Perioperative Acute Kidney Injury

Dr Mukul Kapoor
Director Anesthesia,
Max Smart Super Specialty Hospital, Saket, Delhi
The Problem

Physiological functions of kidney, which

include acid-base control, BP regulation, water
balance & waste excretion, are crucial to
maintenance of homeostasis
Acute kidney injury (AKI) following surgery is
associated with increased morbidity, mortality,
longer hospital stays & significantly increased
health care costs
Development of AKI is associated with an
eightfold increase in all-cause 30-day mortality
Incidence

Approximately 1–5% of hospitalized patients

experience AKI
1% incidence of AKI in a broad general surgery
population across the United States - defined as
a significant reduction in calculated creatinine
clearance to less than 50 ml/min
In Cardiac surgery, Mild renal injury (creatinine
rise <25%) may occur in as many as 50%;
Moderate kidney injury reported in 8-15%; Renal
failure requiring dialysis occurs in 5%

Khetrapal S, et al. Anesthesiology 2009; 110:505-15

Acute Kidney Injury

Acute kidney injury (AKI) is a syndrome with

decrease in urine output and increase in renal
biomarkers, such as blood urea nitrogen & serum
creatinine, which are surrogate markers for
decreased glomerular filtration rate (GFR)
Using these markers as criteria for diagnosing AKI
has limitations including difficult diagnosis of
“functional renal insufficiency” - characterized by
oliguria & creatininemia due to reduction in renal
blood flow
Acute Kidney Injury – From
Attack to Dysfunction
AKI – The spectrum

Acute kidney injury (AKI) - one clinical criterium (urine

output) & one biomarker for renal function (SCr) - AKI
has replaced “acute renal failure”, which corresponded
to severe level of AKI
Acute kidney damage (AKD) - renal parenchymal
damage evidenced by histology or by biomarkers of
renal tissue damage but not by measures of renal
function
Acute kidney attack (AKA) - situations at risk of kidney
injury or dysfunction as in various conditions such as
sepsis, major surgery & nephrotoxic agent
administration
AKI – RIFLE Classification

Vives et al. Interact Cardio Vasc Thorac Surg 2014;icvts.ivu014

AKI - AKIN Classification

Vives et al. Interact Cardio Vasc Thorac Surg 2014;icvts.ivu014

 AKI - KDIGO Classification
Grade Serum Creatinine Urine Output

1 > 0.3 mg/dL increase or 1.5 to 1.9 < 0.5 mL/kg/h for 6 to 12 hours
times baseline serum creatinine
level
2 2.0 to 2.9 times baseline serum creatinine level < 0.5 mL/kg/h for >12
hours

3 3.0 times baseline serum creatinine < 0.3 mL/kg/h for >24
level or serum creatinine increase to hours or anuria for >12
> 4 mg/dL or initiation of renal hours
replacement therapy

http://www.kidney-international.org/
Mortality

Regardless of definition, once renal failure

progresses & patient becomes dialysis
dependant, mortality rates rise (>50%)
Andersson et al. Thorac Cardiovasc Surg1993;41: 237-241
Chertow et al. Am J Med 1998; 104: 343-348
Even with progress of newer dialysis
technology, mortality associated with postop
renal failure has not noticeably improved
Ympa et al. Am J Med 2005;118: 827-832
Milder Kidney Injury?
Patients with milder renal dysfunction not
requiring RRT show decreased survival
Conlon Nephrol Dial Transplant 1999;14: 1158-62
Modest rise in creatinine can negatively affect
quality of life and life expectancy
Lassnigg et al. Critical Care Medicine 2008;36: 1129-37
AKI prolongs ICU stay & increases proportion
of patients discharged to a nursing care facility
AKI is independent predictor of morbidity &
mortality
Renal Blood Flow (RBF)

RBF (25% CO) 500-

600ml
Cortex 80% Cortex
PO2: 40-50 mmHg
Medulla
Medulla 20%
PO2: 10-20 mmHg
Vulnerability of Medulla

Limited blood supply of outer medulla

Low O2 tension (10 mmHg)
Near total extraction of O2 (80%)
Demand relates to solute load
↑ RBF - ↑ GFR - ↑ Solute load - ↑ O2 demand
O2 demand-supply balance is precarious
Slight imbalance can easily result in tubular ischemia
Measures to ↑ RBF can result in ischemia
Pathophysiology of AKI

Demand depends on
energy dependent
absorption of solute
load Cortex
Chloride ions
Na Ions Medulla
Acute Tubular Ischemia

O2 depletion
ATP depletion
Destruction &
disruption of
tubular
epithelium
Ichai C et al. Annals of Intensive Care 2016;6:48
Ichai C et al. Annals of Intensive Care 2016;6:48
General Measures to prevent AKI

Identify High-Risk Patients

Treat volume depletion & CHF to optimize
renal perfusion
Periop hydration, hemodynamic monitoring
& inotropic agents to optimize cardiac
output
Avoid Nephrotoxins (NSAIDS,
Radiocontrast)
Ichai C et al. Annals of Intensive Care 2016;6:48
Preop Strategies to prevent AKI

Optimize cardiac output

Avoid intravascular volume depletion
Continue CHF treatment
Optimize renal function in patients with reversible
AKI
Adequate hydration and avoid loop diuretics
Statin use
Hematocrit optimization
Surgery 5 days after angiography
Intraop Strategies to prevent AKI

Avoid anemia (Hb >50% baseline)

Avoid hemodilution
Use of ANP
Use of fenoldopam
Optimal glucose control (no tight
control)
Pharmacologic Interventions

Glycemic control
Nesiritide (BNP)
Fenoldopam
Mannitol
n-acetylcysteine
Anaritide (ANP)
Dopamine
Loop diuretics
Diltiazem
Clonidine
Sodabicarb infusion
No vasoconstrictor use
No loop diuretics use
Increase Renal Blood Flow

Dopamine stimulates DA-1 & DA-2 dopamine

receptors, increasing renal blood flow &
inhibiting PCT sodium reabsorption but
studies have shown no role in treatment or
prevention of ARF
Fenoldopam (selective DA-1 agonist) use
demonstrated a reduction of renal
dysfunction but beneficial effects may be
offset by systemic hypotension
Inducing Natriuresis

ANP increases natriuresis by increasing GFR &

inhibiting sodium reabsorption by medullary
collecting duct
Recombinant human ANP use to treat ARF
after cardiac surgery in patients who required
inotropic support for heart failure resulted in
significant reduction in incidence of dialysis
ANP infused @ 50 ng/kg/min as opposed to
200ng/kg/min lowers incidence of
hypotension
Inducing Natriuresis

Role of diuretics as well as Mannitol is

controversial
100 patients with postop renal failure given
either intermittent doses of loop diuretics or a
continuous infusion of mannitol, frusemide &
dopamine (2mcg/kg/min)
90% of patients who received intermittent
diuretic required dialysis but only 6.7% of
those who received cocktail required dialysis
Blocking Inflammation

Pentoxifylline (reduce cardiac dysfunction &

TNF release in ischemia-reperfusion),
Pexelizumab (antibody specific for human C5)
& Dexamethasone failed to protect against
renal dysfunction after cardiac surgery
N-acetyl cysteine shown to block
inflammation & oxidant stress in patients &
may hold promise - not been used in
prospective RCT examining renal outcomes
Status of Preventive Drugs

Ichai C et al. Annals of Intensive Care 2016;6:48

Preventing Contrast-Induced Nephropathy

Ichai C et al. Annals of Intensive Care 2016;6:48

 Treating Heart Failure

Nesiritide, human recombinant form of Brain-

type natriuretic peptide (BNP) is used in
treatment of CHF
NAPA investigators randomized 303 patients
with LV dysfunction undergoing cardiac
surgery to receive nesiritide or placebo
Nesiritide attenuated peak increase in
creatinine, decreased hospital stay & improved
survival at 180 days
Other Strategies

In patients who were at highest risk for AKI,

prophylactic hemodialysis has been
attempted
44 patients with a baseline serum creatinine
2.5 mg/dl were randomly assigned to either
periop prophylactic dialysis or dialysis only
when postop ARF indicated the procedure
Mortality was 4.8% in group that received
prophylactic dialysis vs 30.4% in control
Predictors and Biomarkers for Early
Identification of AKI

Changes in S Cr occur late (about 48h after the

trigger) in development of AKI & severe tubular
injury has occurred and may be ongoing by the
time AKI is detected
Regardless of its severity, AKI is characterized by
renal dysfunction seen as ⬆S Cr or ⬇urine output
This phase is preceded by kidney attacks (of
mostly hemodynamic or inflammatory nature),
which lead to irreversible parenchymal kidney
damage
Predictors and Biomarkers for Early
Identification of AKI
Biomarkers are essentially proteins synthesized
subsequent to renal damage
New biomarkers of AKI have been evaluated for
prediction for AKI so as to improve monitoring,
institute early treatment and improve patient
counseling
Over the last 10 years’ multiple renal biomarkers
capable of detecting early acute kidney attacks
have been developed
Predictors & Biomarkers for Early
Identification of AKI

Numerous studies have evaluated plasma & urinary

biomarkers to diagnose early AKI & reported sensitivity
ranging from 70-92% & specificity from 70-95%
Cystatin appears to be a more efficient functional marker
than SCr for GFR
Among the most evaluated markers are
kidney injury molecule-1 (KIM-1)
neutrophil gelatinase-associated lipocalin (NGAL)
lipid acid-binding protein (L-FABP)
interleukin-18 (IL-18)
β2-microglobulin
Insulin growth factor-binding protein 7 (IGFBP 7)
Tissue inhibitor of metalloproteinase-2 (TIMP-2)
Predictors and Biomarkers for Early
Identification of AKI
Data supports these biomarkers to assess early
kidney damage & severity however their
performance & daily use raise several problems
Biomarkers indicate different mechanisms of injury:
ischemia, hypoxia, cellular regeneration or cell cycle
arrest. They are synthesized at different sites & are
activated with different kinetics following kidney
injury
No study truly demonstrates their utility in critically ill
There is no ideal renal biomarker - their future points
towards combined & repeated measurements
Guideline Recommendations

Ichai C et al. Annals of Intensive Care 2016;6:48

Role of Chlorides in AKI

Chloride levels are controlled in a very

tight range
Primarily by the kidney
Around 20,000 mmol of chloride filtered by
the kidney with >99% reabsorbed
Gut also plays a role via Gastric secretions (to
a lessor extent the rest of the GI tract)

Lobo et al. Kidney International advance online publication, 9 April 2014; doi:10.1038/ki.2014.105
Impact of 0.9% saline in Perioperative
setting: Major Abdominal surgery

Shaw AD, et al. Ann Surg. 2012; 255(5):821-9

Impact of hyperchloremia in perioperative
setting
Matched Sample

Probability of Dying and Serum Chloride Level

McCluskey et al. Anesth Analg 2013;117:412–21

Anesth Analg 2013;117:412–21
 Schematic diagram of
sequential effects of
hyperchloremia on
kidney

Lobo DN et al. Kidney International. 2014

Lobo et al. Kidney International advance online publication, 9 April 2014; doi:10.1038/ki.2014.105
Non-specific prevention of AKI

Ichai C et al. Annals of Intensive Care 2016;6:48

Blood Pressure to prevent AKI

Ichai C et al. Annals of Intensive Care 2016;6:48

Maintaining Hemodynamics

Ichai C et al. Annals of Intensive Care 2016;6:48

Conclusion

AKI after surgery is a major perioperative complication

associated with significant morbidity, mortality and
associated costs
Preventive strategies are limited & evidence for most
interventional therapies is as yet not substantive
Current approaches include
deferring elective surgery until there is adequate recovery
following pre-existing renal injury
careful preoperative risk stratification of patients
considering less invasive procedures in those at greatest risk
Thank you