Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients – RENAL trial
The RENAL Study Group. NEJM 2009; 361:1627-1638 doi:10.1056/NEJMoa0902413
- In critically ill adults requiring renal replacement therapy, does higher intensity dialysis compared to lower intensity dialysis reduce mortality?
- Randomised controlled trial
- Prospective, parallel-group trial
- Allocation concealment achieved by computer generated sequence
- Blinding; unblinded to ensure safety with fluid administration
- 1:1 allocation between higher intensity CRRT (40ml/Kg/hr) vs lower intensity CRRT (25ml/kg/hr)
- Primary outcome = 90 day mortality
- Sample size of 1500 calculated based on a 90% power of detecting an absolute risk reduction of 8.5% 90 day mortality (from 60% to 51.5%). This conservative estimate in ARR in mortality was half that found in Ronco’s trial published in the Lancet in 2000.
- 35 ICUs in Australia and New Zealand
- December 2005-November 2008
- Patients had AKI and were deemed to require renal-replacement therapy, and had one of: oliguria unresponsive to fluid therapy (<100ml/6hours), K+>6.5mmol/L, severe acidaemia (pH<7.2), uraemia (>25mmol/l), Creatinine>300umol/L OR clinically significant organ oedema.
- Written informed consent available a priori or delayed
- Exclusion: <18 years, death imminent (<24 hours), protocol violation likely, previous CRRT or dialysis on this hospital admission or long term dialysis.
- 1508 patients were enrolled: 747 assigned to the higher-intensity group and 761 to the lower-intensity group.
- All baseline characteristics were similar between the two groups.
- All patients were treated with CRRT in CVVHDF mode. Replacement fluid was delivered post-filter. The ratio of dialysate to replacement fluid was 1:1. The dose of dialysis (the effluent flow) was determined by the patient weight and was 40ml/kg/hr OR 25ml/kg/hr.
- Blood flow was kept above 150ml/min.
- Fluid removal was achieved by altering the replacement fluid and dialysate flow in equal proportions.
- The filter used was the same in each group.
- The replacement fluid and dialysate fluid was Hemosol BO.
- Primary outcome: all cause death at 90 days
- Death occurred in 322/721(44.7%) patients in the higher-intensity group and 332/743 (44.7%) in the lower-intensity group. p=0.99
- Secondary/Tertiary outcomes: no differences noted (high intensity vs low intensity)
- Death within 28 days of randomisation [38.5% vs 36.9% p =0.52]
- Death in the ICU [34.8% vs 34.2% p=0.81]
- In-hospital death after ICU discharge [9.4% vs 10.2% p=0.6]
- ICU Duration [11.8 days vs 11.8 days p=0.95]
- Hospital Duration [26 days vs 25.7 days p=0.79]
- Duration of mechanical ventilation [7.3 days vs 7.4 days p=0.79]
- Duration of renal replacement therapy [13 days vs 11.8 days p=0.14]
- Dialysis status at Day 90 [6.8% vs 4.4% p=0.14]
- New organ failures; no difference between groups
- Pre-specified subgroups; sepsis, failure of one or more non-renal organs, SOFA score and baseline GFR. There were non-significant differences between each subgroup in 90 day mortality.
- Hypophosphatemia more common in higher intensity group (65.1% vs 54% p<0.0001)
- Increasing the intensity of continuous renal replacement therapy from 25ml/kg/hr to 40ml/kg/hr did not reduce mortality or the rate of dependence on dialysis among critically ill patients
- Well powered study and the largest trial examining this important question
- Allocation concealment
- Complete follow-up
- Predefined statistical analysis plan published before trial conducted
- Separation in groups with the delivered dose 33.4ml/kg/hr in the high intensity group vs 22ml/kg/hr in the lower intensity group
- Pre-specified subgroups
- Delivered dose less than prescribed dose
- This study used mixed diffusive and convective clearance and did not examine if one is superior to the other
- Differences in costs not examined in this trial
The Bottom Line
- Delivering higher intensity dialysis dosing is not without risk. Some of the potential disadvantages are; disturbance in electrolyte concentrations, increased costs and nursing workload, micronutrient depletion and subtherapeutic levels of antibiotics. This is the best trial examining ‘dose’ of dialysis in critically ill patients and stands the test of time, even 8 years after publishing. I will continue my practice of dialysing critically ill patients with AKI at 25ml/kg/hr.
- [article] Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients
- [further reading] Dialysis: getting it right in ICU. Podcast from Celia Bradford for ICN
- [further reading] TBL Editorial: Early vs Late Renal Replacement Therapy