1. Prevention of Acute Kidney
Injury on ICU – Journal Review
Dr James Hayward
RSCH – ICU Teaching 2010

2. Acute Kidney Injury
• Commonly occurs in the course of critical illness
• Independent predictor of adverse outcomes
• Common causes
– Renal hypoperfusion
– SIRS
– Nephrotoxic drug
– Contrast nephropathy

3. Critical Care Nephrology Working
Group of the European Society of ICM
• Volume expansion
• Diuretics
• Inotropes
• Vasopressors/vasodilators
• Hormonal interventions
• Nutrition
• Extracorporeal techniques

4. GRADE criteria
• Grades of Recommendation, Assessment,
Development, and Evaluation.
• Quality of intervention
– Strong = 1 - Intervention’s desirable effects clearly
outweighs the undesirable effects
– Weak = 2 - Balance between risk/benefit is unclear
• Quality of evidence
– A = high - Repeated large RCTs, and good meta-
analyses
– B – Small RCTs
– C = Low grade – Case series

5. Volume Expansion
• Mainstay for correction of
extracellular volume depletion
is isotonic crystalloids.
– Increased chloride load may
result in hyperchloraemic
acidosis and renal
vasoconstriction and altered
organ perfusion.
• Large volume replacement with
colloids risks hyperoncotic
impairment of glomerular
filtration, as well as osmotic
tubular damage particularly in
sepsis.

6. Volume Expansion
• HAS
– no proven benefit
– expensive
• Gelatins
– Unlikely to impair renal function
– Remain intravascular longer than crystalloid but shorter than HES
– May cause histamine release, coagulopathy, prion transmission
• Dextrans
– Good volume expanders
– Anaphylaxis, coagulopathy and AKI may occur
• HES
– Prolonged volume effect
– The polymers undergo hydrolytic cleavage and the products undergo renal
elimination, which may be reabsorbed and contribute to osmotic nephrosis
and possibly medullary hypoxia
– May deposit in tissues and cause pruritis

7. Volume Expansion
• Timely fluid resuscitation is a key aspect to the
surviving sepsis campaign.
• No one has compared fluid resuscitation with no
fluid resuscitation.
• CRYCO study – crystalloid vs colloid in ICU –
colloid group had increased risk of AKI
• VISEP study showed higher incidence of AKI, RRT
and mortality in the group treated with HES vs
Hartmann’s
• Other RCTs have shown no difference.

8. Diuretics
• Olig/anuria is the
common herald of
impending renal
dysfunction and loop
diuretics are commonly
used in this context.
• Theoretical basis is
prevention of tubular
obstruction, reduction in
medullary oxygen
consumption, increased
renal blood flow.

9. Diuretics
• 4 RCTs – no improvement.
• Three meta-analyses showed diuretics do not
alter outcome but do increase the risk of side-
effects.
• One international cohort study showed an
increased risk of death and established renal
failure.

10. Vasopressors and Inotropes
• Increased cardiac
output might equal
increased renal
perfusion
• Various studies quote
different targets
• Those at greatest risk
will need specific
targeted pressures

11. Vasopressors and Inotropes
• Low-dose dopamine – does not prevent, or
ameliorate AKI and some studies have suggested
that it may promote AKI.
• Dobutamine and dopexamine have not been
demonstrated as protective.
• Noradrenaline is frequently used in septic shock
and has been shown to increase diuresis and
creatinine clearance.
• RCT comparing dopamine and noradrenaline as
the initial vasopressor showed no difference
between renal function or mortality.

12. Vasodilators
• Reduced tissue perfusion
causes neurohumoral
activation which will
maintain systemic pressure
at the expense of splanchnic
and renal vasoconstriction.
• In circumstances of
persistent renal
vasoconstriction,
vasodilators might have a
beneficial effect on kidney
function.
• Be careful!

13. Vasodilators - Fenoldopam
• Fenoldopam = pure dopamine A1 agonist
– Thee RCTs compared with placebo or dopamine
• Fenoldopam reduced dialysis free survival and need for RRT
• Fenoldopam caused a significant decrease in mild AKI and a
non-significant decrease in severe AKI
• Compared to dopamine fenoldopam significantly reduced
serum creatinine
– Two large meta-analyses
• 1059 Cardiovascular surgical patients – reduced need for
RRT and reduced in hospital mortality
• 1290 Critical care and surgical patients – reduced incidence
of AKI, need for RRT and hospital mortality.
– No use in prevention of CIN

14. Vasopressors – other.
• Clonidine – 2 RCTs looking and cardiothoracic patients showed
some benefit.
• Natriuretic peptides – looked at only in cardiothoracic patients –
seem to work.
• Phosphodiesterase inhibitors are vasodilators and inotropes and
could modulate the inflammatory response.
– 10 RCTs, 3 meta-analyses have been inconclusive.
– Recent RCT showed reduction in the incidence of CIN by preprocedural
administration of 200mg theophylline in critically ill patients
• Levosimendan – RCT 80 heart failure patients showed short term
improvement in GFR only.
• Angiotensin blockers – two studies evaluating short term enalaprilat
in cardiac surgical patients showed improved cardiac and renal
function

15. Hormonal Manipulation and Activated
Protein C
• IGF-1, and thyroxine have
been shown to accelerate
recovery in animal
models of AKI
• EPO might reduce cell
death and induce tubular
proliferation
• APC has numerate effects
and animal studies have
shown beneficial effects
in ischaemia/reperfusion
AKI

16. Glycaemic control
• Large RCT (van de Berghe) in surgical patients
showed that tight glycaemic control showed
increased survival and a 41% reduction in RRT
• On the medial ICU tight glycaemic control
reduced newly acquired renal injury by 34%, but
not in need for RRT
• Meta-analysis suggests that benefit might be
confined to surgical ICU
• NICE-Sugar trial – showed higher mortality in
patients with tight glycaemic control versus
intermediate control.

17. Other
• IGF – no strong evidence
• Thyroxine – no effect
• Steroids – no beneficial effect
• APC – no effect on the resolution of renal
dysfunction.
• EPO – no effect

18. Metabolic Interventions
• Starvation accelerates
catabolism aqnd
impairs protein
synthesis in the kidney.
• Selenium and other
antioxidants might
reduce reactive oxygen
species damage

19. NAC
• Extensively studied –
– studies that have shown a benefit have been
criticised for having heterogeneous groups and a
higher incidence of CIN in control arm.
– studies have looked at creatinine concentration as
an end point not RRT or death.
– Several studies looking at NAC to prevent renal
dysfunction in other high-risk groups did not
demonstrate a beneficial effect of NAC on renal
function or need for RRT.

20. Extracorporeal Therapies
• May protect the
kidney by removal of
substances, such as
contrast, particularly in
patients with chronic
renal insufficiency.
• Degree of contrast
removed depends on
the filter.

21. Extracorporeal therapies
• Several studies have looked at RRT to limit
contrast nephropathy.
– Periprocedural haemodialysis showed variable benefit
– RCT using 114 patients having cardiac intervention
showed haemofiltration 4-8hrs before and 24hrs after
showed reduced need for ongoing renal support
– Same group then studied pre-hydration, post-
filtration, and pre/post filtration. Those patients
having pre and post filtration had a better outcome.

22. Conclusions
• Difficult to evaluate because of definitions of
AKI and outcome variables.
• Prompt restoration of circulatory “normality”.
– Volume expansion in true hypovolaemia, with
avoidance of HAS, and high molecular weight HES
preparations.
– Then use a vasoconstrictor up to MAP of at least
60-65mmHg, with consideration of premorbidity.
– Vasodilators if circulatory status are
recommended.

23. Contrast Induced Nephropathy (1)
• Prophylactic volume expansion has been extensively
investigated in the prevention of CIN. Benefit is
conferred in certain patient groups.
– Reduced GFR
– Heart failure
– Diabetes
• Isotonic bicarbonate solutions have been shown to
significantly reduce the incidence of CIN but not
ultimately RRT nor mortality.
– Other RCTs have shown no difference but when all are
combined in meta-analysis, bicarbonate still demonstrated
a benefit.

24. Contrast Induced Nephropathy (2)
• No protection against contrast nephropathy
has been observed with diuretics.
• Recent RCT showed reduction in the incidence of CIN
by preprocedural administration of 200mg
theophylline in critically ill patients
• If a patient is at risk of AKI, then CVVH will confer the
most benefit if used pre and post promptly.