When to Start RRT in AKI

Alexander Usorov, MD2/24/09

New Diagnostic Criteria for AKI

• 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

• How volume overloaded?• What should potassium level be?• How severe for metabolic acidosis?• What is the definition of diuretic

resistance?

Dose and Modality

• 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 HDIncreased 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