Q: I work as a hospitalist PA in a large teaching hospital. In our ICU we had a patient diagnosed with acute kidney injury after a coronary artery bypass graft. We consulted nephrology and they decided to start dialysis. There was quite a discussion about whether to use hemodialysis every other day or continuous renal replacement therapy. What is the basis for this question? Is there science behind the answer, or is it determined by nephrologist preference?
The development of intermittent hemodialysis (IHD) revolutionized the care of patients with acute renal failure and allowed the medical establishment means to give these patients a chance to recover from their illness. However, IHD had (and continues to have) many downsides, and mortality in acute renal failure remains high. Thus, there is an ongoing search for the best renal replacement therapy; this search led to modern continuous therapies. Three main questions have arisen from this:
• Which modality is best? IHD is a shorter treatment (2 to 4 hours), typically performed three times per week but as often as daily. Fluid and electrolyte clearance is rapid, making IHD very efficient but increasing the risk for complications, such as hemodynamic instability. Furthermore, the abrupt fluid and electrolyte shifts associated with IHD do not mimic native kidney function. Providing slower treatments delivered continuously over 24 hours has many benefits.
Continuous renal replacement therapy (CRRT) provides clearance of large amounts of fluid and electrolytes over 24 hours, with minimal hemodynamic disturbances. This allows for more gradual shifts in volume and electrolyte levels, reducing the potential for ischemic damage to the kidney and other organs. Also, CRRT more closely replicates normal renal function than IHD.
CRRT is now extremely safe and efficient, although it has been difficult to prove its superiority to IHD in regard to mortality. While there may be no actual benefit to CRRT, it is also likely that its benefit is observed only in certain subsets of patients with renal failure. For example, we do have compelling evidence of increased intracranial pressure during IHD; CRRT is much safer for patients at risk for this development.1 It is also possible that we need to further improve CRRT systems and delivery in order to see a benefit.
Because current data favor neither CRRT nor IHD, most experts recommend choosing a therapy based on patient characteristics. For instance, hemodynamically unstable patients commonly receive generous amounts of fluid daily (antibiotics, nutrition, etc), and thus are often better suited for CRRT because it is more likely to remove higher volumes of fluid successfully, and less likely to contribute to hemodynamic instability than IHD. Conversely, patients with acute electrolyte deviations may benefit more from the rapid electrolyte removal IHD provides.
Additionally, stable patients may be more suitable candidates for IHD because of location (CRRT requires intensive care monitoring) and other variables.2,3 Results from multiple studies have suggested that CRRT may also provide renal protection and consequently improve renal recovery. However, this evidence is not conclusive; the possibility needs further evaluation.1
• What is the optimal dose for dialysis? This question, too, is plagued by inconclusive research findings. Paganini was the first to raise it formally in patients with acute renal failure; his research team found improved survival with higher doses, but had excluded the sickest and healthiest patients (according to probability of survival) from the study.4 This was followed by two additional studies with results that also seemed to support higher doses.1,5
Then in 2008, in a a similar randomized controlled trial, Tolwani et al6 found no survival benefit with higher versus lower dosing; participants in this study were not excluded based on severity of illness. Also, Tolwani’s research team identified failure to achieve prescribed doses as one factor complicating dose comparison.6
Finally, two large randomized controlled trials were performed to evaluate dosage, one in the US7 and one in Australia and New Zealand.8 Neither research team was able to confirm survival benefits with higher-dose renal replacement therapy, and there were inconsistencies between doses used in the study and standard practice in the US. In fact, the low-dose group received dialysis exceeding what is current practice by more than 30%.
The current prevailing opinion is that we should reach a minimum dose: a Kt/V of 1.2, three times a week, for IHD; or a CRRT dose of 20 mL/kg/h. At this time, higher doses do not confer a clear survival benefit. It remains unknown whether certain patients may benefit from a higher dose. Further research is needed.
• When should we initiate therapy? While some study results suggest that early initiation is better, this remains unconfirmed.1 In theory, renal replacement therapy should be initiated early because it improves metabolic control and corrects fluid overload, facilitating management of hemodynamics and ventilation, and reducing the potential for complications caused by uremia-induced physiologic dysfunction. However, it is still unknown which patients would benefit most from early initiation, and the appropriate triggers for when to initiate therapy remain unclear.
So, how do you choose a renal replacement therapy? This is often a matter of opinion, based on evaluation of risks and benefits specific to the patient and clinical expertise with the renal replacement therapies available.
Patient safety must be a primary consideration. IHD and CRRT have dramatically improved in safety and efficacy, but it must yet be proven beyond a doubt which is superior. Outcomes may depend on how the chosen therapy is used to treat specific patient needs—not which therapy is chosen. Further research is needed to identify the best and safest way to provide renal replacement therapy.
Catherine Wells, DNP, ACNP-BC, CNN-NP, Division of Nephrology, University of Mississippi, Jackson
1. Prowle JR, Bellomo R. Continuous renal replacement therapy: recent advances and future research. Nat Rev Nephrol. 2010;6(9):521-529.
2. Abi Antoun T, Palevsky PM. Selection of modality of renal replacement therapy. Semin Dial. 2009; 22(2):108-113.
3. Vanholder R, Van Biesen W, Lameire N. What is the renal replacement method of choice for intensive care patients? J Am Soc Nephrol. 2001;12 suppl 17:S40-S43.
4. Augustine JJ, Sandy D, Seifert TH, Paganini EP. A randomized controlled trial comparing intermittent with continuous dialysis in patients with ARF. Am J Kidney Dis. 2004;44(6):1000-1007.
5. 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 randomised trial. Lancet. 2000;356(9223):26-30.
6. Tolwani AJ, Campbell RC, Stofan BS, et al. Standard versus high-dose CVVHDF for ICU-related acute renal failure. J Am Soc Nephrol. 2008;19(6):1233-1238.
7. Palevsky PM, Zhang JH, O’Connor TZ, et al; VA/NIH Acute Renal Failure Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008;359(1):7-20.
8. Bellomo R, Cass A, Cole L, et al; RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361(17):1627-1683.