Postoperative Acute Kidney Injury

Abstract

Postoperative AKI is a common complication of major surgery and is associated with significant morbidity and mortality. The Kidney Disease Improving Global Outcomes AKI definition allows consensus classification and identification of postoperative AKI through changes in serum creatinine and/or urine output. However, such conventional diagnostic criteria may be inaccurate in the postoperative period, suggesting a potential to refine diagnosis by application of novel diagnostic biomarkers. Risk factors for the development of postoperative AKI can be thought of in terms of preoperative, intraoperative, and postoperative factors and, as such, represent areas that may be targeted perioperatively to minimize the risk of AKI. The treatment of postoperative AKI remains predominantly supportive, although application of management bundles may translate into improved outcomes.

Introduction

AKI is a common complication of patients undergoing major surgery and is associated with both short-term morbidity and mortality and longer-term adverse outcomes, including the development of CKD (13). AKI has been described as a sentinel surgical complication being associated with a higher incidence of many adverse outcomes, including a longer hospital length of stay, intensive care unit (ICU) admission, the need for prolonged mechanical ventilation, tracheostomy, discharge to a nursing facility, and higher 30-day readmission rates (4,5).

In 2012, Kidney Disease Improving Global Outcomes (KDIGO) described the KDIGO AKI diagnostic criteria and categorized AKI into stages 1–3, determined by changes in serum creatinine and/or urine output (6). Recently, postoperative AKI was further defined by joint consensus of the Acute Disease Quality Initiative and Perioperative Quality Initiative as occurring when KDIGO criteria for AKI are met within 7 days of an operative intervention (7). Although postoperative AKI is often low grade (stage 1–2), with relatively modest absolute changes in serum creatinine, these changes can represent quite large reductions in the GFR in healthy individuals, suggesting AKI is often identified late, when significant damage may have occurred. Indeed, some evidence suggests that minor increases in serum creatinine, which fail to meet the KDIGO criteria for AKI diagnosis, are still associated with higher risk of mortality and longer hospital stays in patients undergoing surgery. This includes those undergoing cardiac surgery, suggesting a significant and clinically important group of patients with subclinical AKI (8). Furthermore, the use of serum creatinine to define postoperative AKI is not without confounders; for example, a baseline serum creatinine may be unavailable and AKI may already be established in emergent perioperative cases. Moreover, changes in volume status and total body water, which are encountered with perioperative fluid administration, may mask rises in serum creatinine, particularly in the immediate postoperative period. Some authors have proposed that correcting for volume overload will allow further characterization of patients with AKI; however, this approach is overly simplistic and likely to be inaccurate over more than a few hours after volume expansion (9). Decreases in the production of serum creatinine may occur after surgery, which is related to muscle creatine content and metabolism, and this can result in a fall in serum creatinine independent of GFR, which may mask diagnosis and assessment of AKI and its outcomes (10). AKI may also precede the surgical intervention and may persist for >7 days, at which point it should be classified as postoperative acute kidney disease (11).

Finally, postoperative oliguria is common and not always accompanied by an associated serum creatinine rise. Transient intraoperative oliguria is often witnessed, however the longer-term implications of this are somewhat unclear. Some postoperative oliguria is presumed to be part of an appropriate physiologic response to tissue injury and does not always reflect a true kidney injury; urine output decreases appropriately through the action of antidiuretic hormone in response to pain, nausea, and surgical intervention (1214). Although some of the literature suggests that oliguria and incidence of postoperative AKI are unrelated, there is an increasing body of evidence demonstrating adverse outcomes and a higher incidence of postoperative AKI may be associated with intraoperative oliguria in both cardiac and intra-abdominal surgery (1517). AKI, when defined by oliguria alone, is substantially more common than when a definition using change in serum creatinine is used. For example, Quan et al. (18) demonstrated an increase in postoperative AKI incidence from 8% to 64% when urine output was included in the definition. This has important implications for the interpretation of clinical trials for AKI treatment or prevention, where urine output definitions of AKI are more often applied compared with retrospective epidemiologic studies and routine clinical practice.

Epidemiology

AKI is common in the postoperative cohort; however, the incidence of postoperative AKI varies significantly depending on the type of surgery, urgency, and, as highlighted, the definition criteria used. Unsurprisingly, AKI is most common among patients undergoing cardiac surgery, particularly where cardiopulmonary bypass is used, with AKI complicating more than one in five patients, and 2% of patients requiring KRT, which carries a mortality approaching 60% (1,19,20). Furthermore, the type of cardiac surgery is relevant, with a recent study demonstrating that patients undergoing aortic surgery had higher risk for acute KRT, but also the highest rates of kidney recovery (21). Additionally, patients undergoing valve surgery and requiring KRT postoperatively had the highest risks of all‐cause mortality (hazard ratio, 6.04; 95% confidence interval [95% CI], 5.78 to 6.32) (21). Vascular surgery also carries a higher risk of AKI, with an incidence of between 20% and 70% of postoperative AKI described, depending on the procedure being performed (22,23). Endovascular procedures carry the lowest risk of postoperative AKI, which may be due to a reduction in ischemic-reperfusion injury or because there are fewer hemodynamic insults observed with this technique (24). However, this observation is confounded by differing degrees of urgency and complexity between approaches, with emergent and technically challenging cases potentially more likely to necessitate an open technique. Other procedures that carry a higher risk for AKI include gastric bypass surgery, with a reported 9% incidence of AKI, and liver transplantation, where AKI incidence is >50% and 17% of patients may require KRT (25,26). The rate of AKI in the surgical population who are discharged the same day as their operation remains unknown. Importantly, rates of AKI in patients requiring admission to the ICU after surgery are substantially greater, with rates of up to 50%, in line with a critically ill population in general (19,27). Although the literature base here is large, most studies are retrospective, hence a recent consensus statement has called for more prospective work to be undertaken to better understand the pathophysiology and epidemiology of postoperative AKI (7).

Pathophysiology

AKI is a clinical syndrome of an acute decline in kidney function and, consequently, identification of AKI does not inform as to the underlying cause(s) of kidney injury. Indeed, the causes of postoperative AKI are often complex, multifactorial, and rarely represent a single underlying pathophysiology. This means classifying an AKI by phenotype, although scientifically appealing, is often not pragmatically possible. Figure 1 highlights the major pathologic processes involved in the development of postoperative AKI, which may be considered as preoperative, intraoperative, or postoperative in nature. This classification maintains a clinically relevant narrative at the expense of delineating biologic mechanisms of the kidney pathology. Depending on the complex interaction of these processes, damage may occur with or without loss of function, but the implicated factors remain the same (28).

Figure 1.Figure 1.Figure 1.

Pathophysiology of postoperative AKI. Postoperative AKI often has a multifactorial etiology mediated by common injury pathways that affect the kidney microcirculation, oxygen (O2) demand, and inflammation. In most cases, a combination of preoperative risk factors, intraoperative events, and postoperative events leads to the development of AKI. Baseline risk factors and the persistence and severity of injurious factors in the postoperative setting also determine the outcomes of AKI, acute kidney disease, and, eventually, CKD. Adapted from ref. 81, with permission.

Preoperative Factors

Preoperative factors include patient characteristics such as sex, obesity, and older age, and known kidney dysfunction, hypertension, diabetes, and other comorbidities that are commonly seen in patients requiring complex surgery. However, in routine surgical practice in individuals undergoing major surgery of whatever type, a baseline serum creatinine should be acquired before surgery, preferably at preassessment, together with urinalysis. In individuals with documented proteinuria, this should be quantified and, where necessary, referral to nephrology services should be considered, depending on local practice. Other acute preoperative factors, such as the presence of sepsis, crush injury, or hepatic failure, may complicate emergent surgery (19,2932). Such preoperative factors are often difficult or, indeed, not amenable to optimization before surgery, particularly with emergent or expedited surgical procedures.

Potentially nephrotoxic drugs and intravenous contrast dyes are also used commonly in the perioperative setting, with risk of interstitial nephritis and acute tubular damage. Antihypertensives, particularly angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) are routinely held in the 24 hours before surgical procedures due to the higher risk of intraoperative hypotension associated with their ongoing use. It is thought that ACEis and ARBs may result in higher risk of AKI through a range of mechanisms, including systemic hypotension, and, where used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs), may result in renal artery constriction and interstitial nephritis (33). Therefore, it seems logical that withholding these agents in the perioperative period may be effective at reducing postoperative AKI incidence. However, this is not borne out by recent prospective and retrospective studies (34,35), indeed the STARsurg collaborative concluded that withholding ACEis or ARBs did not demonstrate a protective effect against the development of postoperative AKI within the general surgical population (36). Given that many patients are placed on ACEis or ARBs for both their cardioprotective and kidney-protective features, a risk-benefit analysis of continuing these medications in the perioperative period should be taken on an individualized basis, as should their reintroduction postoperatively.

Intraoperative Factors

Intraoperative factors encompass surgical and anesthetic technique, which may be generic or specific to the operative procedure. Cardiac and vascular surgery may cause kidney injury through a myriad of different mechanisms (28). These broad categories are shown in Figure 2, where a combination of hemodynamic, mechanical, inflammatory, and other mechanisms are implicated. Many of these relate to, or are complicated by, cardiopulmonary bypass. This can cause AKI via the effects of nonpulsatile flow, propagation of inflammatory cascades secondary to blood-bypass circuit interactions, microembolic phenomena, and through the downstream effects of hemolysis resulting in iron-mediated kidney and vascular injury (28). Cardiac surgery conducted without bypass, also known as “off pump,” may lead to lower rates of AKI, yet studies have often failed to find this difference translate into improvements in the need for dialysis or mortality (28,37). As shown in Figure 2, many mechanisms that cause AKI still occur independently of cardiopulmonary bypass. Current consensus does not recommend use of “off-pump” procedures to prevent AKI (28). Although endovascular procedures are less prone to hemodynamic instability and ischemia-reperfusion injury, they require the use of significant amounts of intra-arterial iodinated contrast, which may be particularly problematic in the context of prior CKD. Additionally, these procedures still involve instrumentation of the vasculature and so are prone to micro- or macroatheroembolic events. In some cases, this effect can be ameliorated by approach. For example, observational studies have shown a transradial approach, which avoids the descending aorta, can result in significantly lower rates of postprocedure AKI than a transfemoral approach (38). However, inevitably, instrumentation of vasculature related to the kidneys is unavoidable in many surgical procedures.

Figure 2.Figure 2.Figure 2.

Major pathophysiologic processes contributing to AKI after vascular and cardiac surgery. Hemodynamic perturbations occur because of nonpulsatile flow due to bypass therapy, crossclamping of the aorta, inovasopressor treatment, and volume resuscitation. More specific mechanical causes can also lead to AKI, such as microembolic phenomena, which occur because of cardiopulmonary bypass (CPB). Similarly, volume overload or right heart failure with venous congestion can compromise kidney function; mechanisms here are yet to be elucidated but may relate to “back pressure” on the glomerulus. Tubular toxicity can also occur as a result of the direct effects from free hemoglobin and liberation of free iron. This, alongside multiple other mechanisms, such as cholesterol emboli from crossclamping, blood transfusion, and immune activation from blood-bypass circuit interactions, can increase oxidative stress and lead to activation of inflammatory pathways. Reprinted from ref. 28, with permission.

Intra-abdominal surgery is associated with raised intra-abdominal pressure that is mediated through several mechanisms, including primary gastrointestinal pathology, such as bowel obstruction and ascites; hemorrhage due to trauma or aortic dissection; large volume fluid resuscitation; and iatrogenic mechanisms via peritoneal insufflation during laparoscopic procedures. Raised intra-abdominal pressure represents a higher risk for the development of postoperative AKI. This occurs via venous congestion, an increase in intrarenal pressure, and a reduction in kidney perfusion, which impairs glomerular and tubular function (39,40). At intra-abdominal pressure >15 mm Hg, oliguria and subsequent anuria is witnessed, with a corresponding rise in serum urea and creatinine. These changes appear to be potentially reversible if intra-abdominal hypertension is recognized and reversed in a timely manner (41).

Intra-abdominal or pelvic surgery can also cause postoperative AKI if there is direct urologic injury. Fortunately, this is a rare occurrence, with rates of iatrogenic ureteric injury usually being found to be <1% in colorectal, gynecologic, and urologic populations (4244). The highest rates are seen within gynecology surgery (44). If diagnosed intraoperatively, a repair may be attempted; unfortunately, many patients present late in the postoperative setting and a high-index of suspicion is paramount. Presenting features can include AKI, peritonitis, unexplained fever, and flank pain (45). Imaging via computed-tomography urogram or retrograde pyelography are the investigations of choice for diagnosis in the postoperative period (44,45). Depending on the surgery, specific strategies exist for the prevention, detection, and management of these injuries.

Anesthetic approaches may also influence the risk of postoperative AKI. Maintenance of euvolemia and intraoperative hemodynamic stability are key features in minimizing development of postoperative AKI. Intraoperative hypotension may be related to the vasodilatory and venodilatory effects of both general and regional anesthetic techniques, along with relative volume depletion through preoperative starvation and systemic inflammation, and not solely due to acute blood loss causing an actual volume depletion. It represents a key area of intraoperative management that can reduce incidence of postoperative AKI.

Although differing anesthetic techniques have been the focus of several studies, there remains no consensus that any one technique (regional versus general versus combined, or intravenous versus inhaled agents) demonstrates reduced rates of postoperative AKI compared with others, with all techniques being associated with relative venodilation and intraoperative hypotension (4648).

Postoperative Factors

Postoperative factors include hypovolemia, decreased cardiac output, mechanical ventilation, and exposure to potentially nephrotoxic drugs. Therefore, consideration before the routine use of potential nephrotoxins (including NSAIDS; certain antibiotics, particularly aminoglycosides; and loop diuretics) should be given with consideration to their cumulative effect(s).

Identifying Patients at Risk of Postoperative AKIRisk Prediction Models

For some, risk prediction models represent attractive tools to try to risk stratify patients for targeted interventions or personalized postoperative management. This is because baseline characteristics, including serum creatinine, and time of insult (time of surgery) are usually known. Typically, such models use combinations of independent predictors, which are assigned relative weightings to attempt to predict a clinical outcome. Several models have been developed, although many use older AKI definitions or are validated only in specific surgical subspecialties (19,36,49,50). Many models are not used clinically, however, and they can often struggle to discriminate according to different severities of AKI. Additionally, a trade-off can occur between incorporating intraoperative or postoperative factors to increase prediction accuracy at the expense of a prediction being made later in a patient’s course of treatment, where there is less opportunity to implement protective strategies. Work in this field continues to evolve and novel biomarkers may be able to bootstrap previously validated models. This is valuable work because creation of robust prediction tools may guide preoperative counseling, informed decision making, perioperative optimization, and longer-term care provision.

The Potential of Biomarkers in Identification and Management of Postoperative AKI

Given the limitations of both urine output and serum creatinine in identifying postoperative AKI, much effort has been focused on identifying other, novel biomarkers associated with the pathophysiologic processes underlying AKI. Early identification may then offer an opportunity for timely intervention in a patient cohort at higher risk of AKI, but also, importantly, may prevent intervention where there is no underlying parenchymal kidney injury. Several candidate novel biomarkers of AKI have been the subject of much research in recent years, with most postoperative studies focusing on cardiac and vascular surgery. Indeed, recent enhanced recovery programs after cardiac procedures have advocated for the adoption of AKI biomarkers in their risk stratification (51). In support of this approach, there is some evidence suggesting that patients with critical illness who display positive damage biomarkers, but do not fully meet urine output or creatinine criteria for AKI, have poorer outcomes (52).

Indeed, a recent consensus statement supported the use of a combination of damage and functional biomarkers, along with clinical context, for the prevention and management of AKI and suggest that the addition of biomarkers to the definitions of AKI be considered (53). Many of the biomarkers described to date are indicative of kidney tubular damage. One initially promising biomarker was neutrophil gelatinase-associated lipocalin (NGAL); in the initial reports in children undergoing cardiac surgery, a near ten-fold increase in the urine and plasma levels within 2 hours was identified in the patients who subsequently developed AKI (54). However, subsequent data demonstrated that NGAL levels increase not only in response to evolving AKI but also during other chronic and acute inflammatory conditions, and it has been suggested that the use of NGAL should wait until kidney-specific NGAL assays are available (55). Biomarkers associated with tubular G1 cell cycle arrest, tissue inhibitor of metalloproteinases 2 and IGF-binding protein 7, have been shown to be independent predictors of AKI (56). An immunoassay measuring urinary concentrations of these biomarkers, “NephroCheck” (57), has been created and approved by the US Food and Drug Administration and, as a consequence, NephroCheck has been used in multiple studies, including those by Vandenberghe et al. (58) and Göcze et al. (59). More recently, combinations of biomarkers have been explored; for example, an exploratory study, with a relatively small sample size, looked at using both NGAL and kidney injury molecule-1 to predict AKI. A high area under the curve was shown, however, larger studies will be required to further validate the results (60). Similarly, a combination of serum chitinase 3-like protein 1 combined with NGAL may be promising, with initial results showing a good predictive value for AKI stage 2/3 (61).

Most biomarkers reflect tubular injury or stress occurring after insult. However, some recent evidence suggests there is potential for biomarkers to be used in the preoperative setting to identify those at high risk of developing AKI. Urinary dickkopf-3 (DKK3), a marker of chronic kidney tubular stress associated with kidney fibrosis in the progression of CKD, has been studied in patients who had cardiac surgery. The association between the ratio of preoperative urinary concentrations of DKK3 to creatinine (DKK3/creatinine) and postoperative AKI and longer-term kidney function was assessed. In an initial cohort of 733 patients, elevated DKK3/creatinine levels were associated with significantly higher risk for AKI (odds ratio, 1.65; 95% CI, 1.10 to 2.47; P=0.02), which was independent of baseline kidney function (62). Furthermore, elevated urinary concentrations of DKK3/creatinine significantly improved AKI prediction and were independently associated with significantly lower kidney function at hospital discharge and after a median follow-up of 820 days (interquartile range, 733–910 days). These findings led the authors to propose that urinary DKK3 might aid in the identification of patients in whom preventive treatment strategies are effective. Similarly, soluble urokinase plasminogen activator receptor (suPAR), the circulating form of a glycosyl-phosphatidylinositol membrane protein, is normally expressed at very low levels on a variety of cells, including, on induced expression, monocytes and lymphocytes (63). suPAR levels are strongly predictive of progressive decline in kidney function being linked to proteinuria. Hayek and colleagues (64) measured suPAR levels in patients enrolled in two prospective, observational cohorts undergoing coronary angiography or cardiac surgery. A total of 250 patients underwent cardiac surgery, and AKI developed postoperatively in 67 patients (27%); of those, 14 (6%) had severe (stage 2 or 3) AKI, and eight (3%) underwent dialysis. The risk of AKI was higher with increasing suPAR levels: in the highest suPAR quartile, 40% developed AKI, compared with 16% in the lowest quartile. Of note, the authors also explored the role of suPAR in animal models, concluding that suPAR may be directly involved in the pathogenesis of AKI through sensitizing kidney proximal tubules to injury through modulation of cellular bioenergetics and increased oxidative stress. In addition, the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been examined in risk stratification for postoperative AKI, reflecting the prominent role of heart failure as an AKI risk factor (65). A total of 35,337 patients who had cardiac surgery and measurements of preoperative NT-proBNP and postoperative creatinine were included in the study, with a primary outcome of stages 1–3 AKI. Postoperative AKI occurred in 34% of patients, and stage 2 and stage 3 AKI occurred in 3% and 1% of patients, respectively. The NT-proBNP concentrations significantly correlated with any-stage AKI and more severe AKI. Models including NT-proBNP significantly improved AKI prediction beyond basic models derived from other baseline factors. This is in keeping with the evidence that natriuretic peptides aid preoperative risk stratification for adverse cardiac outcomes in patients at high risk.

The discovery of novel biomarkers also has significant implications for the design of clinical trials. As has been discussed, the occurrence of postoperative AKI is common, yet the development of severe AKI is a much rarer complication. This means trials aiming to study novel therapies targeting AKI treatment are often faced with insufficient power and have difficulty in detecting efficacy of the studied interventions. Novel biomarkers, which may or may not be incorporated in prediction models, can enrich study populations and help ameliorate this issue, thus aiding in the evaluation of emerging therapies.

Many barriers remain before biomarkers can be implemented into routine practice, not least a sound financial case will need to be made that any alternative biomarker is worth the additional cost when compared with serum creatinine, which is cheap and ubiquitously measured. This may come in the form of identifying previous missed populations with, or likely to develop, CKD and the subsequent secondary prevention measures that can then be implemented. However, studies looking to show this are costly and complex to design with long follow-up periods, which will inevitably limit the speed of progress in this area.

Management of Postoperative AKI

Where possible, management should commence with identification of potential underlying risk factors, with the aim of identification and stratification of those patients who are at the highest risk of developing postoperative AKI. Through a process of risk stratification on the basis of previous history, along with planned surgical procedure, this information could then be used to inform a multidisciplinary team regarding preoptimization, surgical technique used, and postoperative destination. Pharmacologic management of AKI has been extensively investigated but, at present, there is no strong evidence to recommend a particular drug therapy (28,66). This may be due to inadequate risk stratification of patients and, as mentioned, biomarkers or models may aid future research here.

Because the above factors are common to most causes of AKI, management of postoperative AKI should follow KDIGO guidelines and include a Kidney Health Assessment tool, where available (7). A diagnostic work-up is required, obstructive causes should be excluded, and prevention of further kidney injury is paramount. Application of the KDIGO care bundle can be applied to the management of postoperative AKI (6). This consists of supportive measures, including volume replacement, maintenance of adequate BP targets, and avoidance of nephrotoxic agents. Of note, this bundle is supportive and generic, meaning, in most cases, the exact phenotype of the AKI may not be clinically relevant or affect management. A notable exception here is the management of obstructive causes of AKI or AKI resulting from direct urologic injury, whereby repair may be indicated. The KDIGO care bundle has been applied in randomized controlled studies using biomarker-enriched populations of high-risk surgical patients. Reductions in the rates of postoperative AKI have been demonstrated, although the long-term benefit of such approaches has not been yet established (59,67). KRT may be required in severe AKI with emergent indications, which have a well-established clinical consensus. Despite there being some supportive evidence for earlier initiation of kidney replacement on the basis of AKI criteria, the overall weight of recent research suggests that this does not improve mortality (6870).

Intraoperative Strategies

Intraoperative hypotension should be avoided. The initial approach to mitigate intraoperative vasodilation-associated hypotension is often fluid therapy, although significant intraoperative fluid overload can potentiate postoperative AKI and cause hemodilution (71). A Cochrane review and separate meta-analysis demonstrated that the use of individualized intraoperative, goal-directed fluid therapy can reduce the risk of postoperative AKI and could mitigate against harm from excessive fluid administration (72). The concomitant use of vasopressors should be considered early if hypotension does not appear to be fluid responsive or resolve adequately. Therefore, individualized and goal-directed intraoperative fluid management strategies may be preferable to target fluid therapy to those who require it (73).

Targeting a mean arterial pressure (MAP) of >65 mm Hg has demonstrated improved outcomes in several observational studies; indeed, an interventional trial using a MAP of >65 mm Hg as part of a goal-directed strategy demonstrated fewer postoperative complications and shorter hospital length of stay (74). Futier et al. (75) demonstrated reduced risk of postoperative organ dysfunction when targeting individualized systolic BPs compared with standard management.

Intraoperative hemodynamic instability also appears to influence the rate of postoperative AKI, with observational studies demonstrating the risk of postoperative AKI being higher when the MAP was <60 mm Hg for >20 minutes, or if the MAP was <55 mm Hg for >10 minutes, suggesting even short periods of profound hypotension intraoperatively may influence postoperative AKI development (7678). It is likely that individualized, goal-directed strategies for patient-specific MAP targets would further improve outcomes; however, more research is needed into which MAP targets should be applied to patient groups, including patients with known hypertension.

As mentioned earlier, fluid overload can potentiate postoperative AKI (71); conversely, over restricting volume resuscitation can lead to undertreatment of hypotension and compromise kidney perfusion. This trade-off has led to research attempting to characterize the “right” amount of fluid required to best mitigate the risk of postoperative AKI. In the RELIEF study, patients undergoing abdominal surgery were randomly assigned to one of two fluid strategies during and up to 24 hours after surgery. This demonstrated that a liberal intravenous fluid strategy was shown to be associated with a lower risk of postoperative AKI when compared with a restrictive fluid strategy (79). Those in the restrictive strategy received a median of 1.9 L intraoperatively and 1.7 L in the 24-hour postoperative period, versus those in the liberal strategy where 3 L were administered each intraoperatively and in the 24-hour postoperative period (79). Per the respective liberal and restrictive strategies, this was broken down into a bolus of 10 versus 5 ml/kg at induction, 8 versus 5 ml/kg infusion during surgery, and 1.5 versus 0.8 ml/kg postoperatively, with a ceiling dose at 100 kg, and it was permitted to reduce fluid administration if there was evidence of overload. The rate of postoperative AKI was 9% in the restrictive strategy versus 5% in the liberal strategy (P<0.001). Of note, in this robust pragmatic international trial, there were no statistically significant differences in other measured outcomes, including disability-free survival at 1 year, septic complications, or surgical site infection (79). Therefore, the results show that restricting fluid administration to the volumes described, which may avoid venous congestion and hemodilution, was not safer in terms of preventing postoperative AKI. The authors caution against the conclusion that this means an unlimited fluid strategy is best, however, because, even in the “liberal-fluid” strategy, patients only gained a median of 1.6 kg, which is well below the 2.5-kg mark that enhanced recovery programs recommend avoiding exceeding. Some may regard this “liberal” arm as still relatively restrictive.

Postoperative Recommendations

Postoperative hypotension may affect up to 30% of patients and is often undetected, representing a cohort of patients for whom there is scope for intervention (80). In those patients identified at high risk of AKI, intensive monitoring of BP and intervention through judicious use of intravenous fluids and/or vasopressive medications is an appropriate response to minimize risk of postoperative AKI. Choice of postoperative analgesia should be decided on an individualized basis, with opioid-sparing effects of NSAIDs weighed against risk of AKI. Where ACEis and ARBs have been withheld, their reintroduction should be considered once there is no evidence of AKI or ongoing requirements for hemodynamic support; again, this needs to be an individualized decision. Importantly, these medications have substantial long-term beneficial effects on cardiovascular and kidney health and, if withheld, a clear plan for safe reintroduction should be ensured. As discussed, practitioners should be vigilant for occult urologic trauma, where specific imaging and management strategies are indicated.

Conclusions

AKI is a common postoperative complication that is associated with significantly higher morbidity and mortality. This may be mitigated through perioperative risk management and early recognition. Given worsening stages of AKI are associated with poorer patient outcomes, early recognition and management is important to prevent further deterioration of kidney function. Risk prediction models for postoperative AKI exist and, combined with biomarkers, they may help in identifying those patients most at risk, allowing appropriate and timely intervention and directing decision making. Treatment bundles, such as the KDIGO bundle, can be used in the management and treatment of AKI; however, future research should look to push past these evidence-based, but nonetheless generic, recommendations and target specific underlying causes of kidney injury.

Disclosures

L.G. Forni reports receiving honoraria from Astute Medical, bioMérieux, Exthera Medical, Fresenius, Gambro/Baxter, and Paion; receiving research funding from, and serving on a speakers bureau for, Baxter; serving as European Society of Intensive Care Medicine General Secretary; having consultancy agreements with Exthea Medical; and having ownership interest in Spiden. J.R. Prowle reports receiving research funding from the Barts and The London Charity, bioMérieux SA, National Institute of Health Research, and Rosetrees Trust; receiving honoraria from Baxter Inc., BBraun, Fresenius Kabi, and Nikkiso Europe GmbH; having consultancy agreements with Baxter, Jafron Biomedical Co. Ltd., Mission Therapeutics Ltd. (Cambridge, United Kingdom), and Nikkiso Europe; being named in a US patent application “Markers of Acute Kidney Injury” in conjunction with Dr. M. Westerman, Intrinsic LifeSciences LLC (La Jolla, CA); and having other interests in, or relationships with, UK Kidney Research Consortium Acute Kidney Injury Clinical Specialties Group (as colead). All remaining authors have nothing to disclose.

Author Contributions

N. Boyer, J. Eldridge, L.G. Forni, and J.R. Prowle wrote the original draft and reviewed and edited the manuscript; L.G. Forni was responsible for administration and visualization; and J.R. Prowle provided supervision.

Copyright © 2022 by the American Society of Nephrology

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