Transcript AKI- Acute Kidney Injury

Kamran fazel MD, FCCM
1
HISTORY
DEFINITION
EPIDEMIOLOGY
ETIOLOGY
SUBTYPE
PROGNOSIS
BIOMARKER
RISK FACTOR
EVALUATION
MANAGEMENT&GUIDELINE
1-HISTORY
Acute Kidney Injury
2nd Century AD: Galen surmises urine formed from kidneys
330-1453 AD: Byzantine physicians describe oliguria as
symptom of AKI, as well as detailed urine findings in AKI;
also, the transition to polyuric phase as late finding in AKI
is recognized
330-1453 AD: likely precursors to ATN described:
Aetius: “..the reasons for the destruction of the kidney are the toxic
influence of remedies and poisons, and external pressure”
Nonus: “…hematuria results from poisonous drugs and serpent
venom…” (Eftychiadis AC, Am J Nephrol 1997)
Acute Kidney Injury
1827: English physician Richard Bright
describes microscopic hematuria,
oliguria, and edema in acute and
chronic renal inflammatory states,
gives eponymic definition for
acute/chronic GN.
Acute Kidney Injury
WWI & WWII: Post-traumatic oliguria
seen in combatants, crush syndrome
evolves as an AKI dx
1950-1960’s: AKI found retrospectively in
~20% of post-op open heart/aortic
surgery
Acute Kidney Injury
WW I: observations of thirst and oliguria in combat
victims led to relationship between blunt trauma and
AKI (Better, OS 1997)
WWII: Spanish surgeon Joseph Trueta observes same in
Spanish Civil War, WWII combatants
Induces renal cortical vasospasm experimentally (Trueta, et al.,
1947)
WWII: Bywaters and Beall link myoglobin to AKI in
crush syndrome during London Blitz (1940)
2-Definition of AKI
UK Renal Association
5th Edition, 2011
Acute kidney injury (AKI) has now replaced the
term acute renal failure and an universal definition
and staging system has been proposed to allow
earlier detection and management of AKI. The
new terminology enables healthcare professionals
to consider the disease as a spectrum of injury.
This spectrum extends from less severe forms of
injury to more advanced injury when acute kidney
failure may require renal replacement therapy
(RRT)
Clinically AKI is characterised by
a rapid reduction in kidney
function resulting in a failure to
maintain fluid, electrolyte and
acid-base homoeostasis.
There are more than 35 definitions of
AKI (formerly acute renal failure) in
literature!
Mehta R, Chertow G: Acute renal failure definitions and classification: Time for change? Journal of American Society of
Nephrology 2003; 14:2178-2187.

Acute Kidney Injury
2001 : Acute Dialysis Quality Initiative (ADQI)
Risk: 1.5x inc in SCr, GFR dec 25%, UOP<0.5 ml/kg/h x 6h
Injury: 2x inc SCr, GFR dec 50%, UOP<0.5 ml/kg/h x 12h
Failure: 3x inc SCr, GFR dec 75%, UOP<0.5/kg/h x 24h
Also anuria x 12 hr
Loss: complete loss (inc need for RRT) > 4 wks
ESRD: complete loss (inc need for RRT) > 3 months
2007: Acute Kidney Injury Network (AKIN)
Modified RIFLE to include ΔSCr o.3 mg/dL from baseline, within
48hr, based on 80% mortality risk
Definition of AKI
As per the Acute Kidney Injury Network:
An abrupt (within 48hrs) reduction in kidney function defined
as an increase in serum creatinine level of 0.3mg/dl
OR
An increase in serum creatinine ≥ 50%
OR
Urine output is < 0.5ml/kg/hr for >6 consecutive hours
RIFLE classification
AKIN classification
Bellomo R, Ronco C, Kellum J, et al.: Acute renal failure-definition, outcome measures, animal models, fluid
therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis
Initiative (ADQI) Group. Critical Care 2004; 8:R204-R212.
Modification of the RIFLE classification by Acute
Kidney Injury Network (AKIN).
Recognizes that small changes in serum creatinine
(>0.3 mg/dl) adversely impact clinical outcome.
Uses serum creatinine, urinary output and time.
Coca S, Peixoto A, Garg A, et al.: The prognostic importance of a small acute decrement in kidney function in
hospitalized patients: a systematic review and meta-analysis. American Journal of Kidney Diseases 2007; 50:712720.
AKIN Serum Creatinine
stage Criteria
Urinary Output Time
Criteria
1
 Cr ≥ 0.3 mg/dL or 
≥ 150-200% from
baseline
< 0.5
mL/kg/hr
> 6 hrs
2
 Cr to > 200-300%
from baseline
< 0.5
mL/kg/hr
> 12 hrs
3
Cr to > 300% from
baseline or Cr ≥
4mg/dL with an acute
rise of at least 0.5
mg/dL
< 0.5
mL/kg/hr
or anuria
X 24 hrs
X 12 hrs
*Patients needing RRT are classified stage 3 despite the stage they were before starting RRT
Mehta R, Kellum J, Shah S, et al.: Acute kidney Injury Network: Report of an Initiative to improve outcomes
in
Acute Kidney Injury. Critical Care 2007; 11: R31.
3-Epidemiology
AKI occurs in
≈ 7% of hospitalized patients.
36 – 67% of critically ill patients (depending on the
definition).
5-6% of ICU patients with AKI require RRT.
Nash K, Hafeez A, Hou S: Hospital-acquired renal insufficiency. American Journal of Kidney Diseases 2002;
39:930-936.
Hoste E, Clermont G, Kersten A, et al.: RIFLE criteria for acute kidney injury are associated with hospital mortality
in critically ill patients: A cohort analysis. Critical Care 2006; 10:R73.
Osterman M, Chang R: Acute Kidney Injury in the Intensive Care Unit according to RIFLE. Critical Care Medicine
2007; 35:1837-1843.
Data from the Intensive Care
National Audit Research Centre
(ICNARC) suggests that AKI
accounts for nearly 10 percent of all
ICU bed days .
4-Etiology
Etiology
Hemodynamic 30%
Parenchymal 65%
Acute tubular necrosis 55%
Acute glomerulonephritis 5%
Vasculopathy 3%
Acute interstitial nephritis 2%
Obstruction 5%
Sepsis
Major surgery
Low cardiac output
Hypovolemia
Medications (20%)
Uchino S, Kellum J, Bellomo R, et al.: Acute renal failure in critically ill patients: A multinational, multicenter study.
JAMA 2005; 294:813-818.
NSAIDs
Aminoglycosides
Amphotericin
Penicillins
Acyclovir
Cytotoxics
Radiocontrast dye
Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer for the
Intensivist. Critical Care Medicine 2010; 38:261-275.
5-Subtype
Acute Kidney Injury Subtype
AKI
PRERENAL
INTRINSIC
POSTRENAL
Acute Kidney Injury
PRERENAL
Volume loss/Sequestration
Impaired Cardiac Output
Hypotension (and potentially hypo-oncotic states)
Net result: glomerular hypoperfusion
Acute Kidney Injury
RENAL/INTRINSIC
Vascular disorders:
small vessel
large vessel
Glomerulonephritis
Interstitial disorders:
Inflammation
intercalative processes
Tubular necrosis:
Ischemia
Toxin
Pigmenturia
Acute Kidney Injury
POSTRENAL
Intrarenal
Crystals
Proteins
Extrarenal
Pelvis/Ureter
Bladder/Urethra
6-PROGNOSIS
Mortality increases proportionately with increasing
severity of AKI (using RIFLE).
AKI requiring RRT is an independent risk factor for inhospital mortality.
Mortality in pts with AKI requiring RRT 50-70%.
Even small changes in serum creatinine are associated
with increased mortality.
Hoste E, Clermont G, Kersten A, et al.: RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: A
cohort analysis. Critical Care 2006; 10:R73.
Chertow G, Levy E, Hammermeister K, et al.: Independent association between acute renal failure and mortality following cardiac surgery.
American Journal of Medicine 1998; 104:343-348.
Uchino S, Kellum J, Bellomo R, et al.: Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 2005; 294:813818.
Coca S, Peixoto A, Garg A, et al.: The prognostic importance of a small acute decrement in kidney function in hospitalized patients: a
systematic review and meta-analysis. American Journal of Kidney Diseases 2007; 50:712-720.
Acute kidney injury has a poor prognosis
with the mortality ranging from 10%-80%
Patients who present with uncomplicated
AKI, have a mortality rate of up to 10%.
In contrast, patients presenting with AKI and
multiorgan failure have been reported to
have mortality rates of over 50%.
If renal replacement therapy is required the
mortality rate rises further to as high as 80%
Non-Oliguric vs. Oliguric vs. Anuric
Oliguric renal failure.
Functionally, urine output less than that required to maintain
solute balance (can’t excrete all solute taken in).
Defined as urine output < 400ml/24hr.
Anuric renal failure.
Defined as urine output < 100ml/24hr.
Less common – suggests complete obstruction, major vascular
catastrophy, or more commonly severe ATN.
Non-Oliguric vs. Oliguric vs. Anuric
Classifying by urine output may help establish a
cause.
Oliguria – more common with obstruction, prerenal
azotemia
Nonoliguric – intrarenal causes – nephrotoxic ATN, acute
GN, AIN.
More importantly, assists in prognosis.
Significantly higher mortality with oliguric renal failure.
80% vs. 25% mortality in Oliguric vs. non-oliguric ARF
Nonoliguric renal failure may also suggest greater
liklihood of recovery of function.
7-BIOMARKER
BIOMARKER RESEARCH IN
DEFINITIONS AND GOALS
a characteristic that is objectively measured
and evaluated as an indicator of normal
biological processes, pathogenic processes, or
pharmacologic responses to a therapeutic
intervention
a biomarker is “any substance, structure or
process that can be measured in the body or
its products and influence or predict the
incidence or outcome of disease”
What is GFR? How is it Calculated?
The Glomerular Filtration Rate (GFR) is the
volume of fluid filtered from glomerular
capillaries into the Bowman’s capsule per
unit time
Suspect AKI in a sick patient with
a modest rise in their creatinine
Large acute drop in GFR with oligoanuria
GFR falls rapidly to near zero
- only shown by oliguria
Slow rise in Cr until
eventually a new steady state is
reached
Only a small early rise in Cr: not easy to recognise as AKI
Limitations to Serum Creatinine as
a Reflection of GFR
The serum creatinine concentration does not
increase above the normal range until the
GFR declines below 50 mL/min, and large
declines in GFR may occur above this level
without a concomitant increase in the serum
creatinine value.
Limitations to Serum Creatinine as
a Reflection of GFR
In a cachectic patient with very low
muscle mass, creatinine generation
may be so feeble that the serum
creatinine level remains “normal”
(<0.9 mg/dL) even in the presence
of a GFR less than 25 mL/min.
Serum creatinine is a useful
marker of stable renal function,
but it is unreliable when GFR is
rapidly changing.
Because it may take up to 48 hours
for GFR to return to baseline, in the
postoperative period the serum
creatinine value may still increase
for a few days while GFR is actually
recovering.
Urine flow rate is an unreliable
marker of acute renal failure and
may vary from anuric (zero flow), to
oliguric
(urinary flow rate <15 mL/hr), to
nonoliguric (15-80 mL/hr), to
polyuric (>80 mL/hr).
Indices of Tubular Injury
 β2-Microglobulin
 Urinary N-Acetyl-β-D-glucosaminidase
 Neutrophil gelatinase-associated lipocalin
(NGAL)
8-Risk Factors
Risk Factors for AKI
Age > 75 yrs
Chronic kidney disease (CKD, eGFR < 60
mls/min/1.73m2)
Cardiac failure
Diabetes mellitus
Hypovolemia
Nephrotoxic medication
Atherosclerotic peripheral vascular disease
Liver disease
Sepsis
Risk Factors for Ischemic Tubular
Injury
Volume depletion
Aminoglycosides
Radiocontrast
NSAIDs, Cox-2 inhibitors
Sepsis
Rhabdomyolysis
Preexisting renal disease
HTN
Diabetes mellitus
Age > 50
Cirrhosis
Radiocontrast-Induced
Acute Renal Failure
 Induces renal vasoconstriction and direct cytotoxicity via
oxygen free radical formation
 Risk factors:
 Renal insufficiency
 Advanced age
- Diabetes
- > 125 ml contrast
 Hypotension
 Usually non-oliguric ARF; irreversible ARF rare
Prevention of Radiocontrast Nephropathy
Intervention
Strength of
Evidence
Clarity of
Risk-Benefit
Grade of Recommendation
Volume expansion
with normal saline
Good
Clear
A: Intervention is always indicated
and acceptable
Volume expansion
with sodium
bicarbonate
Fair
Clear
B: Intervention may be effective and is acceptable
Iso-osmolar contrast
Fair
Clear
B: Intervention may be effective and is acceptable
Theophylline
Fair
Unclear
C: May be considered; minimal or
no relative impact
N-acetylcysteine
Good
Unclear
C: May be considered; minimal or
no relative impact
Hemofiltration
Fair
Unclear
I: Insufficient evidence to recommend for or against
Fenoldopam
Good
Unclear
D: Not useful
Hemodialysis
Good
Unclear
D: Not useful
Avoid use of intravenous contrast in high risk patients
if at all possible.
Use pre-procedure volume expansion using isotonic
saline (?bicarbonate).
NAC
Avoid concomitant use of nephrotoxic medications if
possible.
Use low volume low- or iso-osmolar contrast
Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer
for the Intensivist. Critical Care Medicine 2010; 38:261-275.
Recognition of underlying risk factors
Diabetes
CKD
Age
HTN
Cardiac/liver dysfunction
Maintenance of renal perfusion
Avoidance of hyperglycemia
Avoidance of nephrotoxins
Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer for the
Intensivist. Critical Care Medicine 2010; 38:261-275.
Intravenous albumin significantly reduces the
incidence of AKI and mortality in patients with
cirrhosis and SBP.
Albumin decreases the incidence of AKI after large
volume paracentesis.
Albumin and terlipressin decrease mortality in HRS.
Sort P, Navasa M, Arroyo V, et al.: Effect of intravenous albumin on renal impairment and mortality in
patients with cirrhosis and spontaneous bacterial peritonitis. New England Journal of Medicine 1999; 341:403-409.
Gines P, Tito L, Arroyo V, et al.: Randomised comparative study of therapeutic paracentesis with and
without intravenous albumin in cirrhosis. Gastroenterology 1988; 94:1493-1502.
Gluud L, Kjaer M, Christensen E: Terlipressin for hepatorenal syndrome. Cochrane Database Systematic
Reviews 2006; CD005162.
KDIGO Clinical Practice Guideline
for Acute Kidney Injury
 4.4.3: We suggest using oral NAC, together with i.v. isotonic
crystalloids, in patients at increased risk of CI-AKI.
 4.4.4: We suggest not using theophylline to prevent CI-AKI.
 4.4.5: We recommend not using fenoldopam to prevent CIAKI.
 4.5.1: We suggest not using prophylactic intermittent
hemodialysis (IHD) or hemofiltration (HF) for contrastmediaremoval in patients at increased risk for CI-AKI.
VOL 2 | SUPPLEMENT 1 | MARCH 2012
9-EVALUATION
Baseline Set of Laboratories to Consider
Biochemistry
urea and electrolytes
Hematology
CBC
Urinalysis (+/- microscopy, eosinophils)
Urinary Biochemistry
electrolytes, urea, osmolality
Microbiology
urine/blood culture when/if infection suspected
Imaging
renal ultrasound
CXR, abdominal x-ray
ECG
Acute Kidney Injury
LABORATORY DATA
Creatinine; also BUN/Cr ratio
CBC: anemia, thrombocytopenia
HCO3ˉ: anion gap, lactic acid, ketones
K
CPK/LDH/Uric acid/liver panel
Serologies:
Complement
ESR, RF, ANA, ANCA, AntiGBM
Electrophoresis
Toxicology studies
Evaluation of Renal Failure
Is the renal failure acute or chronic?
laboratory values do not discriminate between acute
vs. chronic
oliguria supports a diagnosis of acute renal failure
Clues to chronic disease
Pre-existing illness – DM, HTN, age, vascular disease.
Uremic symptoms – fatigue, nausea, anorexia,
pruritis, altered taste sensation, hiccups.
Small, echogenic kidneys by ultrasound.
Diagnostic Evaluation of
Renal
Failure
10015%
80Cumulative 60% Correct
Diagnosis 40-
25%
60%
200Hx, PE, Labs
Therapeutic
Trials
Renal
Biopsy
Renal Biopsy-When?




Exclude pre- and post-renal failure, and
clinical findings are not typical for ATN
Extra-renal manifestations that suggest a
systemic disorder
Heavy proteinuria
RBC casts
AKI
 Physical Exam.
 Assessing volume status.

Is the patient intravascularly volume depleted?
 Neck veins – JVP
 Peripheral edema or lack of.
 Orthostatic vitals.
 Not always straightforward.
 Pt. may be edematous (low albumin) or have significant
right sided heart disease.
 BUN/Creatinine ratio.
 > 20:1 – suggest prerenal or obstruction.
 Can be elevated by anything leading to increased urea
production/absorption.




GI bleed
TPN
Steroids
Drugs – Tigecycline.
 Creatinine in anephric state typically only rises
1mg/dl/day.
 If greater – should be concerned for rhabdomyolysis
AKI: Diagnostic studies-urine
Urinalysis for sediment, casts
Response to volume repletion with return to baseline
SCr 24-72 hr c/w prerenal event
Urine Na; FENa
FENa (%) = UNa x SCr x 100
SNa x UCr
FENa < 1%: Prerenal
FENa 1-2%: Mixed
FENa > 2%: ATN
Hansel’s stain
Classic Lab Findings in AKI
Causes
UNa
FeNa
*FeUrea
BUN/Cr
Prerenal
<10
<1%
<35%
>20
Renal
>20
>2%
>50%
<15
Postrenal
>40
>4%
>15
Urine Patterns in Renal Disease
Urinary Pattern
Renal Disease
Hematuria with red cell casts, heavy
proteinuria, or lipiduria
Glomerular disease or vasculitis
Granular and epithelial casts with free
epithelial cells
Acute Tubular Necrosis
Pyuria with white cell and granular casts and
no/mild proteinuria
Tubular or interstitial disease or obstruction
Hematuria and pyuria with no or variable Acute interstitial nephritis, glomerular
casts(excluding red cell casts) disease, vasculitis, obstruction, renal
infarction
Pyuria alone Usually infections, sterile pyuria suggests TB
10-MANAGEMENT&GUIDELINE
5 Key Steps in Evaluating Acute Renal Failure
I. Obtain a thorough history and physical;
review the chart in detail
II. Do everything you can to accurately
assess volume status
III. Always order a renal ultrasound
IV.Look at the urine
V. Review urinary indices
Management
Importantly, manangement of AKI is varied and depends on
the cause. Given no effective pharmaceutical options,
management of AKI is primarily supportive.
Prerenal azotemia is usually responsive to isotonic fluid
repletion
Managament of ATN includes discontinuation of
nephrotoxic agents, optimization of hemodynamics,
continued monitoring of renal function (acid/base status,
electrolyte abnormalities).
Postrenal causes warrant removal of the obstruction.
Maintain renal perfusion
Correct metabolic derangements
Provide adequate nutrition
? Role of diuretics
 Human kidney has a compromised ability to
autoregulate in AKI.
 Maintaining haemodynamic stability and avoiding
volume depletion are a priority in AKI.
Kelleher S, Robinette J, Conger J: Sympathetic nervous system in the loss of autoregulation in acute renal failure.
American Journal of Physiology 1984; 246: F379-386.
 Current studies do not include patients with
established AKI.
 The individual BP target depends on age, comorbidities (HTN) and the current acute illness.
 A generally accepted target remains MAP ≥ 65.
Bourgoin A, Leone M, Delmas A, et al.: Increasing mean arterial pressure in patients with septic shock: Effects on
oxygen variables and renal function. Critical Care Medicine 2005; 33:780-786.
SAFE study – no statistical difference between volume
resuscitation with saline or albumin in survival rates or
need for RRT.
Post – hoc analysis – albumin was associated with
increased mortality in traumatic brain injury subgroup
and improved survival in septic shock patients.
Finfer S, Bellomo R, Boyce N, et al.: A comparison of albumin and saline for fluid resuscitation in the intensive care
unit. New England Journal of Medicine 2004; 350: 2247-2256.
There is no evidence that from a renal protection
standpoint, there is a vasopressor agent of choice to
improve kidney outcome.
Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer for the
Intensivist. Critical Care Medicine 2010; 38:261-275.
KDIGO Clinical Practice Guideline
for Acute Kidney Injury
3.5.1: We recommend not using low-dose
dopamine to prevent or treat AKI.
3.5.2: We suggest not using fenoldopam
to prevent or treat AKI.
VOL 2 | SUPPLEMENT 1 | MARCH 2012
“Renal” dose dopamine doesn’t reduce the incidence of
AKI, the need for RRT or improve outcomes in AKI.
It may worsen renal perfusion in critically ill adults with
AKI.
Side effects of dopamine include increased myocardial
oxygen demand, increased incidence of atrial fibrillation
and negative immuno-modulating effects.
Lauschke A, Teichgraber U, Frei U, et al.: “Low-dose” dopamine worsens renal perfusion in patients with acute
renal failure. Kidney 2006; 69:1669-1674.
Argalious M, Motta P, Khandwala F, et al.: “Renal dose” dopamine is associated with the risk of new onset atrial
fibrillation after cardiac surgery. Critical Care Medicine 2005; 33:1327-1332.
KDIGO Clinical Practice Guideline
for Acute Kidney Injury
3.4.1: We recommend not using
diuretics to preventAKI.
3.4.2: We suggest not using
diuretics to treat AKI, exceptin the
management of volume overload
VOL 2 | SUPPLEMENT 1 | MARCH 2012.
Management Cont.
Things to do for patients with AKI
Renally dose medications
Avoid nephrotoxins
Monitor I/Os
Serial assessment of serum creatinine
Renal Replacement Therapy (i.e dialysis) is the central
component of care for patients with severe AKI
The generally accepted indications for renal replacement
therapy in the setting of AKI include:
Acidosis
Electrolyte disturbance
Ingestion/Intoxication
Volume Overload
Overt Uremia
Acute Kidney Injury
INDICATIONS FOR RENAL REPLACEMENT THERAPY
 Consensus generally includes:
Refractory volume overload
2. Severe metabolic acidosis; HCO3 may be variable, but
declining level of factor; also falling pH to 7.1-7.2
3. Hyperkalemia, with levels > 6.5, or documented rapid rise
refractory to medical therapy
4. Major uremic target organ manifestations i.e. pericarditis,
progressive neuropathy, seizure
5. Platelet dysfunction, bleeding diasthesis
6. AKI in setting of dialyzable drug/toxin
1.
Guideline 8.6 – AKI : Vascular
access for RRT
We recommend that subclavian
access should be avoided in
patients at risk of progressing to
CKD stage 4 or 5 due to the risks of
compromising future, permanent
vascular access.
Guideline 8.7 – AKI : Vascular
access for RRT
We suggest that non-dominant
arm upper limb vasculature
should be preserved as a
contingency for future
permanent access.
When to call nephrology
Any known dialysis patient admitted
Any known renal transplant patient admitted
Any case of AKI where cause not clear
Worsening AKI
Emergency dialysis indications
Suspect glomerulonephritis