General Critical Care

Distinguishing Prerenal Acute Kidney Injury From Acute Tubular Necrosis

Differentiating prerenal AKI from ATN poses a challenge as they may exist on a continuum, and prolonged prerenal states may result in ATN. Causes of hypoperfusion, such as hypovolemia, sepsis, cardiovascular collapse, or vasoplegia, may predict a prerenal injury, whereas the administration of known nephrotoxic substances, such as contrast agents or certain antibiotics, may shift suspicion to ATN. For those patients suspected of prerenal AKI, fluid resuscitation or resolution of hypoperfusion may improve renal function and provide a measure of confirmation as to the nature of the renal insult. Laboratory studies may also aid in making the diagnosis.

The fractional excretion of sodium (FeNa) is a simple test comparing the concentration of sodium in the blood and the urine by the following formula:

A FeNa <1% favors prerenal causes, whereas a FeNa of 1% to 4% is more commonly seen with ATN or intrinsic AKI. Importantly in cardiac surgery, in those patients exposed to diuretics at the time of investigation, urea should be substituted for sodium, as the diuretic may force additional sodium excretion decreasing the utility of FeNa analysis.

Urinalysis may also provide assistance in diagnosis. Prerenal AKI typically results in normal urine studies without pathologically identifiable casts or sediment (note that hyaline and fine granular casts may be identified, but do not indicate renal pathology or nephron damage). Nephron damage and death seen in ATN results in prototypical urinary casts often described as “muddy brown” or “granular.” Damage to the tubular epithelial cells, either by ischemia or toxins, results in cellular sloughing into the tubular lumen, which in turn is then identified as urinary sediment. While the presence of urinary casts or renal epithelial cells is strongly associated with ATN, it is important to recognize that the absence of findings does not exclude the possibility of ATN. ^,

Postrenal Acute Kidney Injury

Postrenal AKI is the result of an obstruction to the drainage of urine that results in the accumulation of urinary waste products within the renal collecting system. Causes of postrenal or obstructive AKI can include prostatic disease in men, benign or malignant lesions in the ureters, bladder, or urethra, renal or ureteral stones, iatrogenic obstructions, or any other impediment to urinary drainage. Diagnosis is typically achieved through imaging such as renal ultrasound or computerized tomography. Rarely endoscopic imaging is required. Treatment is drainage of urine, most commonly by bladder catheterization, but in the setting of an inability to access the bladder via the urethra or ureter pathology, nephrostomy tubes may be required.

Acute Kidney Injury and the Cardiac Surgical Patient

The incidence of AKI in the intensive care unit is 20% to 70%, strikingly higher than the overall AKI in hospitalized patients, which is reported to range from 7% to 18%. For cardiac surgical patients whose AKI results in renal failure and need for renal replacement therapy (RRT), mortality ranges from 40% to 70% ( Box 37.2 ). ^,

BOX 37.2

Acute Kidney Injury

• Acute kidney injury (AKI) resulting in renal failure dramatically increases the risk of mortality.

• AKI due to hypovolemia should be managed with judicious fluid resuscitation and avoidance of hypervolemia.

• A transfusion threshold of 7 mg/dL is reasonable to prevent AKI.

Hemodynamic perturbations are strongly correlated with postoperative renal dysfunction in cardiac surgical patients, partly due to the unique physiology associated with heart failure, temperature regulation, and cardiopulmonary bypass (CPB). What does appear certain is that arterial blood flow, on both the macroscopic and microscopic levels, throughout the kidney, is a major determinate in the development of AKI. This may be especially true in the setting of acute aortic dissection or new onset ischemia causing either depressed cardiac function or acute valvular pathology. ^,

Cardiopulmonary Bypass and the Development of Acute Kidney Injury

CPB is utilized to provide continuous systemic blood flow, exchange of oxygen and carbon dioxide, and when required, the delivery of cardioplegic solutions to cause cardiac arrest during cardiac surgery. Some studies have indicated that nonpulsatile flow is a major risk factor for AKI development. ^, The ideal CPB arterial pressure, or CPB-MAP, for renal protection has not been elucidated as of yet, but there is a strong belief that higher pressures (70–80 mm Hg) may provide better renal perfusion than lower pressures (50–60 mm Hg). In addition, longer CPB and aortic cross-clamp times are associated with a higher rate of renal insult (see Chapter 25 ).

The precise relationship between core temperature on CPB and renal function remains unclear. Hypothermia may convey a degree of renal protection, while hyperthermia is likely to be injurious. The effect of hypothermia on renal function via the examination of two trials initially designed to assess neurocognitive impairment after complex coronary artery bypass grafting (CABG) indicated moderate hypothermia, with antegrade cerebral perfusion during systemic circulatory arrest, appeared to preserve renal function, or at least was not found to be associated with post-CPB AKI. Hyperthermia, however, defined as greater than 37°C, was shown to be an independent risk factor for the development of AKI with a 51% increase in the development of AKI for every minute spent above 37°C. ^, The rewarming phase is the period most likely to result in renal injury due to the drastic increase in oxygen requirement without commensurate increases in oxygen delivery, despite supraphysiologic oxygen saturation. Additionally, hemolysis with catalytic iron and heme release represent proinflammatory damage-associated molecular patterns and may increase the risk of AKI. ^, Differences in oxygen therapy and perioperative statin use have not demonstrated any amelioration of AKI.

Blood Product Transfusion and Acute Kidney Injury

The management of blood product transfusion has been thoroughly discussed in prior chapters (see Chapter 13, Chapter 28 ). However, while optimal transfusion thresholds remain unclear, transfusion of any amount of blood products increases the risk of AKI, and the risk increases with increased transfusion requirements. Additionally, the risk of AKI is highly related to the change in hemoglobin relative to the patient’s baseline, as opposed to the absolute value of hemoglobin. As hemoglobin levels decrease, due to loss or dilution, the risk of AKI increases, with the risk becoming more significant after a 50% decrease in hemoglobin levels. Landmark trials, such as TRICS-III, looked at outcomes after red cell transfusion during intraoperative and postoperative care and showed no difference in outcomes when comparing a hemoglobin transfusion threshold of 7.5 versus 9.5 mg/dL. In the postoperative setting, most intensivists believe that TRICS-III provides compelling evidence to withhold red blood cell transfusions for hemoglobin levels greater than 7 to 8 mg/dL provided there is no other evidence of end-organ dysfunction or ongoing bleeding.

Weighing the risks of blood product transfusion against the development of organ dysfunction from anemia, guidelines were established in 2011 on behalf of the Society of Thoracic Surgeons (STS)/Society of Cardiovascular Anesthesiologists (SCA) that called for a transfusion threshold of 7 mg/dL during CPB, to avoid organ dysfunction.

Fluid Management

Crystalloid selection has long been an area of debate with small- and large-scale studies providing guidance without compelling consistency. Much of the knowledge has been gleaned from other critically ill patient populations, notably those with acute respiratory distress syndrome (ARDS) or large abdominal surgeries. ^, Extrapolating ARDS findings to the cardiac surgical patient indicates that fluid restriction is safe as long as organ function does not worsen, while abdominal surgical patients have an increased risk of postoperative AKI with perioperative hypovolemia. ^, For those patients who have already developed AKI, data from a critical care cohort showed that restrictive fluid management decreased the need for RRT, which has also been borne out in septic shock patients. ^, Consistently, data have shown that the goal of fluid management should be to correct hypovolemia without tipping the patient into functional hypervolemia. The danger lies in the goal of resuscitation being improperly aimed to restore a critically ill patient’s fluid status to their previous outpatient healthy intravascular state. Resolution of hypovolemia, which clinically is evident with recovery of organ function, is sufficient to prevent further deterioration without risking new sequelae of hypervolemia, especially in cardiac surgical patients who may be suffering from impaired cardiac function.

Intravenous (IV) fluid selection may also play a role in the development of AKI, and trials such as the SMART and SALT-ED have shown that balanced IV fluids have a lower risk of kidney injury than 0.9% normal saline. ^, The SMART trial showed that buffered crystalloids decreased the risk of major adverse kidney events, which were defined as either a doubling of serum creatinine or the need for RRT. Notably, 30-day mortality was lower in the buffered fluid group without a difference in median volume requirements between the groups. SALT-ED, however, looked at emergency room patients, and while not finding a difference in total hospital days, did find less progression to AKI for those patients resuscitated with buffered IV fluids compared to normal saline. While these two major trials assessed different patient populations, their consistent finding of benefit for buffered IV fluids strongly suggests that ICU fluid selection can play a determining role in the development of kidney injury. When comparing crystalloid to colloid fluids such as 5% albumin, the CRISTAL trial found no difference in 28-day mortality between crystalloid and colloids. While some secondary endpoints suggest that colloids may have a modest benefit with respect to ventilator-free days and vasopressor-free days, rightful criticism has been given to the patient population, mostly medical ICU patients with median fluid resuscitation needs of 3000 mL. Given that other trials comparing colloid to crystalloid have not found similar findings, the benefit colloids may play in volume resuscitation, or the effect on kidney injury, remains subject to debate. ^,

Use of Vasopressors

Vasopressor selection is an area of constant debate and research within critical care medicine, with most studies comparing norepinephrine versus vasopressin. Norepinephrine owes its vasoactive properties to catecholamine receptors, primarily α ₁ -mediated vasoconstriction and β ₁ -mediated inotropy, whereas vasopressin is an endogenous noncatecholamine vasoconstrictor. The choice of vasopressor is often patient pathology driven. With respect to renal blood flow, norepinephrine is the most frequently used vasopressor, in part due to the Surviving Sepsis Guidelines, which advocated for its use as the first-line vasopressor in septic shock. In head-to-head trials such as VANISH (Vasopressin vs Norepinephrine as the Initial Therapy in Septic Shock), the endpoint of kidney failure–free days was similar, although the vasopressin group did have a lower serum creatinine and higher urine output for the first 7 days, which ultimately resulted in a lower usage of RRT. The VANCS (Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock after Cardiac Surgery) trial is one of the few specifically looking at cardiac surgery patients. Using a composite outcome of 28-day mortality and 28-day free-of-organ failure (including development of AKI that was defined as either requiring RRT or a serum creatinine increase >2.0 mg/dL), vasopressin was superior to norepinephrine. This result was in large part due to a notably lower rate of AKI in the vasopressin group (10.3% vs 35.8%, P < .0001, odds ratio [OR], 0.26). Recently, angiotensin II has been used as a vasopressor, and the ATHOS-3 trial showed similar rates of hemodynamic stability when compared to norepinephrine, with a post hoc analysis of patients requiring RRT trending towards shorter duration with angiotensin II compared to norepinephrine. Ultimately, the choice of vasopressor is complex and requires broad consideration.

Diuretics

While guidelines do not exist specifically for the cardiac surgical population, the 2017 European Society of Intensive Care Medicine recommended against initiation of diuretics for the prevention of kidney injury (grade 1B). However, they did include as a 2B recommendation to consider the use of diuretics for treatment of volume overload in patients who are diuretic responsive. Furosemide does not appear to elevate postoperative serum creatinine in cardiac surgical patients, nor does it offer protection against the development of AKI.