Prevention and treatment of acute kidney injury in the ICU

Dr. Farmer
Prevention and
Treatment of Acute
Kidney Injury in the
ICU


Prevention and Treatment of Acute Kidney
Injury in the ICU
J. Christopher Farmer


Learning Objectives
To discuss…

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Pathophysiology, risk factors, and etiologies of
AKI
Current and emerging methods of early diagnosis
Prevention of AKI
Treatment of AKI


Epidemiology and Pathophysiology


Increasing Incidence of AKI

Nash, et al: Am J Kidney Dis; 2002, 39:390



Arterial Vasodilatation and Renal
Vasoconstriction in Patients with Sepsis


Diagnosis and Classification of AKI


Diagnostic Criteria for AKI
An abrupt (within 48 hours) reduction in kidney function currently defined as:

1.An

absolute increase in serum creatinine of more than
or equal to 0.3 mg/dl, or
2.A percentage increase in serum creatinine of more
than or equal to 50% (1.5 fold from baseline), or
3.A reduction in urine output (documented oliguria of
less than 0.5 ml/kg per hour for more than 6 hours)

Mehta et al: Critical Care; 2007, 11:R31-R39


“RIFLE” Criteria for AKI

Bellomo & the ADQI workgroup: Critical Care; 2004, 8:R204-R212

Classification of AKI Severity

Mehta et al: Critical Care; 2007, 11:R31-R39


Mortality Associated with Rising Serum
Creatinine

Unadjusted
Adjusted for age & sex
Multivariable analyses

Chertow, et al: J Am Soc Nephrol; 2005, 16:3365-3370


FENa = (UNa/PNa) / (UCr/PCr) X 100
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Calculating the FENa is useful in AKI only in the presence of oliguria

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In patients with prerenal azotemia, the FENa is usually less than 1%

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In ATN, the FENa is greater than 1%.

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Exceptions to this rule are ATN caused by radiocontrast nephropathy,
severe burns, acute glomerulonephritis, and rhabdomyolysis

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In the presence of liver disease, FENa can be less than 1% in the
presence of ATN

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Because administration of diuretics may cause the FENa to be greater
than 1%, these findings cannot be used as the sole indicators in AKI


FEUrea = (Uurea/Purea) / (UCr/PCr) X 100
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Fractional excretion of urea (FEUrea) can be
obtained since urea transport is not affected by
diuretics

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FEUrea of less than 35% is suggestive of a prerenal
state


Early Detection of AKI is Difficult

Jo, et al: Clin J Am Soc Nephrol; 2007, 2:356-365


“Earlier” Detection of AKI


Induction of NGAL protein after unilateral or
bilateral ischemia

Mishra, et al: J Am Soc Nephrol; 2003, 14:2534-2543


Urinary IL-18 as an Early Marker of AKI

IL-18 as a marker for the
diagnosis of ATN and
delayed graft function:
•ROC - discriminatory power
of IL-18 for the diagnosis of
ATN
•The area under the ROC
curve was 0.95

Parikh et al: AJKD; 2004, 43:405-14


Future “Cardiac Biomarkers” of AKI?

Parikh et al: KI; 2006, 70:199 -203

Coming soon?
Biomarker

Sample Source

Assay

Commercial Development

NGAL

plasma

Western blot

In development (Biosite)

NGAL

urine

Western blot

In development (Abbott)

IL-18

urine

ELISA

NONE

KIM-1

urine

ELISA

NONE

Cystatin-C

plasma

Immunonephelometry

In development (DadeBehring)


Prevention of AKI


Prevention of AKI
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X

Venkataraman, et al: Crit Care
Med; 2008, 36:S166-S171


Maintaining Renal Perfusion Pressure
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No absolute number is considered adequate with regard to mean
arterial pressure, and target mean arterial pressure should be
individualized based on the patient's baseline physiology
Vasopressors should be used to improve perfusion pressure only after
adequate volume repletion is accomplished
No reliable evidence that norepinephrine is associated with increased
risk of AKI when used to treat arterial hypotension
Intra-abdominal hypertension is associated decreased renal perfusion
and may result in AKI
Prompt recognition, monitoring, and early surgical treatment offer the
best potential for recovery


Role of Loop Diuretics in AKI
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maintaining a greater urine flow to flush out the tubules with loop
diuretics has been advocated to prevent AKI
Two meta-analyses have pooled studies evaluating the role of loop
diuretics in the prevention of AKI
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The first systematic review compared fluids alone with diuretics in people
at risk for AKI from various causes and found no benefit from diuretics with
regard to its incidence, need for dialysis, or mortality
In the second recent meta-analysis (RCTs, n = 849 patients), no difference
among patients treated with loop diuretics was found in hospital mortality,
need for renal replacement therapy, or number of dialysis sessions needed


Treatment of AKI