Update on Perioperative Acute Kidney Injury

Alexander Zarbock, MD; Jay L. Koyner, MD; Eric A. J. Hoste, MD; John A. Kellum, MD

Disclosures

Anesth Analg. 2018;127(5):1236-1245. 

In This Article

Pathophysiology

AKI is a nonspecific clinical syndrome defined by a rapid loss of GFR.[29,30] Even perioperative AKI includes multiple different syndromes (Figure 1), and proper therapy can vary widely.

Figure 1.

Perioperative AKI syndromes. Major mechanisms of acute kidney injury in the perioperative setting. ACEi indicates angiotensin-converting-enzyme inhibitor; AKI, acute kidney injury; ARB, Angiotensin II receptor blockers; HMGB1, High-Mobility-Group-Protein B1; NSAID, nonsteroidal anti-inflammatory drug.

To support clinical diagnosis and facilitate studies, AKI is classified based on specific clinical and laboratory criteria.[2] However, AKI is a clinical diagnosis, and these criteria do not define it in the same way that electrocardiographic changes and troponin do not define myocardial infarction. Azotemia and oliguria are indicative of pathology as well as of normal responses of the kidney to extracellular volume depletion or a decreased renal blood flow. In fact, a "normal" urine output and GFR in the face of volume depletion would actually indicate renal dysfunction. Thus, changes in urine output and GFR are neither necessary nor sufficient for the diagnosis of renal pathology.[31] Still, they serve as the backbone for our existing diagnostic criteria[2]—checklists or similar tools may help in difficult cases.[32] Healthy individuals, particularly younger adults, have substantial renal reserve[33,34] and can lose more than half their renal function before SCr changes.

Pathogenesis of Perioperative AKI

The traditional taxonomy of AKI based on pseudo-anatomic locations (pre, intra, and post) in reference to the kidney is overly simplistic and has given way to specific "AKI paradigms,"[29] including hepatorenal,[35] cardiorenal,[11] nephrotoxic,[36] sepsis-associated,[37] and urinary tract obstruction. These syndromes all have unique pathophysiologies and treatments and may also have different molecular signatures.[38] Surgery can injure the kidney in a number of ways, and surgical patients may be exposed to a number of injurious stimuli in the perioperative period (Figure 1). For treatment, these various syndromes need to be considered separately rather than lumped together as 1 disease. At times, therapies will be diametrically opposed.[30] For example, will a patient with AKI benefit from fluid administration, diuresis, or neither? The answer depends on whether the patient has cardiorenal physiology from acute decompensated heart failure where the answer will usually be diuresis or septic shock and where judicious use of fluids is required (but further fluid use will not be helpful) or nephrotoxic AKI where both fluids and diuretics may be harmful. Perioperative AKI syndromes include hemodynamic-, nephrotoxic-, damage-associated molecular pattern (DAMP)-induced inflammation and obstruction (Figure 1).[29]

Hemodynamic-mediated AKI

Surgery can result in hypovolemia, anesthetics can cause venodilation, and positive pressure ventilation can impair venous return to heart—all 3 reducing preload. Anesthetics can also reduce arterial tone, further compromising perfusion pressure. Clinicians are usually well conditioned to responding to these threats. However, right-sided hemodynamics are critical as well. In cardiac surgery, the right heart may be compromised from cardioplegia. In thoracic surgery, high pleural pressure may increase venous "back pressure" on various organs, including the liver and kidneys. In abdominal surgery, the high pressure may be in the abdomen. In all of these cases, the high venous pressure can injure the kidney by causing congestion within an organ that cannot expand. It may also compromise perfusion, particularly if arterial blood pressure is not increased to account for the loss of perfusion pressure. Therefore, excessive intravenous fluids may contribute to AKI, but overly restrictive fluid management may also be injurious to the kidney.[39]

DAMP-induced AKI

Another consequence of the hemodynamic alterations is the effect of reduced tissue perfusion in remote organs (eg, muscle). Various molecules are released during ischemia–reperfusion, including myoglobin, uric acid, and High-Mobility-Group-Protein B1 (HMGB1). These molecules are in a class of DAMPs that can signal through pattern recognition receptors including Toll-like receptors such as Toll-like receptor 4.[37] Tissue injury because of trauma or surgery itself can also release DAMPs into the circulation. Indeed, even mild ischemia–reperfusion of the arm can illicit the release of HMGB1 into the circulation with the triggering of a stress response in the kidney.[40] Cardiac surgery is associated with AKI, and efforts such as avoiding cardiopulmonary bypass appear to reduce the risk of AKI. In a trial of nearly 3000 patients, cardiac surgery "off-pump" reduced the risk of AKI (17.5% vs 20.8%; relative risk, 0.83; 95% confidence interval [CI], 0.72–0.97; P = .01) compared to standard technique using cardiopulmonary bypass.[41] In addition to the hemodynamic effects of cardiopulmonary bypass, there is often hemolysis, and plasma-free hemoglobin can also function as a DAMP.

Inflammation

Surgery and the healing process that follows is a well-known cause of inflammation. Inflammatory mediators such as tumor necrosis factor-α as well as activation of circulating immune effector cells can injure the kidney. Cardiopulmonary bypass also induces inflammation. Sepsis produces profound systemic inflammation and is also associated with the release of pathogen-associated molecular patterns that signal through some of the same receptors.[37]

Nephrotoxic AKI

Nephrotoxic AKI is a particularly prevalent condition in this population, and it appears quite amenable to practice change.[42] Goldstein[43] at Cincinnati Children's Hospital has spearheaded efforts to reduce nephrotoxicity by identifying patients electronically. Antibiotics can be nephrotoxic in both direct (eg, aminoglycosides) and indirect ways. Allergic interstitial nephritis, for example, may occur even in patients who do not manifest other signs of allergy. Antibiotics also kill bacteria, and some release more bacterial cell products (eg, endotoxin) into the circulation than others. These pathogen-associated molecular patterns can then directly injure the kidney or contribute to systemic inflammation.[44] Certain fluids may also contribute to AKI.[45,46] Hydroxyethyl starch has been linked to AKI and decreased survival in patients with severe sepsis.[45] Although these results were not confirmed in a larger trial,[47] the exposure was less, and there was still some evidence of renal toxicity, albeit only in the rates of acute RRT. Saline increases rates of major adverse kidney events (death, dialysis, or persistent renal dysfunction) in both critically ill and noncritically ill patients.[48,49]

Urinary Tract Obstruction

Colorectal, urological, and gynecological surgery are often associated with urinary retention, although normally not complete obstruction. Drug-associated urinary retention is also a risk. Injury to the ureters is always a potential complication, and unilateral injury can be easily missed. Malfunctioning or misplacement of the Foley catheter or clogging of the catheter can also result in obstruction.

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