Intensity of renal replacement therapy in critically ill patients with acute kidney injury
July 14, 2010 5 Comments
Blog Post by Dr Kaushik Bhowmick FRCA, Specialty Trainee in Anaesthesia & Intensive Care Medicine, Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge, CB23 3RE, UK and
Dr Stephen T Webb MB BCh BAO FRCA EDIC, Consultant in Anaesthesia & Intensive Care Medicine, Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge, CB23 3RE, UK
Acute kidney injury (AKI) is common in critically ill patients in the intensive care unit (ICU). Renal replacement therapy (RRT) is required in approximately 5% of patients in intensive care with severe AKI and is associated with substantial mortality.
There are two broad methods of RRT, continuous and intermittent RRT. Although no significant mortality difference has been demonstrated between the two methods, continuous RRT is preferred method in intensive care units in many countries including UK, Australia and New Zealand. Continuous renal replacement therapy provides continuous fluid removal, steady acid-base and electrolyte correction and relative haemodynamic stability. In spite of much development, the optimal intensity, timing and mode of RRT remain uncertain. One of the many complications of AKI is uraemia. RRT aims not only to reduce the clinical complications of uraemia but also the adverse subclinical pathophysiological effects of uraemia.
Intensity of RRT plays a crucial role in AKI where catabolism is pronounced and urea generation is high. The actual renal replacement dose may be calculated by various models, all of which have limitations. Hence weight-adjusted effulent flow rate in millilitres per kilogram per hour (ml/kg/h) is used as a surrogate for renal replacement dose.
Previous single centre, randomised, controlled trials suggested that higher intensity therapy may be beneficial. Ronco and colleagues compared the intensity of continuous RRT in 425 patients and found that mortality decreased when intensity was increased from 20 ml/kg/h to either 35 ml/kg/h or 45 ml/kg/h.  Recently two large multicentre, randomised, controlled trials have failed to show any benefit from higher intensity therapy. The Veterans Affairs/National Institutes of Health (VA/NIH) Acute Renal Failure Trial Network study included 1124 patients in 27 centres and showed no improvement in 60-day mortality in the higher intensity group.  Patients were assigned to intermittent RRT or continuous RRT depending on haemodynamic stability. Renal replacement was delivered at lower or higher intensity by intermittent RRT (3 or 6 times per week respectively) and continuous RRT (20 ml/kg/h or 35 ml/kg/h respectively). The Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study compared lower and higher intensity continuous RRT (25 ml/kg/h or 40 ml/kg/h) in 1508 patients in 35 centres and found no difference in 90-day mortality.  Secondary outcomes in both trials showed no difference in renal recovery and an increase incidence of hypophosphataemia associated with higher intensity therapy.
Both trials suggest that more than an adequate level of intensity of RRT does not provide additional benefit in critically ill patients with AKI. As higher intensity therapy is more costly than lower intensity therapy, these findings may have significant impact on the both clinical and economic aspects of the practice of RRT in intensive care. Further research is needed to ascertain the optimal timing of initiation of RRT and the effect of continuous as compared with intermittent treatment on renal recovery.
For more information see Core Topics in Critical Care Medicine edited by Fang Gao Smith, in association with Joyce Yeung, and published by Cambridge University Press.
- Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomized trial. Lancet 2000; 355:26-30.
- Palevsky PM, Zhang JH, O’Connor TZ, et al. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008; 359:7-20.
- The RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009; 361:1627-1638.