Update on Perioperative Acute Kidney Injury

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


Anesth Analg. 2018;127(5):1236-1245. 

In This Article

Prevention of AKI

Urine output and SCr, 2 functional biomarkers, are changing very late during the development of AKI and have certain limitations (Table 2). Although recently published evidence demonstrates an association between low urine output and adverse outcomes in pediatric patients[73] and adults,[52] urine output cannot be used to detect kidney damage. Changes of the SCr only become manifest after 50% of the renal mass is lost, leading to the decline of the GFR. Transient changes cannot be detected, although damage has occurred. Therefore, extensive work has identified new damage biomarkers that detect kidney damage before a functional decline (sCr increases and/or urinary output declines) occurs (Table 2).[74–76]

Recent studies have demonstrated that damage AKI biomarkers can detect kidney damage without loss of function.[74,75] Based on these studies, the term "subclinical AKI" was introduced (Figure 2).

Figure 2.

Subclinical AKI: damage without loss of function. Diagnosis of AKI based on damage markers (new biomarkers) and functional (SCr). The use of damage biomarkers allows a detection of kidney damage without a loss of function (subclinical AKI). AKI indicates acute kidney injury; SCr, serum creatinine.

Cardiopulmonary bypass, surgical trauma, or other noxious events might trigger the production and release of DAMPs, proinflammatory mediators, and possible biomarkers of early tubular stress. Different aspects of kidney function and different mechanisms of injury are reflected by different biomarkers. They are able to detect AKI earlier and might identify the underlying etiology. However, before implementing these biomarkers into daily practice, several issues have to be addressed, including the low sensitivity related to the etiological heterogeneity of AKI and low specificity related to extrarenal causes for fluctuations of biomarkers levels.[77] The performance of AKI biomarkers was very good when well-defined kidney injury was examined.[78] However, in heterogeneous patient populations with variable onset and causes of kidney injury, the performance of biomarkers was reduced. To increase the robustness of the predictive performance of AKI, the "renal angina" concept was introduced. This concept combines clinical conditions with comorbidities and biomarkers. Measurement of biomarkers in patients with a certain risk profile considerably improves the negative predictive value of the markers.[79]

Various interventions have been investigated to prevent the development of AKI, but only a few have achieved a promising result.

Hemodynamic Control

Autoregulatory mechanisms control renal blood flow within a broad range of pressures to maintain a stable GFR. Different factors and diseases, including hypertension, kidney disease, and major surgery, might disrupt renal autoregulation, leading to ischemia and kidney injury.[80] Reduced renal blood flow leads to renal hypoxia, inflammation, and fibrosis, which induce microvascular dysfunction in hemodynamic compromised conditions.[80,81] In acutely ill patients, renal ischemia is the most frequent and important pathogenetic AKI factor.[82] Prolonged episodes of hypotension in the intraoperative period may decrease renal perfusion, resulting in AKI in patients with impaired autoregulation.[83] A retrospective study including 5127 patients undergoing noncardiac surgery observed AKI when mean arterial pressure during surgery was <60 mm Hg for >20 minutes and <55 mm Hg for >10 minutes (adjusted OR, 2.34; 95% CI, 1.35–4.05).[84] Based on these data, the duration of a hypotensive episode should be kept as short as possible (Table 2).[84] A general recommendation for a sufficient mean arterial pressure is not available. However, a recently published trial suggests that individualized blood pressure control in the perioperative period might reduce the occurrence of AKI.[85] Optimizing the hemodynamic situation is required in patients at high risk for the development of AKI because it is well known that both hypotension and hypertension can negatively affect renal microcirculation in patients with compromised renal autoregulation.


The main aim of volume resuscitation is the reestablishment of a stable hemodynamic situation and organ perfusion.[86] Several studies in critically ill patients demonstrated that volume overload is associated with organ edema, leading to the development of AKI and worsening of preexisting AKI.[58,87] Due to fluid overload and oliguria in critically ill patients with preexisting AKI, fluid management is very challenging. Hypovolemia and hypervolemia in critically ill patients increase morbidity as well as mortality. However, the intraoperative use of diuretics can only be recommended for managing severe fluid overload and not for preventing AKI.[2] In patients with preexisting renal dysfunction, an association between the use and dose of diuretics and the development of AKI exists.[88] The amount and type of fluid together play a crucial role. Large amounts of 0.9% saline leads to hyperchloremic acidosis and renal vasoconstriction and increase the risk of AKI (Table 2).[89–91] Furthermore, the use of a saline-based solution strategy resulted in a higher postoperative incidence of AKI than the use of a chloride-restrictive fluid strategy.[92] Recently published trials demonstrated that the use of saline in critically ill patients resulted in a higher rate of the composite outcome from death from any cause, persistent renal dysfunction, or RRT than the use of balanced crystalloids.[48,93] Therefore, the use of balanced crystalloids and an adequate perioperative control ensuring hemodynamic stability are recommended.

Remote Ischemic Preconditioning

Remote ischemic preconditioning (RIPC) is a simple technique to provide organ protection. It is triggered by brief episodes of transient ischemia and reperfusion, and the protective effects are not limited to the organ or tissue receiving the preconditioning stimulus but were also traceable in remote organs.

Due to the kidney's high metabolic rate and complex vascular anatomy, it is particularly susceptible to ischemia reperfusion injury.[94] Thus, RIPC was speculated to be an effective procedure to trigger endogenous protection against renal ischemic damage. A typical method to induce RIPC is to put a blood pressure cuff around an arm and inflate the cuff up to 50 mm Hg above the systolic blood pressure to induce an ischemia. After a certain time point (normally 5 minutes), the cuff is deflated and reperfusion of the tissue is allowed. These cycles are repeated several times. To date, the underlying mechanisms of RIPC are not fully elucidated. Evidence indicates that RIPC leads to the release of DAMPs, which subsequently bind to pattern-recognition receptors on the surface of renal tubular epithelial cells, introducing a brief episode of cell cycle arrest through the release of alarm markers.[95]

Several clinical trials showed that RIPC can reduce the occurrence of AKI after surgery (Table 2),[96,97] whereas others showed no effect.[98,99] The results of the different trials are difficult to compare because of the use of different end points and the heterogeneity of trial designs and patient populations. However, it is important to note that some medications (eg, propofol, sulfonamide) mitigate the protective effects of RIPC. Although conflicting results exist, RIPC should be considered as a preventive measure because it does not impose additional costs, is easy to apply, and is not associated with complications.