Wednesday 29 March 2017

Renal replacement therapy (dialysis) in acute kidney injury (acute renal failure) in adults: Indications, timing, and dialysis dose

Author 
Paul M Palevsky, MD 

Section Editor 
Jeffrey S Berns, MD 

Deputy Editor 
Alice M Sheridan, MD 

Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2013. | This topic last updated: Mar 21, 2013.

INTRODUCTION  — The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive, with renal replacement therapy (RRT) indicated in patients with severe kidney injury. Multiple modalities of RRT are currently available. These include intermittent hemodialysis (IHD), continuous renal replacement therapies (CRRTs), and hybrid therapies, such as sustained low-efficiency dialysis (SLED). Despite these varied techniques, mortality in patients with ARF remains high, greater than 50 percent in severely ill patients. (See "Renal and patient outcomes after acute tubular necrosis" .)

The initiation of RRT in patients with AKI prevents uremia and immediate death from the adverse complications of renal failure. It is possible that variations in the timing of initiation, modalities, and/or dosing may affect clinical outcomes, particularly survival. However, there is a paucity of studies in which these issues have been addressed directly.

The optimal timing, type of modality, and dosing strategy for patients with AKI who require RRT will be reviewed here. The different modalities are discussed separately. (See "Continuous renal replacement therapies: Overview" and "Continuous renal replacement therapy in acute kidney injury (acute renal failure)" and"Continuous venovenous hemodiafiltration: Technical considerations" and "Continuous venovenous hemodialysis: Technical considerations" and "Sustained low efficiency or extended daily dialysis" .)

INDICATIONS FOR AND TIMING OF INITIATION OF DIALYSIS  — Accepted indications for renal replacement therapy (RRT) in patients with AKI generally include:

Refractory fluid overloadHyperkalemia (plasma potassium concentration >6.5 meq/L) or rapidly rising potassium levelsSigns of uremia, such as pericarditis, neuropathy, or an otherwise unexplained decline in mental statusMetabolic acidosis (pH less than 7.1)Certain alcohol and drug intoxications

As described in the next section, we suggest initiating dialysis prior to the development of overt symptoms and signs of renal failure due to AKI. (See 'Timing' below.)

The likelihood of requiring RRT is increased in patients with underlying chronic kidney disease in proportion to the degree of reduction in glomerular filtration rate (GFR) at baseline. This was illustrated in a study that compared the prehospitalization estimated GFR (from the most recent serum creatinine) in 1746 hospitalized patients who developed dialysis-requiring acute kidney injury with that of 600,820 hospitalized patients who did not [ 1 ].

Compared to patients with an estimated baseline GFR greater than 60 mL/min per 1.73 m2, the risk of developing AKI requiring dialysis progressively and significantly increased with the severity of underlying CKD. The adjusted odds ratios were 1.7, 4.6, and 20.4 for patients with stage 3 (estimated GFR of 30 to 59 mL/min per 1.73m2), 4 (estimated GFR 15 to 29 mL/min per 1.73m2), and 5 CKD (estimated GFR less than 15 mL/min per 1.73m2), respectively. (See "Overview of the management of chronic kidney disease in adults", section on 'Definition and classification' .)

Timing  — Whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit is unproven. We suggest initiating dialysis prior to the development of symptoms and signs of renal failure due to AKI.

When introduced into clinical practice in the 1940s and early 1950s, RRT was used to principally treat the advanced symptoms of renal failure [ 2-4 ]. Although effective at reversing the metabolic complications of renal failure, dialysis did not clearly lower acute mortality [ 4 ]. Given the severity of illness and the lack of advanced critical care medicine during this period, patients acutely died of complications such as infection, bleeding, and other conditions.

In the 1950s, the concept of prophylactic dialysis was introduced [ 4 ]. Studies published during the 1960s and 1970s suggested that improved outcomes were associated with the initiation of hemodialysis when the blood urea nitrogen (BUN) reached approximately 90 to 100 mg/dL, as compared to waiting until the BUN exceeded 150 to 200 mg/dL [ 5-9 ]. As examples:

Three retrospective studies reported that early (defined variably as BUN less than 93 to approximately 150 mg/dL) versus late initiation of dialysis (BUN greater than 160 to 200 mg/dL) was associated with improved survival (43 to 75 percent for early dialysis versus 12 to 58 percent for late dialysis) [ 6-8 ].One prospective study of 18 patients reported better survival (69 versus 20 percent) with early initiation of dialysis (BUN less than 60 versus 150 mg/dL) [ 9 ].

More recent studies have evaluated the relationship between the timing of CRRT initiation and clinical outcomes. Several non-randomized studies have reported that improved outcomes, including survival, are associated with early versus late initiation of RRT [ 10-13 ].

As an example, in a retrospective analysis of 100 consecutive patients treated using CVVH in a single shock trauma unit, survival was 39 percent in the 41 patients initiated on RRT with a BUN less than 60 mg/dL compared to 20 percent in the 59 patients whose BUN was greater than 60 mg/dL at the time of initiation of RRT [ 10 ].Two analyses of patients developing AKI following cardiac surgery demonstrated higher survival rates in patients in whom CVVH was initiated in response to a urine output of less than 100 mL within eight hours consecutively after surgery despite diuretic administration, compared to patients in whom therapy was withheld until objective laboratory criteria using serum creatinine, BUN and potassium, were present [ 11,12 ].A large multicenter observational study found that early initiation of dialysis may be associated with a survival advantage [ 13 ]. Based upon data from the Program to Improve Care in Acute Renal Disease (PICARD), the risk of death was correlated with the BUN level at the start of dialysis among 243 patients with acute renal failure (low and high degree of azotemia defined by BUN ≤76 mg/dL and >76 mg/dL, respectively). After multivariate adjustment for variables associated with types and severity of comorbid disease and for propensity for initiation of RRT, there was an increased risk of death at 60 days from the diagnosis of acute renal failure for those begun on dialysis at the high BUN level (RR 1.97, 95% CI 1.21-3.2).

Although these studies have reported decreased mortality with earlier initiation of renal support, these results are somewhat suspect given many study design limitations. These include non-randomization of groups, probable differences in indications for initiation, and the lack of inclusion in the analysis of patients with AKI who did not receive RRT because they either recovered renal function or died.

Although small in size, there has been one prospective randomized trial that examined outcomes associated with timing of CRRT [ 14 ]. In this trial, 106 oliguric patients were assigned to early high-volume CVVH, early low-volume CVVH, and late low-volume CVVH. At 28 days, survival was equivalent for all three groups (74, 69, and 75 percent, respectively). However, this study was relatively underpowered to detect survival differences between these interventions and the overall high survival rate relative to other studies of AKI in critically ill patients suggests that the study population was not representative of typical ICU patients. It is worth noting, however, that of the 36 patients in the late-initiation group only 30 received CVVH; four of the remaining patients recovered renal function and two died prior to meeting protocol criteria for initiation of RRT.

Volume overload  — Several observational studies have demonstrated an association between the severity of volume overload at the time of initiation of RRT and mortality risk [ 15-17 ]. In a cohort of pediatric patients with multisystem organ failure, patients who did not survive had significantly greater fluid overloaded (25 versus 14 percent) and higher central venous pressures at the time of initiation of RRT than patients who did survive [ 15 ]. Similarly, in adult patients, initiation of RRT with greater than 10 percent fluid overload was associated with decreased survival than initiation of RRT with less than 10 percent fluid overload [ 17 ].

Although fluid overload may contribute to organ dysfunction and contribute to mortality risk, observational studies cannot establish a causal link between the severity of volume overload and outcomes. Underlying diseases states that drive the use of more aggressive volume resuscitation may account for the increased mortality risk.

Summary  — RRT is indicated for the acute management of life-threatening complications of AKI. These include volume overload unresponsive to diuretics, uremic symptoms and signs (eg, encephalopathy and serositis), severe metabolic acidosis, overdose with a dialyzable drug/toxin, and hyperkalemia. Whether there is a benefit to early initiation of RRT for volume management rather than escalating diuretic dose is not known.

Some retrospective and uncontrolled studies suggest that prophylactic dialysis prior to the development of overt uremia among patients with progressive kidney dysfunction may be associated with reduced mortality. However, it is unproven whether this approach offers any significant clinical or survival benefit.

Despite this, we suggest the initiation of RRT prior to the development of overt symptoms and signs of renal failure due to AKI, such as advanced uremic symptoms (eg, encephalopathy and serositis). However, it is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated. In the absence of other specific indications, RRT is often initiated when the BUN reaches 80 to 100 mg/dL, although there is no consensus and practice patterns vary widely.

The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial. Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT. For this reason, it is not possible to provide evidence-based criteria for the initiation of RRT in AKI.

Similarly, although severity of volume overload at the time of initiation of RRT is associated with increasing mortality risk, current data do not demonstrate that initiating RRT at a specific threshold of fluid overload is associated with improved outcomes.

OPTIMAL MODALITY  — A large number of modalities are available for RRT. These include intermittent hemodialysis (IHD), peritoneal dialysis, continuous renal replacement therapy (CRRT), and hybrid therapies such as SLED.

Continuous renal replacement therapies  — CRRT represents a family of modalities that provide continuous support for severely ill patients with AKI. These include continuous hemofiltration, hemodialysis, and hemodiafiltration, which involve both convective and diffusive therapies. Although superior clearance of middle and larger molecular weight molecules are associated with convective therapies (hemofiltration) compared with diffusive therapies (hemodialysis), there are no studies clearly showing improved clinical outcomes compared with the type of solute transport.

Venovenous versus arteriovenous circuits  — Although the CRRT modalities can be performed using either arteriovenous or venovenous circuits, pump-driven venovenous circuits are preferred since this approach provides higher solute clearances and eliminates the adverse complications associated with arterial cannulation. This was shown in a prospective study that compared two consecutive groups of patients with AKI treated with either CVVHD (25 patients) or CAVHD (28 patients) [ 18 ]. Although survival and clearances were similar between the two groups, there was a significant decrease in the number of access-related complications with CVVHD (2 versus 10).

CRRT versus intermittent hemodialysis  — The two principal outcomes that have been examined with CRRT and IHD are patient survival and recovery of renal function. A paucity of evidence exists that have examined these issues. However, current data suggest that survival and recovery of renal function are similar with both CRRT and IHD.

The majority of studies comparing CRRT and IHD have been observational or retrospective case series [ 19-23 ]. After adjustment for severity of illness, there appears to be no survival benefit associated with CRRT [ 24,25 ]. One observational series has suggested an increased adjusted mortality risk associated with CRRT, although incomplete adjustment for severity of illness may have confounded this finding [ 26 ].

Of greater importance, multiple prospective randomized studies have also compared outcomes of AKI supported using either IHD or CRRT [ 27-30 ]. As examples:

In a multicenter study, 166 patients with AKI were randomly assigned to IHD or CRRT [ 27 ]. CRRT was associated with significantly higher all-cause mortality at 28 days (59.5 versus 41.5 percent) and in-hospital mortality (65.5 versus 47.6 percent). However, despite randomization, patients randomly assigned to CRRT were significantly more likely to have higher APACHE III scores and liver failure. After adjustment for these characteristics, there was no increased risk of death with CRRT (adjusted odds of death of 1.58, CI 0.7-3.3).In the HemoDiafe Study (a prospective multicenter French study), 360 patients with acute renal failure and multi-organ dysfunction syndrome were randomly assigned to intermittent hemodialysis or continuous venovenous hemodiafiltration [ 30 ]. The primary endpoint was survival at 60 days. Severity of illness was similar in both randomized groups, protocol adherence was good, both groups used the same dialysis membranes, and there was a low rate of cross-over from continuous to intermittent therapies (3.3 percent). At 60 days, survival was the same in both groups (32 and 33 percent in the intermittent and continuous groups, respectively). In addition, both therapies were associated with similar rates of hypotension, including the group of hemodynamically unstable patients.

While the HemoDiafe Study was the largest and most rigorously conducted RCT comparing modality of RRT in AKI, definitive conclusions must be tempered by limitations of the trial design and execution. The use of heparin , rather than regional anti-coagulation during continuous therapy, may have contributed to issues of systemic bleeding and clotting of the extracorporeal circuit. In addition, over the duration of the study, the mortality rate in the intermittent therapy arm declined over time, whereas it remained constant in the continuous therapy arm. The reasons for these trends are uncertain and may reflect changes in delivery of intermittent hemodialysis over time. In addition, the mean duration of the hemodialysis treatments were longer than is typically employed in clinical practice, raising questions regarding the ability to translate these results into clinical practice. Importantly, however, this study demonstrates that is possible to successfully perform intermittent hemodialysis in practically all patients with acute renal failure given the findings of similar hypotensive rates with stable and unstable patients and the low cross-over rate from intermittent to continuous therapy.

Meta-analyses that compared outcomes with CRRT and IHD have also been performed [ 31-35 ]. Overall, no survival benefit can be attributed to either modality.

Recovery of renal function — Recovery of kidney function appears to be the same with CRRT and IHD. Although some studies report better recovery with CRRT [36-39 ], these reports only evaluated renal recovery in patients who survived, thereby failing to account for mortality differences between groups. When the analysis combined mortality and nonrecovery of renal function, both groups show similar recovery of function [ 5,40 ]. Randomized studies have also found no such benefit with CRRT [ 28-30 ].Other differences — Advocates for CRRT have claimed that CRRT is associated with the following advantages compared with IHD:Enhanced hemodynamic stability, which may be particularly beneficial in hemodynamically unstable patients [ 28 ].Increased net salt and water removal, thereby permitting superior management of volume overload and nutritional requirements [ 28 ].Enhanced clearance of inflammatory mediators, which may provide benefit in septic patients, particularly using convective modes of continuous therapy [ 41-43 ].Among patients with acute brain injury or fulminant hepatic failure, continuous therapy may be associated with better preservation of cerebral perfusion [ 44 ].

The actual importance of these benefits is uncertain, given the absence of a difference in survival between these modalities. As an example, although convective therapy may provide enhanced clearance of pro-inflammatory mediators, it may also result in removal of beneficial anti-inflammatory mediators. In addition, the maximal achieved extracorporeal clearance of these mediators is low relative to the rates of generation and endogenous clearance.

Comparisons between other modalities of renal replacement therapy  — There are scant data comparing other modalities of RRT in AKI:

A prospective study was performed in Vietnam in which 70 patients with acute renal failure due to either malaria or sepsis (48 and 22 individuals, respectively) were randomly assigned to either peritoneal dialysis or continuous venovenous hemofiltration [ 45 ]. A markedly increased risk of death was observed among the group administered PD (47 versus 15 percent, OR 5.1, 95% CI 1.6-16). Possible reasons for the poorer survival in the PD group include lower overall creatinine clearance, use of acetate (not bicarbonate) in the PD dialysate, and other PD-specific factors that are not yet defined [ 21 ]. In addition, the peritoneal dialysate was made in the study hospital pharmacy, while commercial peritoneal dialysate used in most countries contains lactate instead of acetate. The use of heparin in the hemofiltration arm may also have had therapeutic benefit in patients with malaria. Extrapolation from this study is limited as the study population was very different from that encountered in most developed countries.A randomized controlled trial compared high volume peritoneal dialysis to daily intermittent hemodialysis in 120 patients with acute tubular necrosis [ 46 ]. There were no differences in mortality rate (58 and 53 percent) and recovery of kidney function (28 and 26 percent) in the two treatment arms, although peritoneal dialysis was associated with a shorter duration of need for dialysis.Although SLED has been shown to have similar hemodynamic effects and provides similar metabolic control as CRRT, there are few data comparing outcomes to either IHD or CRRT [ 47 ]. In a single center study of 60 patients treated with either SLED or CRRT, SLED was associated with comparable or better clinical outcomes [ 48 ]. (See "Sustained low efficiency or extended daily dialysis" .)

Summary  — Data do not support the superiority of any particular mode of RRT in patients with AKI. In the majority of patients, selection of modality should therefore be based upon local expertise and availability of staff and equipment. However, in selected patients other factors may prevail. As an example, in patients with acute brain injury or fulminant hepatic failure, continuous therapy may be associated with better preservation of cerebral perfusion.

OPTIMAL DOSING

Intermittent hemodialysis  — Dosing in IHD is based upon the dose delivered per session as well as the frequency of sessions. Thus, outcomes may vary based upon differences in dose per session as applied to a fixed treatment schedule or with differences in treatment schedule as applied to a fixed dose per session. In addition, alterations in the dose per session as well as in the dialysis schedule can also be evaluated.

There have been no studies that have prospectively evaluated the impact of differences in dose per session in patients undergoing IHD on a fixed schedule, such as three times per week. Some data suggest that dosing may have an impact on patients with intermediate levels of disease severity. For example, in a retrospective study of 844 patients in intensive care units with acute renal failure that used Kt/V as a measure of the delivered dose of acute intermittent hemodialysis improved survival was observed with a higher Kt/V (greater than 1) among patients with intermediate levels of illness severity [ 49 ]. By comparison, among those either extremely ill or not very ill, the intensity of the dialysis treatments was less influential on outcome.

In one study that evaluated the impact of frequency of IHD on outcomes, 160 patients with acute renal failure were assigned in an alternating fashion to either daily or every other day hemodialysis [ 36 ]. Enrolled patients were likely to have intermediate levels of illness severity, which was supported by both APACHE scores and the concurrent offering of CRRT at the study center. Compared with every other day dialysis, daily therapy was associated with a significant reduction in mortality (28 versus 46 percent), fewer hypotensive episodes during hemodialysis, and more rapid resolution of acute renal failure (mean 9 versus 16 days). The delivered dialysis dose in the every other day group as assessed by single pool Kt/V was low (0.94 per dialysis). By comparison, the daily dialysis group received the same per treatment delivered dose, but it was delivered twice as frequently. Thus, this study may have best concluded that inadequate therapy is associated with increased mortality.

In contrast, the VA/NIH Acute Renal Failure Trial Network (ATN) Study did NOT find a difference in mortality associated with a more intensive dosing strategy for renal replacement therapy [ 50 ]. The details of this study are discussed in the next section.

The 2012 KDIGO guidelines for AKI recommend delivering a Kt/V of 3.9 per week for patients undergoing intermittent therapy [ 51 ]. While these results are loosely based on the results of the ATN Study, several caveats need to be considered. In the ATN study, the targeted dose of intermittent hemodialysis in both treatment arms was a Kt/V of 1.2 – 1.4 per treatment, with a median delivered Kt/V of 1.3 per treatment [ 50 ]. The weekly dose of dialysis recommended in the KDIGO guidelines is the arithmetic sum of the median dose in the less intensive arm, summed over the course of a week. Since a median delivered Kt/V of 1.3 implies that half of treatments had a delivered Kt/V of less than this value, it is not clear that a per treatment dose of 1.3 represents the appropriate target. In addition, the approach of taking the arithmetic sum of the individual treatment dose to calculate a weekly dose is not consistent with urea kinetic modeling; the weekly dose provided by six treatments with a Kt/V of 0.65 is not equivalent to three treatments with a Kt/V of 1.3 [ 52 ]. We therefore recommend that if intermittent hemodialysis is provided three times per week, the targeted dose of therapy should be a Kt/V of at least 1.2 per treatment with monitoring of the delivered dose of therapy. If this minimum dose is achieved, there is NO evidence that more frequent hemodialysis is associated with improved outcomes unless necessitated for specific acute indications (eg, hyperkalemia). If more frequent intermittent hemodialysis is provided, the targeted dose per treatment may be lower, however the optimal dose is not defined. Surveys of current practice in the United States suggest that monitoring of the delivered dosage of hemodialysis is only infrequently assessed [ 53 ].

The Hanover Dialysis Outcome study compared extended duration dialysis, provided for approximately 8 hours per day, to a more intensive regimen where additional 8-hour treatment sessions were provided to maintain the BUN <42 mg/dL [ 54 ]. No difference in survival or recovery of kidney function was observed with more intensive treatment.

Continuous renal replacement therapy  — For patients on CRRT, we generally aim to provide a delivered effluent flow rate (sum of hemofiltration rate and dialysate flow rate) of at least 20 mL/kg per hour. In order to ensure delivery of this flow rate, we prescribe an effluent flow rate of at least 25 mL/kg per hour. This is consistent with the 2012 KDIGO guidelines that recommend delivering an effluent volume of 20 to 25 mL/kg/h, but which notes that this generally requires prescription of a higher effluent volume to achieve the targeted dose of therapy [ 51 ].

Outcomes of an increased dose of CRRT have been assessed in several randomized controlled trials and two meta-analyses [ 14,55-59 ]. Conflicting results related to survival have been reported.

To address the issue of optimal dose in CRRT and IHD, the United States VA/NIH Acute Renal Failure Trial Network study (ATN), the Randomized Evaluation of Normal versus Augmented Level of RRT study (RENAL) and two meta-analyses were performed. All studies found that, compared with standard intensity dialysis, higher intensity dialysis did not result in improved survival or clinical benefits:

In the United States VA/NIH Acute Renal Failure Trial Network study (ATN), all 1124 patients were treated with IHD, CRRT, or SLED based upon hemodynamic status [ 50 ]. Patients were randomly assigned to one of two dosing arms: 

- Intensive therapy: Hemodialysis and SLED were given six times per week with a target Kt/V of 1.2 to 1.4 per treatment (median delivered dos of 1.3 per treatment), while CRRT was provided with an effluent flow rate of 35 mL/kg per hour. 

- Less intensive therapy: Hemodialysis and SLED were given three times per week with a target Kt/V of 1.2 to 1.4 per treatment (median delivered dos of 1.3 per treatment), while CRRT was provided with a flow rate of 20 mL/kg per hour. 

The death rate at day 60 was the same for both groups (53.6 percent with intensive therapy and 51.5 percent with less intensive therapy). In addition, the duration of renal replacement therapy and the rate of recovery of kidney function or nonrenal organ failure were similar for both treatment arms. The group that received intensive therapy had an increased number of hypotensive episodes. Thus, more intensive renal support beyond that obtained with a standard thrice-weekly regimen (with a target Kt/V of 1.2 to 1.4 per treatment) or standard CRRT (with an effluent flow rate of 20 mL/kg per hour) does not improve clinical outcomes.In the RENAL study (a trial in Australia and New Zealand), 1508 patients with AKI were randomly assigned to CVVHDF at an effluent flow of either 25 or 40mL/kg per hour [ 60 ]. At 90 days, mortality was the same in each group (44.7 percent, odds ratio [OR] 1.00, 95% CI 0.31-1.23). In addition, the incidence of patients who continued to receive renal replacement therapy at 90 days was similar with both dialysis doses (6.8 and 4.4 percent of higher and lower-intensity groups, OR 1.59, 95% CI 0.86-2.92).Two meta-analyses, one consisting of 3841 patients and 8 trials and the other 3999 patients and 12 trials, found that more intense therapy did not improve survival compared with less intensive regimens [ 59,61 ]. There was significant trial heterogeneity.

Observational studies have suggested that the actual delivered effluent volume during continuous renal replacement therapy is substantially less than the prescribed dose. In the DO-RE-MI study of 338 patients treated with CRRT, for example, the median delivered dose of CRRT was 27 mL/kg per hour despite a median prescribed dose of 34.3 mL/kg per hour [ 61 ]. In addition, the actual time on therapy each day in both the ATN and RENAL studies probably exceeded the time on therapy achieved in clinical practice due to enhanced attention to minimizing interruptions in therapy. We therefore suggest that the prescribed dose exceed the desired delivered dose by a factor of approximately 20 to 25 percent to adjust for interruptions in study therapy.

DISCONTINUATION OF THERAPY  — Renal replacement therapy is usually continued until the patient manifests evidence of recovery of kidney function. Most often, recovery is assessed based on empiric data. In oliguric patients, the primary manifestation of recovery of kidney function is an increase in urine output; however, this finding may not be apparent in patients who are nonoliguric. Recovery of kidney function may also be manifest by a progressive decline in serum creatinine concentration after initial attainment of stable values (assessed daily during CRRT or predialysis in patients managed with intermittent hemodialysis) despite a constant dose of renal support. More objective assessment of recovery of kidney function can be obtained by measurement of creatinine clearance. As an example, in the ATN study, creatinine clearance was assessed on six-hour timed urine collections obtained when the urine output exceeded 30 mL/hour [ 50 ]. Since the serum creatinine concentration may not be constant during the collection, the average concentration can be estimated by measuring serum creatinine at the beginning and end of the timed collection, or based on the midpoint serum creatinine concentration. A precise level of kidney function needed to allow discontinuation of renal support has not been established; however, a creatinine clearance less than 12 mL/min is probably inadequate to allow discontinuation of therapy. In the ATN study, renal support was discontinued when the measured creatinine clearance exceeded 20 mL/min and was left to the discretion of providers when in the range of 12 to 20 mL/min [ 50 ].

SUMMARY AND RECOMMENDATIONS

Among patients with life-threatening complications of acute kidney injury (AKI), we recommend the initiation of renal replacement therapy (RRT) ( Grade 1A ). (See 'Indications for and timing of initiation of dialysis' above.)It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit. We suggest initiating dialysis prior to the development of symptoms and signs of renal failure due to AKI ( Grade 2B ). It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated. General practice is to initiate RRT when the BUN reaches 80 to 100 mg/dL, although there is no consensus and practice patterns vary widely. (See 'Indications for and timing of initiation of dialysis' above.)Current data do not support the superiority of either CRRT or IHD. A paucity of data exists concerning the relative benefits of hybrid therapies and acute peritoneal dialysis. Thus, the selection of modality of RRT should be based upon local expertise and experience in combination with the needs of the individual patient. If CRRT is administered, we recommend the use of venovenous circuits rather than arteriovenous circuits ( Grade 1B ). (See 'Optimal modality' above.)We suggest the following strategies for dosage of RRT:

We recommend that intermittent hemodialysis be provided on a three-times per week schedule (alternate days) with monitoring of the delivered dose of dialysis to ensure delivery of a Kt/V of at least 1.2 per treatment ( Grade 1B ).We recommend that CRRT be provided with a delivered effluent flow rate (sum of hemofiltration rate and dialysate flow rate) of at least 20 mL/kg per hour (Grade 1B ). In order to ensure delivery of this flow rate, we prescribe an effluent flow rate of at least 25 mL/kg per hour.

REFERENCESHsu CY, Ordoñez JD, Chertow GM, et al. The risk of acute renal failure in patients with chronic kidney disease. Kidney Int 2008; 74:101.KOLFF WJ. FIRST CLINICAL EXPERIENCE WITH THE ARTIFICIAL KIDNEY. Ann Intern Med 1965; 62:608.MERRILL JP, SMITH S 3rd, CALLAHAN EJ 3rd, THORN GW. The use of an artificial kidney. II. Clinical experience. J Clin Invest 1950; 29:425.TESCHAN PE, BAXTER CR, O'BRIEN TF, et al. Prophylactic hemodialysis in the treatment of acute renal failure. Ann Intern Med 1960; 53:992.Palevsky PM. Dialysis modality and dosing strategy in acute renal failure. Semin Dial 2006; 19:165.PARSONS FM, HOBSON SM, BLAGG CR, McCRACKEN BH. Optimum time for dialysis in acute reversible renal failure. Description and value of an improved dialyser with large surface area. Lancet 1961; 1:129.Fischer RP, Griffen WO Jr, Reiser M, Clark DS. Early dialysis in the treatment of acute renal failure. Surg Gynecol Obstet 1966; 123:1019.Kleinknecht D, Jungers P, Chanard J, et al. Uremic and non-uremic complications in acute renal failure: Evaluation of early and frequent dialysis on prognosis. Kidney Int 1972; 1:190.Conger JD. A controlled evaluation of prophylactic dialysis in post-traumatic acute renal failure. J Trauma 1975; 15:1056.Gettings LG, Reynolds HN, Scalea T. Outcome in post-traumatic acute renal failure when continuous renal replacement therapy is applied early vs. late. Intensive Care Med 1999; 25:805.Demirkiliç U, Kuralay E, Yenicesu M, et al. Timing of replacement therapy for acute renal failure after cardiac surgery. J Card Surg 2004; 19:17.Elahi MM, Lim MY, Joseph RN, et al. Early hemofiltration improves survival in post-cardiotomy patients with acute renal failure. Eur J Cardiothorac Surg 2004; 26:1027.Liu KD, Himmelfarb J, Paganini E, et al. Timing of initiation of dialysis in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol 2006; 1:915.Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, et al. 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; 30:2205.Goldstein SL, Somers MJ, Baum MA, et al. Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int 2005; 67:653.Payen D, de Pont AC, Sakr Y, et al. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care 2008; 12:R74.Bouchard J, Soroko SB, Chertow GM, et al. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int 2009; 76:422.Bellomo R, Parkin G, Love J, Boyce N. A prospective comparative study of continuous arteriovenous hemodiafiltration and continuous venovenous hemodiafiltration in critically ill patients. Am J Kidney Dis 1993; 21:400.van Bommel EF, Ponssen HH. Intermittent versus continuous treatment for acute renal failure: where do we stand? Am J Kidney Dis 1997; 30:S72.Lameire N, Van Biesen W, Vanholder R. Dialysing the patient with acute renal failure in the ICU: the emperor's clothes? Nephrol Dial Transplant 1999; 14:2570.Bellomo R, Boyce N. Acute continuous hemodiafiltration: a prospective study of 110 patients and a review of the literature. Am J Kidney Dis 1993; 21:508.Bellomo R, Farmer M, Parkin G, et al. Severe acute renal failure: a comparison of acute continuous hemodiafiltration and conventional dialytic therapy. Nephron 1995; 71:59.van Bommel E, Bouvy ND, So KL, et al. Acute dialytic support for the critically ill: intermittent hemodialysis versus continuous arteriovenous hemodiafiltration. Am J Nephrol 1995; 15:192.Swartz RD, Messana JM, Orzol S, Port FK. Comparing continuous hemofiltration with hemodialysis in patients with severe acute renal failure. Am J Kidney Dis 1999; 34:424.Guérin C, Girard R, Selli JM, Ayzac L. Intermittent versus continuous renal replacement therapy for acute renal failure in intensive care units: results from a multicenter prospective epidemiological survey. Intensive Care Med 2002; 28:1411.Cho KC, Himmelfarb J, Paganini E, et al. Survival by dialysis modality in critically ill patients with acute kidney injury. J Am Soc Nephrol 2006; 17:3132.Mehta RL, McDonald B, Gabbai FB, et al. A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure. Kidney Int 2001; 60:1154.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; 44:1000.Uehlinger DE, Jakob SM, Ferrari P, et al. Comparison of continuous and intermittent renal replacement therapy for acute renal failure. Nephrol Dial Transplant 2005; 20:1630.Vinsonneau C, Camus C, Combes A, et al. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial. Lancet 2006; 368:379.Kellum JA, Angus DC, Johnson JP, et al. Continuous versus intermittent renal replacement therapy: a meta-analysis. Intensive Care Med 2002; 28:29.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; 40:875.Rabindranath K, Adams J, Macleod AM, Muirhead N. Intermittent versus continuous renal replacement therapy for acute renal failure in adults. Cochrane Database Syst Rev 2007; :CD003773.Bagshaw SM, Berthiaume LR, Delaney A, Bellomo R. Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: a meta-analysis. Crit Care Med 2008; 36:610.Pannu N, Klarenbach S, Wiebe N, et al. Renal replacement therapy in patients with acute renal failure: a systematic review. JAMA 2008; 299:793.Schiffl H, Lang SM, Fischer R. Daily hemodialysis and the outcome of acute renal failure. N Engl J Med 2002; 346:305.Manns B, Doig CJ, Lee H, et al. Cost of acute renal failure requiring dialysis in the intensive care unit: clinical and resource implications of renal recovery. Crit Care Med 2003; 31:449.Jacka MJ, Ivancinova X, Gibney RT. Continuous renal replacement therapy improves renal recovery from acute renal failure. Can J Anaesth 2005; 52:327.Bell M, SWING, Granath F, et al. Continuous renal replacement therapy is associated with less chronic renal failure than intermittent haemodialysis after acute renal failure. Intensive Care Med 2007; 33:773.Palevsky PM, Baldwin I, Davenport A, et al. Renal replacement therapy and the kidney: minimizing the impact of renal replacement therapy on recovery of acute renal failure. Curr Opin Crit Care 2005; 11:548.Ronco C, Tetta C, Mariano F, et al. Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis. Artif Organs 2003; 27:792.Sanchez-Izquierdo JA, Perez Vela JL, Lozano Quintana MJ, et al. Cytokines clearance during venovenous hemofiltration in the trauma patient. Am J Kidney Dis 1997; 30:483.Kellum JA, Johnson JP, Kramer D, et al. Diffusive vs. convective therapy: effects on mediators of inflammation in patient with severe systemic inflammatory response syndrome. Crit Care Med 1998; 26:1995.Davenport A, Will EJ, Davison AM. Continuous vs. intermittent forms of haemofiltration and/or dialysis in the management of acute renal failure in patients with defective cerebral autoregulation at risk of cerebral oedema. Contrib Nephrol 1991; 93:225.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; 347:895.Gabriel DP, Caramori JT, Martim LC, et al. High volume peritoneal dialysis vs daily hemodialysis: a randomized, controlled trial in patients with acute kidney injury. Kidney Int Suppl 2008; :S87.Kielstein JT, Kretschmer U, Ernst T, et al. Efficacy and cardiovascular tolerability of extended dialysis in critically ill patients: a randomized controlled study. Am J Kidney Dis 2004; 43:342.Abe M, Okada K, Suzuki M, et al. Comparison of sustained hemodiafiltration with continuous venovenous hemodiafiltration for the treatment of critically ill patients with acute kidney injury. Artif Organs 2010; 34:331.Paganini, EP, Tapolyai, M, Goormastic, M, et al. Establishing a dialysis therapy/patient outcome link in intensive care unit acute dialysis for patients with acute renal failure. Am J Kidney Dis 1996; 28(Suppl 3):S81.VA/NIH Acute Renal Failure Trial Network, Palevsky PM, Zhang JH, et al. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008; 359:7.KDIGO clinical practice guidelines for acute kidney injury. Kidney Int Suppl 2012; 2.Palevsky PM, Liu KD, Brophy PD, et al. KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury. Am J Kidney Dis 2013.Overberger P, Pesacreta M, Palevsky PM, VA/NIH Acute Renal Failure Trial Network. Management of renal replacement therapy in acute kidney injury: a survey of practitioner prescribing practices. Clin J Am Soc Nephrol 2007; 2:623.Faulhaber-Walter R, Hafer C, Jahr N, et al. The Hannover Dialysis Outcome study: comparison of standard versus intensified extended dialysis for treatment of patients with acute kidney injury in the intensive care unit. Nephrol Dial Transplant 2009; 24:2179.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; 356:26.Saudan P, Niederberger M, De Seigneux S, et al. Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure. Kidney Int 2006; 70:1312.Tolwani AJ, Campbell RC, Stofan BS, et al. Standard versus high-dose CVVHDF for ICU-related acute renal failure. J Am Soc Nephrol 2008; 19:1233.Jun M, Heerspink HJ, Ninomiya T, et al. Intensities of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2010; 5:956.Van Wert R, Friedrich JO, Scales DC, et al. High-dose renal replacement therapy for acute kidney injury: Systematic review and meta-analysis. Crit Care Med 2010; 38:1360.RENAL Replacement Therapy Study Investigators, Bellomo R, Cass A, et al. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009; 361:1627.Vesconi S, Cruz DN, Fumagalli R, et al. Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury. Crit Care 2009; 13:R57.

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