The RENAL STudy: High vs Low Intensity RRT
The evidence for the optimal intensity of renal replacement therapy (RRT) in critically ill patients isn’t clear. Previous trials hadn’t provided definitive evidence of sufficient quality to answer this question. The authors set out to provide this information in the Randomised Evaluation of Normal versus Elevated Level (RENAL) RRT study:
Intensity of Renal-Replacement Therapy in Critically Ill Patients
Bellomo et al.
Intensity of Renal-Replacement Therapy in Critically Ill Patients
Bellomo et al.
What did they do?
Population: 35 ICUs in Australia and New Zealand
Inclusion criteria: Over 18, AKI with one of: Oligouria, K+ >6.5 mmol/L, pH <7.2, urea nitrogen > 25mmol/L, creatinine >300 micromol/L, significant organ oedema, and treating clinician deemed RRT needed.
Exclusion criteria: End stage renal disease, RRT during that hospital stay.
Intervention: Both received CVVH with 1:1 post filter replacement fluid and blood flow of 150ml per minute. The groups were randomised to either high intensity (40ml/kg/hour) or low intensity (25ml/kg/hour) effluent flow.
Primary Outcome: All cause mortality at 90 days.
Secondary Outcomes: 28 day mortality, death in hospital and ICU, hospital and ICU stay, duration of RRT and ventilation, dialysis status at 90 days.
Analysis: Intention to treat analysis. Power calculation for an 8.5% absolute reduction in 90 day mortality (from predicted baseline of 90%)
Inclusion criteria: Over 18, AKI with one of: Oligouria, K+ >6.5 mmol/L, pH <7.2, urea nitrogen > 25mmol/L, creatinine >300 micromol/L, significant organ oedema, and treating clinician deemed RRT needed.
Exclusion criteria: End stage renal disease, RRT during that hospital stay.
Intervention: Both received CVVH with 1:1 post filter replacement fluid and blood flow of 150ml per minute. The groups were randomised to either high intensity (40ml/kg/hour) or low intensity (25ml/kg/hour) effluent flow.
Primary Outcome: All cause mortality at 90 days.
Secondary Outcomes: 28 day mortality, death in hospital and ICU, hospital and ICU stay, duration of RRT and ventilation, dialysis status at 90 days.
Analysis: Intention to treat analysis. Power calculation for an 8.5% absolute reduction in 90 day mortality (from predicted baseline of 90%)
What did they find?
Numbers: 1508 patients underwent randomisation, 44 withdrew/lost to follow up before full analysis. 721 in high intensity (HI) group. 743 in low intensity (LI) group.
Results: Primary outcome:There was no difference in 90 day mortality between the groups (HI was 322/721 (44.7%) vs LI 332/743 (44.7%) (p = 0.99)).
Secondary Outcome: There were no significant differences between the groups in any of the secondary outcomes.
Treatment: The difference in treatment intensity was achieved between the two groups (HI effluent flow 33.4 +/- 12.8 vs 22 +/- 17.8 ml/kg/hour in the LI group (p < 0.001) . HI group had lower creatinine (170 +/- 120 vs 204 +/- 115 micromol/L/day (p < 0.001)) and BUN levels (12.7 +/- 8.5 vs 15.9 +/- 7.9 mmol/L/day ( p < 0.001)). The HI group needed more filters per day (0.93 vs 0.84 (p < 0.001)). Hypophosphatemia was more common in the high intensity group (65.1% vs 54% of patients (p < 0.0001))
Results: Primary outcome:There was no difference in 90 day mortality between the groups (HI was 322/721 (44.7%) vs LI 332/743 (44.7%) (p = 0.99)).
Secondary Outcome: There were no significant differences between the groups in any of the secondary outcomes.
Treatment: The difference in treatment intensity was achieved between the two groups (HI effluent flow 33.4 +/- 12.8 vs 22 +/- 17.8 ml/kg/hour in the LI group (p < 0.001) . HI group had lower creatinine (170 +/- 120 vs 204 +/- 115 micromol/L/day (p < 0.001)) and BUN levels (12.7 +/- 8.5 vs 15.9 +/- 7.9 mmol/L/day ( p < 0.001)). The HI group needed more filters per day (0.93 vs 0.84 (p < 0.001)). Hypophosphatemia was more common in the high intensity group (65.1% vs 54% of patients (p < 0.0001))
Is it any good?
Overall: Yes
Strengths: Randomised. Large numbers (though not quite reaching power calculation target for a significant difference in mortality). Clear predetermined objectives and analysis.
Weaknesses: Not blinded. Didn’t actually achieve targeted intensity in each limb due to down-time (actual doses were 33.4 and 22 ml/kg/hour of effluent). Almost exclusively CVVH, limiting translation to alternate forms of RRT.
Strengths: Randomised. Large numbers (though not quite reaching power calculation target for a significant difference in mortality). Clear predetermined objectives and analysis.
Weaknesses: Not blinded. Didn’t actually achieve targeted intensity in each limb due to down-time (actual doses were 33.4 and 22 ml/kg/hour of effluent). Almost exclusively CVVH, limiting translation to alternate forms of RRT.
Final Thoughts
Higher intensity CVVH doesn’t appear to offer any benefits and probably causes more problems though increased use of filters and a greater incidence of hypophosphatemia.
Written: Tom Heaton
Reviewed: Not done
13th March 2016
Written: Tom Heaton
Reviewed: Not done
13th March 2016
References
1. Bellomo et al. Intensity of Renal-Replacement Therapy in Critically Ill Patients. NEJM. 2009. 361:1627-38.
