Prevention of Acute Kidney Injury on ICU – Journal Review

Dr James HaywardRSCH – ICU Teaching 2010

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

Critical Care Nephrology Working Group of the European Society of ICM

• Volume expansion• Diuretics• Inotropes• Vasopressors/vasodilators• Hormonal interventions• Nutrition• Extracorporeal techniques

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

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.

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

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.

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.

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.

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

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.

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!

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

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

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

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.

Other

• IGF – no strong evidence• Thyroxine – no effect• Steroids – no beneficial effect• APC – no effect on the resolution of renal

dysfunction.• EPO – no effect

Metabolic Interventions

• Starvation accelerates catabolism aqnd impairs protein synthesis in the kidney.

• Selenium and other antioxidants might reduce reactive oxygen species damage

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.

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.

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.

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.

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.

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.