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Perioperative renal protection

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Acute kidney injury (AKI) is a significant cause of perioperative patient morbidity and mortality. The definition of AKI has recently changed and further research is underway to identify clinically relevant biomarkers to aid in the diagnosis of the syndrome. AKI is often multi-factorial in origin and patients with certain preoperative risk factors are at elevated risk of perioperative AKI. An anesthesiologist's main objective for perioperative renal protection is prevention by maintenance of euvolemia, preservation of adequate renal perfusion, and avoidance of nephrotoxins. This review will address the definition and diagnosis of AKI, identify patients at risk of AKI, and critically appraise management options for perioperative renal protection.

Introduction

Anesthesiologists play an important role in perioperative renal protection. To protect means to shield from danger, injury, destruction, or damage. Presently our ability to detect when the kidney is in danger is limited, and often only fully appreciated after the damage has been rendered. The best renal protection is prevention and anesthesiologists are uniquely situated to help in this regard. We are intimately involved in monitoring hemodynamic parameters and volume status, and we administer many medications that may or may not have nephrotoxic effects.

Section snippets

Definition of AKI

The nomenclature to describe an acute deterioration in renal function is not clear-cut and there is no commonly accepted definition. In fact over 35 different definitions have been proposed in the literature.1 The kidneys play a variety of physiologic roles but in the clinical setting renal function is generally monitored by following urine output and serum creatinine levels.

In 2004, the Acute Dialysis Quality Initiative (ADQI) Group proposed the RIFLE criteria to standardize the classification

Evaluation of renal function

As previously mentioned, although the kidney has many physiologic roles renal function is generally measured in terms of GFR, renal blood flow, or tubular function. Indeed AKI is defined in terms of SCr and urine production changes. It may seem illogical then that SCr is not a sensitive marker of acute changes in renal function. As shown in Figure 2, a sudden decrease in GFR leads to a slow rise in creatinine over two to three days.5 Furthermore, as reviewed by Nguyen et al, SCr varies with

Causes of AKI

AKI is generally divided into prerenal, intrinsic renal, or postrenal causes.22 Prerenal AKI is reversible and due to absolute or relative renal hypoperfusion. If the hypoperfusion is not corrected then ischemic acute tubular necrosis (ATN) will result. Other intrinsic renal causes can be broadly grouped as glomerular, tubular, vascular, or interstitial in nature. Postrenal causes of AKI include obstruction of the bladder or ureters.

Pathogenesis of ATN

The term ATN is somewhat flawed as necrosis is not always found on histological exam.23 Renal ischemia and inflammation lead to both vascular and tubular derangements. Vascular effects include increased production of inflammatory mediators such as IL-18 and oxygen free radicals; increased sensitivity to vasoconstrictors and impaired autoregulation; and endothelial injury affecting the balance of prostaglandins, nitric oxide, and endothelin; all of which lead to decreased GFR.23 During ischemic

Epidemiology of AKI

A recent systematic review found that the overall mortality rate from AKI was relatively unchanged between 1956 and 2003 and remained at approximately 50%.24 AKI during the perioperative period had even poorer prognosis with mortality rates of 64% to 83% depending on the surgical population.24 A prospective, multi-centered cohort study of 29,269 ICU patients found that the incidence of AKI was 5.7% with an overall mortality rate of 60.3%.25 The most common causes of AKI were septic shock, major

Patients at risk of perioperative AKI

Identifying preoperative patient risk factors for perioperative AKI is a difficult task given the previous lack of a uniform definition for the disease. Quantitative review of the literature in the form of a meta-analysis has been unsuccessful given this lack of standardization.27 Preoperative risk factors that are commonly cited as linked to increased risk of perioperative AKI are elevated preoperative SCr or BUN, and past history of renal dysfunction.27 Less frequently cited preoperative risk

Part I: perioperative renal protection

Given the high mortality of AKI an anesthesiologist's main objective for perioperative renal protection is prevention. This generally means maintenance of euvolemia, preservation of adequate renal perfusion, and avoidance of any nephrotoxins.

Volume status

Few statements apart from ‘maintenance of adequate intravascular volume’ seem to generate as much controversy for clinicians managing patients at risk of AKI. The face validity of such a statement seems undeniable yet the ideal management strategy remains unknown. If uncorrected hypovolemia and a reduction in oxygen delivery leave the renal medulla susceptible to ischemic ATN.29

Clinical features of hypovolemia such as reduced skin turgor, collapsed peripheral veins, tachycardia, postural

Renal perfusion

Blood flow to the kidney is autoregulated to maintain a stable GFR between a mean arterial pressure (MAP) of approximately 80 to 160 mmHg.42 Autoregulation maintains fluid and salt balance or preserves glomerular structure via a myogenic response and tubuloglomerular feedback.43

Decreased renal perfusion can be due to decreased CO, decreased MAP, or increased renal vasoconstriction.44 An ideal MAP to optimize renal perfusion is not known. In patients with septic shock a MAP of 85 mmHg compared to

Perioperative nephrotoxins

An enormous number of prescription medications, over the counter medications, and herbal medications can potentially cause AKI. In the perioperative period anesthesiologists commonly administer or manage patients exposed to antihypertensive drugs, antibiotics, non-steroidal anti-inflammatory drugs (NSAID's), contrast dyes, and antifibrinolytic medications such as aprotinin.

Antihypertensive drugs

Renal injury can occur with any antihypertensive medication due to lowered blood pressure. Over time this generally resolves as long-term blood pressure control is instituted and autoregulation adjusts.42 In the perioperative setting relative or absolute changes in blood volume can cause prerenal injury. In particular, ACE inhibitors and angiotensin-receptor blockers can exacerbate this change in blood volume due to efferent arteriole vasodilatation.42 These medications should be held until

Antibiotics

Antibiotics commonly used in the perioperative period include cephalosporins, aminoglycosides, and vancomycin. All can be associated with acute interstitial nephritis and dosage adjustment is required in patients with decreased creatinine clearance.56 Aminoglycosides such as gentamicin also accumulate in renal proximal tubule cells and can cause ATN and ototoxicity. Aminoglycoside dosing should be based on creatinine clearance and peak and trough drug levels.57

NSAID's

NSAID's can cause by ischemic ATN and acute interstitial nephritis by altering prostaglandin synthesis.58 Chronic NSAID use predisposes patients to progression of chronic kidney disease.59 With respect to the perioperative period, a systematic review of NSAID's in patients with normal preoperative renal function found a transient reduction in creatinine clearance on the first postoperative day.60 Overall, it is recommended that NSAID's should not be withheld from patients with normal renal

Contrast dyes

Contrast induced nephropathy (CIN) is a form of ATN associated with the use of radiocontrast.62 Risk factors for the development of CIN include: chronic renal insufficiency, diabetes mellitus, dehydration, poor cardiac performance, contrast volume, and high osmolar contrast.63 Multiple studies and meta-analyses have attempted to determine if prophylactic strategies of intravenous hydration, N-acetylcysteine (NAC), or other agents can reduce the incidence of CIN. Overall the best evidence seems

Aprotinin

Aprotinin is a bovine derived serine protease inhibitor initially approved to reduce perioperative bleeding and blood transfusion in coronary artery bypass graft (CABG) patients.65 Its use has extended beyond cardiac surgery to include orthopedic patients and liver transplant patients.66, 67 Recent observational studies in CABG patients suggest that aprotinin may increase the risk of AKI particularly in patients with pre-existing renal dysfunction.68, 69 Further prospective randomized studies

Part II: perioperative renal protection

Beyond maintenance of euvolemia, preservation of adequate renal perfusion, and avoidance of nephrotoxins there is a tremendous amount of research aimed at finding additional pharmacotherapeutic options for prevention and/or treatment of AKI. Many promising treatments for AKI in animal models have failed to translate into successful clinical therapies. To date meaningful interventions are limited but there are recent studies that merit review.

‘Renal dose’ dopamine does not protect patients from

Summary

AKI is the term to describe an abrupt reduction in kidney function and it replaces all previous terms such as ARF. The new definition for AKI needs to be validated by future research. Further development of biomarkers of AKI may aid in the early diagnosis and treatment of the syndrome. Mortality due to perioperative AKI often exceeds 50% and small changes in SCr correlate to significant increases in mortality. Preoperative risk factors for the development of AKI include a past history of renal

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      Citation Excerpt :

      Acute kidney injury (AKI) is a common kidney disorder which is associated with a high risk of mortality [1], and affects between 7% and 18% of inpatients [2,3]. AKI is usually caused by renal IR injury during surgery, septic shock, cardiogenic shock, hypovolemia, and nephrotoxic drugs [4]. The pathophysiology of IR-induced AKI is complex, involving inflammation, apoptosis, oxidative stress and other factors.

    View all citing articles on Scopus

    This work was supported solely by the Intramural Research Fund of the Department of Anesthesiology at Columbia University.

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