Risk Assessment and Perioperative Renal Dysfunction

Influence of Surgery and Anesthesia on Renal Perfusion

The kidney is an elegant system of integrated processes that maintain fluid homeostasis and eliminate waste products. Although the kidney requires only 10% of the total corporeal oxygen consumption, the renal cortex receives 90% of the total RBF and extracts only 18% of the oxygen delivered. In contrast, the renal medulla receives only 10% of the RBF to the kidney, and it is the site of the costly energy- and oxygen-consuming processes that are responsible for reabsorbing tubular sodium and water. In the medulla, 79% of the oxygen delivered is extracted, resulting in a high arteriovenous oxygen gradient in the medulla of the kidney. Thus the medulla is exquisitely sensitive to reductions in RBF. A 40% reduction in RBF may lead to acute tubular necrosis, especially in the presence of other renal insults. Interventions that improve RBF (increased cardiac output [CO], fluid replacement) or decrease medullary oxygen consumption can potentially improve the tolerance to intermittent periods of ischemia. Other conditions, including exposure to radiocontrast dyes and an increased bilirubin concentration or myoglobinuria, can exacerbate the adverse response to renal hypoxia by increasing the osmotic load to the nephron and further increasing oxygen requirements.

Several types of drugs have been shown to be nephrotoxic through a variety of mechanisms. The perioperative use of aminoglycosides or non-steroidal anti-inflammatory drugs may precipitate AKI in the hypoxic kidney. The chronic use of angiotensin-converting enzyme (ACE) inhibitors may lead to an attenuation of the normal compensatory response to a decrease in renal perfusion. Aprotinin, which is an anti-inflammatory serine protease inhibitor that was used intraoperatively to reduce blood loss, is concentrated in the kidney, and as previous studies suggested, its use was associated with postoperative AKI and renal failure requiring renal replacement therapy. Further, a combination of ACE inhibitors and aprotinin can have a synergistic adverse effect on renal function in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).

AKI itself is defined by an abrupt loss of kidney function, resulting in the accumulation of metabolic waste and byproducts and the loss of fluid and electrolyte regulation. There has been a shift from terms such as “renal dysfunction” and “renal failure” to the more accepted term of “kidney injury” to better reflect the knowledge that a small degree of renal dysfunction may not necessarily result in complete organ failure but still have profound physiologic consequences and can result in significant morbidity and increased mortality. There are many—over 30—definitions of AKI using various clinical criteria. Indeed, the lack of consensus of a single clear and universally accepted definition of AKI has been a source of controversy and confusion in the field, as well as a barrier to research of the disease and advancement in knowledge of AKI.

Three of the most well-known definitions are the Acute Dialysis Quality Initiative RIFLE criteria, the Acute Kidney Injury Network (AKIN) criteria, and the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, which have been developed over years as knowledge of AKI has improved. RIFLE criteria used the idea of stages of kidney injury, known as “risk,” “injury,” “failure,” “loss of kidney function,” and “end-stage renal disease,” from which the acronym was derived, and used increases in creatinine (Cr) and decreases in urine output (UO) as metrics. The AKIN criteria were developed later and revised the RIFLE criteria, removing the “loss of kidney function” and “end-stage renal disease” stages and simplifying the names of the first three stages to stages 1, 2, and 3. They also modified the time scale over which these perturbations occur, reducing the time to 48 hours from the RIFLE criteria’s original 7-day window. The KDIGO criteria are the most recent and allow correction of volume status and obstructive causes of AKI before classification. The KDIGO definition of AKI involves an increase in serum creatinine (sCr) by 0.3 mg/dL or more within 48 hours, or an increase in sCr to 1.5 times baseline or more within the prior 7 days, or UO less than 0.5 mL/kg/h for 6 hours. Further criteria are then used to stage AKI.

Anesthesia (both general and regional) and surgery, independently and synergistically, could impair renal homeostasis during operative procedures. Both types of anesthesia are associated with peripheral vasodilation, thus leading to a reduction of circulating blood volume and renal perfusion. Vasodilation and the resultant reduction in RBF are particularly a concern in a patient who has been nil per os (NPO) for 8 or more hours, was prescribed a chronic diuretic or an ACE inhibitor, has suffered recent vomiting or diarrhea, has undergone a recent bowel preparation, or is actively bleeding. No studies have demonstrated that general anesthesia is superior to regional anesthesia in limiting the likelihood for postoperative AKI.

Regarding general anesthesia in particular, there have been investigations into the possible adverse renal effects of inhalational anesthetics and their fluoride ion metabolic byproducts. Of the clinically used inhalational agents, sevoflurane and enflurane release the greatest number of fluoride moieties. However, the pharmacokinetics of these volatile agents greatly limits the likelihood of renal dysfunction secondary to fluoride exposure. Choice of an inhalational agent has been found to have little relevance for inducing postoperative AKI, as it was reflected by a lack of elevation of AKI biomarkers in the patients who underwent elective cardiac surgery. An interaction between sevoflurane and soda lime or barium hydroxyl carbon dioxide could also pose a potential risk for producing a potentially nephrotoxic haloalkene known as “compound A.” However, the metabolic pathways for this compound in humans limit the likelihood of compound A–induced nephrotoxicity. Indeed, there are no published reports of AKI induced by exposure to sevoflurane in surgical patients.

Patient Characteristics and the Risk of Postoperative Acute Kidney Injury

Patient-specific factors (identifiable in the preoperative period) that are associated with postoperative AKI fall generally into one of three categories: (1) patient characteristics suggesting impaired renal functional reserve, (2) physiologic findings associated with impaired renal perfusion, or (3) pathophysiologic processes that cause renal injury. Potential risk factors include advanced age; abnormal sCr values; DM; and any sign, symptom, or factor indicative of a reduced CO and thus compromised renal perfusion ( Fig. 8.1 ). However, the low incidence of postoperative AKI necessitating renal replacement therapy (< 2.0% even in high-risk populations) and the lack of sensitive, routine laboratory studies that identify AKI even when it does not result in an increase in Cr or blood urea nitrogen (BUN) have challenged investigators to identify factors that are associated with postoperative AKI.