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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2008  |  Volume : 19  |  Issue : 4  |  Page : 529-536
Renal Replacement Therapy in Acute Kidney Injury: Which Method to Use in the Intensive Care Unit?

UCL Center for Nephrology, Royal Free and University College Medical School, London, United Kingdom

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Over the last three decades the treatment options for patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT) have expanded from basic acute peritoneal dialysis and intermittent hemodialysis (IHD), to now include a variety of continuous modalities (CRRT), ranging from hemofiltration, dialysis and/or hemodiafiltration, and a variety of hybrid therapies, variously described as extended daily dialysis and/or hemodiafiltration, with the possibility of additional adjunct therapies encompassing plasma separation and adsorption techniques. Current evidence does not support that one modality is superior to any other in terms of patients' survival in the intensive care unit, or at discharge. There have been two prospective audits, which have reported improved renal recovery in the survivors who were treated by CRRT rather than IHD, but this has not been confirmed in randomized controlled trials. Thus the choice of RRT modality should be guided by the individual patients' clinical status, the medical and nursing expertise in the local intensive care unit, and the availability of RRT modality.

Keywords: Acute, Renal, Failure, Intensive, Care, Units, Replacement, Therapy, Hemodialysis, Hemofiltration, Hemodiafiltration

How to cite this article:
Davenport A. Renal Replacement Therapy in Acute Kidney Injury: Which Method to Use in the Intensive Care Unit?. Saudi J Kidney Dis Transpl 2008;19:529-36

How to cite this URL:
Davenport A. Renal Replacement Therapy in Acute Kidney Injury: Which Method to Use in the Intensive Care Unit?. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2022 Aug 10];19:529-36. Available from: https://www.sjkdt.org/text.asp?2008/19/4/529/41300

   Introduction Top

In many developed countries, continuous therapies have become the predominant mode of delivery of RRT in the ICU setting, and the majority of centers offer continuous veno­venous hemofiltration (CVVH) or continuous veno-venous hemodiafiltration (CVVHDF). [1] Although, clinical practices vary from country to country, a recent multi-national survey reported that 80% of patients who need RRT were treated with continuous thera­pies, 16.9% with intermittent therapies, and 3.2% with either peritoneal dialysis or slow continuous ultrafiltration. [2]

   Continuous renal replacement therapy Top

Continuous renal replacement therapies (CRRT) have blossomed since the original description by Kramer of a simple arterio­venous ultrafiltration device thirty years ago. [3] The clearances achieved with original spontaneous arteriovenous hemofiltration (CAVH) circuits were often around 16 ml/min, so additional intermittent hemodia­lysis was often required. To improve clea­rances, counter-current dialysate flow was added (CAVHD), [4],[5] followed by pumps so that circuits only required a venous blood supply (continuous veno-venous hemofiltra­tion or continuous veno-venous hemodialysis and/or continuous veno-venous hemodiafil­tration). [6] Over time, the amount of renal replacement treatment delivered to patients has increased from 20-35 ml/kg/h. [7] Subse­quently, there has been an ongoing debate as to the amount of clearance required, resulting in what is termed "low volume" (20-40 ml/kg/h) and high volume therapies (70-100 ml/kg/h, usually in pulses of 6-8 hours). [8] There is currently an ongoing trial of two doses of veno-venous hemofiltation in ICU patients with acute kidney injury to try and determine whether increasing the dose of renal replacement therapy improves patients' survival.

Although there are fundamental differen­ces between CRRT modes in terms of the amount of diffusive (dialysis) and convective (filtration) clearances [Table 1], there have been no studies that demonstrate a diffe­rence between these two basic factors in terms of patients' survival and/or renal reco­very, even with greater middle molecule clea­rances with convective mode.

Whereas for intermittent hemodialysis and/ or hemodiafiltration dialysates and re-infu­sion fluids are standard with minor differen­ces in electrolyte composition, the CRRT dialysates and re-infusion fluids differ not only in electrolyte composition, but also lactate/bicarbonate and chloride content. CRRT fluids that have a high chloride and low lactate content can lead to hyperchlo­remic acidosis; conversely, CRRT fluids with a lower chloride content and higher lactate can similarly result in a hypochloremic al­kalosis. [9] Although bicarbonate based fluids have been shown to more effectively correct metabolic acidosis and improve cardiovas­cular stability compared to those containing lactate, [10] the choice of buffer base has not been proven to affect patient survival. Spe­cially designed dialysates and/or replacement fluids are required for CRRT systems using trisodium citrate anticoagulation, due to the potential citrate and sodium overload. [11]

Not all ICUs have access to nephrology input and dialysis trained nurses, so CRRT allows the staff in these units to initiate treatment of patients with acute kidney in­jury (AKI). Although probably less training is required to operate CRRT than hemo­dialysis machines, more nurse time is spent operating the machine [Table 2], and as for all machines, operator competency is re­quired. [12] One of the problems with the recent series of CRRT machines has been the ability of the operator to over-ride alarms. This may potentially result in fluid imba­lances between the prescribed rate of fluid loss and that achieved in clinical practice. CRRT is more costly than intermittent and hybrid therapies, as both the machines and consumables (blood lines, dialyzers, and/or hemofilters) are more expensive. However, the main cost is the sterile substitution fluid and/or dialysate, particularly when high volume therapies are performed. Some cen­ters have started to produce on-line ultra­pure replacement solutions/dialysates to re­duce these costs. [13]

CRRT is only a successful therapy when applied continuously, otherwise patients may not receive adequate solute control. [14] Indeed, one retrospective review found that only 68% of patients received their prescribed dose of CRRT. [15] Circuit clotting and down time is a much greater problem with CRRT than intermittent and hybrid thera­pies, particularly in compromised ICU pa­tients due to activation of mononuclear cells and platelets. [16]

   Intermittent therapies Top

In the early 1980s, intermittent hemodia­lysis (IHD) was practiced in the ICU simi­larly to that of treating chronic kidney failure patients. Patients were often dialyzed thrice weekly, using bio-incompatible low flux cellulosic dialyzers, low sodium, acetate based dialysate at body temperature and with machines that did not have accurate volume regulation. However, performance of the HD machines improved with the introduction of new important features such as volume control, blood volume monitoring, and bio­feedback control along with high synthetic flux bio-compatible membranes and bicar­bonate dialysate. In addition, the impor­tance of daily or at least alternate day extended treatments along with higher so­dium and lower dialysate temperatures is now recognized. [17],[18] Such "bundle" effect has been demonstrated to markedly impact on reducing IHD associated hypotension. [19] In a recent prospective randomized study, many ICU patients were successfully trea­ted with IHD, and had a similar outcome to those treated by CRRT. [18] Remarkably, the number of patients transferred from IHD to CRRT due to cardiovascular insta­bility was less than those transferring from CRRT to IHD.

Intermittent hemofiltration (IHF), which was introduced in the 1980s for chronic kidney failure patients and used in ICUs, has mainly been superseded by intermittent hemodiafiltration (IHDF). As with CRRT, the main cost was the sterile replacement fluids. IHDF requires ultrapure water to re­duce costs. Many ICUs have no access to water treatment plant in the chronic hemodia­lysis unit. However with the addition of simple particle filters, in combination with carbon filters and portable reverse osmosis machines, some units can provide dialysate water of ultrapure quality, especially when using dialysis machines fitted with addi­tional ultrafilters.

   Hybrid therapies Top

Hybrid therapies encompass a group of treatments, which are essentially based on extending the duration and slowing down the rate of diffusion of IHD. Most regimens use standard IHD machines with slower blood and dialysate flow rates [Table 3]. In addition, there is a batch IHD machine (Genius®, Fresenius Bad Homberg, Germa­ny) in which the blood and dialysate flows are linked by a single pump, so that the flow rates are of similar magnitude. Dia­lysis with this machine can be extended for more than 12 hours by slowing flow rates down to 100 ml/min, although 150-200 ml/ min is more common in clinical practice.

Depending on the design, hybrid therapies can provide diffusive clearances of small solutes such as urea around 36 ml/kg/h, [20] and greater solute clearances of vitamin B12 or α 2-microglobulin close to 50-66% of that with CRRT. Furthermore, hybrid the­rapies can also be set up to provide hemo­diafiltration that achieves large solute clea­rances comparable to those with CRRT.

Whereas circuit thrombosis has been re­ported in 20-25% of hybrid therapies using standard hemodialysis machines, clotting is much less frequent with the batch dialysate therapies, such as the Genius®. [21] This may be due to the difference in blood pump technology between the systems, with much greater leukocyte and platelet activation with the standard occlusive roller pump.

   Peritoneal Dialysis Top

A recent worldwide survey disclosed that the use of peritoneal dialysis (PD) in adult AKI is on the decline. [2] However, acute PD is still successfully practiced in pediatric AKI, particularly post cardiac surgery, and in pa­tients with single organ failure. PD mac­hines are useful but not obligatory. Clea­rances achieved in pediatric AKI are com­parable to those targeted for end-stage kidney disease. [22]

However, there have been debates as to whether PD can provide adequate clea­rances for treating adult AKI. One study from Brazil, reported an average urea clea­rance of 17.3 ± 5 ml/min, comparable to those of the non-pumped forms of arterio­venous hemofiltration and/or dialysis, by using 2 liter-fill volumes, 65-80 minutes dwell times, and glucose concentrations in excess of 2.0%. [23] However, studies that used smaller dwell volumes, and shorter dwell times demonstrated compromised clearan­ces. [24],[25] Some authors have therefore sug­gested that PD could not control toxins in patients with hypercatabolic AKI, which resulted in the development of novel PD techniques such as continuous flow through PD with recycling of the peritoneal dialysate effluent. [26]

However, the number of patients suitable for PD may be limited by surgical proce­dures and complications that include me­chanical leaks and peritonitis.

   Comparison of RRT modalities Top

In hemodynamically unstable critically ill patients, prospective randomized clinical trials have failed to confirm the hypothesis that CRRT is superior to IHD. In many of the earlier trials, there was a bias for the more critically ill patients to receive CRRT rather than IHD. In the last 6 years how­ever, five randomized prospective con­trolled trials comparing, CRRT and IHD have been published. [18],[27],[28],[29],[30] None of these trials demonstrated any difference in mortality attributable to the selected RRT modality. Although some did observe greater hemo­dynamic stability during CVVHD compared to IHD, [28] and similarly more effective fluid removal during CVVHD compared to IHD. However, the most recent of these studies, the Hemodiafe study, reported no signifi­cant differences in cardiovascular stability between the CRRT and IHD groups, [18] but this was the first study to deliberately apply cooled dialysate in combination with a very high dialysate sodium during IHD, and delivered the highest Kt/V dose to the IHD group, in comparison to other earlier studies. [17] Similarly meta-analyses have failed to show any significant effect of RRT mo­dality on patient outcome. [31],[32]

Moreover, there are special circumstances such as cerebral edema and increased intracranial pressure where low volume CRRT benefited patients than high volume CVVH or IHD. [33],[34] Typically these patients have been excluded from the randomized controlled trials.

Many ICU patients experience hemodynamic instability that can be aggravated by intra-dialytic hypotension during IHD. This proposed that CRRT may be associated with more probable recovery of renal func­tion than IHD. [35] Two prospective clinical audits reported increased renal recovery in the survivors treated by CRRT compared to IHD, [36],[37] but this has not been con­firmed in randomized prospective controlled trials. [18]

Studies comparing other forms of RRT have been limited. No studies have directly compared "hybrid" treatments to either IHD or CRRT, although "hybrid" therapies have been shown to provide similar hemody­namic stability and solute control when compared to CRRT. [21]

In summary, analysis of the currently published studies does not allow evidence­based guidelines for the selection of RRT modality for the treatment of AKI. Hope­fully, the recently completed Veterans stu­dy in the USA, currently the largest ran­domized prospective study designed to investigate the effect of treatment modality in AKI (CRRT vs. hybrid vs. IHD), [38] will provide useful information in determining the optimal treatment modality for AKI. Therefore, until this trial is concluded, the selected modality should be guided by the individual patient's clinical status, medical and nursing expertise, and the availability of RRT modality.

   References Top

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2.Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005;294(7):813-8.  Back to cited text no. 2    
3.Kramer P, Wigger W, Rieger J, Matthaei D, Scheler F. Arteriovenous haemofiltration: a new and simple method for treatment of over-hydrated patients resistant to diuretics. Klin Wschr 1977;55(22):1121-2.  Back to cited text no. 3    
4.Sigler MH, Teehan BP. Solute transport in continuous haemodialysis: a new treatment for acute renal failure. Kidney Int 1987;32 (4):562-71.  Back to cited text no. 4    
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6.Gibney RT, Kimmel PL, Lazarus M. The Acute Dialysis Quality Initiative-part I: Definitions and reporting of CRRT tech­niques. Adv Ren Replace Ther 2002;9(4): 252-4.  Back to cited text no. 6    
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8.Honore PM, Jamez J, Wauthier M, et al. Prospective evaluation of short-term, high­volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock. Crit Care Med 2000;28(11):3581-7.  Back to cited text no. 8    
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11.Davenport A. Replacement and dialysate fluids for patients with acute renal failure treated by continuous veno-venous haemo­filtration and/or haemodiafiltration. Contrib Nephrol 2004;144:317-28.  Back to cited text no. 11  [PUBMED]  
12.Gibney N, Cerda J, Davenport A, et al. Volume management by renal replacement therapy in acute kidney injury. Acute Dialysis Quality Initiative. Int J Artif Organs 2008;31(2):145-55.  Back to cited text no. 12    
13.Teo BW, Demirjian S, Meyer KH, Wright E, Paganini EP. Machine-generated bicar­bonate dialysate for continuous therapy: a prospective, observational cohort study. Nephrol Dial Transplant 2007;22(8):2304-15.  Back to cited text no. 13    
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15.Uchino S, Fealy N, Baldwin I, Morimatsu H, Bellomo R. Continuous is not continuous: The incidence and impact of circuit 'down-time' on uraemic control during continuous veno-venous haemofiltration. Intensive Care Med 2003;29(4):575-8.  Back to cited text no. 15    
16.Davenport A. The coagulation system in the critically ill patient with acute renal failure and the effect of an extracorporeal circuit. Am J Kid Dis 1997;30(5):S20-7.  Back to cited text no. 16    
17.Schiffl H, Lang SM, Fischer R. Daily dialysis and the outcomes of acute renal failure. N Engl J Med 2002;346(5):305-10  Back to cited text no. 17    
18.Vinsonneau C, Camus C, Combes A, et al. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple­organ dysfunction syndrome: a multicentre randomised trial. Lancet 2006;368(9533): 379-85.  Back to cited text no. 18    
19.Schortgen F, Soubrier N, Delclaux C, et al. Hemodynamic tolerance of intermittent hemodialysis in critically ill patients. Am J Respir Crit Care Med 2000;162(1):197-202.  Back to cited text no. 19    
20.Marshall MR, Tianmin M, Galler D, Rankin AP, Williams AB. Sustained low­efficiency daily diafiltration (SLEDD-f) for critically ill patients requiring renal replacement therapy: towards an adequate therapy. Nephrol Dial Transplant 2004;19 (4):877-84.  Back to cited text no. 20    
21.Fliser D, Kielstein JT. A single-pass batch dialysis system: An ideal dialysis method for the patient in intensive care with acute renal failure. Curr Opin Crit Care 2004; 10(6):483-8.  Back to cited text no. 21    
22.McNeice KL, Ellis EE, Drummond-Webb JJ, Fontenot EE, O'Grady CM, Blaszak RT. Adequacy of peritoneal dialysis in patients following cardiopulmonary bypass surgery. Pediatr Nephrol 2005;20(7):972-6.  Back to cited text no. 22    
23.Gabriel DP, Nascimento GV, Caramori JT, Martim LC, Barretti P, Balbi AL. High volume peritoneal dialysis for acute renal failure. Perit Dial Int 2007;27(3):277-82.  Back to cited text no. 23    
24.Phu NH, Hien TT, Mai NT, et al. Hemo­filtration and peritoneal dialysis in infec­tion-associated acute renal failure in Viet­nam. N Engl J Med 2002;347(12):895-902.  Back to cited text no. 24    
25.Chitalia VC, Almeida AF, Rai H, et al. Is peritoneal dialysis adequate for hyper­catabolic acute renal failure in developing countries? Kidney Int 2002;61(2):747-57.  Back to cited text no. 25    
26.Ronco C, Amerling R. Continuous flow peritoneal dialysis: current state-of-the-art and obstacles to further development. Contrib Nephrol 2006;150:310-20.  Back to cited text no. 26  [PUBMED]  [FULLTEXT]
27.Augustine JJ, Sandy D, Seifert TH, Paganini EP. A randomized controlled trial comparing intermittent with continuous dialysis in patients with ARF. Am J Kid Dis 2004;44(6):1000-7.  Back to cited text no. 27    
28.John S, Griesbach D, Baumgartel M, Weihprecht H, Schmieder RE, Geiger H. Effects of continuous haemofiltration VS intermittent haemodialysis on haemodyna­mics and splanchnic regional perfusion in septic shock patients: a prospective rando­mized clinical trial. Nephrol Dial Transplant 2001;16(2):320-7.  Back to cited text no. 28    
29.Mehta RL, McDonald B, Gabbai F, et al. A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure. Kidney Int 2001;60(3):1154-63  Back to cited text no. 29    
30.Uehlinger DE, Jakob SM, Ferrari P, et al. Comparison of continuous and intermittent renal replacement therapy for acute renal failure. Nephrol Dial Transplant 2005;20 (8):1630-7.  Back to cited text no. 30    
31.Kellum JA, Angus DC, Johnson JP, et al. Continuous versus intermittent renal replacement therapy: a meta-analysis. Intensive Care Med 2002;28(1):29-37.  Back to cited text no. 31    
32.Tonelli M, Manns B, Feller-Kopman D. Acute renal failure in the intensive care unit: a systematic review of the impact of dialytic modality on mortality and renal recovery. Am J Kidney Dis 2002;40(5): 875-85.  Back to cited text no. 32    
33.Davenport A, Will EJ, Davison AM. Early changes in intracranial pressure during hemofiltration treatment in patients with grade 4 hepatic encephalopathy and acute oliguric renal failure. Nephrol Dial Transplant 1990;5(3):192-8.  Back to cited text no. 33    
34.Davenport A, Will EJ, Davidson AM. Improved cardiovascular stability during continuous modes of renal replacement therapy in critically ill patients with acute hepatic and renal failure. Crit Care Med 1993;21(3):328-38.  Back to cited text no. 34    
35.Palevsky PM, Baldwin I, Davenport A, Goldstein S, Paganini E. Renal replacement therapy and the kidney: Minimizing the impact of renal replacement therapy on recovery of acute renal failure. Curr Opin Crit Care 2005;11(6):548-54.  Back to cited text no. 35    
36.Uchino S, Bellomo R, Morimatsu H, et al. Continuous renal replacement therapy: a worldwide practice survey. The Beginning and Ending Supportive Therapy for the Kidney (B.E.S.T. Kidney) Investigators. Intensive Care Med 2007;33(9):1563-70.  Back to cited text no. 36    
37.Bell M, SWING, Granath F, Schon S, Ekbom A, Martling CR. Continuous renal replacement therapy is associated with less chronic renal failure than intermittent haemodialysis after acute renal failure. Intensive Care Med 2007;33(5):773-80.  Back to cited text no. 37    
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Correspondence Address:
Andrew Davenport
UCL Center for Nephrology, Royal Free & University College Medical School, Hampstead Campus, Rowland Hill Street, London NW3 2PF
United Kingdom
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Source of Support: None, Conflict of Interest: None

PMID: 18580008

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  [Table 1], [Table 2], [Table 3]

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