Current version
Guideline 5 Acute Kidney Injury 19/06/2008 (FINAL with minor amendment as shown on left) (pdf 420kb)
Previous versions
Guideline 5 Acute Kidney Injury 08/04/2008 (FINAL) (pdf 420kb)
Guideline 5 Acute Kidney Injury 29/01/2008 (DRAFT) (pdf 668kb)
Final printed versions will be prepared with support from Kidney Research UK
Feedback
Please send comments to the lead authors listed adjacent, or comment on the Renal Association Discussion Board
Read All the Guidelines
The current version is shown below. Printable files for the current version as well as previous versions can be downloaded from the box to the right. The current version is the final version following a period for feedback. The amended version is not likely to be changed until the next formal revision in 2010.
Lead authors of this guideline were Dr Andrew Davenport, Dr Suren Kanagasundaram, Dr Andrew Lewington and Dr Paul Stevens.
Please send feedback to andrew.davenport@royalfree.nhs.uk and paul.stevens@ekht.nhs.uk or comment on the Renal Association Discussion Board
PLEASE NOTE
Guidelines 8.3 and 8.4 (including audit measures) have been updated on 19th June 2008 to take account of the ATN study results published in the NEJM 2008.
1. Definition and epidemiology (Guidelines 1.1- 1.2)
2. Assessment, prevention and pharmacological treatment (Guidelines 2.1- 2.10)
3. Treatment facilities and referral to renal services (Guidelines 3.1 – 3.4)
4. Choice of renal replacement modality (Guideline 4.1)
5. Choice of dialyser/haemofilter membrane and buffer (Guidelines 5.1 – 5.3)
6. Vascular access for RRT (Guidelines 6.1 – 6.6)
7. Anticoagulation for extracorporeal therapies (Guidelines 7.1 – 7.4)
8. Renal replacement therapy prescription (Guidelines 8.1 – 8.5)
9. Timing of initiation of renal replacement treatment (Guidelines 9.1 – 9.5)
10. Nutritional support (Guidelines 10.1 – 10.4)
(Audit measures 1-11)
1. Definition and epidemiology (Guidelines 1.1- 1.2)
2. Assessment, prevention and pharmacological treatment (Guidelines 2.1- 2.10)
3. Treatment facilities and referral to renal services (Guidelines 3.1 – 3.4)
4. Choice of renal replacement modality (Guideline 4.1)
5. Choice of dialyser/haemofilter membrane and buffer (Guidelines 5.1 – 5.3)
6. Vascular access for RRT (Guidelines 6.1 – 6.6)
7. Anticoagulation for extracorporeal therapies (Guidelines 7.1 – 7.4)
8. Renal replacement therapy prescription (Guidelines 8.1 – 8.5)
9. Timing of initiation of renal replacement treatment (Guidelines 9.1 – 9.5)
10. Nutritional support (Guidelines 10.1 – 10.4)
Evidence-based clinical practice guidelines for Acute Kidney Injury (AKI) have been hampered by the protean nature of the syndrome and by the many different definitions that have been used in the literature. To address this issue an independent collaborative network of international experts representing the majority of nephrology and intensive care societies worldwide established the Acute Kidney Injury Network (AKIN). The AKIN included representatives from the Acute Dialysis Quality Initiative (ADQI) group which previously devised the RIFLE staging system for AKI1. Following a series of meetings the AKIN has proposed that the term acute kidney injury (AKI) represent the entire spectrum of acute renal failure (and will therefore replace this term throughout this document)2,3. The AKIN has also proposed uniform standards for diagnosing and staging AKI (modified from the RIFLE staging system). It is hoped that these proposed standards will be universally adopted to allow their validation in future studies.
Acute kidney injury is a clinical syndrome characterised by a rapid reduction in renal excretory function underpinned by a variety of causes. Acute kidney injury is classically divided into pre-renal, renal (intrinsic) and post-renal (table) and the relative incidence of each of these is dependent on age, gender and clinical setting. Pre-renal AKI is functional and by definition not associated with any additional histopathological change. It is a consequence of decreased renal perfusion, which leads to a reduction in glomerular filtration rate (GFR). Just as AKI has replaced the term acute renal failure, volume responsive AKI has been suggested to replace the term pre-renal, as the key management issue is whether appropriate fluid resuscitation will improve or restore renal function. Intrinsic AKI occurs when there is damage (potentially reversible) to the structures of the nephron, such as the glomeruli, tubules, vessels, or interstitium. Post-renal AKI follows obstruction of the urinary collection system. The major cause of intrinsic AKI is acute tubular necrosis (ATN). This disorder is typically caused by ischaemic or nephrotoxic injury to the kidney, which can result from several distinct renal insults, often in combination with each other. Pre-renal AKI (volume responsive) and ischaemic ATN may occur as a continuum of the same pathophysiological process and together account for 75% of the causes of AKI4.
Early series describing AKI noted a predominance of surgical, obstetric and traumatic causes but in recent years the epidemiology of AKI in the UK has changed considerably with an increase in the age at presentation and a shift in predominant aetiologies to medical causes. The distinction between community- and hospital-acquired AKI is important for the differential diagnosis, treatment, and eventual outcome of patients with AKI. The reported prevalence of AKI from US data ranges from 1% (community-acquired) up to 7.1% (hospital-acquired) of all hospital admissions4,5. A clear understanding of the true incidence of AKI is dependent on the population being studied and the criteria used to define AKI. The population incidence from UK data ranges from 172 per million population (pmp) per year from early data6 up to 486-630 pmp/year from more recent series7-9, again depending on definition. The incidence of AKI requiring renal replacement therapy (RRT) ranged from 22 pmp/year6 up to 203 pmp/year8. An estimated 5–20% of critically ill patients experience an episode of AKI during the course of their illness and AKI requiring RRT has been reported in 4·9% of all admissions to intensive-care units10. Data from the Intensive Care National Audit Research Centre suggests that AKI accounts for nearly 10 percent of all ICU bed days11.
AKI is common in hospitalised patients and also has a poor prognosis. Non-ICU AKI, in which the kidney is usually the only failed organ, carries a mortality rate of up to 10%12,13. In contrast, ICU AKI is often associated with sepsis and with non-renal organ system failure14, with mortality rates of over 50%. These rates rise to 80% when RRT is required15. Predictably, death rates increase with an increasing number of failing organ systems but over 65% of survivors recover renal function and discontinue RRT1. AKI is not just a reflection of co-existent pathologies but contributes, directly, to mortality16-18, possibly associated with an increased risk of “non-renal” complications such as bleeding and sepsis17.
Causes of acute kidney injury
Pre-renal
(volume responsive)
Intrinsic
Post-renal
Hypovolaemia
· Vomiting and diarrhoea
· haemorrhage
Decrease in effective circulating volume
· cardiac failure
· septic shock
· cirrhosis
Drugs
· ACE inhibitors
Glomerular
· Glomerulonephritis
Glomerular endothelium
· vasculitis
· HUS
· malignant hypertension
Tubular
· acute tubular necrosis
· rhabdomyolysis
· myeloma
Interstitial
· interstitial nephritis
Obstruction
· renal calculi
· retroperitoneal fibrosis
· prostatic hypertrophy
· carcinoma
· cervical carcinoma
· urethral stricture
· bladder neoplasm
· pelvic neoplasm
· retroperitoneal neoplasm
1. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, and the ADQI workgroup. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs. The second international consensus conference of Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8: R204-R212
2. Mehta RL, Kellum JA, Shah SV, et al. 2007. Acute Kidney Injury Network (AKIN): report of an initiative to improve outcomes in acute kidney injury. Critical care, 11, R 31
3. Molitoris BA, Levin A, Warnock D, et al. Improving outcomes of acute kidney injury: report of an initiative. Nat Clin Pract Nephrol 2007; 3 (8): 439-442
4. Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis 2002; 39: 930–936
5. Kaufman J, Dhakal M, Patel B, et al. Community-acquired acute renal failure. Am J Kidney Dis 1991; 17: 191-198
6. Feest TG, Round A, Hamad S. Incidence of severe acute renal failure in adults: results of a living community based study. BMJ 1993;306: 481–483.
7. Stevens PE, Tamimi NA, Al Hasani MK, et al. Non-specialist management of acute renal failure. QJM 2001; 94: 533–540.
8. Metcalfe W, Simpson KM, Khan IH, et al. Acute renal failure requiring renal replacement therapy: incidence and outcome. QJM 2002; 95: 579–583.
9. Hegarty J, Middleton R, Krebs M et al. Severe acute renal failure. Place of care, incidence and outcomes. QJM 2005; 98: 661-666
10. Metnitz PGH, Krenn CG, Steltzer H, et al. Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med 2002; 30: 2051–2058.
11. Intensive-Care National Audit Research Centre 2005 www.icnarc.org
12. Hou SH, Bushinsky DA, Wish JB, Cohen JJ, Harrington JT. Hospital-acquired renal insufficiency: a prospective study. Am J Med 1983; 74:243-8
13. Shusterman N, Strom BL, Murray TG, Morrison G, West SL, Maislin G. Risk factors and outcome of hospital-acquired acute renal failure. Clinical epidemiologic study. American Journal of Medicine 1987; 83:65-71
14. Liaño F, Junco E, Pascual J, Madero R, Verde E. The spectrum of acute renal failure in the intensive care unit compared with that seen in other settings. The Madrid Acute Renal Failure Study Group. Kidney International 1998; 53:S16-24
15. Cosentino F, Chaff C, Piedmonte M. Risk factors influencing survival in ICU acute renal failure. Nephrology, Dialysis, Transplantation 1994; 9:179-82
16. Chertow GM, Levy EM, Hammermeister KE, et al.: Independent association between acute renal failure and mortality following cardiac surgery. American Journal of Medicine 104:343-348, 1998
17. Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality: a cohort analysis. JAMA 1996; 275: 1489-1494
18. Uchino S, Bellomo R, Goldsmith D et al. An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Critical Care Medicine 2006; 34:1913-1917
Guideline 1.1 – AKI : Definition and Epidemiology
An internationally accepted and agreed uniform definition of acute kidney injury (AKI) should be adopted to enable comparisons of incidence and outcomes, assess the utility of severity of illness scoring systems, and interpret the efficacy of therapeutic interventions
Guideline 1.2 – AKI : Definition and Epidemiology
Serum creatinine and urine output should continue to be viewed as the best existing markers for AKI.
Guideline 2.1 – AKI : Assessment, Prevention & Pharmacological Treatment
Patients at risk of AKI should be identified in the community and the hospital.Risk factors should be identified and preventative measures instituted as early aspossible. Prescription of appropriate intravenous fluids should be carefullyconsidered following assessment of the patient's volume status.
Guideline 2.2 – AKI : Assessment, Prevention & Pharmacological Treatment
Undergraduate and postgraduate medical trainees should be taught theprinciples of prevention and treatment of AKI.
Guideline 2.3 – AKI : Assessment, Prevention & Pharmacological Treatment
All patients presenting with AKI should as a minimum have an adequate history, examination and initial assessment to determine the likelihood of whether their AKI is pre-renal, renal or post-renal in nature. This should encompass relevant past history, social and treatment history; assessment of volume status; reagent strip urinalysis and an assessment of renal morphology and presence or absence of obstruction where indicated.
Guideline 2.4 – AKI : Assessment, Prevention & Pharmacological Treatment
All patients presenting with AKI should have reagent strip urinalysis performed supplemented with urine microscopy where indicated
Guideline 2.5 – AKI : Assessment, Prevention & Pharmacological Treatment
Urine biochemistry is of limited value in the assessment of patients presenting with AKI and need not be routinely performed.
Guideline 2.6 – AKI : Assessment, Prevention & Pharmacological Treatment
All patients undergoing contrast media examinations who are at risk from AKI should have adequate precautions undertaken. These should include temporary discontinuation of diuretics and ACEI/ARBs unless contraindicated, temporary discontinuation of Metformin and NSAIDs, consideration of iso-osmolar contrast agents and administration of prophylactic pre-procedure treatment with intravenous isotonic sodium bicarbonate or 0.9% sodium chloride.
Guideline 2.7 – AKI : Assessment, Prevention & Pharmacological Treatment
Loop diuretics and dopaminergic agents should not be routinely used for the prevention and treatment of AKI.
Guideline 2.8 – AKI : Assessment, Prevention & Pharmacological Treatment
There is little clinical data to support the use of mannitol to prevent AKI secondary to rhabdomyolysis.
Guideline 2.9 – AKI : Assessment, Prevention & Pharmacological Treatment
Pharmacological therapy currently has no role to play in the treatment of AKI.
Guideline 2.10 – AKI : Assessment, Prevention & Pharmacological Treatment
Therapeutic drug dosing must be adapted to altered kinetics in AKI.
Guideline 3.1 – AKI : Treatment facilities & referral to renal services
The critical care nephrology interface should be defined at each locality to ensure timely and appropriate placement of patients with AKI according to their clinical condition. Local critical care networks should be utilised to facilitate this process.
Guideline 3.2 – AKI : Treatment facilities & referral to renal services
Appropriate transfer and triage of AKI patients from the non-specialist, non-critical care ward to the renal unit should be facilitated through the development of local guidelines and transfer protocols.
Guideline 3.3 – AKI : Treatment facilities & referral to renal services
Renal units should be equipped to provide level 2 care for patients with severe AKI (AKI stage 3 or AKI requiring RRT) or do so in conjunction with critical care services.
Guideline 3.4 – AKI : Treatment facilities & referral to renal services
Nephrologists and intensivists should work together to provide care for patients with AKI on the ICU. Nephrology trainees should be trained to care for critically ill patients with AKI.
Guideline 3.5 – AKI : Treatment facilities & referral to renal services
Patients with persistent renal impairment after AKI who do not require long term RRT should be managed according to local CKD practice.
Guideline 4.1 – AKI : Choice of renal replacement therapy modality
Choice of RRT modality should be guided by the individual patient’s clinical status, medical and nursing expertise, and availability of modality.
Guideline 5.1 – AKI : Choice of dialyser/haemofilter membrane
Choice of haemodialysis/haemofiltration membrane should be dictated by RRT modality.
Guideline 5.2 – AKI : Choice of dialyser/haemofilter membrane
Synthetic or modified cellulosic membranes should be used in preference to unmodified cellulose.
Guideline 5.3 – AKI : Choice of dialysate/replacement fluid
Bicarbonate should be the preferred buffer for dialysate and replacement fluid in CRRT techniques unless regional citrate anticoagulation is employed.
Guideline 6.1 – AKI : Vascular access for RRT
Acute access for renal replacement therapy should be veno-venous rather than arterio-venous.
Guideline 6.2 – AKI : Vascular access for RRT
Dialysis catheters should be of an adequate length to minimise the risks of access recirculation.
Guideline 6.3 – AKI : Vascular access for RRT
The access site and catheter type should be chosen with regard to the phase of the patient’s illness and be changed at appropriate intervals to minimise the risk of infection.
Guideline 6.4 – AKI : Vascular access for RRT
Access should be placed by experienced or appropriately supervised staff. Real-time ultrasound guidance should be used to aid placement of upper body access. It is advisable that real-time ultrasound guidance be used for the insertion of femoral access.
Guideline 6.5 – AKI : Vascular access for RRT
In patients at risk of progressing to CKD stage 4 or 5, subclavian access should be avoided due to the risks of compromising future, permanent vascular access. Upper limb vasculature should be preserved as a contingency for future permanent access.
Guideline 6.6 – AKI : Vascular access for RRT
Local policies on prevention of catheter-related infection should be optimised by reserving the catheter for extracorporeal treatment only.
Guideline 7.1 – AKI : Anticoagulation for extracorporeal therapies
Anticoagulation for RRT should be tailored according to patient characteristics and the modality of RRT chosen.
Guideline 7.2 – AKI : Anticoagulation for extracorporeal therapies
Regional anticoagulation with citrate reduces risk of haemorrhage compared to systemic heparinisation. The complexity of the technique means that this should be in routine use on any unit on which it is employed in order to allow sufficient levels of expertise to be maintained.
Guideline 7.3 – AKI : Anticoagulation for extracorporeal therapies
Prostacyclin is a suitable alternative to unfractionated heparin for those at increased risk of bleeding, but may cause haemodynamic instability.
Guideline 7.4 – AKI : Anticoagulation for extracorporeal therapies
In CRRT patients at highest risk of bleeding, and in intermittent therapies, a no-anticoagulation, saline flush strategy can be used. However, ultrafiltration requirements are increased, effective intermittent HD time is reduced and the technique runs the risk of membrane fibre rupture.
Guideline 8.1 – AKI : Renal Replacement Therapy prescription
The delivered dose of RRT should be assessed to ensure the adequacy of the prescription.
Guideline 8.2 – AKI : Renal Replacement Therapy prescription
The prescribed dose should be assessed at each session (for intermittent haemodialysis) and daily (for continuous techniques) to account for any measured shortfalls in delivered dose.
Guideline 8.3 – AKI : Renal Replacement Therapy prescription
Patients with AKI and multi-organ failure treated by CRRT should receive treatment doses equivalent to ultrafiltration rates ≥ 20 ml/kg/hr. A proportionate upward adjustment to the prescribed ultrafiltration rate should be made in pre-dilutional continuous haemofiltration.
Guideline 8.4 – AKI : Renal Replacement Therapy prescription
Patients with AKI and multi-organ failure treated by intermittent haemodialysis should receive either alternate day haemodialysis with at least the minimum dose considered appropriate for ESRD (URR>65% or eKt/V>1.2) or daily haemodialysis.
Guideline 8.5 – AKI : Renal Replacement Therapy prescription
RRT dosing methods that require an assessment of patient weight should be performed with an actual, measured weight rather than an extrapolation from pre-morbid readings.
Guideline 9.1 – AKI : Timing of initiation of renal replacement treatment
The decision to start RRT in patients with AKI should remain a clinical decision based on fluid, electrolyte and metabolic status of each individual patient.
Guideline 9.2 – AKI : Timing of initiation of renal replacement treatment
RRT should be initiated once AKI is established and unavoidable but before overt complications have developed.
Guideline 9.3 – AKI : Timing of initiation of renal replacement treatment
The threshold for initiating RRT should be lowered when AKI occurs as part of multi-organ failure.
Guideline 9.4 – AKI : Timing of initiation of renal replacement treatment
The initiation of RRT may be deferred if the underlying clinical condition is improving and there are early signs of renal recovery.
Guideline 9.5 – AKI : Timing of discontinuation of renal replacement treatment
An improvement in the clinical condition and urine output would justify temporary discontinuation of ongoing renal support to see if AKI is recovering.
Guideline 10.1 – AKI : Nutritional support
Nutritional support for patients with AKI must take into account not only the specific metabolic disturbances associated with the kidney injury and the underlying disease process but also the treatment modality employed.
Guideline 10.2 – AKI : Nutritional support
Enteral nutrition, wherever possible, is the recommended form of nutritional support for patients with AKI.
Guideline 10.3 – AKI : Nutritional support
Referral to a dietician for individual assessment is recommended as nutrient requirements for patients will vary considerably dependent upon the course of the AKI, underlying disease and need for RRT.
Guideline 10.4 – AKI : Nutritional support
Patients with AKI should receive 25-35 kcal/kg/day and up to a maximum of 1.7g amino acids/kg/day if hypercatabolic and receiving CRRT. Trace elements and water soluble vitamins should be supplemented as required.
1. Incidence and outcome of AKI stage 3 subdivided into
2. Proportion of patients developing AKI stage 3, who had renal ultrasound examination < 24 hrs after admission or in-patient referral
3. Proportion of patients presenting with AKI in whom reagent strip urinalysis and urine microscopy are recorded (unless anuric)
4. Proportion of CKD (stages 4/5 eGFR ≤30 ml/min) patients developing contrast media-associated AKI not given hypo-osmolar contrast media, and appropriate prophylactic pre-procedure treatment with sodium containing fluid
5. Proportion of patients with single organ failure requiring RRT in a level 3 bed
6. Proportion of catheters inserted under real time ultrasound guidance
7. Incidence of catheter-related bacteraemia and sepsis
8. Incidence of heparin induced thrombocytopenia
9. Proportion of patients treated by alternate day haemodialysis who receive Kt/V ≥1.2 per session
10. Proportion of patients with AKI-3 reviewed by dietician within 48 hours
11. Proportion of patients with AKI-3 receiving < 70% prescribed nutrition
Many of these audit measures are more suitable for local audit than national audit conducted by the UK Renal Registry.
Guideline 1.1 – AKI : Definition & Epidemiology
An internationally accepted and agreed uniform definition of acute kidney injury (AKI) should be adopted to enable comparisons of incidence and outcomes, assess the utility of severity of illness scoring systems, and interpret the efficacy of therapeutic interventions
Audit measure
1. Incidence and outcome of AKI stage 3 subdivided into:
Rationale
There are still deficiencies in our knowledge and much of what we do is based on consensus and anecdotal practice, rather than high quality evidence. This situation has been partly engendered by the lack of a uniform definition of AKI. Some series in the literature have used dialysis dependence, others arbitrary levels of serum creatinine, or combinations of both, subdivided or not subdivided into oliguric and non-oliguric AKI. In clinical practice, AKI is classified according to changes in serum and/or urinary biomarkers and urine output.
More recently it has been recognised that smaller changes in serum creatinine than those initially considered in the RIFLE staging criteria developed by the ADQI might be associated with adverse outcomes1. The AKIN has therefore modified the RIFLE criteria to reflect this in the AKI staging system (table 2). Acute kidney injury stage 1 which maps to the Risk category of RIFLE now includes an absolute rise in serum creatinine as part of the criteria. The AKI stage 2 and 3 map to the Injury and Failure categories of RIFLE respectively. The Loss and ESKD (end-stage kidney disease) categories of RIFLE have been removed from the AKI staging system but remain as outcomes.
The AKIN has provided the following diagnostic criteria for AKI: An abrupt (within 48 hours) reduction in kidney function currently defined as an absolute increase in serum creatinine of either ≥ 26.4µmol/L or a percentage increase ≥ 50% (1.5 fold from baseline) or a reduction in urine output (documented oliguria of <0.5 mL/kg/h for > 6 hours).
These diagnostic criteria include both an absolute and a percentage change in creatinine to accommodate variations related to age, gender, body mass index and reduces the need for a baseline creatinine. As changes in volume status influence serum creatinine levels the diagnostic criteria should be used in the context of clinical presentation and following adequate fluid resuscitation. It is recognised that accurate measurement of urine output may not be routine outside of the intensive care unit (ICU). Urine output may be influenced by the use of diuretics or the presence of urinary tract obstruction, which must be excluded. However a reduction in urine output is a sensitive indicator of renal dysfunction and often precedes a rise in serum creatinine in critically ill patients. The proposed diagnostic criteria for AKI aim to increase clinical awareness of the condition and allow the potential for preventative strategies to minimise further kidney injury.
Acute Kidney Injury Network staging system for AKI
AKIN stage
Serum Creatinine criteria
Urine output criteria
1
SCr ≥ 26.4 µmol/L
or
SCr ≥ 150-200% (1.5-2 fold) from baseline
< 0.5 mL/kg/hr for > 6 hr
2
SCr > 200 - 300 % (>2-3 fold) from baseline
< 0.5 mL/kg/hr for >12 hr
3
SCr > 300 % (>3 fold) from baseline
or
SCr ≥ 354 µmol/L with an acute rise of ≥ 44 µmol/L in ≤ 24 hr
or
initiated on RRT (irrespective of stage at time of initiation)
< 0.3 mL/kg/hr for 24 hr
or
anuria for 12 hr
Note: Changes in serum creatinine or urine output occurring within a 48 hour time period. SCr denotes serum creatinine and RRT denotes renal replacement therapy
Only one criterion (serum creatinine or urine output) needs to be fulfilled to qualify for a stage.
References
1. Praught ML, Shlipak MG. Are small changes in serum creatinine and important risk factor? Current Opinions in Nephrology and Hypertension 2005; 14, 265-270
Guideline 1.2 – AKI : Definition & Epidemiology
Serum creatinine and urine output should continue to be viewed as the best existing markers for AKI.
Rationale
There are inherent problems in using serum creatinine as a marker of GFR in a dynamic state of changing renal function1. Creatinine concentration depends not only on urinary clearance of creatinine but also on the rate of production and the volume of distribution. Nevertheless, creatinine measurements are readily available and cheap. However in clinical practice, pre-existing baseline results may not always be available, and similar baseline values do not always reflect similar renal function due to variations in underlying renal reserve, muscle bulk and in hydration status. Creatinine measurements can also be affected by the clinical scenario (table 3), by the presence of chromogenic substances, including bilirubin, and by the laboratory assay utilised. The AKIN staging systems also use urine output because urine output, although less specific, is more sensitive to changes in renal function than biochemical markers. It is recognised as an important predictor of mortality from AKI.
There is clearly a need to find better, alternative bio-markers to creatinine. Serum and/or urinary biomarkers currently being researched include Kidney Injury Molecule-1 (KIM-1), IL-18, and neutrophil gelatinase-associated lipocalin (NGAL)2-5. All of these markers predict AKI well before changes in serum creatinine. Serum cystatin C has also been advocated for assessment of renal function in AKI6, as its generation is less variable between individuals than creatinine, and rapid fully automated immunonephelometric assays are now available. Although it is now recognized that cystatin C may be affected by age, sex, body habitus, smoking status, proteinuric states, chronic liver disease, malignancy, C reactive protein, renal transplantation, thyroid disease, and some drugs, including steroids and chemotherapy, daily changes in serum cystatin C concentration predict progression to RIFLE stage F (AKI stage 3) earlier than corresponding serum creatinine measurements6. However cystatin C measurements, as with other current AKI biomarkers, do not predict RRT requirement. Neither do they identify those destined to recover kidney function with conservative support alone.
Causes of alterations in serum urea and creatinine measurements
Alteration
Cause
Serum urea
Increased
cardiac failure
dehydration
gastrointestinal haemorrhage
severe burns
systemic sepsis
tumour lysis
haematoma
hyperalimentation
steroid therapy
Decreased
liver disease
starvation
pregnancy
Serum creatinine
Increased
rhabdomyolysis
hypothyroidism
African ethnicity
cephalosporins (infants)
trimethoprim
cimetidine
unconjugated bilirubin
Reduced
muscle wasting
amputation
chronic organ disease
liver disease
obesity
vegetarian diet
infants/young children
elderly
References
1. Bellomo R, Kellum JA, Ronoc C. Defining acute renal failure: physiological principles. Intensive Care Med 2004; 30:33-37
2. Hewitt SM, Dear J, Star RA. Discovery of protein biomarkers for renal diseases
J Am Soc Nephrol. 2004;15(7):1677 - 1689
3. Vaidya VS, Ramirez V, Ichimura T, Bobadilla NA, Bonventre JV. Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol 2006; 290(2): F517 - F529
4. Parikh CR, Mishra J, Thiessen-Philbrook H, Dursun B, Ma Q, Kelly C, Dent C, Devarajan P, Edelstein CL. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int 2006; 70: 199-203
5. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P. Identification of Neutrophil Gelatinase-Associated Lipocalin as a Novel Early Urinary Biomarker for Ischemic Renal Injury. J Am Soc Nephrol 2003; 14:2534-2543
6. Herget-Rosenthal S, Marggraf G, Husing J, Goring F, Pietruck F, Janssen O, Philipp T, Kribben A. Early detection of acute renal failure by serum cystatin C. Kidney Int 2004; 66: 1115-1122
Guideline 2.1 – AKI : Assessment, Prevention & Pharmacological Treatment
Patients at risk of AKI should be identified in the community and the hospital. Risk factors should be identified and preventative measures instituted as early as possible. Prescription of appropriate intravenous fluids should be carefully considered following assessment of the patient's volume status.
Rationale
Published series of AKI suggest that up to 30% of cases may be preventable, with a further significant percentage potentially remediable through simple interventions such as volume repletion, discontinuing and/or avoiding certain potentially nephrotoxic agents, and earlier recognition of conditions causing rapid progression of AKI .1-3
Risk factors for patients developing AKI include pre-existing chronic kidney disease (CKD), older age (> 60 years old), sepsis, cardiac failure, liver disease, diabetes mellitus, nephrotoxic medication particularly in the setting of hypovolaemia. In the community clinical suspicion may be aroused in the patient with risk factors that develops fever, vomiting, diarrhoea, urinary tract symptoms or signs of hypovolaemia. This should trigger further investigation and appropriate treatment or referral.
In the hospital AKI following surgery is an important contributor to postoperative morbidity and mortality. The causes are multifactorial and therefore involve the identification of the high risk patients and institution of preventative measures. Avoidance of pre- and peri-operative hypovolaemia is an essential component of patient management.
Prescription of intravenous fluid should follow a careful assessment of patient volume status i.e. hypovolaemic, euvolaemic, hypervolaemic. Accurate clinical assessment of patient volume status remains a significant challenge for medical practitioners. Consideration should then be made regarding the nature of the fluid lost and therefore the nature of the fluid that needs to be replaced. There is no evidence base to favour the prescription of crystalloid or colloids to protect renal function in the peri-operative period, although there have only been a handful of studies looking at this4. Following the selection of the appropriate fluid the rate of fluid replacement must be guided by clinical assessment with consideration for safety limits. The patient's volume status must be continually monitored and a decision made regarding when to stop intravenous fluids.
It is important to recognise that the daily sodium intake in health is between 70 and 100 mmol/day. Following surgery the body's physiological response is to retain sodium and water. The selection of the type of fluid to be prescribed is important as excessive peri-operative fluid therapy with 0.9% sodium chloride (Na 154mmol/l, Cl 154mmol/l) can potentially lead to sodium, chloride and water overload which contributes to postoperative morbidity and mortality5 whereas excessive peri-operative fluid replacement with 5% dextrose will increase the risk of developing hyponatraemia.
Fluid replacement prescriptions should be tailored to the needs of the patient. Potassium containing solutions (Hartmann's and Ringer's Lactate) should be used cautiously in patients who develop AKI, due to the potential risk of exacerbating hyperkalaemia.
1. Stevens PE, Tamimi NA, Al Hasani MK, et al. Non-specialist management of acute renal failure. QJM 2001; 94: 533–540
2. Vijayan A, Miller SB. Acute renal failure: prevention and nondialytic therapy. Semin Nephrol 1998; 18:523-532
3. Davidman M, Olson P, Kohen J, Leither T, Kjellstrand C. Iatrogenic renal disease. Arch Intern Med 1991; 151:1809-1812
4. Zacharias M, Gilmore ICS, Herbison GP et al. Interventions for protecting renal function in the perioperative period (Review). Cochrane Database of Systematic Reviews 2005; Issue 3, CD003590
5. Lobo DN, Macafee DAL, Allison SP. How perioperative fluid balance influences post-operative and outcomes. Best Practice and Research Clinical Anaesthesiology 2006; 20 (3), 439-455
Guideline 2.2 – AKI : Assessment, Prevention & Pharmacological Treatment
Undergraduate and postgraduate medical trainees should be taught the principles of prevention and treatment of AKI.
AKI may be encountered in all branches of medicine and the opportunity to teach trainees should be embraced by Nephrologists. The assessment, prevention and treatment of AKI should be an essential module in undergraduate and postgraduate medical training.
Guideline 2.3 – AKI : Assessment, Prevention & Pharmacological Treatment
All patients presenting with AKI should as a minimum have an adequate history, examination and initial assessment to determine the likelihood of whether their AKI is pre-renal, renal or post-renal in nature. This should encompass relevant past history, social and treatment history; assessment of volume status; reagent strip urinalysis; and an assessment of renal morphology and presence or absence of obstruction where indicated.
Audit measure
Rationale
AKI is most frequently caused by an ischaemic or nephrotoxic insult to the kidney; a small percentage of cases may be caused by acute interstitial nephritis or acute glomerulonephritis1. In patients with hospital-acquired AKI the cause is frequently multi-factorial with multiple risk factors. Assessment of the patient with AKI therefore starts with a careful history and examination, including a thorough evaluation of the patient's notes and drug treatment records where available. Any evidence of previous CKD should be sought from either previous hospital attendances/admissions or the patient's GP. A focused history must identify pre-existing risk factors and potential causes for AKI including reduced fluid intake and/or increased fluid losses, urinary tract symptoms and recent drug ingestion. AKI secondary to systemic disease may be associated with other clinical features such as fever, rash and joint pains. Clinical examination must include assessment of volume status which is guided by clinical signs including core temperature, peripheral perfusion, heart rate, blood pressure and jugular venous pressure. The presence of renovascular disease may be suspected if there are audible bruits and impalpable peripheral pulses. The abdomen must be examined carefully for the presence of a palpable bladder. An underlying vasculitis or interstitial nephritis may be suspected if there is a rash. A baseline set of laboratory investigations should be sent including urinalysis, biochemistry, haematology and microbiology (urine culture ± blood culture) with more specific renal investigations being dependent upon the clinical presentation Further investigations may include ECG, chest x-ray, abdominal x-ray and renal tract ultrasound (see below). A diagnosis may often be made after clinical evaluation, assessment of volume status and simple urinalysis, supplemented by renal imaging - but not if these very basic assessments do not take place.
In the majority of cases AKI can be effectively treated and resolved by adequate volume replacement, treatment of the underlying medical condition (e.g. sepsis, haemorrhage) and avoidance of nephrotoxic medications. In the critically ill patient fluid replacement is best achieved through the rapid infusion of repeated small volumes (250 ml of crystalloid or colloid) and close monitoring using a CVP line and urinary tract catheter. Lactate and base excess measurements may also be helpful in conjunction with clinical judgment in assessing response to volume loading. The variation in cardiac output during the respiratory cycle falls as patients become optimally filled2. With respect to the use of colloids it should be acknowledged that there have been earlier reports regarding the use of high molecular weight hydroxy ethyl starch and an increased risk of AKI3,4. The multi-centre German trial, Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis Trial (VISEP), reported a significantly higher incidence of AKI in patients receiving 10% hydroxyethyl starch compared to Ringer’s lactate5,6. It is therefore probably prudent to recommend that high molecular weight hydroxyethyl starches be used cautiously in patients who are at risk of developing AKI. The French equivalent of the UK Blood Transfusion service recommends an upper limit on the volume of starch solutions used in resuscitation of patients7. A large well controlled prospective study is needed to conclusively prove the safety of administering hydroxyethyl starch on a daily basis in this patient group.
Bladder catheterisation is not essential in all cases of AKI but it does enable measurement of hourly urine output and total urine volume. Strict attention to asepsis should be paid in those who are catheterised. If the patient develops oligo-anuria the catheter should be removed to reduce the risk of infection. Urine volume may not be diagnostic, particularly when diuretics have already been administered, but it is nevertheless important to quantify. Oliguric AKI is associated with a poorer prognosis and knowledge of urine volume is part of fluid balance management in any critically ill patient.
As part of the usual stress response to surgery there is an increased secretion of antidiuretic hormone (ADH) and an up regulation of the renin-angiotensin-aldosterone system resulting in avid salt and water retention8. In this setting the urine output is dependent upon the amount of solute delivered to the kidney for excretion. The amount of solute delivered is directly proportional to the rate of endogenous protein breakdown. In a starved postoperative patient the rate of endogenous protein breakdown is reduced and therefore the urine output is decreased. In addition there is a loss of the kidney’s concentrating ability such that 800 to 1200ml (twice the usual volume) of urine may be required to excrete the daily endogenous solute load. As a consequence there is decreased urine output and free water clearance in the first 12-24 hours following surgery9. It is therefore questionable as to how useful measurements of urine output, free water clearance and fractional excretion of sodium are as measures of renal function in the immediate post operative period. It has been reported that there is no association between a urine output per se and the development of AKI provided that the patient is not hypovolaemic10.
Lower urinary tract obstruction may also be diagnosed by the finding of a significant post-micturition residual bladder volume, easily measured and treated by placing a catheter in the bladder. Alternatively lower urinary tract obstruction may be diagnosed non-invasively by ultrasound, which is also the gold standard test for diagnosis of upper tract obstruction through the finding of hydronephrosis and/or hydroureter. However it must be remembered that upper urinary tract obstruction may not be initially detected by ultrasound in a patient who is volume depleted. It is therefore recommended to repeat the renal tract ultrasound if upper urinary tract obstruction is suspected once the patient is adequately fluid resuscitated. There are other circumstances when ultrasound may not be diagnostic, such as in retroperitoneal fibrosis or early in the course of obstructive disease, in which case additional imaging studies may be considered such as dynamic nuclear medicine studies or CT. Dynamic nuclear medicine studies will be of little diagnostic use if the patient has oligo-anuric AKI.
1. Liaño F, Pascual J, and the Madrid Acute Renal Failure Study Group. Epidemiology of acute renal failure: a prospective, multicenter, community-based study. Kidney International 1996; 50:811-818
2. Pinsky MR, et al Fluid and volume monitoring. Int J Artif Organs 2008; 31: 111- 126
3. Schortgen F, et al. Effects of hydroxyethyl starch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 2001; 357: 911-916
4. Cittanova ML, et al. Effects of hydroxy ethyl starch in brain-dead kidney donors on renal function in a kidney transplant recipients. Lancet 1996; 348: 1620-1622
5. Bagshaw S, et al. Fluid resuscitation and the septic kidney. Current Opinions in Critical Care 2006; 12: 527-530
6. Brunkhorst et al. German Competence Network Sepsis (SepNet).Intensive insulin therapy and pentastarch resuscitation in severe sepsis.N Engl J Med. 2008; 358:125-139
7. Schortgen F et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet. 2001; 357:911-916
8. Lobo DN, Macafee DAL, Allison SP. How perioperative fluid balance influences post-operative and outcomes. Best Practice and Research Clinical Anaesthesiology 2006; 20 (3), 439-455
9. Gann DS, Kenney PR, Special problems of fluid and electrolyte management in surgery. In Chan, JCM and Gill, JR eds Kidney Electrolyte Disorders. Churchill Livingstone Inc USA 1990; 343-362
10. Alpert RA, Roizen MF, Hamilton WK, et al. Intraoperative Urinary Output Does Not Predict Postoperative Renal Function in Patients Undergoing Abdominal Aortic Revascularisation. Surgery 1984; 95, 707-711
Guideline 2.4 – AKI : Assessment, Prevention & Pharmacological Treatment
All patients presenting with AKI should have reagent strip urinalysis performed supplemented with urine microscopy where indicated
Audit measure
Rationale
Positive protein values of 3+ and 4+ on reagent strip testing of the urine suggests intrinsic glomerular disease. A reagent strip positive for blood suggests the presence of red blood cells (> 5/high power field). Although red cell morphology may not be particularly useful1 the observation of large numbers of red cells in the presence of proteinuria suggests a glomerular aetiology for AKI. The suspicion is strengthened by the finding of red cell casts on a freshly collected sample of urine. Haematuria may also be found in cases of lower urinary tract obstruction often in association with tumours and less commonly associated with calculi, infection or severe renal ischaemia due to arterial or venous thrombosis. Characteristically myoglobinuria will cause a positive reagent strip reaction for haematuria without evidence of red cells on urine microscopy. Increased numbers of white cells (> 5 per high power field) are non-specific but are found more commonly with acute interstitial nephritis, infection and glomerulonephritis. Eosinophiluria is not a very specific test for interstitial nephritis and has a very poor positive predictive value. However, the value of eosinophiluria in interstitial nephritis is in ruling out the disease, the negative predictive value for patients with AKI is greater than 90%2. The presence of crystalluria may provide vital information3. Ethylene glycol poisoning produces a shower of oxalate crystals, tumour lysis syndrome can produce urate crystal deposition, and a number of drugs may lead to AKI and crystalluria including sulphonamides, acyclovir, triamterene, indinavir and cathartics high in phosphates.
1. Favaro S, Bonfant L, D'Angelo A, Giacomini A, Normanno M, Calo L. Is the red cell morphology really useful to detect the source of haematuria? Am J Nephrol 1997; 17:172-175
2. Rossert J. Drug-induced acute interstitial nephritis. Kidney Int 2001; 60:804-817
3. Fogazzi GB. Crystalluria: a neglected aspect of urinary sediment analysis. Nephrol Dialysis Transplant 1996; 11:379-387
Guideline 2.5 – AKI : Assessment, Prevention & Pharmacological Treatment
Urine biochemistry is of limited value in the assessment of patients presenting with AKI and need not be routinely performed
Rationale
Various measures have been claimed to aid in the diagnosis of AKI including urine specific gravity, urine osmolality, urine/plasma creatinine and urea ratios, urinary sodium, fractional excretion of sodium (FENa), fractional excretion of urea (FEUrea), freewater clearance and creatinine clearance. All of these have limitations and their specificity and sensitivity in clinical practice often means that a single measurement may be inconclusive except in extreme circumstances1-3. In pre-renal AKI there is increased urinary sodium reabsorption and increased urinary urea reabsorption. This should therefore be reflected by low urine sodium concentrations, low FENa and low FEUrea, and increased blood urea:creatinine ratios. Urinary electrolytes should be interpreted with caution, particularly in the elderly (who may already have an impaired concentrating ability), and in patients on diuretics or with a salt-losing state. In such patients the FEUrea may possibly be a more useful index41. The normal FEUrea is greater than 45%. Levels of less than 35% are associated with pre-renal AKI. Patients with pre-renal AKI not on diuretics have both low FENa (<1%) and low FEUrea. However patients with pre-renal AKI on diuretics have levels of FENa greater than 2% but still have low levels of FEUrea. In comparison, patients with ATN have both high FENa and high FEUrea. One clinical situation where measurement of urinary electrolytes may have clinical utility is in the diagnosis of hepatorenal syndrome as the cause of AKI in patients with liver disease. The diagnostic criteria for hepatorenal failure include a urine sodium of less than 10 mmol/L (although not a major diagnostic criterion)4.
1. Kellen M, Aronson S, Roizen MF, Barnard J, Thisted RA. Predictive and diagnostic tests of renal failure: A review. Anesth Analg 1994; 78:134-142
2. Espinel CH, Gregory AW. Differential diagnosis of acute renal failure. Clin Nephrol 1980; 13:73-77
3. Carvounis CP, Nisar S, Guro-Razuman S. Significance of the fractional excretion of urea in the differential diagnosis of acute renal failure. Kidney Int 2002; 62:2223-2229
4. Arroyo V, Gines P, Gerbes AL et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club Hepatology 1996; 23:164-176
Guideline 2.6 – AKI : Assessment, Prevention & Pharmacological Treatment
All patients undergoing contrast media examinations who are at risk from AKI should have adequate precautions undertaken. These should include temporary discontinuation of diuretics and ACEI/ARBs unless contraindicated, temporary discontinuation of Metformin and NSAIDs, consideration of iso-osmolar contrast agents and administration of prophylactic pre-procedure treatment with intravenous isotonic sodium bicarbonate or 0.9% sodium chloride.
Audit measure
Rationale
Acute kidney injury secondary to radiological contrast media is uncommon in the general population. It classically occurs within 72 hours of receiving the contrast media and usually recovers over the following five days. Its incidence increases significantly in patients with risk factors and is associated with an increased short and long-term mortality1. The kidney injury results from a combination of afferent arteriolar vasoconstriction and direct toxicity of the contrast media to the tubular epithelial cells. Prevention is important as there is no specific treatment and involves the evaluation of potential risk factors (see section 5.2.1) and clinical assessment of the patient's volume status2. It should also be considered whether alternative imaging could be utilised such as magnetic resonance angiography or whether carbon dioxide can be used to reduce the amount of contrast agent required3.
Adequate hydration is of paramount importance to the patient's management prior to the procedure and if at risk of developing contrast nephropathy should receive intravenous 0.9% sodium chloride. Intravenous 0.9% sodium chloride at a rate of 1 mL/kg/hour for 12 hours pre- and post- procedure has been shown to be more effective than 0.45% sodium chloride in reducing contrast induced AKI4. More recently it has been demonstrated that isotonic bicarbonate given at a rate of 3 mL/kg/hour for 1 hour pre-procedure and 1 mL/kg/hour for 6 hours post-procedure in comparison to 0.9% sodium chloride under the same conditions gives superior protection5. However it has not yet been established whether this regimen is superior to 0.9% sodium chloride given for 12 hours pre- and post-procedure. Nevertheless, the shorter sodium bicarbonate regimen has obvious advantages in avoiding an overnight stay. Potentially nephrotoxic medications should be withheld or avoided. Metformin should be stopped on or prior to the day of study and not restarted until renal function has been demonstrated to be stable because of the risk of lactic acidosis. Low osmolar agents are associated with a decreased risk of nephrotoxicity as compared to the high osmolar agents, particularly in those at risk from contrast media-associated AKI6. Patients with CKD should receive the iso-osmolar nonionic contrast agent iodixanol which has been shown to reduce the risk of contrast induced nephropathy in this patient group7. The dose of contrast media should be minimised and further exposure to contrast media should be delayed until full recovery of renal function unless absolutely necessary. Renal function should be checked up to 48-72 hours following the procedure if in a high risk group to ensure stable renal function.
There have been a number of small inadequately powered studies investigating the protective effects N-acetylcysteine which have been subject to a number of meta-analyses. The most recent meta-analyses have commented on the inconsistency of studies to date making a definitive conclusion difficult8,9. Currently there is no compelling evidence for the routine use of N-acetylcysteine10. A recent small study indicated that intravenous isotonic sodium bicarbonate combined with 1200 mg bd oral N-acetylcysteine was more effective than 0.9% sodium chloride combined with N-acetylcysteine11. Unfortunately this study did not include a comparative arm for intravenous fluid therapy alone.
1. Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality: a cohort analysis. JAMA 1996; 275: 1489-1494
2. Stacul F, Adam A, Becker CR, et al. Strategies to reduce the risk of contrast-induced nephropathy. American Journal of Cardiology 2006; 98, 59K-77K
3. Shaw DR, Kessel DO. The current status of the use of carbon dioxide in diagnostic and interventional angiographic procedures. Cardiovasc Intervent Radiol 2006; 29: 323-331
4. Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media associated nephropathy: randomised comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002; 162: 329-336
5. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004; 291: 2328-2334
6. Barrett BJ, Carlisle EJ. Meta-analysis of the relative nephrotoxicity of high-and low-osmolality iodinated contrast media. Radiology 1993; 188:171-178
7. McCullough PA, Bertrand MD, Brinker JA et al. A Meta-analysis of the renal safety of isosmolar iodixanol compared with low-osmolar contrast media. J Am Coll Cardiol 2006; 48 (4) 692-699
8. Kshirsagar AV, Poole C, Mottl A et al. N- acetylsysteine for the prevention of radio contrast induced nephropathy: a meta-analysis of prospective controlled trials. J Am Soc Nephrol 2004; 15: 761-769
9. Nallamothu BK, Shojania KG, Saint et al. Is N- acetylsysteine effective in preventing contrast-related nephropathy? A meta-analysis. Am J Med 2004; 117: 938-947
10. Kellum J, LeBlanc M, Venkataraman R. Acute renal failure. Clinical Evidence 2006; 15, 1-24
11. Briguori C, Airoldi F, D’Andrea D, Bonizzoni E, Morici N, Focaccio A, Michev I, Montorfano M, Carlino M, Cosgrave J, Ricciardelli B, Colombo, A. Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL) A Randomized Comparison of 3 Preventive Strategies. Circulation 2007; 115:1211-1217
Guideline 2.7 – AKI : Assessment, Prevention & Pharmacological Treatment
Loop diuretics and dopaminergic agents should not be routinely used for the prevention and treatment of AKI.
Rationale
There is currently no evidence to support the use of a specific pharmacological therapy in the treatment of AKI. The rationale behind the use of loop diuretics was based on their putative ability to reduce the energy requirements of the cells of the ascending limb of Henle and therefore ameliorate the resultant ischaemic damage1. Loop diuretics have also been used to convert patients with oliguric AKI to non-oliguric AKI (recognised to have a better prognosis), to facilitate the management of fluid and electrolyte disturbances and reduce the requirement for renal replacement therapy (RRT). Of concern has been the demonstration that the use of loop diuretics is associated with an increased risk of failure to recover renal function and mortality, perhaps related to the resultant delay in commencing RRT appropriately2. A recent meta-analysis of nine randomised controlled trials concluded that furosemide is not associated with any significant clinical benefits in the prevention and treatment of AKI in adults3. High doses can be associated with an increased risk of ototoxicity which is an important consideration particularly in those patients ventilated on the ICU.
Dopamine is a non-selective dopamine receptor agonist which at low-dose (0.5-3.0 µg/kg/min) induces a dose-dependent increase in renal blood flow, natriuresis and diuresis in healthy humans4. It has been proposed that dopamine may potentially reduce ischaemic cell injury in patients with AKI by improving renal blood flow and reducing oxygen consumption through inhibition of sodium transport. There have been a multitude of studies investigating the use of dopamine in the prevention and treatment of AKI which were most recently reviewed in a meta-analysis that concluded that there is no good evidence to support any important clinical benefits to patients with or at risk of AKI5. A possible explanation as to why dopamine is not beneficial has been provided by a study demonstrating that low-dose dopamine can worsen renal perfusion in patients with AKI6. Additionally the use of dopamine is associated with side-effects which include cardiac arrhythmias, myocardial and intestinal ischaemia7.
Fenoldopam, in contrast to dopamine is a selective dopamine A-1 receptor agonist which decreases systemic vascular resistance whilst increasing renal blood flow to both the cortex and medullary regions in the kidney8. It has been used in patients with hypertensive emergencies9 and has been noted to improve renal function in patients with severe hypertension10. The majority of small clinical studies that have been performed to date have investigated fenoldopam's ability to prevent the development of AKI without providing conclusive evidence. A beneficial effect of fenoldopam in critically ill patients with or at risk of AKI has been suggested by a meta-analysis of 16 randomised studies11. The meta-analysis concluded that fenoldopam reduces the need for renal replacement therapy and mortality in patients with AKI. Such results highlight the need for large multicentre randomised controlled trials to be performed before the use of fenoldopam can be recommended.
1. Heyman SN, Rosen S, Epstein FH et al. Loop diuretics reduce hypoxic damage to proximal tubules of the isolated perfused rat kidney. Kidney Int 1994; 45: 981-985
2. Mehta RL, Pascual MT, Soroko S et al. Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA 2002; 288: 2547-2553
3. Ho KM, Sheridan DJ. Meta-analysis of frusemide to prevent or treat acute renal failure. BMJ 2006; 333 (7565): 420-425
4. Denton MD, Chertow GM, Brady HR. Renal-dose dopamine for the treatment of acute renal failure: scientific rationale, experimental studies and clinical trials. Kidney Int 1996; 49:4-14
5. Friedrich JO, Adhikari N, Herridge MS. Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death. Ann Intern Med 2005; 142: 510-524
6. Lauschke A, Teichgraber UKM, Frei U et al. Low-dose dopamine worsens renal perfusion in patients with acute renal failure. Kidney Int 2006; 69: 1669-1674
7. Schenarts PA, Sagraves SG, Bard M et al. Low-dose dopamine: a physiologically based review. Current Surgery 2006; 63 (3): 219-225
8. Mathur VS, Swan SK, Lambrecht LJ et al. The effects of fenoldapam, a selective dopamine receptor agonist, on systemic and renal haemodynamics in normotensive subjects. Crit Care Med 1999; 29: 1832-1837
9. Murphy MB, Murray C, Shorten GD. Fenoldapam: a selective peripheral dopamine receptor agonist for the treatment of severe hypertension. N Engl J Med 2001; 345: 1548-1557
10. Schusterman NH, Elliott WJ, White WB. Fenoldapam, but not nitroprusside, improves renal function in severely hypertensive patients with impaired renal function. Am J Med 1993; 95: 161-168
11. Landoni G, Biondi-Zoccai GGL, Tumlin JA et al. Beneficial impact of fenoldapam in critically ill patients with or at risk for acute renal failure: a meta-analysis of randomised clinical trials. Am J Kidney Dis 2007; 49 (1): 56-68
Guideline 2.8 – AKI : Assessment, Prevention & Pharmacological Treatment
There is little clinical data to support the use of mannitol to prevent AKI secondary to rhabdomyolysis.
Rationale
Rhabdomyolysis results from skeletal muscle injury and cell lysis with the release of myoglobin and other muscle breakdown products. Myoglobin is freely filtered by the kidneys and is directly toxic to the tubular epithelial cells particularly in the setting of hypovolaemia and acidosis. There are a number of causes including trauma, burns, compartment syndrome and drugs (cocaine, ecstasy, statins). Management includes volume assessment and close monitoring with aggressive fluid resuscitation and alkalinisation of the urine. Fluid resuscitation with 0.9% sodium chloride is preferred at a rate of 10-15ml/kg/hr to achieve high urinary flow rates (>100ml/hr), with the cautious addition of sodium bicarbonate 1.4% to maintain urinary pH> 6.51. Mannitol is still used because of its properties as an osmotic diuretic and free radical scavenger by many centres although there is little clinical data to support its use2. Inappropriate use of mannitol can precipitate pulmonary oedema particularly if used with hypertonic sodium bicarbonate.
1. Sever MS, Vanholder R, Lameire N. Management of crush related injuries after disasters. N Eng J Med 2006; 354: 1052-1063
2. Brown CVR, Rhee P, Chan L et al. Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference? J Trauma 2004; 56: 1191-1196
Guideline 2.9 – AKI : Assessment, Prevention & Pharmacological Treatment
Pharmacological therapy currently has no role to play in the treatment of AKI.
Rationale
Although a number of studies have demonstrated the success of pharmacological therapy in experimental models of AKI these therapies have not been shown to be effective in human AKI1,2. This partly reflects the difficulty in designing experimental models that adequately reflect the heterogeneity of AKI in humans. Clinical trials evaluating the role of insulin like growth factor3 and atrial natriuretic peptide4 in AKI have failed to show any benefit and pharmacological therapy is currently not recommended.
1. Miller SB, Martin DR, Kissane J, Hammerman MR. Insulin like growth factor 1 accelerates recovery from ischaemic acute tubular necrosis in the rat. Proc Natl Acad Sci 1992; 89: 11876-11880
2. Shaw SG, Weidmann P, Hodler J et al. Atrial natriuretic peptide protects against acute ischaemic renal failure in the rat. J Clin Invest 1987; 80: 1232-1237
3. Hirschberg R, Kopple J, Lipsett P et al. Multicentre clinical trial of recombinant human insulin like growth factor 1 in patients with acute renal failure. Kidney Int 1999; 55: 2423-2432
4. Allgren RL, Marbury TC, Rahman SN et al. Anaritide in acute tubular necrosis. N Eng J Med 1997; 336: 828-834
Guideline 2.10 – AKI : Assessment, Prevention & Pharmacological Treatment
Therapeutic drug dosing must be adapted to altered kinetics in AKI
Rationale
Inappropriate drug dosing of patients with AKI is an important cause of adverse drug events1. Pharmacokinetics including the volume of distribution, clearance and protein binding are altered by organ failure in the critically ill patient. Drug doses need to be adjusted appropriately with the correct assessment of kidney function to reduce toxicity. There is an important role for the clinical pharmacist on the ICU. A number of publications have demonstrated the clinical and economic benefits of the critical care pharmacist2.
1. Schiff GD, Klass D, Peterson J, et al. Linking laboratory and pharmacy: opportunities for reducing errors and improving care. Arch Intern Med 2003; 163: 893-900
2. Kane SL, Weber RJ, Dasta JF. The impact of critical care pharmacists on enhancing patient outcomes. Intensive Care Med 2003; 29: 691-698
Guideline 3.1 – AKI : Treatment facilities & referral to renal services
The critical care nephrology interface should be defined at each locality to ensure timely and appropriate placement of patients with AKI according to their clinical condition. Local critical care networks should be utilised to facilitate this process.
Guideline 3.2 – AKI : Treatment facilities & referral to renal services
Appropriate transfer and triage of AKI patients from the non-specialist, non-critical care ward to the renal unit should be facilitated through the development of local guidelines and transfer protocols.
Guideline 3.3 – AKI : Treatment facilities & referral to renal services
Renal units should be equipped to provide level 2 care for patients with severe AKI (AKI stage 3 or AKI requiring RRT) or do so in conjunction with critical care services.
Guideline 3.4 – AKI : Treatment facilities & referral to renal services
Nephrologists and intensivists should work together to provide care for patients with AKI on the ICU. Nephrology trainees should be trained to care for critically ill patients with AKI.
Guideline 3.5 – AKI : Treatment facilities & referral to renal services
Patients with persistent renal impairment after AKI who do not require long term RRT should be managed according to local CKD practice.
Audit measure
Rationale
It is recognised that non-renal specialist management of patients with AKI can potentially result in suboptimal management. The National Service Framework for Renal Services recommends that patients at risk of or suffering from AKI should be identified promptly, with hospital services delivering high-quality, clinically appropriate care in partnership with specialised renal teams1. The most appropriate facility for the management of AKI will depend on the presence or absence of non-renal organ failure, the need for RRT and the need for renal specialist input. The latter will at least partly be determined by the need for RRT, the likelihood that AKI may be transient and self-limiting, and the aetiology of AKI – particularly if an esoteric diagnosis is possible2.
Different models of care will be determined by local resource availability and geography but there are essentially three different in-patient venues – the critical care unit, the renal unit and the non-specialist ward. Interaction between different disciplines is important to ensure correct initial placement of the patient and smooth subsequent transfer as the patient’s clinical condition changes or as more information comes to light. The interaction between renal and critical care units may be termed the ‘critical care nephrology’ interface. That between the renal unit and non-specialist wards, the ‘AKI outreach’ interface. These settings need not necessarily be at the one site but efficient communications between them will help circumvent the barriers imposed by local geography.
Although most critical care units in the UK are now performing their own RRT (whether guided by a nephrologist or not), at least 40% have no step-down unit on which on-going RRT can be conducted after other, non-renal organ failures, have resolved3. A recent survey from the Greater Manchester area has confirmed the potential for inappropriate critical care bed use by those with single-organ (renal) failure4. This is likely to be due to either limited bed availability on the base renal unit or on a non-specialist ward from which RRT can be performed, or lack of sufficient RRT resource. The use of local critical care networks will define the scale of the problem and help inform resource allocation. Similarly, renal units, on whom the burden of ongoing management will fall, should collect data that will help inform future resource allocation. Although the risk of ESRD after AKI is relatively small, absolute numbers may be significant5. Added to the burden of CKD that has been ‘created’ by only partially recovered AKI, these on-going commitments may add, considerably, to renal service workloads.
Early contact with the renal service is advisable for those patients who are likely to need ongoing RRT after the need for intensive care has passed. It should also be borne in mind that not all critical care unit AKI can be attributed to ATN and those involved in its management should consider more esoteric aetiologies2.
The transfer of patients between critical care and renal services is not a purely one way process, with significant numbers of patients receiving RRT on a tertiary critical care unit having been previously known to the renal unit [unpublished data, N.S. Kanagasundaram].
The interface between renal services and non-specialist, non-critical care wards requires an understanding of when specialist input might be needed, particularly with regard to the indications for RRT and the diagnosis of AKI2. The Greater Manchester survey found significant delays in transfer to renal services that may have adversely affected patient outcomes4. Clearly, renal services cannot accommodate all patients with AKI but appropriate triage and transfer may be facilitated through local educational programmes – mirroring those established for CKD – and through the development of local protocols for treatment and transfer. Severity scoring tools employed at the time of planned transfer may help determine whether patients require renal unit or intensive care.
The Department of Health report ‘Comprehensive Critical Care’ has recommended that patients with single organ failure requiring observation or intervention should receive level 2 (high dependency unit, HDU) care. Those needing advanced respiratory support or basic respiratory support plus support of two or more other organ systems should receive level 3 (intensive) care6. A failure to provide appropriate level 2 care may lead to undue pressures on level 3 care facilities. Mortality rates may increase when patients for whom level 2 care is indicated are cared for in a general ward setting7. Clearly, the suggestion that AKI ‘requiring observation or intervention’ should receive level 2 care, could encompass the entire spectrum of AKI but, for practical purposes, it would seem reasonable to confine this to those with AKIN stage 3. Renal units should thus be equipped to provide level 2 care or do so in conjunction with critical care services.
1. The National Service Framework for Renal Services-Part Two: Chronic Kidney Disease, Acute Renal Failure and End of Life Care. Department of Health February 2005
2. Kanagasundaram NS, Paganini P: Acute renal failure on the intensive care unit. Clin Med. 5:435-440., 2005
3. Wright SE, Bodenham A, Short AI, Turney JH: The provision and practice of renal replacement therapy on adult intensive care units in the United Kingdom. Anaesthesia 58:1063-1069, 2003
4. Hegarty J, Middleton R, Krebs M et al. Severe acute renal failure. Place of care, incidence and outcomes. QJM 2005; 98: 661-666
5. Lins RL, Elseviers MM, Daelemans R: Severity scoring and mortality 1 year after acute renal failure. Nephrol Dial Transplant. 21:1066-1068. Epub 2006 Feb 1013, 2006
6. Anonymous: Comprehensive critical care: a review of adult services, edited by UK DoH, London, Department of Health UK, 2000
7. Lyons RA, Wareham K, Hutchings HA, Major E, Ferguson B: Population requirement for adult critical-care beds: a prospective quantitative and qualitative study. Lancet. 355:595-598., 2000
Guideline 4.1 – AKI : Choice of renal replacement therapy modality
Choice of RRT modality should be guided by the individual patient’s clinical status, medical and nursing expertise, and availability of modality.
Rationale
Analysis of the currently published studies does not allow evidence-based guidelines for the selection of RRT modality for the treatment of AKI. In the early 1980s the options for RRT therapy were limited to intermittent haemodialysis (IHD) and peritoneal dialysis (PD), the currently available therapies in the developed world now include various forms of continuous renal replacement therapy (CRRT) and newer “hybrid” therapies such as extended duration dialysis (EDD), sustained low-efficiency dialysis (SLED) and the GeniusÒ system. Despite the increasing technological sophistication of RRT, key clinical management issues such as the optimal dosing of therapy and whether the selection of treatment modality impact on patient and renal survival remain to be determined.
Although it is widely perceived that CRRT is superior to IHD in haemodynamically unstable critically ill patients, prospective randomised clinical trials have failed to confirm this supposition. In many of the earlier trials there was a bias for the more critically ill patients to receive CRRT rather than IHD. For example, Swartz and colleagues1 retrospectively compared patients treated with CVVH or IHD and reported a two-fold greater mortality in patients treated with CVVH. However after adjusting for severity of illness, there was no difference. Similarly, in a prospective study, mortality was 79% in patients treated with CRRT compared to 59% in the IHD treated group, but after adjustment for co-morbidities, the modality of RRT was no longer a risk factor for outcome2.
Five randomised prospective controlled trials comparing CRRT and IHD from Europe and the USA have been published recently3-7. The smallest of these trials was designed to compare the effects of CVVH and IHD on systemic haemodynamics and splanchnic perfusion in patients with septic shock, with an overall mortality of 70% in both the CVVH and IHD groups3. In a multi-center USA trial of 166 patients with AKI, Mehta and colleagues reported intensive care unit and hospital mortality rates of 59.5% and 65.5%, respectively, in patients randomised to CRRT as compared to 41.5% and 47.6%, respectively, in patients randomised to IHD (p<0.02). Again, after covariate adjustment, there was no difference in mortality attributable to modality of RRT4. In addition in this study there was a high rate of crossover between the treatment modalities. In a single US center trial 80 patients were studied, and although greater haemodynamic stability and fluid removal rates were reported during CVVHD compared to IHD, there was no difference in survival5. Similarly a Swiss study randomizing 125 patients to either CVVHDF or IHD, reported an ICU mortality of 34% and 38% respectively for the two modes of RRT, and no difference in final hospital mortality6. Once again, the Hemodiafe study, a multicenter randomised controlled trial of 359 patients, also reported no difference in mortality according to mode of RRT used (IHD vs CVVHDF)7. This study is noteworthy as IHD was successfully delivered to patients despite marked haemodynamic instability with very little crossover between treatment groups. The authors deliberately chose cooled dialysate in combination with a very high dialysate sodium concentration to minimize cardiovascular instability during IHD, and compared to other studies delivered the highest Kt/V dose in the IHD group.
Meta-analyses comparing outcomes between the various modalities of RRT have been published, suggesting no difference in patient outcome, or a possible advantage of CRRT in the critically ill patient8-12. These analyses did not include the more recent Swiss and French studies, and were confounded by the various modalities used in the CRRT groups, varying from CAVH, to CVVH, CVVHD and CVVHDF (see review of nomenclature and physical processes13)
Many ICU patients have haemodynamic instability which, coupled with the frequency of intra-dialytic hypotension during IHD, has led to the suggestion that CRRT may be associated with an increased likelihood for recovery of renal function14.
Studies comparing other forms of RRT have been limited. No studies have directly compared “hybrid” treatments to either IHD or CRRT, although “hybrid” therapies have been shown to provide similar haemodynamic stability and solute control when compared to CRRT15. There are two limited studies comparing peritoneal dialysis to CRRT in adults, both reporting an advantage of CRRT, although the dose of dialysis delivered by peritoneal dialysis was low16,17. In paediatric practice, particularly post cardiac surgery, peritoneal dialysis remains an effective form of RRT, in single organ failure18 although the technique is contraindicated in those with abdominal pathology and may not provide satisfactory clearances in those adults with hypercatabolism or a high urea distribution volume due to fluid overload.
In summary, analysis of the currently published studies does not allow evidence-based guidelines for the selection of RRT modality for the treatment of AKI. However, as with the Veterans ATN study, most clinicians chose intermittent haemodialysis/haemofiltration for cardiovascularly stable patients, and continuous or hybrid therapies for those with cardiovascular compromise and multi-organ failure19. The modality chosen should therefore be guided by the individual patient’s clinical status, local medical and nursing expertise, and the availability of RRT modality.
Advantages and disadvantages of different RRT modalities in AKI
Modality
Use in haemodynamically unstable patients
Solute clearance
Volume control
Anti-coagulation
Peritoneal dialysis
Yes
moderate
moderate
No
Intermittent haemodialysis
No
high
moderate
Possible without
Hybrid techniques
Possible
high
good
Possible without
CVVH
Yes
moderate/high
good
Possible without
CVVHD
Yes
moderate/high
good
Possible without
CVVHDF
Yes
high
good
Possible without
(CVVH – continuous haemofiltration, CVVHDF – continuous haemodiafiltration)
1. 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; 34:424-432
2. Guerin 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; 28:1411-1418
3. John S, Griesbach D, Baumgartel M et al. Effects of continuous haemofiltration vs intermittent haemodialysis on systemic haemodynamics and splanchnic regional perfusion in septic shock patients: a prospective, randomized clinical trial. Nephrol Dial Transplant. 2001;16:320-327
4. Mehta RL, McDonald B, Gabbai FB et al. A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure. Kidney Int. 2001; 60:1154-1163
5. Augustine JJ, Sandy D, Seifert TH, Paganini EP. A randomized controlled trial comparing intermittent with continuous dialysis in patients with AKI. Am J Kidney Dis. 2004; 44:1000-1007
6. Uehlinger DE, Jakob SM, Ferrari P, Eichelberger M, Huynh-Do U, Marti H-P,Mohaupt MG, Vogt B, Rothen HU, Regli B, Takala J, Frei FJl. Comparison of continuous and intermittent renal replacement therapy for acute renal failure. Nephrol Dial Transplant 2005; 20: 1630-1637
7. Vinsonneau D CC, Combes A, Costa de Beauregard MA, Klouche K, Boulain T, Pallot JL, Chiche JD, Taupin P, Landais P, Dhainaut JF. A prospective, multicentre, randomized clinical trial comparing continuous venovenous hemodiafiltration to intermittent hemodialysis for the treatment of Acute Renal Failure in intensive care unit patients with multiple organ dysfunction syndrome. Lancet 2006; 368: 379-385
8. Kellum JA, Angus DC, Johnson JP et al. Continuous versus intermittent renal replacement therapy: a meta-analysis. Intensive Care Med. 2002; 28:29-37
9. 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; 40:875-885
10. 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; 31:449-455
11. Jacka MJ, Ivancinova X, Gibney RT. Continuous renal replacement therapy improves renal recovery from acute renal failure. Can J Anaesth. 2005;52:327-332
12. 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; 11:548-554
13. Kanagasundaram NS. Renal replacement therapy in acute kidney injury: an overview.Br J Hosp Med 2007; 68(6):292-297.
14. 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; 43:342-349
15. Chang JW, Yang WS, Seo JW et al. Continuous venovenous hemodiafiltration versus hemodialysis as renal replacement therapy in patients with acute renal failure in the intensive care unit. Scand J Urol Nephrol. 2004; 38:417-421
16. Gangji AS, Rabbat CG, Margetts PJ. Benefit of continuous renal replacement therapy in subgroups of acutely ill patients: a retrospective analysis. Clin Nephrol. 2005; 63:267-275
17. Swartz RD, Bustami RT, Daley JM et al. Estimating the impact of renal replacement therapy choice on outcome in severe acute renal failure. Clin Nephrol. 2005; 63:335-345
18. Strazdins V, Watson AR, Harvey B. Renal replacement therapy for acute renal failure in children: European guidelines. Pediatr Nephrol 2004; 19: 199-207
19. The VA/NIH acute renal failure trial network. Intensity of renal support in critically ill patients with acute kidney injury. NEnglJMed 2008; 359:
Guideline 5.1 – AKI : Choice of dialyser/haemofilter membrane
Choice of haemodialysis/haemofiltration membrane should be dictated by RRT modality
Guideline 5.2 – AKI : Choice of dialyser/haemofilter membrane
Synthetic or modified cellulosic membranes should be used in preference to unmodified cellulose
Guideline 5.3 – AKI : Choice of dialysate/replacement fluid
Bicarbonate should be the preferred buffer for dialysate and replacement fluid in CRRT techniques unless regional citrate anticoagulation is employed
Rationale
There is currently no clinical evidence that favours synthetic over modified cellulosic membranes for treating patients with AKI. Until relatively recently there was a marked cost difference between unmodified cellulosic (cuprophane), modified cellulosic and synthetic membranes1-8. Laboratory experiments showed that synthetic membranes tended to cause less activation of complement, and mononuclear cells, and studies were set up to evaluate whether membrane choice affected outcomes in AKI. Due to the differences reported in original studies, several meta-analyses have been conducted9,10. These showed that although there was a possible patient survival and renal recovery advantage when synthetic membranes were compared to cuprophane membranes, there was no difference between synthetic and altered cellulosic membranes.
Lactate and acetate have been largely replaced by bicarbonate as the primary buffer for dialysate used in IHD for ESRD and this practice has propagated, by default, to IHD for AKI. In a similar fashion, bicarbonate has become the primary buffer for both replacement and dialysate fluids in CRRT. Driven by concerns about exacerbating existing lactic acidosis, particularly in those with liver failure, the development of commercially available bicarbonate-based fluids that circumvent the inherent instability of such solutions has led to their increasing utilisation. Evidence of benefit over lactate-based solutions is inconsistent with some studies showing no substantive differences in metabolic parameters, pH, or haemodynamic status11,12 whilst others have shown improved haemodynamic stability13,14 and more rapid control of systemic acidosis15. Despite these conflicting data, the likelihood of benefit, especially in the sickest patients, and the ready availability of commercially-prepared bicarbonate fluid, seems to justify its widespread use in CRRT.
1. Schiffl H, Lang SM, Konig A et al. Biocompatible membranes in acute renal failure: prospective case-controlled study. Lancet. 1994; 344:570-572
2. Aber BL, Lau J, Schmid CH et al. Effect of biocompatibility of hemodialysis membranes on mortality in acute renal failure: a meta-analysis. Clin Nephrol. 2002;57:274-282
3. Schiffl H, Sitter T, Lang S et al. Bioincompatible membranes place patients with acute renal failure at increased risk of infection. ASAIO J. 1995; 41:M709-712
4. Hakim RM, Wingard RL, Parker RA. Effect of the dialysis membrane in the treatment of patients with acute renal failure. N Engl J Med. 1994;331:1338-1342
5. Himmelfarb J, Tolkoff Rubin N, Chandran P et al. A multicenter comparison of dialysis membranes in the treatment of acute renal failure requiring dialysis. J Am Soc Nephrol. 1998; 9:257-266
6. Jorres A, Gahl GM, Dobis C et al. Haemodialysis-membrane biocompatibility and mortality of patients with dialysis-dependent acute renal failure: a prospective randomised multicentre trial. International Multicentre Study Group. Lancet. 1999; 354:1337-1341
7. Gastaldello K, Melot C, Kahn RJ et al. Comparison of cellulose diacetate and polysulfone membranes in the outcome of acute renal failure. A prospective randomized study. Nephrol Dial Transplant. 2000; 15:224-230
8. Albright RC, Jr., Smelser JM, McCarthy JT et al. Patient survival and renal recovery in acute renal failure: randomized comparison of cellulose acetate and polysulfone membrane dialyzers. Mayo Clin Proc. 2000; 75:1141-1147
9. Kurtal H, von Herrath D, Schaefer K. Is the choice of membrane important for patients with acute renal failure requiring haemodialysis? Artif Organs. 1995; 19:391-394
10. Subramanian S, Venkataraman R, Kellum JA. Influence of dialysis membranes on outcomes in acute renal failure: a meta-analysis. Kidney Int. 2002; 62:1819-1823
11. Alonso A LJ, Jaber BL. Biocompatible haemodialysis membranes for acute renal f