This presentation discusses the evidence for renal replacement therapy in the ICU for acute renal failure.

1. Dialysis for Acute Renal Failure in
Critically Ill Patients

2. AKI Classification Systems 2: AKIN
Stage Creatinine Criteria Urine Output Criteria
1 1.5 - 2 x baseline (or rise > 26.4 mmol/L) < 0.5 ml/kg/hour for > 6 hours
2 >2 - 3 x baseline < 0.5 ml/kg/hour for > 12 hours
3
> 3 x baseline (or > 354 mmol/L with acute
rise > 44 mmol/L)
< 0.3 ml/kg/hour for 24 hours or anuria for
12 hours
Patients receiving RRT are Stage 3 regardless of creatinine or urine output

3. Mortality by AKI Severity
17
47
48
64
40
NONE CREAT 150-299 CREAT > 300 RRT ESRD
Bagshaw, S et al. Am J Kidney Dis 2006; 48: 402-409

5. CI indicates confidence interval.aPooled estimate should be viewed with caution (I2 = 90%). bP2SH is a newly developed high-flux membrane
Figure Legend:
From: Renal Replacement Therapy in Patients
With Acute Renal Failure: A Systematic Review
JAMA. 2008;299(7):793-805. doi:10.1001/jama.299.7.793

6. Dialysis Strategies
Early vs Usual
IRRT vs CRRT
Daily vs Alternate Days
Low Dose vs High Dose

7. Timing of renal replacement therapy
initiation in acute renal failure
Seabra VF et al. Timing of renal replacement therapy init Am J Kidney Dis. 2008;52:272–284
Systematic Review and Meta-analysis
5 RCT studies, 18 cohort studies
Mortality Up to 180 Days
Early Usual Risk Ratio
RCTs 31/125 (25%) 59/145 (41%) 0.64 [0.04-1.04]
Cohorts 473/1050 (45%) 642/1058 (61%) 0.72 [0.54-0.82]

8. A comparison of early versus late initiation of renal
replacement therapy in critically ill patients with acute
kidney injury: a systematic review and meta-analysis
Karvellas et al. Critical Care 2011, 15:R72

9. Conclusion
This systematic review suggests that early institution of RRT in critically ill
patients with AKI may have a measurable benefit on survival.
However, existing evidence is based on mostly smaller studies with important
differences in design and quality, and only two randomised trials.
In the absence of novel evidence from a multi-centric suitably-designed
randomised trial, conclusive treatment recommendations on the optimal time to
initiate RRT remain uncertain.

11. Timing of Renal Replacement Therapy
Initiation in Acute Renal Failure
Jamale et al. Am J Kidney Dis. 2013;61:1116-21
RCT
208 adults with acute kidney injury with progressively worsening azotemia in a tertiary-care referral
center in western India
Early Usual P Value
BUN/Cr at initiation 72/7.4 101/10.4 < 0.001
In Hospital Mortality 20.5% 12.2% 0.2
HD-dependence at 3
months
4.9% 4.7% 0.9

12. Dialysis Strategies
Early vs Usual
IRRT vs CRRT
Daily vs Alternate Days
Low Dose vs High Dose

13. Intermittent versus continuous renal replacement therapy for
acute kidney injury patients admitted to the intensive care
unit: results of a randomized clinical trial
Robert L. Lins, et al. Nephrol Dial Transplant (2009) 24: 512–518
X p= 0.42
SHARF 4 Study
316 patients with ARF in ICU, 42 hospitals
April 2001 to March 2004
CRRT IRRT
# of Patients 172 144
Hospital Mortality 58.1% 62.5%

14. Outcome in patients randomized to intermittent
or continuous renal replacement therapy
Robert L. Lins, et al. Nephrol Dial Transplant (2009) 24: 512–518

15. Outcome in patients randomized to intermittent
or continuous renal replacement therapy
Robert L. Lins, et al. Nephrol Dial Transplant (2009) 24: 512–518

16. Outcome in patients randomized to intermittent
or continuous renal replacement therapy
Robert L. Lins, et al. Nephrol Dial Transplant (2009) 24: 512–518

17. Intermittent versus continuous renal replacement
therapy for acute renal failure in adults
Robert Rabindranath et al. Cochrane Database Syst Rev2007;3:CD003773-CD003773

18. Comparison CRRT versus IRRT, Outcome: Mean
arterial pressure at end of study period
Robert Rabindranath et al. Cochrane Database Syst Rev2007;3:CD003773-CD003773

19. Summay of 3 Met-analyses Comparing
Continious vs Intermittent Dialysis in AKI
3 Meta-analyses
Effect on Mortality
Studies (N) Risk Ratio
CRRT vs IHD
Kellum et al. Intensive Care Med
2007
13 (1400)
0.93 [0.79-1.09]
0.72 [0.60-0.87] (adjusted)
Rabindranath et al. Cochrane
Rev 2007
15 (1550) 1.01 [0.92-1.12]
Pannu et al. JAMA 2008 7 (918) 1.10 [0.99-1.23]
Bouchard et al. Adv Chron Kidney Disease, 2008;15: 235-47
No consistent effect on recovery of renal function or development of CKD

20. Meta-analysis of Dialysis Modality and
Chronic Dialysis Dependence
Schneider et al. (2013) Intensive Care Med, 39: 987-9
Updated Meta-analysis, 23 Studies
Rates of Dialysis Dependence
IHD CRRT RR
Observational (n=16)
479/1476
(32.4%)
224/2023
(11.0%)
1.99
[1.53-2.59]
RCT’s (n=7)
38/240
(15.8%)
32/232
(13.8%)
1.15
[0.78-1.68]
Combined
517/1716
(30.1%)
256/2255
(11.5%)
1.73
[1.35-2.20]

22. Positive Fluid Balance is Associated with Increased
Mortality in Dialysis Requiring AKI
The RENAL Replacement Therapy Investigators, Crit Care Med 2012 Vol. 40, No. 6

23. Positive Fluid Balance is Associated with Increased
Mortality in Dialysis Requiring AKI
The RENAL Replacement Therapy Investigators, Crit Care Med 2012 Vol. 40, No. 6

24. Continuous Renal Replacement in AKI
A. Liver failure***
B. Hypotension*
C. Severe volume overload*
D. Excessive obligatory intake*
E. Hypercatabolic states or inability to meet nutritional requirement
F. Severe sepsis
G. ARDS
H. Severe hypercalcemia, hypophosphtemia, tumor lysis syndrome
*** Stronger, * Week

25. Dilalysis Strategies
Early vs Usual
IRRT vs CRRT
Daily vs Alternate Days
Low Dose vs High Dose

27. Daily Hemodialysis And The Outcome
Of Acute Renal Failure
Schiffl et al. N Engl J Med, Vol. 346, No. 5

28. Palevsky et al. N Engl J Med 2008;359:7-20

29. Intensity of Renal Support in Critically
Ill Patients with Acute Kidney Injury
Palevsky et al. N Engl J Med 2008;359:7-20
1124 patients in the two groups were similar
IHD 3 vs 6 times per week
Or CVVHDF 20 vs 35 mm/kg/hr
53.6% vs 51.5%
(odds ratio, 1.09; 95% confidence interval, 0.86
to 1.40; P = 0.47).

30. Intensity of Renal Support in Critically
Ill Patients with Acute Kidney Injury
Palevsky et al. N Engl J Med 2008;359:7-20

31. Summary of Evidence
Daily vs Alternate Days Dialysis
Effect on Mortality
Study Subjects Modality Intensity Outcome P Value
Schiffl et al, NEJM
2001
146 IHD 3 vs 6 times wk 46% vs 28% 0.001
Palevsky et al
NEJM 2008
1124 IHD or CVVHDF
3 vs 6 times wk
20 vs 35 ml/kg/h
54% vs 52% 0.47

32. Dilalysis Strategies
Early vs Usual
IRRT vs CRRT
Daily vs Alternate Days
Low Dose vs High Dose

33. Dialysis Dose and AKI Outcome
Low Dose vs High Dose Dialysis
Effect on Mortality
Study Subjects Modality Dose Outcome P Value
Romeo et al, Lancet 2000 425 CVVH 20 vs 35 vs 45 ml/kg/h 59% vs 43% vs 42% 0.000
Bouman et al, Crit Care Med 2002 106 CVVH 20 vs 48 ml/kg/h 26% vs 31% 0.8
Saudan et al, Kidney Int 2006 206
CVVH or
CVVHDF
25 vs 42 ml/kg/h 61% vs 41% 0.03
Tolwani et al, JASN 2008 200 CVVH 20 vs 35 ml/kg/h 44% vs 51% NS
Bellomo et al, NEJM 2009 1508 CVVH 25 vs 40 ml/kg/h 45% vs 45% 0.99

34. Intensity of Continuous Renal-Replacement
Therapy in Critically Ill Patients
RENAL Study
1464 patients with ARF, in 35 ICUs
Dec 2005 to Nov 2008
Low Intensity
25 ml/kg/hr
High Intensity
40 ml/kg/hr
# of Patients 743 721
90 Day Mortality 44.7% 44.7% X
Rinaldo Bellomo et al. N Engl J Med 2009;361:1627-38

35. Intensity of Continuous Renal-Replacement
Therapy in Critically Ill Patients
Rinaldo Bellomo et al. N Engl J Med 2009;361:1627-38