Continuing Education Activity

Perioperative acute kidney injury (AKI) is a common yet under-recognized problem that increases mortality, morbidity, and increases the cost of hospitalizations. It can lead to the development of chronic kidney disease and the need for renal replacement therapy. AKI is a complication of both cardiac and non-cardiac surgery. Once renal injury develops, there are few therapeutic options available that can reverse the damage, and as such, prompt recognition and early intervention are critical to prevent the progression of the disease. This activity reviews the risk factors, diagnosis, and treatment of perioperative AKI and highlights the role of the interprofessional team in the care of patients with this condition.

Objectives:

• Describe the pathophysiology of perioperative acute kidney injury.
• Outline the risk factors for developing perioperative acute kidney injury.
• Summarize the treatment considerations for patients with perioperative acute kidney injury.
• Review the importance of collaboration and communication among members of the interprofessional team to improve outcomes for patients affected by perioperative acute kidney injury.

Introduction

Perioperative acute kidney injury (AKI) is a serious yet under-recognized problem in patients who have recently undergone surgery. Due to increasing age and number of comorbidities, perioperative AKI is increasing in incidence and has significant morbidity and mortality.[1] Postoperative AKI is of particular concern because when compared to patients without postoperative AKI, the risk of short- and long-term mortality is increased, and both costs of hospitalization and utilization of resources are significantly increased. Early recognition of AKI and implementation of early goal-directed therapy is critical to reducing the incidence of progression to chronic kidney disease, renal replacement therapies (RRT), and death.[2]

Etiology

Perioperative acute kidney injury is defined as an abrupt decline in renal function that occurs within hours to days of surgery.[3] It is multifactorial but considered to be due to two primary mechanisms: renal hypoperfusion in the perioperative period and systemic inflammation that occurs as a direct response to surgery.[1]

Epidemiology

Perioperative AKI is a common and highly underrecognized medical problem.[1] Since a standard definition is lacking, many cases are unrecognized and underreported. Nonetheless, AKI is estimated to occur in approximately 12% of hospitalized patients annually.[3] Meersch et al. reported 2,147 cases per million per population year as of 2017, with 30% to 40% of these cases occurring in surgical patients. Of these surgical patients, those receiving cardiac surgery with cardiopulmonary bypass use are at the highest risk for the development of AKI. Other populations with increased AKI risk include gastric bypass surgery in morbidly obese patients, patients undergoing a liver transplant, and surgical patients with preexisting chronic kidney disease. Chronic kidney disease serves as an independent risk factor for morbidity and mortality in the postoperative period.[4] Other patient-associated risk factors for AKI include a preoperative creatinine level greater than 1.2 mg/dl, advanced age, Black race, preexisting hypertension, active congestive heart failure, pulmonary disease, insulin-dependent diabetes mellitus, peripheral vascular disease, presence of ascites, and high body mass index.[5]

Pathophysiology

Perioperative AKI does not arise from a single insult, but instead develops as the result of several, with hypoperfusion and inflammation thought to be the main drivers.[1] Perioperative AKI is due to inflammation caused by hemodynamic instabilities, nephrotoxicity, damage-associated molecular pattern (DAMP), and obstruction.[3] Decreases in mean arterial pressure (MAP) due to hypovolemia or systemic effects of anesthetics contribute to renal hypoperfusion. Once the intrinsic compensatory mechanisms of the kidneys, mediated through sympathetic nervous system activation leading to the production of antidiuretic hormone and angiotensin-II, are surpassed, the kidneys are unable to maintain an adequate glomerular filtration rate (GFR) and renal function is reduced. In patients with underlying chronic renal disease, autoregulation is impaired, exacerbating the effects of hypoperfusion. Additionally, surgical stimulation induces systemic inflammation leading to microcirculatory effects, endothelial dysfunction, and increased leukocyte migration. The net result of these inflammatory changes is damage to the renal tubules and AKI.[1]

History and Physical

Overall, AKI is non-specific in presentation, and clinical signs on physical examination are related to the degree of renal function that has been lost and the underlying insult, i.e., hypotension or hypovolemia.[6] Intraoperative hypotension, before and after incision, as well as the duration and depth of the hypotension, have been significantly correlated with AKI.[7] Intraoperative hypotension plays a significant role in the subsequent development of AKI. It can occur before incision, which is often preventable, or after incision, which is not as easily prevented. Post-incision hypotension is multifactorial and can be due to blood loss, changes in noxious stimulation, or positioning or vessel compression. One study demonstrated intraoperative hypotension in half of the patients, and hypotension occurred four times as often post-incision.[7]

Evaluation

Several criteria are used to define AKI, including Acute Kidney Injury Network (AKIN), Risk, Injury, Failure, Loss, ESKD (RIFLE), and Kidney Disease Improving Global Outcomes (KDIGO).[1] These criteria utilize serum creatinine (sCr) levels, glomerular filtration rate (GFR), and urine output. sCr increases late in the process of AKI development and is not recognized until approximately 50% of the renal mass is lost. The criteria for each classification system can be found below.

AKIN: Any of the following within 48 hours: Increased sCr x1.5, sCr increase 0.3 mg/dl or more, or urine output less than 0.5 ml/kg/h for more than 6 hours[5]

RIFLE: Any of the following within 7 days: Doubled sCr, glomerular filtration rate (GFR) decrease more than 50%, or urine output less than 0.5 ml/kg/hour[5]

KDIGO: Any of the following: Increase in sCr by ≥ 0.3 mg/dl (≥ 26.5 micromoles/l) within 48 hours, increase in sCr to 1.5 times baseline which is presumed to have occurred within the prior seven days, or urine volume less than 0.5 ml/kg/hour for 6 hours[5]

Innovations in laboratory analysis of AKI have determined the existence of AKI biomarkers that can be detected before renal mass is lost.[3] These biomarkers are surrogates of early stress on the renal tubules. They are mobilized secondary to cardiopulmonary bypass and surgical stimulation and reflect underlying mechanisms of renal injury since different biomarkers are released in response to specific insults. Of note, insults due to G1 cell cycle arrest are associated with tissue-inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) biomarkers and are predictive of major adverse kidney events, including death, persistent renal dysfunction, and need for dialysis.[8] Other biomarkers being studied for similar purposes are neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin C.[5]

Early identification of high-risk patients can be made using these biomarkers, with early application of KDIGO bundles. In patients for whom bundled care is initiated early, there are lower rates of moderate and severe AKI when compared to patients with AKI that are treated with standard therapy.[8]

Treatment / Management

When AKI develops, goal-directed therapy to reach adequate cardiac output and oxygen delivery levels has been documented to reduce mortality resulting from AKI.[9] Unfortunately, studies have shown that the development of lactic acidosis or hypotension intraoperatively is a late indicator of decreased renal perfusion. As such, cardiac output and renal blood flow should be maintained with aggressive fluid resuscitation, and when fluids alone are not sufficient, inotropes are necessary. The use of 0.9% saline is strongly associated with the development of hyperchloremia and reduced renal blood flow. In ICU patients, limiting the chloride content of intravenous fluids has been associated with a lower risk of postoperative AKI and the need for RRT.[10] The use of hydroxyethyl starches, when compared to colloids, has been linked to increased rates of AKI and increased need for RRT in some investigations. In contrast, it has not been shown to increase AKI in other studies, and as such, remains a topic of controversy. The use of hydroxyethyl starches, including low-molecular-weight starches, in the perioperative period, is not recommended in patients with an increased risk of AKI.[10]

Several medications have been controversial in the treatment of AKI. Dopamine was thought to be useful in AKI as it promoted increased renal blood flow at low doses, but this has not been born out in studies. Fenoldopam is a selective dopamine-1 agonist that has been shown to reduce the need for RRT. Nonetheless, this has only been consistently demonstrated in patients having undergone cardiac surgery, and its use is limited by its ability to cause systemic hypotension. Diuretics are beneficial in improving urine output. However, diuretics increase serum creatinine and can worsen AKI. Atrial natriuretic peptide (ANP) is effective in reducing the need for RRT in post-cardiac surgery patients, yet, like fenoldopam, its utility is limited by systemic hypotension.[11]

The KDIGO bundle recommends specific measures to help prevent AKI. These include avoidance of substances that are nephrotoxic, optimizing volume status to maintain sufficient perfusion pressures, maintaining normoglycemia, and monitoring serum creatinine, urine output, and perhaps monitoring of hemodynamics. The KDIGO bundle, if implemented early based upon biomarkers, reduces the development of AKI in postsurgical patients.[12]

Prompt nephrology referral is vital in the management of AKI. Studies of hospitals without nephrology coverage have demonstrated recognition of AKI was delayed with an associated increase in resulting CKD and decreased survivability.[2] Nephrology referral within 18 hours of initial insult reduces the progression of AKI and preserves renal function. If there are life-threatening complications, such as volume overload that is unresponsive to diuretics, metabolic disorders, or electrolyte disturbances, renal replacement therapy should be initiated immediately.[12]

Differential Diagnosis

There are a variety of perioperative AKI syndromes that must be considered, including hemodynamic, nephrotoxic, damage-associated molecular pattern (DAMP)-induced inflammation, and obstruction. If oliguria develops as the presenting symptom of AKI, mechanical obstruction of the urinary tract must be considered. Obstruction is especially common in colorectal, urological, and gynecological surgical procedures. Additionally, drug-induced urinary retention should also be excluded. If a Foley catheter is in place, it should be inspected to ensure that it is not obstructed or kinked. Increased release of antidiuretic hormone secondary to pain, nausea, surgery, and other non-renal stimulation should be considered, as should increased aldosterone secretion.[3]

Prognosis

Perioperative AKI is associated with an up to ten-fold increase in mortality, reduced long-term survival, and increased development of chronic kidney disease with subsequent need for hemodialysis following hospital discharge. AKI requiring renal replacement therapy is an independent risk factor for death.[4]

Complications

As previously discussed, the development of perioperative AKI places the patient at risk of progression to chronic renal disease and may require long-term renal replacement therapy.[4]

Deterrence and Patient Education

For patients that have developed perioperative AKI, there are several things they should be advised of in order to preserve renal function, including avoiding nephrotoxic agents. Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause interstitial nephritis, which can lead to the development of AKI or the worsening of existing AKI. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are known to affect renal autoregulation, although the avoidance of these mediations in the perioperative period is currently a topic of debate.[11]

Enhancing Healthcare Team Outcomes

Early recognition of perioperative AKI is the first step in improving care. The risk-adjusted cost of caring for a patient with perioperative AKI is $42,600 per episode of care, versus $26,700 per episode of care in a patient without AKI.[2] Unfortunately, nephrology consultation is usually made after an AKI has become severe, typically with serum creatinine increasing more than 101% from baseline, at which point renal replacement therapy is often required.[13] Soares et al. described the importance of nephrologist involvement in interprofessional care teams in making early identification of AKI and implementing strategies to slow or stop the progression of AKI. AKI is also strongly associated with nutritional impairments, including negative nitrogen balance, alterations in serum concentrations of amino acids, gluconeogenesis, and insulin resistance. As such, registered dieticians have an essential role in ensuring that patients with AKI have adequate nutritional requirements to meet these deficiencies.[13] Pharmacists also have an important role in the interprofessional care team in the management of perioperative AKI. Clinical pharmacists have the expertise to perform medication reconciliations to prevent drug-drug interactions. They can also adjust the dose of medications based upon renal function, as needed, for changing the glomerular filtration rate, as this will be dynamic as AKI worsens or improves. These interventions by pharmacists have shown to prevent the progression of renal disease to the point of requiring RRT in patients with chronic renal disease, and it is reasonable that they can have similar outcomes in acute renal injury.[14]