Acute Kidney Injury

dr. Lauhil Mahfudz, SpB

 Definition of AKI
• 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.
 DEFINITION
ABRUPT DECREASE IN RENAL FUNCTION
RESULTING IN THE ACCUMULATION OF
NITROGENOUS COMPOUNDS SUCH AS
UREA AND CREATININE
 Definition of AKI
• RIFLE classification
• AKIN classification
 RIFLE 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.
 AKIN classification
• 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; 50:712-720.
 AKIN classification
AKIN Serum Creatinine Urinary Output Time
stage Criteria Criteria
1  Cr ≥ 0.3 mg/dL or  < 0.5 > 6 hrs
≥ 150-200% from mL/kg/hr
baseline
2  Cr to > 200-300% < 0.5 > 12 hrs
from baseline mL/kg/hr
3 Cr to > 300% from < 0.5 X 24 hrs
baseline or Cr ≥ 4mg/dL mL/kg/hr X 12 hrs
with an acute rise of at or anuria
*Patients needing RRT are classified stage 3 despite the stage they were before starting RRT
least 0.5 mg/dL

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.
 Definition of AKI
• AKI is an abrupt (within 48 hrs) reduction in kidney
function currently defined as an absolute increase
in serum creatinine of ≥ 0.3 mg/dL (≥ 26.4 μmol/L),
a percentage increase in serum creatinine of ≥
50%, or a reduction in urine output (documented
oliguria of < 0.5 mL/kg/hr for > 6hrs.

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.
 Acute vs Chronic Renal Failure
• History
– Known Chronic
– Recent Toxic Exposure
– Recent Hypoxic Insult
– Recent Trauma
– Known Diseases Associated with ARF
– Prev. Abnormal Lab Results Suggesting Chronic
 Acute vs Chronic Renal Failure
• Rapidly Rising Creatinine = Acute
• Kidney Size
– Small = Chronic
• Renal Ultrasound
– Increased Echogenicity = Chronic
• Urine Flow Rate
– Oliguric or Anuric usually = Acute
 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.
 Mortality according to RIFLE
• Mortality increases proportionately with
increasing severity of AKI (using RIFLE).
• AKI requiring RRT is an independent risk factor
for in-hospital 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; 294:813-818.
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 RENAL FAILURE
CLASSIFICATION BY URINE VOLUME

OLIGURIC: <400 CC/ 24 Hrs

NON-OLIGURIC: >500 CC/24 Hrs

ANURIC <50 CC/24 Hrs

 ETIOLOGY OF ACUTE RENAL FAILURE

• PRE-RENAL 55-60%

• POST RENAL <5%

• RENAL 35-40%
 PRE-RENAL ACUTE RENAL FAILURE

• MOST COMMON CAUSE OF ARF

• RESULTS FROM DECREASED RENAL PERFUSION
• TREATMENT OF THE CAUSE RESTORES RENAL
FUNCTION TUBULAR FUNCTION INTACT *
• PROLONGED PRE-RENAL FAILURE MAY LEAD TO
ATN
 CAUSES OF PRE-RENAL AZOTEMIA

• Intravascular volume depletion

• Decreased cardiac output
• Systemic vasodilation
– Antihypertensives
– Sepsis
• Renal vasoconstriction
• Drugs impairing autoregulation
– Ace inhibitors NSAID
MECHANISMIS OF PRE RENAL ARF
 POST-RENAL ACUTE RENAL FAILURE

• ACCOUNTS FOR 2-15% OF ALL ARF

• OBSTRUCTION TO URINE FLOW
– INCREASED TUBULAR PRESSURE
– VASOCONSTRICTION
• DECREASED RENAL BLOOD FLOW
• MUST BE BILATERAL TO RESULT IN ARF
– UNLESS : SINGLE KIDNEY OR PRIOR CHRONIC
RENAL FAILURE
 POST RENAL ACUTE RENAL FAILURE

• SUSPECT OBSTRUCTION IN ANURIA

• ETIOLOGY MAY BE AGE DEPENDENT
– YOUNG = CONGENITAL ABNORMALITY
– OLDER MALE = PROSTATIC ENLARGEMENT
• ARF MOST OFTEN ASSOCIATED WITH LESIONS
IN:
– BLADDER, PROSTATE OR URETHRA
 RENAL-ACUTE RENAL FAILURE

• VASCULAR DISEASE
– VASCULITIS (SLE, POLYARTERITIS ETC.)
– SCLERODERMA
– THROMBOEMBOLIC DISEASE
– MALIGNANT HYPERTENSION
 RENAL--ACUTE RENAL FAILURE

• GLOMERULAR DISEASE
– ACUTE GLOMERULONEPHRITIS
• POST INFECTIOUS GN
• CRESCENTIC GN
– ANCA POSITIVE DISEASES
• GOODPASTURE’S DIS.
– ANTI- GLOMERULAR BASEMENT ANTIBODY
 ACUTE INTERSTITIAL NEPHRITIS
DRUG INDUCED
• NSAID (FENOPROFEN)
PENICILLINS
• SULFONAMIDES
ALLOPURINOL
• CEPHALOSPORIN
PHENYTOIN
• RIFAMPIN ( 2ND TIME)
THIAZIDES
• QUINOLONES
FUROSEMIDE
• CIMETIDINE
 RENAL --ACUTE RENAL FAILURE

• ACUTE TUBULAR NECROSIS

– ISCHEMIC INJURY
– TOXIC INJURY
• ENDOGENOUS TOXINS
– HEMOGLOBINURIA

– MYOBLOBINURIA (RHABDOMYOLYSIS)

– ENDOTOXEMIA
 RENAL-- ACUTE RENAL FAILURE

• ACUTE TUBULAR NECROSIS

– EXOGENOUS TOXINS
• AMINOGLYCOSIDES
• RADIOGRAPHIC CONTRAST
• HEAVY METAL COMPOUNDS
• ETHYLENE GLYCOL
• METHANOL
• CARBON TETRACHLORIDE
• CIS PLATIN
 HIGH RISK SETTINGS FOR ATN

CLINICAL SETTING FREQUENCY

• GEN.MED. --SURG. 3-5%
• INTENSIVE CARE 5-25%
• OPEN HEART SURG 5-20%
• AMINOGLYCOSIDE 10-30%
• BURNS 20-60%
• RHABDOMYOLYSIS 20-30%
• CIS-PLATIN 15-25%
 Common causes of AKI
• 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.
 Common causes of AKI in ICU
• Hepatorenal syndrome
• Trauma
• Cardiopulmonary bypass
• Abdominal compartment syndrome
• Rhabdomyolysis
• Obstruction

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.
 DIAGNOSTIC APPROACH TO ARF

• HISTORY
• PHYSICAL EXAMINATION
• ASSMENT OF URINE VOLUME
• URINE ANALYSIS
• BLOOD CHEMISTRY
• BLOOD AND URINE INDICES
• RADIOLOGIC STUDIES
 Nephrotoxins
• 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.
 Prevention of AKI
• 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.
Prevention of Contrast-Induced Nephropathy

• 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.
 Management of AKI
• Maintain renal perfusion
• Correct metabolic derangements
• Provide adequate nutrition
• ? Role of diuretics
 Maintaining renal perfusion
• 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.
 Maintaining renal perfusion
• Current studies do not include patients with
established AKI.
• The individual BP target depends on age, co-
morbidities (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.
 Volume resuscitation – which fluid?

• 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.
 Which inotrope/vasopressor?
• 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.
 Renal vasodilators?
• “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.
 INDICATIONS FOR DIALYSIS IN ACUTE
RENAL FAILURE
 UREMIC SYMPTOMS
~ nausea
~ neurologic
 SEVERE FLUID OVERLOAD
 REFRACTORY ELECTROLYTE
DISORDERS
~hyperkalemia
 SEVERE REFRACTORY ACIDOSIS
 INDICATIONS FOR DIALYSIS IN ACUTE
RENAL FAILURE

• PERICARDITIS
• NEUROPATHY
• MENTAL STATUS CHANGE
• SEIZURES
• BLEEDING
• TOXINS----ETHYLENE GLYCOL, METHANOL
• PROPHYLACTIC
~recent studies fail to document benefit
 MORTALITY ASSOCIATED WITH SETTING OF
ATN
• OVERALL MORTALITY 40-60%
• POST TRAUMATIC 70-90%
• MEDICAL CAUSE 15-40%
• SURGICAL CAUSE 40-80%
• NON-OLIGURIC 26% *
• OLIGURIC 50% *
CAUSES OF DEATH IN ATN
Terima Kasih