When to Start RRT in AKI
Alexander Usorov, MD
2/24/09
New Diagnostic Criteria for AKI
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Acute Dialysis Quality Initiative
Plus several Critical Care Societies
Equals Acute Kidney Injury Network or AKIN
The fundamental goal is to improve the
outcomes for patients who are at risk
• The first AKIN conference was held in
Amsterdam in September 2005
• Focused on the development of uniform
standards for definition and classification of AKI
RIFLE-AKI
Indications for RRT in AKI
• Volume overload unresponsive to diuretics
• Metabolic acidosis refractory to medical
management
• Intoxication with dialyzable drug or toxin
• Uremic symptoms
– Encephalopathy
– Pericarditis
– Uremic bleeding
• Progressive azotemia in the absence of specific
symptoms
Indications are open to
interpretations
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How volume overloaded?
What should potassium level be?
How severe for metabolic acidosis?
What is the definition of diuretic
resistance?
Dose and Modality
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VA/NIH trial vs Schiffl’s trial
Ronco
Mehta
Vinsonneau (Contniuous venouvenous
hemodiafiltration vs intermittent HD for
ARF in pts with multiorgan dysfunction
syndrome. Lancet 2006)
Timing?
• Less data available
• Early literature (1950s-1960s) is significant for the
concept of prophylactic HD in AKI
• Introduced by Dr. Paul E Teschan
• Observational report using prophylactic HD in 15 pts with
oliguric ARF from Renal Center of the US Army Surgical
Research Unit
• HD initiated prior to BUN reaching 200 mg/dL or uremic
sxs
• Comparison was done to author’s past experience
• Improvement in mortality, clinical course, uremic sxs
Cont
RCTs
• Conger et al conducted a study on US Naval
Hospital Ship USS Sanctuary between April and
October of 1970
• 18 patients with post-traumatic AKI
– Intensive HD arm with pre-HD BUN<70 and SCr <5
– Non-intensive regimen with delaying HD until BUN
approached 150 and SCr approached 10 or if
clinically indicated
• Survival - 5/8 pts (64%) vs 2/10 (20%) pts
• Major complications (Gram-neg. sepsis,
hemorrhage) were less freq in intensive arm
Increased Mortality in Early HD
• Gillum et al examined 34 pts at University of
Colorado in 1986
• Pts were paired and randomly assigned once
SCr reached 8
– Intensive regimen with pre-HD BUN<60 and SCr <5
– Less intensive regimen: BUN and SCr reached 100
mg/dL and 9 mg/dL
• Average time from AKI to HD: 5+2 vs 7+3 days
• Higher mortality in the intensive HD group
Conventional wisdom
• In the absence of uremic symptoms, start
hemodialysis if BUN is around 100 mg/dL
• No additional benefit seen with earlier HD
initiation nor more intensive HD
prescription
Moving On
• Further studies focused mostly on the
timing of initiation of CRRT
• Gettings et al published a retrospective
analysis of 100 consecutive patients with
post traumatic AKI in 1999
• Early vs late initiation based on BUN < or
> 60 mg/dL at initiation of therapy
Cont.
• Early group
– CRRT initiated on hospital day 10+15
– Mean BUN of 43+13
• Late group
– CRRT initiated on HD 19+27
– BUN of 94+28
• Survival – 39% in early vs 20% in late
group
• Critical points:
– Non-randomized, retrospective
– More pts with multisystem organ failure or
sepsis in late group
– More pts oliguric on first day of CRRT in early
than late group, leading to suggestion that
there was a confounding effect (?physician
bias)
More Retrospective Studies
• Elahi et al reported a series of 64 consecutive patients
s/p cardiac surgery at a single UK center between
January 2002 and January 2003
• In 28 pts, CVVHDF was started once BUN>84, SCr>2.8,
or serum K>6, despite medical therapy and regardless of
UOP
• Remaining 36 pts, CVVHDF was initiated when UOP
was <100ml over 8 hrs despite Lasix
• Similar demographics and baseline clinical
characteristics
• Surgery to renal support time was 2.6+2.2 days vs
0.8+0.2 days
Limitations of the studies
• All recent studies are retrospective
• Using BUN as a surrogate measure of AKI
duration is problematic
• Urea generation varies from patient to
patient
• Volume of distribution of urea in critically ill
patients is variable as well
• Bias by indication
How about a prospective study of
CRRT timing?
• Bouman et al randomized 106 criticall ill patients with
AKI to three groups:
– Early high-volume CVVHDF (35 pts)
– Early low-volume CVVHDF (35 pts)
– Late low-volume CVVHDF (36 pts)
• Two early groups – txt started within 12 hrs of meeting
inclusion criteria:
– Oliguria x 6 hrs despite hemodynamic optimization
– Measured cr clearance <20 ml/min on a 3-hr timed collection
• Late groups:
– BUN>112
– K>6.5
– Pulmonary edema present
Outcome
• No significant differences in survival were
observed
• Critical point is that 28-day mortality was only
27%, much lower than in prvsly reported studies
of critically ill patients with AKI
• Small sample size lead to low statistical power
• Interestingly, 6/36 pts in late group never got
RRT (2 pts died and 4 pts recovered renal fxn)
So When Do We Initiate RRT?
• Inadequate data available to answer this
question
• Observational data suggests better
outcomes are associated with early RRT
initiation
• ? If “less sick” patients are included in
these early groups
• Also, most pts with AKI are not treated
with RRT