Renal replacement therapy: Dose

OVERVIEW

• Optimal dose of renal replacement therapy (RRT) is controversial… the definition of dose in clinical practice is also a little controversial!
• In clinical practice the “dose” of CRRT is the effluent flow rate (= ultrafiltrate + dialysate)

CONTINUOUS RENAL REPLACEMENT THERAPY (CRRT)

• CRRT is used in most critically patients with renal failure in Australia and New Zealand
• To date at least six RCTs have assessed the relationship between intensity of CRRT in terms of effluent flow rate and outcomes of acute kidney injury
• Although several clinical trials suggest an improvement in survival with higher doses of CRRT results have not been consistent across all studies

DOSE

Typical dose of CRRT is 25-35 mL/kg/h (higher in some ICUs)

• The dose of CRRT can be thought of as the  volume of blood “purified” per unit time
• In clinical practice the “dose” of CRRT is the effluent flow rate (= ultrafiltrate + dialysate)
• More definitively the dose is the clearance rate of a representative marker solute; usually indexed to body weight (K/wt = L/kg/h)

Key terms and calculations

• Clearance (K) = volume of blood cleared (L) / time (min)
• Efficiency = clearance (K) (L/min)
• Intensity (Kt) = clearance (K) x duration (t)
• Efficacy (Kt/V) = intensity (Kt) / Vd (volume of distribution) = fractional clearance for a given solute (no units); the given solute is typically urea (Vd = 0.6 L/min)

Kt/V

• in hemodialysis the US National Kidney Foundation Kt/V target is ≥ 1.3, so that one can be sure that the delivered dose is at least 1.2
• In peritoneal dialysis the target is ≥ 1.7/week
• Kt/V cannot be measured in critically ill patients as Vd is dynamic
• Kt/V is estimated by effluent flow rate (“dose”) in CRRT, but needs to be modified if pre-dilution replacement fluids are given (see comments on this page below)

EVIDENCE SUMMARY

• Ronco et al, 2000 (using post-dilution hemofiltration) and Saudan et al, 2006 found that lower doses around 20 -25ml/kg/h were inferior to higher effluent flows of around 35 to 45 mL/kg/h in terms of survival (15 to 20% reduction in mortality)
• Two other studies by Bouman et al, 2002 (48 vs 20 mL/kg/h) and Tolwani et al, 2008 (20 vs 35 ml/kg/hr) however found no difference in survival with higher effluent rates
• The VA/HIH Acute renal failure Trial Network or ATN study in NEJM 2008 found that mortality at 60 days was no different between two intensity arms. In the less intensive arm both IHD and SLED were used as standard practice of thrice per week and CVVHDF effluent flow at 20 mL/kg/h. In the more intensive arm IHD and or SLED were used six times per week and CVVHDF at an effluent flow rate of 35 mL/kg/h
• TheRENAL study by the ANZICS CTG in  NEJM 2009 compared 25 v 40 mL/kg/h (non-blinded MCRCT with n = 1508). No difference in mortality between the two groups at 90 days, a higher incidence of hypophosphatemia in the higher dose group. This study has excellent external validity to the ANZ setting, included patients with CKD and had lower rates of sepsis compared to the early positive trials,

References and Links

• CCC – RRT Indications
• CCC – RRT principles in fluid management
• CCC – RRT Types
• CCC – RRT terminology and nomenclature
• CCC – RRT troubleshooting
• CCC – Renal Literature Summaries

Social media and web resources

• DerangedPhysiology.com — Determining the dose of renal replacement therapy

Journal articles

• Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, Zandstra DF, Kesecioglu J. Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: a prospective, randomized trial. Crit Care Med. 2002 Oct;30(10):2205-11. PMID: 12394945.
• Eknoyan G,et al; Hemodialysis (HEMO) Study Group. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med. 2002 Dec 19;347(25):2010-9. PMID: 12490682. [Free Fulltext]
• RENAL Replacement Therapy Study Investigators, Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009 Oct 22;361(17):1627-38.PMID: 19846848. [Free Fulltext]
• Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, La Greca G. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet. 2000 Jul 1;356(9223):26-30. PMID: 10892761.
• Saudan P, Niederberger M, De Seigneux S, Romand J, Pugin J, Perneger T, Martin PY. Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure. Kidney Int. 2006 Oct;70(7):1312-7. PMID: 16850022.
• Tolwani AJ, Campbell RC, Stofan BS, Lai KR, Oster RA, Wille KM. Standard versus high-dose CVVHDF for ICU-related acute renal failure. J Am Soc Nephrol. 2008 Jun;19(6):1233-8. PMC2396940.
• VA/NIH Acute Renal Failure Trial Network, Palevsky PM, Zhang JH, O’Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008 Jul 3;359(1):7-20. doi: 10.1056/NEJMoa0802639. Epub 2008 May 20. Erratum in: N Engl J Med. 2009 Dec 10;361(24):2391. PMC2574780.