© Borgis - New Medicine 2/2010, s. 66-70
*László Medve1, Emil Préda1, Tibor Gondos2
Acute renal replacement therapy in the intensive care unit: theoretical foundations and terms
1Dr. Kenessey Albert Hospital, Department of Anaesthesiology and Intensive Care Medicine, Balassagyarmat
Head: Dr. Szabó Géza, General Director
2Semmelweis University, Faculty of Health Science, Department of Oxyology and Emergency Care, Budapest
Head: Prof. Dr. Mészáros Judit, Dean of Faculty
The incidence of acute renal failure (ARF) in intensive care units (ICUs) has been continuously on the rise over the years. In the current education system nurses do not receive adequate training to carry out RRT in the ICUs; therefore, in the following, we will provide an overview of the theoretical basics of ARF and will summarize the problems of current treatment modalities. The AKIN Working Group created the concept of acute kidney injury (AKI), replacing the nomenclature of ARF, and set the stages. Recent prospective studies have demonstrated that an early start of RRT is beneficial and increases the patient survival rate. Many factors can affect the completion of treatment and the modality of treatment. RRT needs a well equipped intensive care unit with a well trained staff. During the training process, it is worth for at least one or two specialists to spend a few weeks at a chronic dialysis station, and in an intensive care unit, where haemodialysis is routinely administered. After becoming familiar with the theoretical basis of RRT and after fulfilling the requirements for optimal treatment conditions, our department may begin the introduction and selection of optimal treatment modalities for renal replacement procedures. During the practical application of the chosen treatment method, we may still encounter problems.
The incidence of acute renal failure (ARF) in intensive care units (ICUs) has been continuously on the rise over the years (1, 2, 3, 4). This appears to be primarily related to the increasing number of patients with severe sepsis and multiple organ failure. There are no widely accepted guidelines when to begin the renal replacement therapy (RRT) in these cases; however, there is a consensus to start RRT immediately after early signs of ARF are recognized. There is a reasonable request for the ICUs to carry out RRT, because the technical background, with the new, mobile, easy to use equipment is readily available. In the current education system nurses do not receive adequate training to carry out RRT in the ICUs; therefore, in the following, we will provide an overview on the theoretical basics of ARF and will summarize the problems of current treatment modalities.
The most recent literature data suggest that 1-25% of patients admitted to ICUs have ARF and 72.4% of these patients need renal support therapy (5). Unfortunately, despite the rapidly improving intensive care, the mortality of patients admitted with ARF is still high (15-60%).
In recent years, expert groups have developed a uniform definition of ARF, and grading systems to evaluate its severity (RIFLE and AKIN criteria). These are adopted and used by many intensive care societies worldwide. Both RIFLE and AKIN criteria define ARF as renal impairment when there is a sudden kidney failure (within 48 hours) when the absolute increase of the serum creatinine level exceeds or is equal to 0.3 mg/dl (26.4 mmol/l), which is expressed as an increase of 50% of the baseline value; and the decrease of urine output by 0.5 ml/kg body weight/hour below the baseline value over a period of 6 hours. The criteria above include the level of serum creatinine, absolute and percentage changes, thus eliminating the age, gender, body mass index-related individual differences and the need for basic knowledge of creatinine value. However, this system assumes that at least two serum creatinine measurements are made within 48 hours (7).
Criteria for the classification of the degree of severity of ARF
The Acute Dialysis Quality Initiative (ADQI) at the 2002 Consensus Conference of Vicenza issued the RIFLE criteria to define ARF (5, 6). Evaluating diagnostic and prognostic usefulness of criteria is ongoing; it appears that the nomenclature and definitions are, in general, good, but they need refining. Efforts of refining the criteria resulted in an AKI-network consensus, which modified the RIFLE criteria. Therefore, from 2007 we are no longer talking about ARF, but acute renal impairment. Currently, several multicentre studies have demonstrated that the RIFLE (R = risk, I = injury, F = failure, L = loss, E = end-stage renal disease) classification is valid for assessment of the severity of ARF (tab. 1). The AKIN Working Group created the concept of acute kidney injury (AKI), replacing the nomenclature of ARF, and set the stages (tab. 2). From the point of view of routine practice, the RIFLE and AKIN criteria are almost the same; there are only three subtle differences.
Table 1. Risk, Injury, Failure, Loss, and End-stage Kidney (RIFLE) classification.
|Class||Glomerular filtration rate criteria||Urine output criteria|
|Risk||Serum creatinine × 1.5||< 0.5 ml/kg/hour × 6 hours|
|Injury||Serum creatinine × 2||< 0.5 ml/kg/hour × 12 hours|
|Failure||Serum creatinine × 3, or serum creatinine ≥ 4 mg/dl with an acute rise > 0.5 mg/dl||< 0.3 ml/kg/hour × 24 hours, or anuria × 12 hours|
|Loss||Persistent acute renal failure = complete loss of kidney function > 4 weeks|
|End-stage kidney disease||End-stage kidney disease > 3 months|
Table 2. Classification/staging system for acute kidney injurya.
|Stage||Serum creatinine criteria||Urine output criteria|
|1a||Increase in serum creatinine of more than or equal to 0.3 mg/dl (≥ 26.4 ?mol/l) or increase to more than or equal to 150% to 200% (1.5- to 2-fold) from baseline||Less than 0.5 ml/kg per hour for more than 6 hours|
|2b||Increase in serum creatinine to more than 200% to 300% (> 2- to 3-fold) from baseline||Less than 0.5 ml/kg per hour for more than 12 hours|
|3c||Increase in serum creatinine to more than 300% (> 3-fold) from baseline (or serum creatinine of more than or equal to 4.0 mg/dl (≥ 354 ?mol/l) with an acute increase of at least 0.5 mg/dl (44 ?mol/l))||Less than 0.3 ml/kg per hour for 24 hours or anuria for 12 hours|
|aModified from RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease) criteria. The staging system proposed is a highly sensitive interim staging system and is based on recent data indicating that a small change in serum creatinine influences outcome. Only one criterion (creatinine or urine output) has to be fulfilled to qualify for a stage.|
b200% to 300% increase = 2- to 3-fold increase.
cGiven wide variation in indications and timing of initiation of renal replacement therapy (RRT), individuals who receive RRT are considered to have met the criteria for stage 3 irrespective of the stage they are in at the time of RRT.
1. According to the AKIN, a slight increase in serum creatinine values is enough to define ARF.
2. AKIN introduced the time factor because the ARF diagnosis needs an elevated serum creatinine for at least 48 hours.
3. They eliminated the „loss and ESRD” category, because it represents the outcome of kidney disease and not the diagnosis.
Renal replacement indications for treatment of ARF
ARF may require RRT if the patient's glomerular filtration rate (GFR) decreases acutely and the level of toxic material increases significantly and/or there is a fluid overload. In practice, however, conventional indications for the treatment of ARF, the aetiology of which may be renal or non-renal, are accepted (tab. 3). When considering the indications, the rule of thumb is that the existence of one condition provides grounds for consideration of RRT, the presence of two conditions is a clear indication, and the presence of more indications means that RRT has to be initiated even before reaching pathological creatinine levels. The non-renal indication of continuous RRT is not yet sufficiently well established.
Table 3. Renal and non-renal indications of renal replacement therapy.
|RENALIS INDICATION||NON RENAL INDICATION|
|Non obstructív oliguria (urine < 200 mL/12 h) or anuria||Dialysing agent poisoning|
|Progressive azotemia, even without clinical signs (blood urea > 30 mmol/l or blood urea nitrogen > 100 mg ||Hiperthermia (core temperature > 39,5°C)|
|Metabolic acidosis, drug therapy refractory||The need of large quantities of blood in coagulation, in which there is pulmonary edema/ARDS risk|
|The existence of uremic organ symptoms: encephalopathy, myopathy, pericarditis, uremic bleeding diathesises|
|Hyperkalemia, drug therapy, refractory (plasma K +> 6.5 mmol/l or rapidly rising)|
|Progressive severe hyper/hyponatremia (Na +> 160 or <115 mmol/l)|
|Clinically significant organ edema, especially pulmonary edema|
|Intravascular fluid administration which is drug therapy refractory|
The timing of initiation of treatment
In the literature, there is a distinction between early and late start of RRT, taking serum urea, creatinine levels and urine output into consideration (8, 9). Recent prospective studies have demonstrated that an early start of RRT is beneficial and increases the patient survival rate. When considering the potential advantages of early initiation we should always consider the theoretical risk of hypotension, the threat of bleeding as a result of anti-coagulation as well as the mechanical and infectious complications of the central venous input.
The treatment dosage
Previous studies suggested that the increase in the volume of ultrafiltration improved patients' survival, but there were no differences in the improvement of renal function between the groups (18). A recently published multicentre study did not find evidence for this. High-dose haemofiltration did not reduce mortality. It failed to improve the return to good renal function and to reduce the number of multiple organ failures, compared to conventional-dose treatment (10). Another large multicentre study (RENAL study) confirmed these findings (11). Currently, ≥ 20 ml/kg/h is the recommended minimum dose in the case of continuous techniques and 1.2 Kt/V for the daily intermittent dialysis in the intensive care unit.
Timing of treatment completion
Many factors can affect the completion of treatment and the modality of treatment. This includes patient factors (e.g., haemodynamic stability, volume status, urine volume), and other factors (availability of personnel, cost, coagulation of extracorporeal circuit).
The concept of renal replacement therapy
RRT has two basic physical-chemical concepts that we need to be aware of: water and solute removal (12).
During RRT, water removal plays an important role in cleansing the blood from harmful substances (acids, uraemic toxins, potassium, etc.). This process is called ultrafiltration, which, under physiological conditions, takes place in the renal glomerulus. This requires the presence of a pressure regulator. If the regulatory pressure is higher than the oncotic pressure, liquid flow through the semipermeable membrane will occur. The difference between the regulatory pressure and the oncotic pressure is the transmembrane pressure (TMP).
For the removal of unwanted solute materials through the membrane, we need to create an electro-chemical gradient, which can be set up through the backflow of toxin-free dialysis solution. This process is called diffusion. The diffusion of solute through the membrane will continue until the concentration difference between the two sides of the membrane reaches the same value. This solute transport characterizes haemo- and peritoneal dialysis. The solute can be removed by ultrafiltration of the solvent, when the solvent and solute move together through the membrane. This phenomenon is called convective transport. Then the ultrafiltrate, which was removed, is replaced by a toxin-free substitution fluid. This process characterizes haemofiltration. TMP creates convective transport through the semipermeable membrane, when the small molecular weight materials are presented in equal concentration on both sides of the membrane, while the high molecular weight materials remain on the high-pressure side. The solute diffusion rate depends on the molecular weight, the porosity of the membrane, the blood flow, the dialysis fluid flow rate, the protein affinity and the concentration gradient between the two sides of the membrane (14). If we use standard low-flux, cellulose-based membranes (conventional dialysis techniques) the removal of medium molecular weight substances (>500 Da) is reduced. Using synthetic high-flux membranes (cut-off: 20-40 kDa), higher molecular weight materials may be removed (17).
RRT includes internal and external blood filtering methods: The internal way is peritoneal dialysis therapy, during which water and dissolved substances are transported through the peritoneal membrane using the oncotic and the osmotic concentration gradient functions. One of the external techniques is intermittent renal replacement therapy (IRRT) for up to 12 hours in duration, and includes the „extended daily dialysis” (EDD) and the „slow, low-efficiency dialysis” (SLED) treatment modalities. The other external blood filtering technique is continuous renal replacement therapy (CRRT), which can substitute renal function for 24 hours (15, 19, 20).
During haemodialysis we use dialysis solutions of different composition, flowing on the opposite side of the membrane against the blood, which accelerates the diffusion of dissolved substances in the haemofilter or ultrafilter of the haemodialysis unit and/or dialysate.
The fluid and dissolved substances removed during the haemofiltration can be replaced by administering general physiological solutions, which are used in large volumes to replace the ultrafiltrate. Pre-dilution or post-dilution methods may be applied. The pre-dilution liquid is pumped at the proximal end of the haemofilter, while the post-dilution fluid infusion is connected distally to the dialysis filter. With the pre-dilution method we can reach a higher ultrafiltration rate, by which the solute clearance can be increased, but it also increases the necessary amount of substitution solutions. Pre-dilution decreases the clearance of dissolved materials, when using a constant ultrafiltration rate, which is caused by the dilution of blood in the filter (16).
Renal replacement treatment conditions:
RRT needs a well equipped intensive care unit with a well trained staff (tab. 4-5). In a separate paper we discuss the practical issues regarding the different treatment modalities (13).
Table 4. Personal indications of renal replacement therapy.
|Renal replacement therapy personal indications||On call/shift|
? experienced physician in haemodialysis who can evaluate, and manage the haemodialysis process
? can prove his/her experience
? had taken an acredited haemodyalisis course
? has experience in heamodyalis
? is cannule punctures,is
|Intensive care nurse:|
? experienced ICU nurse, who has the ability to do the haemodialysis
? can prove his/her experience
? had taken an accredited hemodalysis course
? can administer by him/herself the fluid and extract the ultrafiltrate
? in case of complications can stop the process
? has experience in maneuvering dialysis cannules
Table 5. Renal replacement therapy technical indications.
|Renal replacement therapy technical indications||Piece|
|Multifunctional hemodialysis machine||1|
|? Hemodialysis cannules||5|
|? Circulation cartridge systems (arterial, venous -, ultrafiltering pipe systems, high flux membrane)||10|
|? Collector pouch||20|
|? Substitution fluid (5 l/per bag)||50|
During the training process, it is worth for at least one or two specialists to spend a few weeks at a chronic dialysis station, and in an intensive care unit, where haemodialysis is routinely administered. During the shifts there must be available all the time at least one specialist who is familiar with dialysis catheter insertion, haemodialysis device assembly, definition of treatment parameters and calibration of equipment and is capable of recognizing and treating possible complications, as well as regular closure of the treatment. All persons involved in the care of the patient need to know how to control treatment parameters, how to properly complete the treatment in urgent cases, and how to disconnect the dialysis catheter.
After becoming familiar with the theoretical basis of RRT and after fulfilling the requirements for optimal treatment conditions, our department may begin the introduction and selection of optimal treatment modalities for renal replacement procedures. However, during the practical application of the chosen treatment method, we may still encounter problems. In order to solve them we will need to learn from our experience during the acquisition, assessment and management of practical issues involving RRT.
1. Pisoni R, Wille KM, Tolwani AJ: The epidemiology of severe acute kidney injury: from BEST to PICARD, in acute kidney injury: new concepts. Nephron Clin Pract 2008; 109(4): 188-91. 2. Mehta RL et al.: Spectrum of acute renal failure in the intensive care unit: The PICARD experience. Kidney International 2004; 66: 1613-1621. 3. Uchino S et al.: Continuous renal replacement therapy: A worldwide practice survey. The Beginning and Ending Supportive Therapy for the Kidney (B.E.S.T. Kidney) Investigators. Intensive Care Med 2007; 33: 1563-1570. 4. Bagshaw SM, George C, Bellomo R: Early acute kidney injury and sepsis: a multicentre evaluation, Critical Care 2008; 12: R47. 5. Mehta RL et al.: for the Acute Kidney Injury Network, Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury, Critical Care 2007; 11: R31. 6. Hoste EAJ et al.: RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Critical Care, 2006; 10: R73. 7. Kellum JA, Bellomo R, Ronco C: Definition and classification of acute kidney injury. Nephron Clin Pract 2008; 109(4): c182-7. 8. Paul M Palevsky: Renal replacement therapy I: indications and timing. Critical Care Clinics 2005; 21(2): 347-356. 9. Gibney RT et al.: When should renal replacement therapy for acute kidney injury be initiated and discontinued? Blood Purif 2008; 26(5): 473-84. 10. The VA/NIH Acute Renal Failure Trial Network: Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury 2008; 359: 7-20. 11. Finfer S et al.: RENAL Study Investigators. The RENAL (Randomised Evaluation of Normal vs. Augmented Level of Replacement Therapy) study: statistical analysis plan. Crit Care Resusc 2009 11(1): 58-66. 12. Ronco C, Bellomo R: Basic mechanisms and definitions for continuous renal replacement therapies. Int J Artificial Organs 1996; 19: 95-99. 13. Medve L, Preda E, Gondos T: The practice of renal replacement therapy in the intensive care unit. 14. Brunet S et al.: Diffusive and convective solute clearances during continuous renal replacement therapy at various dialysate and ultrafiltration flow rates. Am J Kidney Dis 1999; 34: 486-492. 15. Pannun et al.: Renal Replacement Therapy in Patients With Acute Renal Failure. JAMA 2008; 299(7): 793-808. 16. Michael Joannidis1 and Heleen M Oudemans-van Straaten: Clinical review: Patency of the circuit in continuous renal replacement therapy, Critical Care 2007; 11: 218 (doi:10.1186/cc5937). 17. Locatelli F, Di Filippo S, Manzoni C: Removal of small and middle molecules by convective techniques. Nephrol Dial Transplant 2000; 15 (Suppl. 2): 37-44. 18. Mehta RL et al.: Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11: R31. 19. Paganini EP: Continuous replacement modalities in acute renal dysfunction. In: Paganini EP, ed. Acute continuous renal replacement therapy. Boston: Martinus Nijhoff 1986: 7-42. 20. Bellomo R, Ronco C, Mehta R: Nomenclature for continuous renal replacement therapies. Am J Kidney Dis 1996; 28: S2-S7.