(AKI) Acute Kidney

Injury
Daulat Tampubolon, MD
Koja Hospital

Definition of AKI

There are more than 35 definitions of AKI

(formerly acute renal failure) in literature!

Diagnostic criteria for AKI includes an

abrupt (within 48 hours) reduction in kidney
function defined as an absolute increase in
serum creatinine of either 0.3 mg/dl or more
(>/= 26.4 umol/L) or a percentage increase
of 50% or more (1.5 fold from baseline) or a
reduction in urine output.

Definition of Acute Kidney Injury (AKI)

based on Acute Kidney Injury
Network
Stage

Increase in Serum
Creatinine

Urine Output

1.5-2 times baseline

OR
0.3 mg/dl increase
from baseline

<0.5 ml/kg/h for >6 h

2-3 times baseline

<0.5 ml/kg/h for >12

h

3 times baseline
OR
0.5 mg/dl increase if
baseline>4mg/dl
OR
Any RRT given

<0.3 ml/kg/h for >24

h
OR
Anuria for >12 h

RIFLE criteria for diagnosis of AKI

based on The Acute Dialysis Quality
Initiative
Increase in S
Urine output
Cr

Risk of renal injury

0.3 mg/dl increase

< 0.5 ml/kg/hr for > 6 h

Injury to the kidney

2 X baseline

< 0.5 ml/kg/hr for >12h

Failure of kidney
function

3 X baseline OR
Anuria for >12 h
> 0.5 mg/dl increase if
SCr >=4 mg/dl

Loss of kidney
function
End-stage disease

Persistent renal failure

for > 4 weeks
Persistent renal failure
for > 3 months

Am J Kidney Dis. 2005 Dec;46(6):1038-48

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.

Increase in Creatinine without

AKI

Inhibition of tubular creatinine

secretion
Trimethoprim, Cimetidine, Probenecid

Interference with creatinine assays in

the lab (false elevation)
acetoacetate, ascorbic acid, cefoxitin
flucytosine

Increase in BUN without AKI

Increased production
GI Bleeding
Catabolic states (Prolonged ICU stay)
Corticosteroids
Protein loads (TPN-Albumin infusion)

New Biomarkers in AKI

Alternatives to Serum Creatinine

Urinary Neutrophil Gelatinase-Associated

Lipocalin (NGAL)
Ann Intern Med 2008;148:810-819

Urinary Interleukin 18
Am J Kidney Dis 2004;43:405-414

Urinary Kidney Injury Molecule 1 (KIM-1)

J Am Soc Nephrol 2007;18:904-912

NGAL:

Expressed in proximal and distal nephron

Binds and transports iron-carrying molecules
Role in injury and repair
Rises very early (hours) after injury in animals, confirmed in children having CPB

IL-18:
Role in inflammation, activating macrophages and mediates ischemic renal injury
IL-18 antiserum to animals protects against ischemic AKI
Studied in several human models

KIM-1:
Epithelial transmembrane protein, ?cell-cell interaction.
Appears to have strong relationship with severity of renal injury

Urine analysis
Unremarkable in pre and post renal causes
Differentiates ATN vs. AIN. vs. AGN
Muddy brown casts in ATN
WBC casts in AIN
RBC casts in AGN

Major Disease Categories

Causing AKI
Disease Category
Prerenal azotemia caused by acute renal
hypoperfusion

Incidence

Intrinsic renal azotemia caused by acute

diseases of renal parenchyma:

35-40%

-Large renal vessels dis.

-Small renal vessels and glomerular dis.
-ATN (ischemic and toxic)
-Tubulo-interestitial dis.
-Intratubular obstruccttion

Postrenal azotemia caused by acute

obstruction of the urinary tract

55-60%

*>90%*

<5%

Prerenal Azotemia

Intravascular volume depletion

bleeding, GI loss, Renal loss, Skin loss, Third space loss

Decreased cardiac output

CHF

Renal vasoconstriction
Liver Disease, Sepsis, Hypercalcemia

Pharmacologic impairment of
autoregulation and GFR in specific
settings
ACEi in bilateral RAS, NSAIDS in any renal
hypoperfusion setting

Intrinsic Renal Azotemia

Large Renal Vessel Disease

Thrombo-embolic disease

Renal Microvasculature and Glomerular Disease

Inflammatory: glomerulonephritis, allograft rejection
Vasospastic: malignant hypertension, scleroderma crisis, pre-eclampsia,
contrast
Hematologic: HUS-TTP, DIC

Acute Tubular Necrosis (ATN)

Ischemic
Toxic

Tubulo-interestitial Disease
Acute Interestitial Nephritis (AIN), Acute cellular allograft rejection, viral
(HIV, BK virus), infiltration (sarcoid)

Intratubular Obstruction
myoglobin, hemoglobin, myeloma light chains, uric acid, tumor lysis,
drugs (indinavir, acyclovir, foscarnet, oxalate in ethylene glycol toxicity)

Postrenal azotemia
Stones
Blood clots
Papillary necrotic tissue
Urethral disease
anatomic: posterior valve
functional: anticholinergics, L-DOPA
Prostate disease
Bladder disease
anatomic: cancer, schistosomiasis
functional: neurogenic bladder

Initial diagnostic tools in

AKI

History and Physical exam

Detailed review of the chart, drugs administered,
procedures done, hemodynamics during the procedures.
Urinalysis
SG, PH, protein, blood, crystals, infection
Urine microscopy
casts, cells (eosinophils)
Urine lytes
Renal imaging
US, Mag-3 scan, Retrograde Pyelogram
Markers of CKD
iPTH, size<9cm, anemia, high phosphate, low bicarb
Renal biopsy

5 Key Steps in Evaluating Acute Kidney Injury

1)

2)

3)
4)
5)

Obtain a thorough history and physical; review the

chart in detail
Do everything you can to accurately assess volume
status
Always order a renal ultrasound
Look at the urine
Review urinary indices

Prevention of AKI in ICU

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.

Antibiotics

Aminoglycosides (10-15% Incidence of Acute Tubular Necrosis)

Occurs in 10-20% patients on 7 day course

Results in non-oligurics; increased Creatinine

A single dose early in septic course is usually safe

Sulfonamides

Amphotericin B (Incidence 80-90%)

Levofloxacin

Ciprofloxacin

Rifampin

Tetracycline

Acyclovir (only nephrotoxic in intravenous form)

Pentamidine

Chemotherapy and Immunosuppressants

Cisplatin

Methotrexate

Mitomycin

Cyclosporine

Heavy Metals

Mercury Poisoning

Lead Poisoning

Arsenic Poisoning

Bismuth

Lithium related kidney disorders

Polydipsia and Nephrogenic Diabetes Insipidus

Acute Renal Failure

Dialysis indications: Creatinine >2.5 or Seizures, ALOC, Rhabdomyolysis

Chronic kidney disease with fibrosis

AntiHyperlipidemics

Statins

Gemfibrozil

Associated with Acute Renal Failure due to Rhabdomyolysis

Fenofibrate (Tricor)

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.

Prevention of AKI in hepatic

dysfunction
Intravenous

albumin significantly reduces the

incidence of AKI and mortality in patients with
cirrhosis.
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.

Management of AKI in ICU

Treatment

is largely supportive in nature

Maintain renal perfusion
Correct metabolic derangements
Provide adequate nutrition
? Role of diuretics
Renal Replacement therapy remains the
cornerstone of management of minority of
patients with severe AKI

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
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?

no statistical difference between volume

resuscitation with saline or albumin in
survival rates or need for RRT.
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.

Volume resuscitation how

much fluid?
Fluid

conservative therapy decreased

ventilator days and didnt increase the need
for RRT in ARDS patients.
Association between positive fluid balance
and increased mortality in AKI patients.

Wiedeman H, Wheeler A, Bernard G, et al.: Comparison of two fluid management strategies in acute lung
injury. New England Journal of Medicine 2006; 354:2564-2575.
Payen D, de Pont A, Sakr Y, et al.; A positive fluid balance is associated with worse outcome in patients with
acute renal failure. Critical Care 2008; 12: R74

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 (<5 g/kg of body weight/min)

increases RBF and, to a lesser extent, GFR.
Dopamine is unable to prevent or alter the course of
ischaemic
or
nephrotoxic
AKI].
Furthermore,
dopamine, even at low doses, can induce tachyarrhythmias,
myocardial
ischaemia,
and
extravasation out of the vein can cause severe
necrosis .Thus, the routine administration of
dopamine to patients for the prevention of AKI or
incipient AKI is no longer justified.
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.

Role of ANP analogues in AKI?

61 patients in 2 cardiothoracic ICU with post-op

AKI assigned to receive recombinent ANP
(50ng/kg/min) or placebo

The need for RRT before day 21 after

development of AKI was significantly lower in ANP
group (21% vs 47%)

The need for RRT or death after day 21 was

significantly lower in ANP group (28% vs 57%)

Crit Care Med. 2004 Jun;32(6):1310-5

Is there a role for Fenoldopam in

prevention or treatment of AKI in ICU
setting?

Dopamine-1 receptor agonist, lack of Dopamine-2, and

alpha-1 receptor effect, make it a potentially safer drug
than Dopamine!

Reduces in hospital mortality and the need for RRT in AKI

Reverses renal hypoperfusion more effectively than

renal dose Dopamine

So far so good specially in cardiothoracic ICU patients,

awaiting more powered trials in other groups!
J Cardiothorac Vasc Anesth. 2008 Feb;22(1):23-6.
J Cardiothorac Vasc Anesth. 2007 Dec;21(6):847-50
Am J Kidney Dis. 2007 Jan;40(1):56-68
Crit Care Med. 2006 Mar;34(3):707-14

Is there a role for diuretics in the

treatment of AKI in ICU setting?

Loop diuretics may convert an oliguric into a nonoliguric form of AKI that may allow easier fluid
and/or nutritional support of the patient. Volume
overload in AKI patients is common and diuretics
may provide symptomatic benefit in that
situation. However, loop diuretics are neither
associated with improved survival, nor with better
recovery of renal function in AKI.

JAMA. 2002 Nov 27;288(20):2547-53

Crit Care Resusc. 2007 Mar;9(1):60-8

NAC

The most recent trials seem to confirm a

potential positive preventive effect of Nacetylcysteine (NAC), particularly in
contrast-induced nephropathy (CIN), NAC
alone should never take the place of IV
hydration in patients at risk for CIN; fluids
likely have a more substantiated benefit. (150
mg/kg in 500 mL saline (0.9%)] over 30 min immediately before contrast
exposure and followed by 50 mg/kg in 500 mL saline (0.9%) over the
subsequent 4 h )

EPO

Erythropoietin (EPO) has tissue-protective

effects and prevents tissue damage during
ischaemia and inflammation, and currently
trials are performed with EPO in the
prevention of AKI post-cardiac surgery, CIN
and post-kidney transplantation.

Case 1

26 yo F is involved in a MVA, with multiple

fractures, blunt chest and abdominal trauma. She
was briefly hypotensive on arrival to ED, received
6L NS and normalized BP. Non contrast CT
showed small retroperitoneal hematoma. On
day#2 her SCr is 0.9 mg/dl, lipase is elevated and
tense abdominal distension is noted. US showed
massive ascites. UOP drops to <20 cc/hr despite
of 10 L total IV intake. On day#3, SCr is 2.1mg/dl,
CVP is 17, UNa is 10 meq/L, with a bland
sediment.

What is the cause of her AKI?

What bedside diagnostic test and therapeutic
intervention is indicated?

Bladder pressure was 29 mmHg

UOP and SCr improved with emergent

paracenthesis.

Dx: Abdominal Compartment Syndrome

causing decreased renal perfusion from
increased renal vein pressure.

Case 2

59 yo M, s/p liver transplant in 2001 and acute on chronic

rejection, now decompensated ESLD, is admitted with
worsening ascites, hepatic encephalopathy and GI bleed
(which is now controlled). The only medications he has
been receiving are Lactulose and omeprazole. He has been
hemodynamically stable with average BP~100/70
mmHg.He had a 3.5 L paracenthesis on day 2. His SCr has
been slowly rising from 1.2 to 4.7 mg/dl within the 2nd to
4th day of admission and his UOP has dropped to 150
cc/day. His daily FeNa is <1% despite of 2 L fluid challenge.
His Urine sediment is blend. His renal US is normal.

What is the cause of his AKI?

 Patient

required HD.

He

had a second liver transplant

and came off HD after the
surgery with stable SCr of 1.4
mg/dl.

Dx:

Hepatorenal Syndrome
(HRS)

Hepatorenal Syndrome
Major diagnostic criteria:
No improvement with at least 1.5 L fluid challenge
SCr >1.5 mg/dl or GFR< 40 cc/min
Absence of proteinuria (<500 mg/d)
Other causes are rouled out (obstruction, ATN, etc.)
Minor diagnostic criteria:
Urine volume < 400 cc/day
UNa < 10 meq/L
SNa < 130 meq/L
Urine RBC < 50/hpf

Case 3

45 yo M with CHF and Bipolar Disorder on

Lithium for 10 years, admitted for
abdominal pain after a heavy meal, which
turned out to be due to acute
cholecyctitis. He was kept NPO on D5
1/2NS 50 cc/hr. Next morning he felt well
but thirsty and hungry, BP=120/80,
I/O=1200/4500. His SCr rose from 1.2 to
1.9 mg/dl. SNa 149 meq/L. UNa 10 meq/L.
UOsm 190 mOsm/Kg.

What is the cause of his AKI?

Patients IVF was changed to NS, replacing

80% of UOP per hour. SCr and SNa
improved to baseline in 2 days.

Dx: Prerenal azotemia secondary to

renal free water loss in DI.

Case 4

54 yo F with CAD, on statin, started a new

exercise program with intense weight
training. She was brought to ED with neck
pain, and LE weakness. VS stable, normal
UOP, with dry mucosa. LE muscle strength
2/5 bilaterally. BUN 40 mg/dl, creatinine=8
mg/dl. FeNa 1.5%. Renal US normal. UA:
1.010, 3+ blood, few RBCs, few granular
casts.

What would be the next test to order?

What may be the cause of her AKI?

Her CPK=57,700
She was treated with IV NaHCO3 to
alkalinize urine to PH>6.5 .
Her UOP remained normal but she
required HD for uremia.

Dx: ATN due to Rhabdomyolysis

Case 5

72 yo M with DM, and prostate cancer metastatic to the

bone, s/p radiotherapy, on hormonal therapy. He is
admitted with weakness, progressive weight loss, and
persistent nausea. His med list also includes Diclofenac
sodium daily for hip pain. BP=150/90, 350cc of urine
collection immediately after foley placement, and
normal exam. BUN=107 mg/dl, creatinine=9.8 mg/dl
(2.0 almost for 6 months), which remained unchanged
with hydration. Uric acid=8.2 mg/dl. UA: 1.010, 1+
protein, 1+ blood, few RBCs, no cast, no WBC. US
showed 10-11 cm kidneys, no hydronephrosis.

What seems to be the cause for his AKI?

Patient was initiated on HD for uremia and

remained HD dependent for his
symptomatic uremia.
Patient and his family were concerned
about his renal recovery (outcome), so a
renal Bx was done showing severe chronic
interstitial nephritis, with fibrosis and
glomerulosclerosis.

Dx: ESRD due to chronic tubulointerstitial disease secondary to

NSAIDs

Case 6

38 yo M with post ERCP pancreatitis, is admitted to ICU,

intubated for hypoxic respiratory distress, is anuric, febrile,
and hypotensive, requiring massive volume resuscitation,
on two vasopressors. He has received 11 L of NS and other
IV meds within the last 8 hours and currently his CVP~12,
has coarse crackles, and 2+ edema. His Creatinine rose
from 1.2 to 3.5 the morning after the above event, FeNa >
1%, UNa 45 meq/L, UA: 1.010, no protein, no blood,
moderate epithelial cells, many muddy brown granular cell
casts, moderate epithelial cell casts. US showed normal
sized kidneys with no hydronephrosis.

What is the cause of his AKI?

He was started on CVVH (continuous

venovenous hemofiltration )for volume
control. Has had a long hospital stay
complicated with polymicrobial bacteremia
and VAP (Ventilator-associated
pneumonia).

Dx: ATN secondary to renal ischemia

and sepsis

Natural Clinical Course of ATN

Initiation Phase (hours to days)

Continuous ischemic or toxic insult
Evolving renal injury
ATN is potentially preventable at this time
Maintenance Phase (typically 1-2 wks)
Maybe prolonged to 1-12 months
Established renal injury
GFR < 10 cc/min, The lowest UOP
Recovery Phase
Gradual increase in UOP toward post-ATN diuresis
Gradual fall in SCr (may lag behind the onset of
diuresis by several days)

Thank you!