Renal Replacement Therapy for Acute Kidney Injury




Abstract


The indications, timing of initiation, and choice of modality and intensity of delivered therapy are factors that must be considered in prescribing renal replacement therapy (RRT) to patients with acute kidney injury (AKI). This chapter outlines current concepts in the use of RRT for AKI.




Keywords

acute kidney injury, continuous renal replacement therapy (CRRT), hemodialysis, hemodiafiltration, hemofiltration, peritoneal dialysis, prolonged intermittent renal replacement therapy (PIRRT), renal replacement therapy

 






  • Outline



  • Goals of and Indications for Renal Replacement Therapy, 739



  • Modalities of Renal Replacement Therapy, 739




    • Intermittent Modalities, 741



    • Continuous Modalities, 741




  • Timing of Initiation of Renal Replacement Therapy, 743



  • Selection of Modality of Renal Replacement Therapy, 745



  • Dose of Renal Replacement Therapy, 746




    • Intermittent Hemodialysis and Prolonged Intermittent Renal Replacement Therapy, 747



    • Continuous Renal Replacement Therapy, 748



    • Effect of Dose on Recovery of Kidney Function, 749



    • Volume Management, 749



    • Summary and Recommendations, 749




  • Technical Aspects of Management of RRT in AKI, 750




    • Vascular Access, 750



    • Anticoagulation, 750



    • Membrane Composition, 752



    • Procedure-Related Complications, 752



    • Medication Dosing, 753




  • Outcomes, 753



  • Summary, 753


The incidence of acute kidney injury (AKI) in hospitalized patients varies from 5% to 20%, depending on the definition of AKI used and clinical setting. Most critically ill patients develop AKI as part of multiple organ failure (MOF) and have an increased risk for morbidity and reported mortality rates of 40% to 70% when renal replacement therapy (RRT) is required. Since intermittent hemodialysis (IHD) became a common clinical tool for patients with severe AKI in the 1960s, options for RRT have expanded considerably. Biocompatible membranes, bicarbonate dialysate, and dialysis machines with volumetric ultrafiltration control have improved the ability to provide IHD to patients in the intensive care unit (ICU). Along with advances in methods of IHD, continuous renal replacement therapies, including hemofiltration and hemodiafiltration, and hybrid forms of prolonged intermittent RRT have gained widespread acceptance in the treatment of dialysis-requiring AKI.


The indications, timing of initiation, and choice of modality and intensity of delivered therapy are factors that must be considered in prescribing RRT to patients with AKI. This chapter outlines current concepts in the use of RRT for AKI.




Goals of and Indications for Renal Replacement Therapy


The treatment of AKI with RRT has several interrelated goals: (1) to maintain fluid and electrolyte, acid–base, and solute homeostasis; (2) to prevent complications of uremia; and (3) to allow other supportive measures (e.g., antibiotics, nutrition support) to proceed without limitation. Ideally, therapeutic interventions should be designed to achieve those goals while minimizing the risk for further insults to the kidney and facilitating recovery of kidney function. In practice, the use of RRT is commonly based on physician preferences and experience. No evidence-based criteria have been established to guide modality choice, thereby making comparisons among centers or strategies at the same or different institutions difficult. An important consideration is to recognize that patients with AKI are distinct from those with end-stage renal disease (ESRD). The rapid decline of kidney function in AKI does not permit the adaptive responses that characterize the course of the patient with chronic kidney disease (CKD). Consequently, the traditional indications for renal replacement, developed for patients with advanced CKD, are not necessarily valid in this context ( Box 49.1 ). For instance, massive volume overload, resulting from volume resuscitation, a common strategy used for MOF, may be an indication for dialysis, even in the absence of significant elevations in blood urea nitrogen (BUN) or plasma creatinine. In this instance, it may be more appropriate to consider RRT in the ICU patient as a form of renal support as opposed to “replacement.” Indeed, some of the traditional indications for dialysis (e.g., uremic pericarditis, pleuritis, or other serositis) would be considered “rescue indications” suggesting undue delay in initiation of RRT.



BOX 49.1


Conventional Indications for Renal Replacement Therapy


Volume overload


Hyperkalemia


Metabolic acidosis


Drug intoxications


Uremic manifestation


Progressive azotemia in the absence of overt uremia


Potential Expanded Criteria for Renal Support


Volume management in heart failure, sepsis, and multisystem organ failure


Acid–base management in respiratory failure with low-tidal-volume ventilation


Nutrition management


Indications for Renal Replacement Therapy




Modalities of Renal Replacement Therapy


The most common RRT modalities used for AKI include IHD, prolonged intermittent renal replacement therapy (PIRRT), continuous renal replacement therapy (CRRT), and peritoneal dialysis (PD) ( Tables 49.1 and 49.2 ). IHD, PIRRT, and CRRT are extracorporeal therapies that require vascular access in the form of a large-bore, double-lumen central venous catheter, whereas PD requires the placement of an intraabdominal dialysis catheter.



TABLE 49.1

Renal Replacement Therapy Modalities for Acute Kidney Injury
































Modality Usual Duration Access
Intermittent hemodialysis <6 hours Vascular
Prolonged intermittent renal replacement therapy 8–16 hours Vascular
Continuous renal replacement therapies Continuous Vascular
Slow continuous ultrafiltration
Continuous venovenous hemofiltration
Continuous venovenous hemodialysis
Continuous venovenous hemodiafiltration
Peritoneal dialysis Variable Peritoneal

Most commonly provided as pump-driven venovenous therapies; may also be provided as arteriovenous therapy.



TABLE 49.2

Comparison of Key Characteristics of Modalities of Renal Replacement Therapy Used for Management of Acute Kidney Injury






































































Characteristic IHD PIRRT CRRT PD
Access Vascular Vascular Vascular Peritoneal
Duration <6 hours 8–16 hours Continuous Continuous
Mode of solute removal Diffusion Diffusion Diffusion
(CVVHD, CVVHDF) and convection
(CVVH, CVVHDF)
Diffusion
Hemodynamic tolerability Low High High High
Rate of solute removal Rapid Intermediate Slow Slow
Ultrafiltration rate Rapid Intermediate Slow Slow
Ultrafiltration control Yes Yes Yes No
Risk of membrane clotting Low Intermediate High None
Need for anticoagulation Variable Variable Often None
Treatment of intoxication or severe hyperkalemia Rapid Intermediate Slow Slow

CRRT, Continuous renal replacement therapy; CVVH, continuous venovenous hemofiltration; CVVHD, continuous venovenous hemodialysis; CVVHDF, continuous venovenous hemodiafiltration; IHD, intermittent hemodialysis; PD, peritoneal dialysis; PIRRT, prolonged intermittent renal replacement therapy.


The various modalities of RRT use varying proportions of diffusion and convection for solute transport and ultrafiltration, driven either by hydrostatic or osmotic gradients, for volume management. With extracorporeal therapies, some solutes may also be removed by adsorption onto the membrane. The relative contributions of diffusion, convection, and adsorption depend on the solute, the membrane, the geometry of the dialyzer, and operating conditions such as blood and dialysate flow rates and ultrafiltration rate. Ultrafiltration, which is used for volume management and which drives convective clearance, occurs by application of a hydrostatic pressure across the membrane from the blood to effluent side in IHD, PIRRT, and CRRT and by an osmotic gradient in PD. In diffusion, blood is exposed to dialysate across a semipermeable membrane and solute transfer across the membrane is driven by the concentration gradient between blood and dialysate. With extracorporeal therapies, the concentration gradient is maximized and maintained throughout the length of the membrane by running the dialysate countercurrent to the blood flow. Solute clearance is dependent on molecular size, membrane characteristics such as pore size, charge, water permeability, and extracorporeal circuit factors such as dialysate and blood flow rates. Small molecular weight solutes (<500 Daltons) are cleared efficiently by diffusion because their mobility in solution is high. As molecular weight increases, the mobility of solutes in solution diminish and diffusive clearance decreases. Convective clearance occurs when application of a hydrostatic pressure or osmotic gradient across a semipermeable membrane forces solvent (i.e., plasma water) across the membrane by ultrafiltration and ‘‘drags’’ with it small- and middle-molecular-weight solutes by bulk flow. The size of solutes that can be removed by convection is determined primarily by the size selectivity and charge characteristics of the membrane. For solutes that are smaller than the size cutoff of the membrane, the major determinant of convective clearance is the rate at which ultrafiltration occurs.


Intermittent Modalities


Intermittent Hemodialysis


IHD primarily uses diffusion for small-solute clearance and ultrafiltration for volume removal. However, high-flux dialyzers can provide convective clearance of larger solutes through increased membrane porosity, enhanced transport capacity, and internal filtration and backfiltration. IHD is typically delivered 3 or more days per week, 3 to 5 hours per session, with a blood flow rate of 300 to 500 mL/min and a dialysate flow rate of 500 to 800 mL/min. The duration and frequency of IHD sessions are determined by the patient’s specific metabolic and volume requirements and degree of hemodynamic stability. Because IHD allows for rapid solute and volume removal, it is preferred for rapid correction of severe electrolyte disturbances, such as hyperkalemia, and treatment of amenable drug intoxications. The higher blood flow rate and shorter duration of therapy allows IHD to be performed with less or no anticoagulation compared with other extracorporeal RRT modalities. However, the rapid solute and fluid removal predispose to intradialytic hypotension, which occurs in 30% to 50% of acute IHD treatments. Strategies for improving hemodynamic stability include cooling the dialysate, sodium modeling, increasing the dialysate calcium concentration, performing intermittent ultrafiltration, and prolonging the duration of therapy to slow the rate of ultrafiltration. Despite this, approximately 10% of patients with AKI cannot tolerate IHD because of hypotension. Furthermore, as the result of rapid intracellular fluid and solute shifts that may cause disequilibrium between the brain and extracellular compartments, IHD can increase intracranial pressure and exacerbate cerebral edema in patients with fulminant hepatic failure and acute brain injury.


Prolonged Intermittent Renal Replacement Therapies


Prolonged intermittent renal replacement therapies are hybrid therapies used as an alternative to CRRT in critically ill patients with AKI. Significant heterogeneity exists in practice with regard to PIRRT technology, prescription, and anticoagulation. These techniques attenuate the hemodynamic effects of IHD by prolonging therapy duration and adapting conventional hemodialysis machines to provide lower blood-pump speeds (100 to 300 mL/min) and dialysate flow rates (100 to 300 mL/min). Treatment sessions may range from 6 hours every other day to greater than 12 hours daily. Diffusion-based PIRRTs have been described as sustained low efficiency (daily) dialysis (SLEDD), extended daily dialysis (EDD), slow continuous dialysis (SCD), and “go slow dialysis.” When both convective and diffusive therapy are used together, they have been described as low-efficiency daily diafiltration (SLEDD-f) and sustained hemodiafiltration (S-HDF) ; the term accelerated venovenous hemofiltration (AVVH) has been used to describe solely convective therapy. PIRRT can also be provided using CRRT equipment, delivering treatment for 8 to 16 hours per day with proportionally augmented dialysate or replacement fluid flow rates.


PIRRTs combine advantages of both CRRT and IHD. They allow for improved hemodynamic stability by removing solute and fluid over a longer period while avoiding the need for 24-hour therapy and expensive CRRT machines and solutions. At the same time, they provide high solute clearances as in IHD and allow for scheduling of required diagnostic and therapeutic patient procedures without interruption of therapy. Furthermore, the therapy can be delivered at night to allow for patient mobilization during the day. Studies have indicated that PIRRTs provide comparable hemodynamic control to CRRT. Appropriate adjustment of dosing of medications, especially antibiotics, is complicated by the significant variation in practice of delivery of PIRRT and the extended time of dialysis and small-solute clearance. For example, with IHD a given antimicrobial may be removed and reach subtherapeutic levels the last 2 hours of a given session and the medication can be redosed immediately after dialysis in 1 to 2 hours. However, with PIRRTs, a given antimicrobial may reach subtherapeutic concentrations after 2 to 3 hours of the session with another 6 to 10 hours remaining, and a midtreatment dose may be needed. Clear data do not exist on how to approach these dosing questions in PIRRT, and decisions must be individualized with close coordination with clinical pharmacy experts.


Continuous Modalities


Peritoneal Dialysis


In PD the peritoneum is used as a semipermeable membrane for diffusive removal of solutes. Dialysate consisting of a sterile, lactate-buffered electrolyte solution is instilled into the peritoneal cavity through a catheter, where it dwells for a prescribed period to allow solutes to diffuse from the blood into the dialysate. The saturated dialysate is then drained and discarded, and fresh dialysate reintroduced. Varying high concentrations of dextrose (or other nonelectrolyte solutes) are used in the dialysate to create an osmotic gradient for ultrafiltration. Acute PD can be performed intermittently or continuously and either manually or by an automated cycler. PD techniques for AKI include acute intermittent peritoneal dialysis (IPD), continuous equilibrated peritoneal dialysis (CEPD), tidal peritoneal dialysis (TPD), continuous flow peritoneal dialysis (CFPD), and high-volume peritoneal dialysis (HVPD). IPD is characterized by frequent short exchanges using volumes of 1 to 2 L and dialysate flows of 2 to 6 L/h. It can be done manually or by using an automated cycler. CEPD is characterized by long dwells of 2 to 6 hours with up to 2 L of dialysate each. It is similar to continuous ambulatory PD used for chronic outpatient PD, except that the patients are not ambulatory. TPD consists of an initial infusion of dialysate (typically 3 L) followed by a variable dwell and partial drain of the solution, leaving a residual amount of dialysate in constant contact with the peritoneal membrane until the final drain. This approach is thought to enhance clearance of small solutes by reducing the loss of dialytic time that is associated with the drainage and reinfusion of dialysate; however, clinical experience with TPD has not confirmed any advantage over other PD techniques in terms of clearance or ultrafiltration. In CFPD, inflow and outflow of dialysate occurs simultaneously through two access routes with maintenance of a fixed intraperitoneal volume. This technique is performed with high dialysate flow rates (150 to 300 mL/min) and produces greater small-solute clearance than conventional automated PD. HVPD uses a cycler to provide continuous therapy with frequent exchanges (18 to 48 exchanges per 24 hours, 2 L per exchange) with dialysate volume ranging from 36 to 70 L per day and high small-solute clearance.


Advantages of PD include technical simplicity, hemodynamic stability, lack of need for anticoagulation or vascular access, and lower cost. Because solute and fluid removal is gradual, it may be a safer modality among patients at risk for increased intracranial pressure. Disadvantages include the need for specialized training for catheter insertion, complications of PD catheter placement, risk for peritonitis, potential inability to provide sufficient solute clearance in hypercatabolic patients, unpredictable ultrafiltration rates, hyperglycemia, excessive protein loss across the peritoneal membrane, and potential respiratory compromise from increased abdominal pressure. PD is contraindicated in patients with recent abdominal surgery, abdominal drains, postoperative or traumatic diaphragm incompetence, or ileus. Acute PD is useful in AKI patients with hemodynamic instability or difficult vascular access issues or in AKI patients located in regions with limited resources or access to hemodialysis techniques.


Continuous Renal Replacement Therapy


Continuous renal replacement therapy (CRRT) encompasses various modalities developed specifically to manage critically ill patients with AKI who cannot tolerate IHD because of hemodynamic instability. CRRT allows for better hemodynamic tolerance than IHD by providing slower solute and fluid removal per unit time. It is designed to be performed 24 hours a day with typical blood flow rates of 100 to 300 mL/min. Potential advantages of CRRT over IHD include better hemodynamic tolerance, more continuous solute clearance, and better control of volume status. The main disadvantages of CRRT include vascular access and filter clotting, greater need for anticoagulation, decreased patient mobility, and increased costs and demands on ICU nurse time compared with IHD.


CRRT employs diffusion, convection, or a combination of both for solute clearance. The different modalities of CRRT for solute removal include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), and continuous venovenous hemodiafiltration (CVVHDF). In CVVH, solute clearance occurs by convection and is augmented by increasing the volume of ultrafiltrate produced. A “replacement” or “substitution” fluid is infused in the blood before the hemofilter (prefilter or predilution) or after the hemofilter (postfilter or postdilution) in varying amounts to replace the excess volume and electrolytes lost across the membrane from the high ultrafiltration rates. The use of postfilter replacement fluid is limited by the filtration fraction, which is the fraction of plasma water that is removed from blood during ultrafiltration and is defined as the ratio of ultrafiltration rate to plasma water flow rate. Filtration fraction should be kept <0.25 to prevent increased risk of clotting because of hemoconcentration and protein-membrane interactions. Although adding some of the replacement fluid prefilter reduces the filtration fraction, it also dilutes the concentration of solutes entering the hemofilter, thereby decreasing solute clearance at a fixed ultrafiltration rate. This reduction in clearance can be offset by increasing the ultrafiltration rate, which again increases filtration fraction, albeit to a value that is lower than before predilution. In CVVHD, solute removal occurs primarily by diffusion. In contrast to IHD, the dialysate flow rates (typically 0.5 to 3 L/h, or 8 to 50 mL/min) in CVVHD are significantly slower than the blood flow rates (100 to 300 mL/min), resulting in complete or near-complete saturation of the dialysate. Ultrafiltration is used only for volume control with rates much lower than required for convective solute clearance. CVVHDF uses a combination of convection and diffusion for solute removal and requires use of both dialysate and replacement fluid.


Despite increased clearance of middle-molecular-weight molecules with convective techniques, no study has found that CVVH or CVVHDF improves patient survival compared with CVVHD. In a metaanalysis comparing the outcomes of hemofiltration to hemodialysis for the treatment of AKI, the authors found no difference in patient survival or clinical outcomes such as organ dysfunction, vasopressor use, or renal recovery. Hemofiltration was associated with an increased clearance of larger molecules but also a shorter CRRT filter and circuit life. Although cytokines can be removed by convective therapy, most controlled studies have failed to demonstrate an improvement in outcome. High-volume hemofiltration (HVHF) with ultrafiltration rates >50 mL/kg/h has been attempted to augment the clearance of cytokines in AKI patients with sepsis and septic shock. However, a metaanalysis of four randomized controlled trials comparing HVHF to standard volume CVVH did not find any survival benefit with HVHF. The High Volume Veno-venous Hemofiltration Versus Standard Care for Post-cardiac Surgery Shock (HEROICS) Study was a randomized controlled trial in which patients with severe cardiogenic shock requiring high-dose catecholamines 3 to 24 hours after cardiac surgery were randomly assigned to early HVHF at 80 mL/kg/h for 48 hours followed by standard-volume CVVHDF versus standard care. Standard care involved initiating CVVHDF for conventional indications in the setting of AKI. Early HVHF did not lower 30-day mortality (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.64 to 1.56; P =1.00) or improve any other clinical outcomes. Multiple reasons may underlie this failure of augmented middle molecule clearance with convective clearance to improve clinical outcomes, including the fact that achieved cytokine clearances are still relatively low compared with their biological half-lives and that both pro- and antiinflammatory mediators are nonselectively removed. Given insufficient data to recommend one type of CRRT modality over another, the choice of CRRT modality should be based on clinician preference and expertise.




Timing of Initiation of Renal Replacement Therapy


Although whether or not to provide dialytic support with RRT and when to start are two of the most fundamental questions facing nephrologists and intensivists in caring for patients with AKI, the optimal timing of acute RRT for AKI is not defined. An improvement in survival associated with early initiation of RRT was first suggested by case series with historical controls conducted in the 1960s and 1970s. However, given that BUN concentrations at the start of dialysis in the “early” treatment groups in these studies were high by modern standards, their relevance to current practice is limited. Moreover, over the last 30 years, the severity of illness of hospitalized patients continues to increase, especially among the critically ill population, and life support technologies have rapidly progressed, allowing for improving survival, which further limits comparisons of distantly historical studies. More recent single-center observational studies that were restricted to AKI after trauma and coronary artery bypass surgery suggested a benefit to dialysis initiation at lower BUN concentrations. A prospective multicenter observational cohort study performed by the Program to Improve Care in Acute Renal Disease (PICARD) analyzed dialysis initiation—as inferred by BUN concentration—in 243 patients from five geographically and ethnically diverse clinical sites. Survival rates were slightly lower for patients who started dialysis at higher BUN concentrations, despite a lesser burden of organ system failure. Adjusting for age, hepatic failure, sepsis, thrombocytopenia, and serum creatinine and stratified by site and initial dialysis modality, initiation of dialysis at higher BUN was associated with an 85% increased relative risk (RR) for death (RR = 1.85; 95% CI, 1.16 to 2.96).


Although the maintenance of BUN concentrations below arbitrarily set levels is usually a reference for starting dialysis treatment, BUN reflects factors not directly associated with kidney function, such as catabolic rate, nutritional intake (especially protein intake), and volume status. Plasma creatinine is influenced by age, race, muscle mass, and catabolic rate, and its concentration is also affected by changes in extracellular volume status (decreasing as total body volume increases). In a prospective multicenter observational study conducted at 54 ICUs in 23 countries, timing of RRT was stratified into “early” or “late” by median urea at the time RRT started and also categorized temporally from ICU admission into early (less than 2 days), delayed (between 2 and 5 days), or late (more than 5 days). Timing by serum urea indicated no significant difference in mortality (63.4% for urea ≤ 24.2 mmol/L vs. 61.4% for urea > 24.2 mmol/L). However, when timing was analyzed relative to ICU admission, late RRT was associated with greater crude mortality (72.8% late vs. 62.3% delayed vs. 59% early; P = 0.001) and covariate-adjusted mortality (OR, 1.95; 95% CI, 1.30 to 2.92; P = 0.001). Overall, late RRT was associated with a longer duration of RRT and a longer stay in hospital and greater dialysis dependence, which was attributed to accumulation of volume, worsening acidemia, and/or life-threatening electrolyte derangements. In addition, timing of initiation of RRT relative to ICU admission may also reflect differences with regard to whether AKI was present at ICU admission or developed as a complication during ICU admission, which may also influence these outcomes.


An important methodological flaw underlies these observational studies and limits their interpretation. By only including patients who actually received RRT rather than all patients in whom AKI was present and might have been considered as candidates for early RRT, these observational cohorts excluded patients with early AKI who either recovered kidney function or died without ever receiving RRT. Because the clinical question is not early versus late initiation of RRT, but early initiation of RRT versus a delayed approach to management, failure to include these patients who do not receive RRT may provide a biased assessment of the benefits of early initiation of RRT.


Several randomized controlled trials have attempted to address this issue ( Table 49.3 ). In an older study of critically ill patients, Bouman et al. randomly assigned 106 critically ill patients with AKI to early or late initiation of dialysis. The early initiation group started CVVH within 12 hours of developing a low urine output (less than 30 mL/h for 6 hours, not responding to diuretics or hemodynamic optimization) or a creatinine clearance less than 20 mL/min. CVVH was started in the late initiation group when classic indications were met. Although underpowered to detect survival differences, the study did not find differences in ICU or hospital mortality between the early and late groups or in renal recovery among survivors.



TABLE 49.3

Randomized Controlled Trials Evaluating Timing of Renal Replacement Therapy in Acute Kidney Injury



































































































Study Number of Patients Study Setting Study Design RRT Modality Criteria for Initiation of RRT Percentage of Patients Receiving RRT Mortality
Early Late Early Late Early Late P value
Bouman, 2002 106 ICU Two centers CRRT 12 h from enrollment BUN >112 mg/dL
K > 6.5 mmol/L
Pulmonary edema
70/70
(100%)
30/36 (83%) 28.6% 25% 0.80
Jamale, 2013 208 Community-acquired AKI Single center IHD BUN > 70 mg/dL
Cr > 7 mg/dL
Usual care
Mean BUN 101 ± 33 mg/dL
Mean Cr 10.4 ± 3.3
93/102 (91%) 88/106 (83%) 20.6% 12.3% 0.20
Combes, 2015 224 Post–cardiac surgery Multicenter CRRT Post–cardiac surgery shock Usual care 111/112 (99%) 64/112 (57%) 46% 38% 0.72
Wald, 2015 100 ICU Multicenter IHD and CRRT Stage 2 AKI K > 6 mmol/L
HCO 3 < 10 mmol/L
>72 h from enrollment
48/48 (100%) 33/52 (63.4%) 37.5% 36.5% 0.92
Zarbock, 2016 231 Surgical ICU Single center CRRT Stage 2 AKI Stage 3 AKI 112/112 (100%) 108/119 (91%) 39.3% 54.7% 0.03
Gaudry, 2016 319 ICU Multicenter IHD and CRRT Stage 3 AKI BUN > 112 mg/dL
K > 6 mmol/L
pH < 7.15
Oliguria > 72 h
pulmonary edema
305/311 (98%) 157/308 (51%) 48.5% 49.7% 0.79

AKI, Acute kidney injury; BUN, blood urea nitrogen; Cr, creatinine; CRRT, continuous renal replacement therapy; ICU, intensive care unit; IHD, intermittent hemodialysis; RRT, renal replacement therapy.


Two more recent clinical trials—Artificial Kidney Initiation in Kidney Injury (AKIKI) and Early Versus Late Initiation of Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury (ELAIN) —reached divergent conclusions. The AKIKI trial was a multicenter randomized controlled trial conducted in France that assigned 620 patients who reached Kidney Disease: Improving Global Outcomes (KDIGO) stage 3 AKI to either immediate initiation of RRT or a delayed initiation strategy in which RRT was not begun until specific metabolic parameters or life-threatening indications developed. Ninety-eight percent of the patients in the early arm received RRT compared with only 51% of the patients randomized to the delayed therapy arm. The median time from development of stage 3 AKI to initiation of RRT was 4.3 hours in the early treatment arm and 57 hours in the delayed arm; the predominant modality of RRT used was IHD. There was no difference in survival at 60 days between the early and delayed RRT groups (48.5% vs. 49.7%; P = 0.79). Comparing the patients who received RRT, early RRT was associated with lower mortality compared with the patients initiated late (48.5% vs. 61.8% at 60 days); however, those patients in the delayed initiation arm who did not receive RRT had a substantially lower mortality (37.1% at 60 days) than those patients who received RRT. Although these patients represented a lower risk population, with lower severity of illness at randomization, the inability to prospectively identify patients who ultimately do not receive RRT illustrates the need to include them in analyses of early versus delayed strategies of initiation.


The ELAIN trial was a single-center study that randomly assigned 231 patients with KDIGO stage 2 AKI to either immediate RRT or delayed initiation until they reached KDIGO stage 3 AKI or developed life-threatening indications. CVVHDF was the modality of RRT used in all patients and only 9 of 118 in the delayed group did not receive RRT. The median time from reaching KDIGO stage 2 AKI to initiation of RRT was 6.0 hours in the early RRT arm compared with 25.5 hours in the late arm. Mortality at 90 days was 39.3% in the early RRT group versus 54.7% in the delayed group ( P = 0.03) with a hazard ratio (HR) for death of 0.66 (95% CI, 0.45 to 0.97) in the early group. Two additional multicenter trials (Standard Versus Accelerated Initiation of Renal Replacement Therapy in AKI [STARRT-AKI; ClinicalTrial.gov #NCT01557361 ] and Initiation of Dialysis Early Versus Delayed in Intensive Care Unit [IDEAL-ICU; ClinicalTrial.gov #NCT01682590 ]) are ongoing. Pilot data from 100 participants enrolled in the pilot phase of the STARRT-AKI trial indicated a separation in time from eligibility in the two arms of approximately 24 hours with no significant difference in mortality between the two treatment groups (38% in the accelerated arm vs. 37% in the standard arm).


The role of volume overload as an independent criterion for initiation of RRT in critically ill patients with AKI should be noted. Over the last 10 to 15 years, multiple studies in critically ill patients have demonstrated that volume overload is detrimental to critically ill patients both with and without AKI, contributing to mortality and to other morbidities such as duration of ICU length of stay, time on mechanical ventilation, and intraabdominal hypertension. Almost all patients requiring acute RRT, especially in the ICU, have some degree of volume accumulation or frank volume overload, and there is a strong association between volume overload at time of RRT initiation and increased risk for death in both adults and pediatric populations. Furthermore, retrospective data suggest that the excess hospital mortality seen in AKI seems primarily driven by fluid overload, hyperkalemia, and metabolic acidosis rather than by azotemia.


Much of the uncertainty regarding timing of initiation of RRT rests with difficulty that is often present in assessing the trajectory of AKI in an individual patient. Will oliguria be transient or prolonged? Will kidney function begin to recover in a matter of hours or days, or will the AKI be prolonged? Novel biomarkers of kidney injury such as neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinase-2 (TIMP-2), and insulin-like growth factor–binding protein 7 (IGFBP7) have been proposed as prognostic markers; however, further validation is required for widespread adoption in clinical decision-making. The role of functional testing, such as the furosemide stress test, also has potential but requires further validation.


In considering the optimal timing of initiation of RRT in AKI, safety concerns associated with RRT need to be considered. Whether blood based or peritoneal membrane based, acute RRT requires access insertion and maintenance, both of which can cause visceral and vascular injury, including bleeding, vascular laceration, acute arteriovenous fistula formation, pneumothorax, and abdominal wall or mesenteric injury, as well as infection, although the risks associated with vascular catheter insertion have been reduced with the adoption of bedside ultrasound guidance for insertion. In addition, RRT is associated with risks of hypotension and leukocyte and platelet activation from exposure to the extracorporeal circuit, both of which may delay recovery of kidney function.


Thus the clinical decision to initiate RRT must balance both uncertainty regarding risks and benefits for the individual patient. The KDIGO Clinical Practice Guidelines for AKI have encapsulated this uncertainty in the ungraded recommendations to “initiate RRT emergently when life-threatening changes in fluid, electrolyte, and acid-base balance exist;” but to also “consider the broader clinical context, the presence of conditions that can be modified with RRT, and trends of laboratory tests—rather than single BUN and creatinine thresholds alone—when making the decision to start RRT.”




Selection of Modality of Renal Replacement Therapy


Multiple factors need to be taken into consideration in the selection of modality of RRT, including clinical setting, hemodynamic status, volume status, medication dosing, nutritional needs and the nursing and medical expertise and resources and available. Based on randomized controlled trials and metaanalyses, CRRT and IHD are generally considered to be complementary therapies with no clear evidence that either modality provides a survival advantage. However, CRRT may be preferable to IHD in specific clinical settings. In the setting of significant acute brain injury or fulminant hepatic failure, CRRT may better protect cerebral perfusion by avoiding the rapid shifts in blood osmolality which are associated with the more rapid solute clearance during IHD and may lead to increased intracranial pressure and decreased cerebral perfusion pressure. Furthermore, CRRT has been associated with less need for escalation of vasopressors and with achievement of greater net negative fluid balance. Therefore CRRT may be better suited for some critically ill AKI patients who cannot not tolerate fluid shifts and fluctuations in metabolic parameters.


The effect of modality of RRT on recovery of kidney function has been debated. Although observational studies have found CRRT to be associated with higher rates of renal recovery, the evidence is insufficient and most studies only evaluated renal recovery in patients who survived. Studies analyzing combined mortality and nonrecovery of renal function between groups have found no difference in recovery of kidney function. In a retrospective propensity matched cohort, Wald et al. compared CRRT with IHD as the initial RRT modality in critically ill adults with AKI and found that CRRT was associated with a lower likelihood of chronic dialysis (HR 0.75; 95% CI, 0.65 to 0.87). However, a subsequent retrospective cohort study of 638 critically ill patients who received RRT for AKI and survived to hospital discharge or 90 days found no difference in renal recovery based on initial RRT modality. Multiple randomized controlled trials have analyzed recovery of kidney function as a secondary endpoint and have found no difference in recovery of kidney function, based on dialysis independence, as a function of modality of RRT. A metaanalysis of predominantly observational studies reported CRRT as the initial RRT modality to be associated with higher rates of renal recovery among survivors; however, when the analysis was limited to randomized controlled trials, no benefit with regard to renal recovery was observed.


It has been postulated that continuous hemofiltration might have immunomodulatory benefits based on removal of proinflammatory mediators such as interleukin (IL)-6, IL-8, IL-1, and tumor necrosis factor by convection or by adsorption to the membrane. Despite some encouraging results, the clinical benefit of conventional CRRT in sepsis has been disappointing and the preferential use of convective as opposed to diffusive modalities cannot be supported by the data. A number of factors may contribute to this absence of benefit, including concomitant removal of both pro- and antiinflammatory mediators and relatively low extracorporeal cytokine clearance compared with endogenous clearance rates.


Efforts at further augmenting cytokine clearance have used higher hemofiltration volumes, high-cutoff membranes (with a molecular weight range of up to 60 kDa), and coupled plasma filtration and adsorption (CPFA). In a pilot study using a high-cutoff membrane for hemofiltration in septic AKI, clearance rates for IL-6 and IL-1 were found to be augmented and vasopressor requirements decreased ; however, benefits with regard to patient survival could not be demonstrated. Similarly, compared with conventional CRRT, CPFA in septic shock improves hemodynamics and decreases need for vasopressor support but has not been found to reduce mortality or other important clinical outcomes. Similarly, the High Volume in Intensive Care (IVOIRE) and HEROICS trials were unable to demonstrate benefit to high-volume (70 to 80 mL/kg/h) hemofiltration in either sepsis-associated AKI or post–cardiac surgery cardiogenic shock compared with conventional management. Thus use of these novel approaches to CRRT cannot be recommended for clinical practice.


There are limited data comparing other modalities of RRT in AKI. The few studies comparing IHD with PIRRT have not found a clear modality benefit. Studies comparing PIRRT with CRRT have found that PIRRT provides comparable hemodynamic stability and solute control to CRRT with no significant differences in mortality. A metaanalysis of studies comparing CRRT and PIRRT indicated no difference in mortality, recovery of kidney function, fluid removal, days in the intensive care unit, or solute control.


Several small randomized controlled trials have compared PD with other RRT modalities in AKI. In a prospective study performed in Vietnam, 70 patients with AKI caused by either malaria or sepsis (48 and 22 individuals, respectively) were randomly assigned to either PD or CVVH. PD was associated with significantly increased risk for death (47% vs. 15%, OR 5.1, 95% CI, 1.6 to 16). In this study the mortality rate for patients on CVVH was unusually low and PD was not performed using the most recent technological advances such as use of bicarbonate-based dialysate and soft catheters. In contrast, a prospective randomized controlled trial performed in Brazil compared the effect of HVPD and daily hemodialysis (DHD) on AKI patient survival. A total of 120 patients with acute tubular necrosis (ATN) were assigned to HVPD or DHD. The delivered dose, assessed as weekly Kt/V, was 3.67 in HVPD and 4.77 in DHD ( P = 0.01). Metabolic control, mortality rate (58% and 53%), and renal function recovery (28% and 26%) were similar in both groups, whereas HVPD was associated with a significantly shorter time to the recovery of renal function. Another randomized controlled trial comparing high-volume PD to PIRRT found no difference in mortality. A metaanalysis of seven cohort studies and four randomized trials studies comparing PD with extracorporeal therapies in the setting of AKI suggested there were no significant differences in outcomes between patients treated with PD and IHD or hemodiafiltration (HDF).


Because studies comparing modalities of RRT for AKI have not demonstrated superiority of any individual modality with regard to survival or recovery of renal function, selection of RRT modality should be tailored to specific needs of the patient. Most clinicians choose IHD for AKI patients who are hemodynamically stable and CRRT or PIRRT for AKI patients who are hemodynamically unstable, are fluid overloaded, and/or have sepsis and multiorgan failure. Data suggest that given slower rates but more prolonged duration of fluid removal, CRRT may provide more effective volume management than conventional IHD, whereas volume control with CRRT and PIRRT are comparable. Similarly, the slower solute and volume removal with CRRT provides better preservation of cerebral perfusion, making it the preferred treatment compared with IHD in patients with fulminant hepatic failure or cerebral edema. In contradistinction, IHD is favored in patients who need rapid solute removal, such as patients with marked hyperkalemia or drug intoxications. Pragmatically, CRRT and PIRRT require more continuous patient observation and are generally restricted to patients in critical care units. Given the continuous nature of CRRT, treatment interruptions are necessary if the patient needs to be moved for diagnostic imaging or surgical procedures. Breaks in time on treatment with PIRRT and IHD may also facilitate earlier initiation of physical therapy and minimize periods of prolonged immobilization. Transitions between modalities of therapy are common, reflecting the changing needs of patients during their hospital course. Finally, choice of RRT modality must also reflect the modalities available and physician and nursing expertise at the individual hospital as well as considerations of resources, cost, and provider preference.




Dose of Renal Replacement Therapy


Assessment of dose of acute RRT is complex and can be considered as a multidimensional construct encompassing clearance of small solutes (most often modeled based on urea clearance), larger solutes (so-called “middle” molecules), ultrafiltration, treatment duration, and treatment frequency. The relative significance of these factors varies based on the modality of RRT. For example, although treatment duration and frequency are important parameters for intermittent modalities such as IHD and PIRRT, their significance only relates to unplanned interruptions of therapy in the continuous therapies. There are also important interrelationships between duration and frequency of treatment and solute clearance and ultrafiltration: When an intermittent treatment is provided more frequently (e.g., daily IHD), less solute and volume removal during each treatment is required to achieve the same overall dose of therapy than if provided on a less frequent schedule (e.g., every other day or three times per week). In addition, when solute clearance is primarily provided by diffusion, clearance of larger solutes is more dependent on duration and membrane surface area and can be dissociated from clearance of smaller solutes such as urea. Similarly, ultrafiltration may be completely dissociated from solute clearance. Despite this multidimensional complexity, the majority of studies evaluating the relationship between delivered dose of therapy and outcomes have focused primarily on small-solute clearance, primarily modeled as urea clearance ( Table 49.4 ).



TABLE 49.4

Randomized Controlled Trials Evaluating Intensity of Renal Replacement Therapy in Acute Kidney Injury

































































































Study Number of Patients Study Design RRT Modality Dose of RRT Mortality
Less Intensive More Intensive Less Intensive More Intensive P value
Ronco, 2000 425 Single center CRRT CVVH at 20 mL/kg/h CVVH at 35 or 45 mL/kg/h 59% 42% <0.005
Schiffl, 2002 160 Single center IHD IHD with Kt/V 0.94 ± 0.11
delivered every other day
IHD with Kt/V 0.92 ± 0.16 delivered daily 46% 28% 0.01
Bouman, 2002 106 Two centers CRRT 24–36 L per 24 h 5 28% 25% 0.80
Saudan, 2006 206 Single center CRRT CVVH at 25 ± 5 mL/kg/h CVVHDF at
24 ± 6 mL/kg/h UF and
15 ± 5 mL/kg/h dialysate
61% 46% <0.001
Tolwani, 2008 200 Single center CRRT CVVHDF at 20 mL/kg/h CVVHDF at 35 mL/kg/h 60% 64% 0.56
Palevsky, 2008 1124 Multicenter IHD
PIRRT
CRRT
IHD and PIRRT with delivered Kt/V1.32 ± 0.37 delivered three times per week
CVVHDF at 20 mL/kg/h
IHD and PIRRT with delivered Kt/V of 1.31 ± 0.33 delivered six times per week
CVVHDF at 35 mL/kg/h
52% 54% 0.47
Bellomo, 2009 1508 Multicenter CRRT CVVHDF at 25 mL/kg/h CVVHDF at 40 mL/kg/h 45% 45% 0.99
Faulhaber-Walter, 2009 156 Single center PIRRT Target BUN 48–70 mg/dL Target BUN < 42 mg/dL 39% 44% 0.47

BUN, Blood urea nitrogen; CRRT, continuous renal replacement therapy; CVVH, continuous venovenous hemofiltration; CVVHDF, continuous venovenous hemodiafiltration; IHD, intermittent hemodialysis; PIRRT, prolonged intermittent renal replacement therapy; RRT, renal replacement therapy.


Intermittent Hemodialysis and Prolonged Intermittent Renal Replacement Therapy


The intensity of IHD and PIRRT is a function of both the dose of dialysis provided during each individual treatment and the frequency of treatments. In the chronic dialysis setting, the dose of small-solute clearance during treatment is usually quantified in terms of urea removal, using either formal urea kinetic modeling or approximated by regression equations incorporating fractional urea reduction and ultrafiltration. The standard parameter used to quantify dialysis dose in terms of the kinetics of urea clearance is the dimensionless term Kt/V, where K is the dialysis urea clearance, t is the duration of dialysis and V is the volume of distribution of urea. Calculation of Kt/V is based on the assumption that patients are in a relative steady state, with a stable rate of urea generation and renal and extrarenal urea clearance, and a relatively constant volume status with little variation in estimated dry weight and ultrafiltration volumes between treatments. During AKI, these assumptions are often violated; total body water and urea generation rates may vary widely over time in an individual patient, as may renal and extrarenal urea clearance. In the chronic dialysis setting, Kt/V is often based on single-pool variable volume models of urea distribution, although multiple compartment and equilibrated models may provide a more accurate assessment. In addition, assessment of Kt/V across modalities using differing schedules is complex, because it is not a simple arithmetic function. For example, reducing the delivered Kt/V per treatment by half while doubling the frequency of treatment (e.g., from every other day to daily hemodialysis) results in an increased effective weekly dose of therapy. As a result, various models have been developed to relate the dose of therapy delivered on different schedules, normalizing based on the peak predialysis urea concentration, the mean predialysis urea concentration, or the time-averaged urea concentration. None of these models have been rigorously validated in clinical practice. Despite these limitations, urea kinetics have been successfully used in the AKI setting and serve as the basis for clinical practice guidelines for IHD delivery in AKI.


There have been no prospective randomized controlled trials evaluating the optimal delivered dose of dialysis on a standard every other day or thrice weekly schedule. A single-center observational study performed more than two decades ago evaluated survival in 844 critically ill patients with AKI requiring RRT, 417 of whom received only IHD and another 242 who received a combination of IHD and CRRT. Although there was no correlation between the delivered dose of dialysis and outcomes among patients with either very low or very high severity of illness, delivery of a Kt/V > 1 per treatment three times per week was associated with better survival than a lower delivered dose of dialysis among patients with intermediate severity of illness. Thus in the absence of more robust data, it is generally suggested that when IHD is provided to patients with AKI on a three-times-per-week schedule that the dose per treatment be at least equivalent to the minimum accepted dose for a patient with ESRD.


The effect of increasing the frequency of IHD was assessed in a single-center study that assigned 160 critically ill patients in alternating order to daily or every-other-day IHD. Although the prescribed Kt/V was 1.2 per treatment, the delivered Kt/V was only 0.94 ± 0.11 per treatment in the alternate-day group and 0.92 ± 0.16 in the daily IHD group. All-cause mortality 14 days after the last IHD session was 28% in the daily treatment group compared with 46% in patients receiving alternate-day IHD ( P = 0.01) and the duration of IHD was 9 ± 2 days in the daily treatment arm compared with 16 ± 6 days in the alternate-day treatment arm. Although suggesting a benefit to more frequent dialysis, the low delivered dose of dialysis per treatment in the alternate-day arm may have been inadequate, resulting in a high rate of complications, including infection, gastrointestinal bleeding, and altered mental status. Thus, although more frequent IHD may improve clinical outcomes when the delivered dose of therapy is low, this study is not informative regarding the need for more frequent IHD when a higher delivered dose per treatment is achieved.


The Hanover Dialysis Outcome Study randomly assigned 148 critically ill patients with AKI to two different intensities of PIRRT: a standard-dose arm in which the target BUN level was 56 to 70 mg/dL or a more intensive strategy in which the frequency of treatment was increased to maintain the BUN level < 42 mg/dL. The more intensive strategy was not associated with either decreased mortality at 28 days (44.4% in the intensive arm vs. 38.7% in the less-intensive arm; P = 0.47) or improved recovery of kidney function (60% vs. 63%; P = 0.77).


The VA/NIH Acute Renal Failure Trial Network (ATN) study was a multicenter randomized controlled trial that compared strategies of more-intensive and less-intensive RRT in 1124 critically ill patients with AKI. Unlike the previously described trials, which restricted patients to a single modality of RRT, patients in the ATN study moved between modalities of RRT as their hemodynamic status changed, receiving IHD when hemodynamically stable and CRRT or PIRRT when hemodynamically unstable. In the more-intensive arm, IHD and PIRRT were provided 6 days per week and CRRT at an effluent flow rate of 35 mL/kg/h; in the less-intensive arm IHD and PIRRT were provided on a thrice weekly schedule and CRRT at an effluent flow rate of 20 mL/kg/h. The median delivered Kt/V during IHD was 1.3 per treatment in both study arms. More-intensive therapy was not associated with better outcomes (60-day mortality of 53.6% with more-intensive therapy vs. 51.5% with less-intensive therapy; P = 0.47) 16 with no difference between treatment arms when stratified by the percentage of time treated with IHD. Although there was no difference in recovery of kidney function overall, in the subset of patients who only received IHD, more-intensive therapy was associated with delayed time to recovery of kidney function.


Continuous Renal Replacement Therapy


During continuous hemofiltration, the concentration of urea and most non–protein-bound small solutes in the ultrafiltrate approximates that of plasma water. Similarly, during continuous hemodialysis, with blood flow rates much higher than dialysate flow rates, urea and other small solutes achieve near complete equilibration between blood and dialysate. Thus, during CRRT, so long as clotting or excessive protein layering is not contributing to membrane fouling, the clearance of urea and other low-molecular-weight solutes approximates effluent flow rate. Thus the dose of CRRT is generally expressed in terms of effluent flow rate normalized to body weight (Q E ). The daily delivered Kt/V can be estimated as Q E × 24/V urea , where V urea is the volume of distribution of urea. Approximating V urea as 600 mL/kg, the daily delivered Kt/V can be estimated as 0.04 × Q E . Thus at a continuous effluent flow of 20 mL/kg/h, the delivered Kt/V will be approximately 0.8 per day, and at 35 mL/kg/h, the delivered Kt/V will be approximately 1.4 per day.


A series of studies published between 2000 and 2009 evaluated the relationship between the delivered dose of CRRT and outcomes in critically ill patients. In the first of these studies, 425 patients at a single center were randomly assigned to CVVH at an effluent flow of 20, 35 or 45 mL/kg/h with postfilter infusion of replacement fluid. Individuals receiving CVVH at the two higher doses experienced lower mortality rates assessed 14 days after discontinuation of RRT than those receiving the lower dose of CVVH (42% and 43% vs. 59%; P < 0.005). In a subsequent single-center study, 206 critically ill patients with AKI were randomly assigned to receive CVVH, with a mean effluent flow of 25 ± 5 mL/kg/h, or CVVHDF delivered with a similar ultrafiltration rate (24 ± 6 mL/kg/h) augmented by the addition of dialysate flow (18 ± 5 mL/kg/h). Survival at both 28 days and 90 days was higher among patients who received augmented clearance with CVVHDF (90-day survival of 34% in the CVVH arm vs. 59% in the CVVHDF arm; P = 0.005). However, the benefits of higher doses of CRRT were not seen across all studies. In a two-center study of 106 patients assigned to early, HVHF (median 48.2 [interquartile ratio (IQR) 42.3 to 58.7] mL/kg/h), early low-volume hemofiltration (median 20.1 [IQR 17.5 to 22.0] mL/kg/h), or late low-volume hemofiltration (median 19.0 [IQR 16.6 to 21.1] mL/kg/h), the augmented dose of continuous hemofiltration was not associated with improved survival at 28 days (74.3% vs. 71.8%; P = 0.80). Similarly, in a single-center trial in which 200 critically ill patients with AKI were randomly assigned to CVVHDF with prefilter administration of replacement fluid at a total effluent flow of either 20 mL/kg/h or 35 mL/kg/h, survival to earlier of either ICU discharge or to day 30 was 49% in the higher-dose arm compared with 56% in the lower-dose arm (OR 0.75; 95% CI, 0.43 to 1.32; P = 0.32). The Randomized Evaluation of Normal Versus Augmented Level (RENAL) Replacement Therapy Study was a multicenter randomized controlled trial conducted at 35 intensive care units in Australia and New Zealand that randomly assigned 1508 patients to CVVHDF with postfilter administration of replacement fluid at a total effluent flow of either 25 mL/kg/h or 40 mL/kg/h. Overall mortality at 90 days was 44.7% in both treatment arms ( P = 0.99). Similarly, in the ATN study, no difference in survival was identified between the more-intensive strategy of RRT that used CVVHDF at 35 mL/kg/h and the less-intensive strategy that used CVVHDF at 20 mL/kg/h. Several studies have used even higher doses of CVVH, up to 70 mL/kg/h, in patients with sepsis-associated AKI without finding a benefit to more intensive CRRT.


Effect of Dose on Recovery of Kidney Function


Although recovery of kidney function was comparable between the more-intensive and less-intensive management strategies in each of the individual trials described earlier, more intensive RRT was associated with delayed recovery of kidney function in a patient-level metaanalysis pooling data from the majority of the individual studies. In a subgroup analysis, delayed recovery of kidney function was observed in patients initially managed using CRRT but not in patients initially managed using intermittent renal replacement therapy, although the latter finding may reflect the smaller number of intermittent dialysis patients included in the analysis. In a separate analysis of patients in the ATN study who were treated exclusively with IHD, six times per week dialysis was also associated with delayed recovery of kidney function. The reason for delay in recovery of kidney function is not understood. Although this may reflect the effect of more episodes of intradialytic hypotension among patients treated with more frequent IHD, intensity of therapy is not associated with hypotension during CRRT. More aggressive solute control may diminish the solute load and contribute to lower urine output associated with more intensive RRT, which may mask early recovery of kidney function.


Volume Management


Volume management needs to be considered as an independent aspect in the dosing of acute RRT. Fluid excess has been found to be independently associated with increased mortality in observational studies of AKI in both adult and pediatric populations, where fluid excess is defined as a percentage of premorbid weight. In the largest pediatric study the percentage fluid excess at dialysis initiation correlated with mortality risk, even after adjustment for severity of illness. Ultrafiltration must be tailored to individual patient needs, with a goal of reversing severe volume overload without causing intravascular volume depletion and hypotension, which might adversely affect recovery of kidney function.


Summary and Recommendations


Although the data from recent trials indicate that augmented intensity of RRT is not associated with clinical benefit in patients with AKI, these data should not be interpreted as demonstrating that the delivered dose of RRT does not matter. Although a minimum dose of RRT is not clearly established, using the data from these multiple trials, and drawing analogies to accepted minimum doses of RRT in ESRD, general recommendations regarding dosing can be made. Although these general recommendations apply to the vast majority of patients, individualization of treatment prescription for each patient is appropriate.


For patients receiving IHD, a thrice weekly treatment schedule is generally sufficient if an spKt/V urea of at least 1.2 per treatment (corresponding to a urea reduction ratio [URR] of ≥0.67) is achieved. In patients who are hypercatabolic, have severe electrolyte disturbances (e.g., hyperkalemia) or persistent metabolic acidosis, or have severe volume overload or require obligate administration of large volumes of fluids, a more frequent hemodialysis schedule may be necessary. In addition, treatment frequency may need to be increased if the targeted dose of therapy per treatment cannot be achieved. In patients receiving dialysis for AKI there may be a marked discrepancy between the prescribed and delivered dose of dialysis, with delivered Kt/V as much as 30% lower than prescribed as the result of hypotension, dialyzer clotting, and catheter dysfunction. Monitoring of the delivered dose of therapy is therefore necessary to ensure adequacy of treatment.


For patients being treated with CRRT, a total effluent flow of 20 to 25 mL/kg/h is generally appropriate; however, more intensive treatment may be required for patients who are very hypercatabolic or for control of electrolytes or acid–base status. As with IHD, the delivered dose of therapy may be less than prescribed as the result of system clotting and time off of therapy for diagnostic tests or surgical procedures. Thus a prescribed dose of 25 to 30 mL/kg/h may be necessary to achieve the target delivered dose.

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Feb 24, 2019 | Posted by in NEPHROLOGY | Comments Off on Renal Replacement Therapy for Acute Kidney Injury

Full access? Get Clinical Tree

Get Clinical Tree app for offline access