Avoiding Kidney Injury:

Recommendations for

Adult Surgical Patients

Objectives

• Provide an overview of the literature regarding the prevention and recognition of

kidney injury

• Summarize recommendations to prevent & identify AKI as outlined in the literature

• For an overview of kidney disease, reference:

– MPOG Avoiding Kidney Injury - Overview, Pathophysiology, Definitions

• For specialty specific recommendations, reference the following sections of the

toolkit:

– Avoiding Kidney Injury - Pediatrics

– Avoiding Kidney Injury - Obstetrics

– Avoiding Kidney Injury - Cardiac Surgery

Recommendations for

Avoiding AKI

KDIGO Stage Based Recommendations

KDIGO Guideline Bundles

• Single center trial

• Implemented “bundle” of KDIGO guidelines

– Optimization of volume state and hemodynamics

– Avoidance of nephrotoxic drugs

– Normoglycemic management

• Randomized high risk patients undergoing cardiac

surgery

• ↓AKI in patients receiving the bundled protocol

• Need for further multi-center adequately powered

studies

KDIGO Guideline Bundles

- Single center study, adult patients >18 years

- Utilized an AKI care bundle, an electronic

recognition of AKI based on KDIGO Criteria, and an

EHR alert

- Compared patients who received the AKI care

bundle vs. those who did not" to save some space

- 10 fold increase in care bundle usage after integration of

EHR alert

- Completion of an AKI CB within 24 hours of abnormal

blood test was associated with less progression to higher

AKI stages and significantly lower in-hospital, 30-day and

60-day case fatality.

- Used “AUDITS” bundle

Implementation of AKI Care Bundle in NHS hospital

• London hospital implemented daily audit process to

assess care for patients with AKI

– 2011: Pre-intervention audit of 100 patients with AKI

(KDIGO definition used)

– 2012: Intervention applied- AKI Care Bundle

implemented

– 2013: Post-intervention audit of 92 patients with AKI

• Outcomes:

– Hospital mortality decreased in the post-intervention

group (10% post vs. 12% pre)

– AKI was recognized more often in the post-intervention

group (68% post vs 51% pre)

– Higher rates of nephrotoxic medication discontinuation

post-intervention (73% post vs. 29% pre)

More AKI Bundles for Review

Please contact MPOG to share

your AKI Prevention Bundle &

Quality Improvement story!

NHS Think Kidneys

Aintree University Hospital

Recommendations

Early recognition of AKI

● Optimizes treatment and prevents progression

● EHR alerts/AI/Diagnostic Tools

● Provider education

Avoid nephrotoxins

● Antimicrobials

● Contrast

● NSAIDs

Avoid hyperglycemia

● Patient Risk Factors

● Glycemic Range Targets

● Insulin Therapy

Avoid hypotension

● Relative vs. absolute hypotension

● Restrictive vs. Liberal Fluid Therapy

● Vasopressor use

● Sepsis Implications

Identify patients at risk of

developing AKI

● Patient risk factors

● Procedure risk factors

● Anesthesia related risk factors

Recommendation #1:

Identify patients at risk

for AKI

Categories of AKI Risk Factors

• Patient-related, such as:

– Diabetes

– Hypertension

– Sepsis

• Procedure-related, such as:

– Cardiopulmonary bypass & duration

– Emergency Surgery

– Organ Transplant

• Anesthesia-specific, such as:

– Vasopressor use

– Diuretic use

– Hypotension

Patient Risk Factors

6-8

• Preoperative level of kidney function

• Chronic Vascular Disease

• Arterial Hypertension

• Cardiac Failure/Cardiac Decompensation

• Diabetes (insulin or oral therapy

requirements)

• Acute medical conditions (sepsis, major

surgery, mechanical ventilation,

hemodynamic instability)

• Hypertension

• Peripheral Vascular Disease

• Congestive Heart Failure

• Sepsis

• Ascites

• Cerebrovascular disease

• Mild to Moderate preoperative renal

insufficiency

• Age >65

• COPD

• Chronic Kidney Disease

• BMI ≥ 25 (Overweight) (Ju 2018)

Patient-related risk factors are more strongly associated with mortality

than the type of procedure.

Procedure Related Risk Factors

6,8-9

• Gastric bypass surgery for morbid

obesity- 8.5% incidence AKI

• Cardiopulmonary bypass (CPB) &

duration

• Aortic cross clamping & duration

• Hemodilution (cardiac surgery)

• Duration of surgery

• Intraperitoneal surgery

• Repair of AAA

• Organ Transplant (non-renal also)

– Liver transplant:

– 33% AKI

– 17% require renal replacement

therapy

• Use of intra-aortic balloon pump

• Type of cardiac surgical procedure

• Intra-abdominal hypertension

• Emergency surgery

• Bleeding complications

Anesthesia-related Risk Factors

6,8-9

Potentially modifiable AKI risk factors in both cardiac and noncardiac surgery

– Hemodilution

– Hemoglobin level

– Intraoperative transfusion

– Hypotension

– Inadequate oxygen delivery

– Use of diuretics

– Selective renal ischemia

– Ischemia reperfusion injury

– Bleeding complications

– Intraoperative Hypertension

– Nephrotoxic agents (eg abx, contrast agents)

Novel Predictive Techniques

• Use of predictive analytics and machine learning techniques present new

opportunities to identify risk and potentially prevent AKI:

– Thottakara et al recently used a machine-learning computational approach to develop a KDIGO AKI

preoperative forecasting model

– Used 59 variables from the electronic health record

– Included patients undergoing any type of major surgery

– Reported an AUC of 0.86 in the internal validation cohort

Recommendation #2:

Avoid Hypotension

Pathophysiology: How Hypotension contributes to AKI

• Kidneys able to compensate for hypoperfusion to a certain extent

• ↓ renal perfusion → ↓GFR (without damage to parenchyma) as adaptive response

– Prostaglandin signaling → ↓ afferent arteriole resistance and ↑ blood flow to glomeruli and

maintains capillary pressure

– Renin-angiotensin-aldosterone system and release of angiotensin II → ↑efferent arteriole

resistance

• Once hypoperfusion drops below compensatory range, vasoconstrictors released by renal

sympathetic nerves →↑afferent arteriole resistance→↓in GFR and renal blood flow→tubular cell

damage and cell death

Image Source: Gumbert et al. Anesthesiology 2020

Intraoperative Hypotension: Contributing Factors

HYPOPERFUSION

Renal Ischemia

& Decreased

Glomerular

Filtration

Hypotension and AKI

• Intraoperative hypotension, even for short durations is associated with postoperative

acute kidney injury

14-18

• Individualized management strategy aimed at achieving SBP within 10% of baseline

resulted in lower incidence of AKI as compared to the control group (treat SBP<80

mmHg OR lower than 40% from baseline)

• Associations based on relative hypotension and AKI are no stronger than associations

based on absolute hypotension- anesthetic management of hypotension can be

based on intraop values alone

Hypotension and AKI

Associations between intraoperative

hypotension and AKI are dependent upon

patient’s baseline risk for AKI

❖ Patients with low baseline risk demonstrated no

associations between intraop hypotension and

AKI

❖ Patients with medium risk demonstrated

associations between hypotension (MAP<50)

and AKI

❖ Patients with high risk demonstrated

associations between hypotension (MAP<60)

and AKI

Restrictive Fluid Protocols may lead to AKI

RELIEF Study

– 3000 patients undergoing abdominal

surgery

– 1490 patients in restrictive fluid therapy

group (median 3.7L in 24 hours postop)

– 1493 patients in liberal fluid therapy group

(median 6.1L in 24 hours postop)

– AKI incidence of 8.6% in restrictive vs.

5.0% in liberal

– Restrictive fluid protocols in abdominal

surgery → higher chance for AKI with no

benefit to survival

Cardiac Output directed fluid therapy: Controversial

• Use cardiac output to guide fluid resuscitation efforts → improve perfusion without fluid

overload

– Supported by meta-analysis of 65 studies including 9308 patients in total

– Found GDFT using fluid and inotropes & targeting cardiac output and oxygen

delivery (DO

) was most effective in reducing AKI incidence

– Benefits more significant for high risk patients undergoing orthopedic or major

abdominal surgery

– OPTIMISE Trial: Did not find significant difference in outcomes for GDFT group

– Pragmatic, multicenter, randomized, observer-blinded

– 734 high-risk patients undergoing major abdominal surgery

– Need for further research as GDFT protocols vary widely and could explain the

variance in results

Using hemodynamic parameters to reduce AKI

• Large meta-analysis including 65 RCTs and 9308 patients conducted to examine the

effects of hemodynamic goal-directed therapy (GDT) on morbidity (including AKI)

• All procedure types included

– Major abdominal & orthopedic surgeries benefit most from GDT in reducing AKI

– Intraoperative management through 8 hours after surgery

• 741 patients in the combined studies developed AKI

– 421 were in the control group

– 320 were in the goal-directed therapy group

• Fluids + inotropes significantly reduced AKI

• Using CO or DO

as hemodynamic target showed significant reduction in AKI

• Fluid administration alone did not reduce AKI

Perioperative Fluid Management

• Balanced crystalloid solutions with electrolyte compositions are the preferred fluid for

resuscitation

– Isotonic Solutions and Major Adverse Renal Events Trial (SMART)

– Saline against Lactated Ringer’s or Plasma-Lyte in the Emergency Department (SALT-ED)

• 0.9% Normal saline may cause adverse effects related to acid-base balance, renal

vasoconstriction ↓glomerular filtration, ↑ risk of AKI

Hydroxyethyl Starch (HES)

• Hydroxyethyl starch-containing solutions may increase AKI occurrence

– Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial

– Need for further research, should be used cautiously

• In a study comparing the use of HES vs. crystalloids for GDFT in 202 high risk patients

undergoing colorectal surgery:

– No difference in postoperative complication rates

– HES group had lower 24h fluid balance (+3610 ml vs. +4226 ml in the crystalloid group)

• Crystalloid versus Hydroxyethyl Starch Trial (CHEST) published in 2012 initially found

an increased need for renal replacement therapy in patients receiving HES vs.

crystalloids;

Later analysis (2016) did not find this to be true- no difference in patient

outcomes

Vasopressor Use

• Majority of vasopressor studies focus on patients in the ICU (not intraoperatively)

• European Society of Intensive Care Medicine recommendations:

– Norepinephrine recommended as first-choice vasopressor to protect kidney function (Grade 1B

evidence)

– Suggest vasopressin in patients with vasoplegic shock after cardiac surgery (Grade 2C evidence)

• INPRESS Randomized Controlled Trial

– 298 patients randomized to receive norepinephrine to maintain SBP within +/-10% of baseline OR

to standard management maintaining SBP>80 or within 40% of baseline

– Norepinephrine infusion group resulted in less renal dysfunction (38.1% vs. 51.7%)

• Large RCT compared dopamine and norepinephrine as initial vasopressor in patients

with shock: no difference in renal function or mortality but dopamine caused more

arrhythmic events in patients with cardiogenic shock

• Farag et al. (2019) study concluded that vasopressor infusions given during complex

spine surgery were not associated with kidney injury

AKI and Sepsis

• 1 in 3 patients with sepsis will develop AKI

• Most common cause of AKI in critically ill

• Fluid overload associated with worse outcomes

• Vasopressors key to treating refractory

hypotension

– Norepinephrine favorable choice

– Vasopressin in septic shock not associated with

improved kidney outcomes but may decrease need

for RRT

• Nephrotoxins should be avoided but may be

essential for management of underlying infection

causing sepsis

Image Source: Prowle JR Clin J Am Soc Nephrol 2018

Recommendation #3:

Glycemic Control

Pathophysiology: How Dysglycemia causes AKI

• Hyperglycemia occurs in 40% of non-cardiac

surgeries and 80% of cardiac surgeries.

• Hyperglycemia leads to tissue injury

through:

– Oxidative Stress

– Inflammatory Marker Release

– Vascular permeability

• Kidney specific damage has been seen in

animal studies exposing subjects to transient

hyperglycemia:

– Severe kidney damage

– Decreased renal cortical perfusion and oxygen delivery

– Elevated plasma creatinine

Image Source: Mendez et al. Current Diabetes Reports 2016

Risk Factors predicting Hyperglycemia

Patients without diabetes:

• Black ethnicity

• Female

• Immunosuppression

• High BMI

• Renal failure

• Hypertension

• Hypercholesterolemia

Patients with diabetes:

• Older Age

• Minority Ethnic Group

• Male

• High BMI

• High Risk Surgical Procedure

Impact of Hyperglycemia

• Increased BMI may predispose patients to AKI due to difficult volume assessment and

resuscitation risking pre-renal AKI.

• In a 2 center study of gastrointestinal surgery, average cost of hospitalization and

complications, including AKI (p= <0.0001) for non diabetic patients with normoglycemia was

$20,273 compared to $72,675 for non-diabetic patients with hyperglycemia

Role of Anesthetics and Hyperglycemia in Renal Injury

• Surgery induced stress may disguise the role of

anesthesia in postoperative renal complications.

• Acute hyperglycemia, intra-renal inflammation and

Renin Angiotensin System activation were

independently triggered in rats receiving 1 hour of

anesthesia.

• Blood glucose significantly increased within 10

minutes of receiving anesthesia

• Acute hyperglycemia affects inflammation more

potently than chronic hyperglycemia

• RAS activation causes significant renal injury in

patients with acute and chronic hyperglycemia.

‘Perfect’ Glycemic Range

● Glycemic control is an independent, and modifiable, predictor of poor outcomes in surgical patients

● AKI may further complicate glycemic control as it associated with insulin resistance and reduced renal

clearance of insulin.

○ Maintaining a blood glucose of 80-110 mg/dL has not proven to have protective effects on the

kidneys in patients who already have AKI.

● Multiple Recommendations for ‘Perfect’ Glycemic Range

Source Recommended Glucose Range

KDIGO (2012) controversial recommendation as these thresholds have not

been examined in a randomized controlled trial and the risks of

hypoglycaemia are significant

110 - 149 mg/dL

NICE-SUGAR (2009): Normoglycemia in Intensive Care Evaluation: Survival

Using Glucose Algorithm Regulation - randomized control trial suggests

adopting

higher glycemic values in critically ill patients to avoid the risks of

tight glycemic benchmarks. A blood glucose target of 81 - 108 mg/dL resulted

in higher mortality than a target of < 180 mg/dL without preventing AKI

< 180 mg/dL

ERPB (2009): European Renal Best Practice statement on KDIGO Guidelines

(Systematic Review) There is benefit in avoiding hyperglycemia > 210 mg/dL

however, the relative risk of death is much higher in patients with

hypoglycemia and thus offsets the small benefit of targeting a lower blood

glucose

110 - 180 mg/dL

Perioperative Glucose Control: Tight vs. Moderate

Meta Analysis of 12 RCT showed a decreased relative risk of AKI with glucose controlled <150 mg/dL

with an increased risk of hypoglycemic events

• Very Tight Glucose Control ( < 110 mg/dL)

• Moderate Tight Glucose Control (111 - 150 mg/dL)

Intensive Insulin Therapy

• Systematic review of 5 RCTs demonstrated intensive insulin therapy reduced

the incidence of AKI in adult surgical patients by 38%.

• When compared to a liberal glycemic control strategy (>200), moderate glucose

control (150-200) for diabetics undergoing surgery was associated with a

significantly lower risk of mortality.

– No difference was found between strict (<150) vs moderate (150-200)

• Intensive insulin therapy and a carbohydrate-restrictive strategy were

comparable in their effects on the incidence of acute kidney injury evaluated

using the RIFLE criteria

• Oral antidiabetic medication are not recommended based on limited efficacy

and adverse effects including hypoglycemia and lactic acidosis with

metformin.

Summary: Hyperglycemia and AKI

• Increased risk of AKI at both high and low blood glucose range. Treat hyperglycemia while avoiding

glycemic variability and hypoglycemia. KDIGO recommends moderate targets for glycemic

control.

• Utilize insulin therapy to manage hyperglycemia during the perioperative period in diabetic and

non-diabetic surgical patients.

• Treat hyperglycemia with moderate glycemic targets.

Recommendation #4:

Avoid Nephrotoxins

Avoiding Nephrotoxic Drugs

• Nephrotoxic drugs are associated with increased risk of AKI

2,8,42,49

• Cincinnati Children’s avoidance of AKI quality improvement program

– Proactively screened for nephrotoxic drug exposure in EHR

– Monitored daily SCr for patients exposed

– Reduced exposure rate to nephrotoxic drugs by 38%

– Reduced AKI rate by 64%

Avoidance of Nephrotoxic Drugs

Antimicrobials Contrast NSAIDs

- Avoid use of aminoglycosides

unless no other suitable options,

use topical/local administrations

if possible, and avoid dosing with

multiple administrations per

day.

- Avoid amphotericin B, use

antifungals as appropriate. Use

lipid formulation of amphotericin

B if applicable.

- Assess risk for contrast induced

AKI prior to study. Explore

alternatives if patient is at risk.

- For patients at risk, use lowest

possible dose of iso-osmolar or

low-osmolar iodinated contrast

and utilize isotonic sodium

chloride or sodium bicarbonate

IV fluid solutions.

- Concurrent use of other

nephrotoxic drugs with contrast

increases risk for CI-AKI.

- NSAID use can increase AKI risk

close to twofold

- GFR is reduced with NSAID use

d/t loss of vasodilatory

prostaglandin

Nephrotoxic Drugs- Indirect

• Antibiotics ⟶ breakdown of bacteria ⟶ bacteria cell products in circulation ⟶

systemic inflammation and damage to kidneys and/or kidney injury

• Allergic interstitial nephritis may cause damage to kidneys without other signs of

allergy

Recommendation #5:

Early Recognition of AKI

• Early recognition of AKI patients through EHR alerts is associated with lower in-

hospital mortality, lower risk of death, and lower risk of progression to later AKI

stages

• Proactive screening for nephrotoxic drugs and regular SCr monitoring in patients

receiving nephrotoxic drugs reduced exposure by 38% and AKI by 64%

• American Society of Nephrology launched AKI!NOW initiative to promote early

recognition and management of AKI which help optimize treatment and prevent

progression.

AKI!NOW Recommendations:

– Provider education at all levels in healthcare regarding AKI, particularly around identifying

patients at risk

– Generate specific guidance on AKI evaluation and management

– Develop global toolkit

– Engage hospital administration and make AKI a part of quality initiative

– Raise awareness of AKI as complication of other disease processes

Interventions under

Research

Other Proposed Pharmacologic Interventions

• Low dose “renal dopamine” prophylaxis

– Theorized to prevent renal vasoconstriction

– More harm than good

• High dose furosemide

– Literature does not support loop diuretics for kidney protection only

• N-acetylcysteine/supplements such as selenium, zinc, vitamin C, E, and B1

– Antioxidants

– Not currently supported in literature

• Statin therapy

– Potential anti inflammatory, antioxidative, and endothelial protective properties

– Not currently supported in literature, may actually worsen AKI

• Dexmedetomidine

– Theory: ↑renal blood flow, ↓ oxidative insult to kidney

– Preliminary research shows dexmedetomidine may be helpful, need for further research

Remote Ischemic Preconditioning

• Application of controlled ischemia to remote tissues or organs

to create a protective adaptive response in distant organs

• Typical protocol for AKI prevention includes inflating a blood

pressure cuff around the upper arm to 200-300 mmHg for five

minutes and released. Cycle is repeated several times

• Mixed results in studies -> differing protocols, patient

populations, and study design

• Protective effect may be lessened in cases with propofol

Conclusion: Further investigation needed before adopting into practice

Summary

1. Anesthesia providers should focus on reducing the anesthesia-related intraoperative risk factors

associated with AKI such as:

– Hypotension

– Hyperglycemia

– Use of nephrotoxic agents

2. Assessing risk factors preoperatively can assist anesthesia providers in identifying patients who

may require additional interventions to prevent AKI.

3. Early Recognition of AKI optimizes treatment and reduces risk of progression to later stages of

kidney disease.

References

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