of approximately 50% in the GFR.¹⁸ Serum creatinine level is assessed daily to follow the trend of kidney function and to determine whether the kidney function is stable, getting better, or getting worse.¹⁸

Trauma patients have different demographics from those of other critical care populations. They are always emergency admissions, are younger, are more often male, and have fewer coexisting illnesses.29 A 5-year retrospective study of 9449 trauma admissions to critical care units in Australia and New Zealand used the RIFLE criteria to determine incidence of AKI in the first 24 hours after admission; AKI developed in 18% of trauma patients.²⁹ However, if patients were older or had preexisting comorbid illnesses, their risk of AKI rose to 35%.²⁹ Although these AKI numbers are high, they likely underestimate the true incidence because the study did not include patients in whom AKI developed more than 24 hours after admission to the critical care unit.²⁹

Trauma patients with major crush injuries have an elevated risk of kidney failure because of the release of creatine and myoglobin from damaged muscle cells, a condition called rhabdomyolysis.30 Myoglobin in large quantities is toxic to the kidney. Overall survival from rhabdomyolysis is 77%.³⁰

The level of creatine kinase (CK), a marker of systemic muscle damage, increases in patients with rhabdomyolysis. One trauma service reported that of 2083 trauma patients admitted to critical care, 85% had elevated CK values, and acute kidney failure resulting from rhabdomyolysis developed in 10%.³¹ A CK level of 5000 units/L was the lowest abnormal value in patients in whom AKI associated with rhabdomyolysis developed.³¹

Volume resuscitation is the primary treatment for preservation of adequate kidney function and prevention of AKI. In many hospitals, the intravenous (IV) fluids are alkalinized by the addition of sodium bicarbonate, and the urine output is increased by intravenous administration of the diuretic mannitol.³⁰ A bicarbonate and mannitol regimen is instituted to prevent acidosis and hyperkalemia, because both are frequent complications of rhabdomyolysis. Close attention is paid to urine output, CK levels, increases in serum creatinine levels, and any signs of compartment syndrome in all patients admitted with this diagnosis.

High-molecular-weight contrast medium is a potential cause of nephrotoxicity.13,35 Kidney-protection strategies include identification of patients at high risk and use of alternative imaging modalities that do not involve contrast. If radiopaque contrast use is inevitable, smaller contrast volumes should be used for each study, and low-osmolar, or iso-osmolar (iohexol), contrast media that are less nephrotoxic should be selected.^35,36

The best method of prevention is aggressive hydration with intravenous normal saline during and after the procedure.37,38 After some diagnostic intravascular catheterization procedures, the alert patient is asked to drink several liters of water over a 12-hour period to protect the kidney. Avoiding dehydration is vital. In research studies, the addition of sodium bicarbonate or N-acetylcysteine did not confer additional protection to the vulnerable kidney beyond hydration with normal saline only.^37–39

Several medications have been investigated to mitigate the risk of AKI in at-risk patients who undergo diagnostic studies involving radiopaque contrast agents. The agents include oral N-acetylcysteine, intravenous sodium bicarbonate, and an intravenous infusion of fenoldopam.37–40 In randomized, controlled trials, N-acetylcysteine has not lived up to its early promise.^37–40 For sodium bicarbonate, the picture is mixed, with some studies reporting a benefit^39,41 and other studies reporting no effect.^37,38 Because N-acetylcysteine and sodium bicarbonate are inexpensive and have almost no side effects, many physicians prescribe them on an empirical basis, even though the research evidence is not yet conclusive.

In summary, the mainstay measures to protect the kidney from contrast-induced AKI are to use the smallest dose of low- or iso-osmolar contrast media possible, provide vigorous fluid volume expansion, stop all nephrotoxic drugs, and avoid repeat contrast media injections within 48 hours.⁴²

Hemodynamic monitoring includes surveillance of the CVP, pulmonary artery occlusion pressure, cardiac output, and cardiac index.43 A less high-tech method that is also important consists of a daily weight and focused physical assessment.

Physical signs and symptoms are used to assess fluid balance. Signs that suggest extracellular fluid (ECF) depletion include thirst, decreased skin turgor, and lethargy. Signs that imply intravascular fluid volume overload include pulmonary congestion, increasing heart failure, and rising blood pressure. The patient with untreated AKI is edematous. The following factors contribute to this state:

In critical illness, even though there is peripheral edema and the patient may have gained 8 L of fluid over his or her “dry-weight” baseline, the patient may remain “intravascularly dry” and hemodynamically unstable, because the retained fluid is not inside a vascular compartment and cannot contribute to maintenance of hemodynamic stability. The patient with AKI is assessed frequently for pitting edema over bony prominences and in dependent body areas.

Electrolyte levels require frequent observation, especially in the critical phases of AKI (Table 20-4). Potassium may quickly reach levels of 6.0 mEq/L or higher. Specific electrocardiographic changes are associated with hyperkalemia: peaked T waves, a widening of the QRS interval, and ultimately, ventricular tachycardia or fibrillation. If hyperkalemia is identified, all potassium supplements are stopped.⁴⁴