Table 1 A comparison of intermittent vs continuous dialysis therapies Time Pump speed Dialysis membrane Dialysis flow rate Replacement fluid Fluid removal CRRT 24 hours 100–180 mL/min 0.9 m2 High flux 0–2 L/h 1–3 L/h +100 mL/h to –500 mL/h same direction as water. This process requires the use of replacement fluid to prevent iatrogenic acidosis and electrolyte depletion as well as excessive fluid removal. The solutes in the removed filtrate are in the same concentration as those in the plasma, and solute concentration in the remaining plasma is diluted with substitution fluid. Combining diffusive and convective clearance with hemodiafiltration allows improved clearance of both small and large molecular weight substances. Using this method, blood urea nitrogen (BUN) clearances in the range of 23–30 mL/min can be achieved, even in hypotensive patients (McDonald and Mehta 1990). The choice of modality is dependent on several factors including availability, cost, physician expertise, hemo- dynamic stability, and the primary purpose of the procedure (fluid removal vs solute clearance). There is currently only limited information comparing diffusive with convective blood purification techniques; results with CRRT techniques should be compared with those obtainable with IHD, which remains the gold standard therapy. The most commonly applied modalities are continuous venovenous hemofiltration (CVVH), continuous veno- venous hemodialysis (CVVHD), and continuous venovenous hemodiafiltration (CVVHDF). Arteriovenous (AV) modes of CRRT have been used in the past, whereby dialysis access was obtained through the femoral artery and the femoral vein. This type of CRRT used the patient’s own cardiac output to drive blood through the dialysis circuit. AV forms of CRRT have fallen out of favor in recent years due to the high access complication rate and the development of external circuit pumps. See Table 1 for a comparison of intermittent vs continuous dialysis therapies. When should renal replacement therapies be started? There is no commonly accepted definition for the timing of initiating renal replacement therapy in ARF. It has been suggested that patient outcome can be improved by early or more intensive dialysis to keep the BUN under 80–100 mg/dL (29–36 mmol/L). Recent nonrandomized studies have not been able to document significant benefit of prophylactic dialysis (Gillum et al 1986; Conger 1995). It is interesting to note that the average urea concentration at initiation of CRRT in a recent Italian study of dialysis dosage was 17 mmol/L (Ronco 2000), however there is considerable variation in practice. A recent American survey of ICU dialysis practices found that the mean BUN Therapeutics and Clinical Risk Management 2005:1(2) 143 Renal replacement therapy IHD 4–6 hours 200–500 mL/min 1.1–2.1 m2 +/– High flux 500–750 mL/min None 500–1000 mL/h Abbreviations: CRRT, continuous renal replacement therapies; IHD, intermittent hemodialysis. and creatinine values at the initiation of dialysis were 34 mmol/L and 398 µmol/L, respectively (Lewis 1997). However, because the BUN may reflect many factors other than the timing of initiation, no absolute value for BUN or creatinine should be used to determine when to initiate dialysis. Only one randomized controlled trial has looked at the effect of timing of initiation of renal replacement therapy on outcome. Bouman et al randomized 106 critically ill patients with ARF to early vs late initiation of dialysis. Early initiation was started within 12 h of patients meeting the following criteria; low urine output (< 30 cc/h) × 6 h refractory to optimization of hemodynamics and diuretics, and creatinine clearance of < 20 mL/min (Bouman et al 2002). The late initiation group was started on dialysis when the classic indications for dialysis were met (volume overload, hyperkalemia, urea greater than 40 mmol/L). There was no significant difference between the groups in terms of ICU or hospital mortality, and no difference with respect to recovery of renal function. The results of this study must be interpreted with some caution however, as the study was underpowered to detect a clinically significant difference and the mortality rate in all treatment groups was very low. The Acute Dialysis Quality Initiative (ADQI) consensus statement on dialysis treatment (Kellum, Mehta, et al 2002), makes no recommendations on the timing of initiation of renal replacement therapy beyond those defined by the conventional criteria that apply to chronic renal failure. How is dialysis dose measured in acute renal failure? In the end-stage renal failure population, dialysis dose has been quantified using a technique called urea kinetic