Page 1
E Hoste, PEACE protocol draft version 1.9, 05December 2014 1
PrEvalence of Acute and Chronic Kidney
Disease treated by Renal Replacement
Therapy in the ICU Environment (PEACE)
A prospective international, multi-centre, prevalence study on the epidemiology of the use
of renal replacement therapy for ICU patients who have acute kidney injury and chronic end
stage kidney disease.
Study protocol version 1.9
Page 2
E Hoste, PEACE protocol draft version 1.9, 05December 2014 2
Steering Committee
Luis Forni, Worthing, United Kingdom
Eric Hoste, Gent, Belgium
Michael Joannidis, Innsbruck, Austria
John Kellum, Pittsburgh, USA
Marlies Ostermann, London, United Kingdom
Advisory Committee
Consists of active members of the ESICM working group on Acute Kidney Injury interested in
this study
Study coordination
Guy François, ESICM Clinical Trials Group,[email protected]
Chief investigator contact details
Eric Hoste
Intensive Care unit
Ghent University Hospital
De Pintelaan 185
9000 Gent, Belgium
[email protected]
phone:+32 9 332 4197
Fax: +32 9 332 4997
Funding:
European Society of Critical Care Medicine, section on Acute Kidney Injury
Rue Beliard 19, 1040 Brussels, Belgium
Tel: +32 2 559 03 50
Page 3
E Hoste, PEACE protocol draft version 1.9, 05December 2014 3
e-mail: [email protected]
Contents
Steering Committee ......................................................................................................................................... 2
Advisory Committee ........................................................................................................................................ 2
Study coordination .......................................................................................................................................... 2
Chief investigator contact details ............................................................................................................... 2
Funding: ............................................................................................................................................................... 2
Introduction: ...................................................................................................................................................... 4
Aims: ..................................................................................................................................................................... 5
Methods: .............................................................................................................................................................. 5
Ethics committee approval................................................................................................................................................ 6
Inclusion criteria: ................................................................................................................................................................... 6
Exclusion criteria: .................................................................................................................................................................. 6
Data recording (this is a not yet definitive list) ....................................................................................................... 6
ICU data: ..................................................................................................................................................................... 6
Data on the patients present in the ICU at time of the study date (March 25th or April 22nd
2015) ........................................................................................................................................................................... 7
Recording of data on severity of illness and processes of care for RRT, at time:......................... 8
Outcomes for all patients included in the study (present at time of the index date) ............... 12
Publication policy ......................................................................................................................................... 13
Publications ............................................................................................................................................................................13
Authorship ...............................................................................................................................................................................13
References ....................................................................................................................................................... 14
Page 4
E Hoste, PEACE protocol draft version 1.9, 05December 2014 4
Introduction:
Acute kidney injury (AKI) is a common finding in intensive care unit (ICU) patients.
Approximately 30 to 65% of patients experience an episode of AKI, and 5% of ICU patients
are treated with renal replacement therapy [1-4]. AKI is associated withimportant short term
and long-term morbidity as well as mortality, and therefore also with costs. Finally, there is a
close link between chronic kidney disease (CKD) and AKI. CKD patients are at greater risk for
developing AKI, and survivors of AKI treated with renal replacement therapy (AKI-RRT), may
develop chronic kidney disease (CKD) and end stage kidney disease (ESKD).
Different aspects of RRT modality may impact on outcomes, and data that have emerged
over the last decade have improved evidence and also rejected commonly accepted dogma.
Initial data suggested a better outcome when a higher dose of treatment was applied [5,6].
However, one small and two large prospective randomised controlled trials failed to
reproduce these earlier findings [7-9]. Observational data seems to suggest that continuous
RRT (CRRT) modalities are associated with better outcomes[10]. However, relative small,
randomized studies and meta-analyses do not demonstrate such a benefit [11-16].
Observational data suggests that CRRT is associated with improved renal recovery, and also
examining the data from the 2 large randomized studies on intensity of RRT suggest that
CRRT confers a benefit [8,9,17-19]. Also, despite RRT being available for over 50 years there
are no clear consensus guidelines for the initiation of RRT. A recent survey found that up to
89 different combinations of indications are used[20]. Recently, the Acute Kidney Injury
Network and the Kidney Disease: Improving Global Outcomes (KDIGO) group, formulated
recommendations for this[21,22]. Recent observational studies indicated that commonly
accepted cut offs such as serum urea concentration are probably not that important [23-25].
Furthermore, timing of initiation may have an effect on outcome. Some studies suggest that
early initiation is associated with better outcome, on the other hand others could not
demonstrate a benefit and have even demonstrated inferior outcomes[7,26-29].
The most recent survey in Europe showed that CRRT is the preferred modality among
intensivists, and that despite the recently published evidence treatment doses are similar to
those of a decade ago [30].
Page 5
E Hoste, PEACE protocol draft version 1.9, 05December 2014 5
Data on the use of renal replacement therapy (RRT) for AKI and for CKD in ICU patients are
either on specific patient groups, such as cardiac surgery patients, based on surveys, or dates
back for at least a decade[2,20,30-34]. Furthermore, these studies suffered from exclusion
bias, as patients who fulfilled criteria for initiation of RTT, but who were denied RRT, were
not considered. That this may be an important consideration is illustrated by findings from a
recent small single centre study that demonstrated similar mortality rate between RIFLE-F
patients who were and who were not treated with RRT [35]. Therefore, the Acute Kidney
Injury Network (AKIN) recommended measuring the epidemiology of AKI[36,37].
We anticipate that the evidence that has been generated on different topics of RRT for ICU
patients may have influenced current practice. Also, we anticipate regional differences in
RRT practice.
Aims:
Assessment of the prevalence of severe AKI (defined as KDIGO class 3) and CKD (defined by
treatment with renal replacement therapy (RRT)), in ICU patients, present at time of the
study inclusion day.
Assessment of modalities of RRT used for treatment of AKI.
Assessment of indications for initiation of RRT currently described in literature.
Assessment on who is performing RRT.
Assessment of severity of illness at time of data recording.
Assessment of renal outcomes and ICU, hospital, 30-d, and 60-d mortality.
Methods:
Prospective observational study in a cohort of patients present in the ICU at time of the
index date.
Recording of prevalence of CKD-RRT at time of the index study day, and AKI stage 3
(according to KDIGO)[38], including AKI-RRT during ICU stay with a maximum follow up till
day 28 following the index study day.
Recording of outcomes at time:
AKI stage 3 (without RRT)
AKI-RRT
Page 6
E Hoste, PEACE protocol draft version 1.9, 05December 2014 6
ICU discharge
Hospital discharge
30-d follow up
60-d follow up
Coded data registry in paper case record forms (CRF). Code lists will be kept in the
participating hospital in a locked room. Only the site principle investigator has access to the
code lists. Data will be recorded anonymously in an electronic CRF through a secured
website.
Ethics committee approval
The study will be conducted according to Good Clinical Practice guidelines. Ethics committee
approval is required according to local regulations.
Inclusion criteria:
1. Patients present in the ICU at time of the study data (date starting at 0:00 h, and
ending at 23:59 h) (index ICU stay), either March 25th 2015 or April 22nd 2015.
2. ≥18 y
3. When required by local EC regulations and EC approval, informed consent (written or
oral) by the patient or relative.
Exclusion criteria:
None
Data recording (this is a not yet definitive list)
ICU data:
Type of ICU, number of beds, nurse/patient ratio day and night, …
Page 7
E Hoste, PEACE protocol draft version 1.9, 05December 2014 7
Data on the patients present in the ICU at time of the study date (March 25th or April 22nd
2015)
Age
Gender
Race (for CKD-EPI/MDRD)
Body weight at time of admission to the ICU or hospital)
Height
Baseline creatinine, defined as a stable/representative creatinine concentration
recorded within a 6-month period before ICU admission.
o When this is not available the electronic CRF will propose a baseline based on
serum creatinine at time of hospital admission, ICU admission, or a back-
calculated serum creatinine concentration based on demographic criteria and
the CKD-EPI equation. As the creatinine concentrations at time of hospital and
ICU admission may represent an episode of AKI, the investigator is asked what
value is most representative. If none of these 3 alternative values are
acceptable, e.g. because the patient is admitted with AKI, and also has
chronic kidney disease, the investigator can indicate a most representative
value e.g. a nadir concentration obtained during hospital stay.
Creatinine at time of hospital admission
Creatinine at time of ICU admission
These data will generate for each patient the creatinine and urine output cut off values for
meeting AKI stage 3 criteria. This will allow the investigator to easily identify AKI stage 3 in
the index patients during ICU stay.
Admission data:
Admission date hospital and ICU
Referred from home, ER, ward, other ICU
Reason for ICU admission and main admission diagnosis (medical, emergency surgical,
elective surgical, to be expanded)
Page 8
E Hoste, PEACE protocol draft version 1.9, 05December 2014 8
Recording of data on severity of illness and processes of care for RRT, at time:
First meeting AKI stage 3 criteria based upon creatinine or urine output criteria
Initiation of RRT.
For patients who progress from AKI stage 3 to initiation of RRT during the study period, data
will be recorded at both time points.
When RRT was already initiated at time of the index study date, the investigator needs to
record data at time of initiation.
Dataset:
Date of first meeting AKI -3 criteria / Date of initiation of RRT
Kidney function at time of AKI stage 3 without RRTandat time of initiation of RRT
o Urine volume preceding 24-h
o Urine output criterion oliguria or anuria
o Cumulative ICU volume balance/body weight as a proportion [39]? We can
ask for in units who are able to report this (those with electronic records)
o Serum creatinine
o Serum urea/BUN
o Na
o K
o Cl
o Ca
o P
o Mg
o Uric Acid
o pH
o HCO3-
o Albumin (cfr [40])
o Base deficit
Date of initiation
Who made the decision (you can tick more than 1)
Page 9
E Hoste, PEACE protocol draft version 1.9, 05December 2014 9
o Nephrologist
o Intensivist
Indication(s) – tick boxes and values (you can tick more than 1)
o Hyperkalaemia
o Anuria/oliguria with/without volume overload
o Acidosis – low pH - BD
o Urea concentration
o Creatinine
o Phosphorus
o Lactate
o Low Creatinine clearance (indicate figure)
o FE sodium
o FE urea
o Chronic end stage kidney disease
o Other …
In case of AKI-3: why did you not initiate RRT?
Modality at time of initiation/ study date in tick boxes
o CVVH
o CVVHD
o CVVHDF
o CAVH
o CAVHD
o SLEDD – indicate duration
o Intermittent dialysis - indicate duration
o Peritoneal dialysis
o …
For continuous therapies - Replacement fluid buffer:
o bicarbonate
o lactate
o acetate
o other: …
For continuous therapies – replacement fluid:
Page 10
E Hoste, PEACE protocol draft version 1.9, 05December 2014 10
o Pre-dilution
o Post dilution
o Both, indicate proportion
For PD
o Machine/manual
o Acute intermittent PD/chronic equilibrated PD/Tidal PD/High volume
PD/continuous flow PD
o Who placed the PD catheter
Intensivist/nephrologist/surgeon
And where: OR, ICU, other
o Dwell time
o Dwell volume
o Number of exchanges per 24 h
o Type of PD fluid used
Who sets up the RRT machine (you can tick more than 1)
o Renal nurse/doctor
o ICU nurse/doctor
Who monitors the RRT machine (you can tick more than 1)
o Renal nurse
o ICU nurse
Duration of RRT
o prescribed:
o administered:
Dose of RRT:
o Not known
o Intermittent therapies: Kt/V (indicate also prescribed Kt/V) and frequency per
week, urea reduction ratio, …
o Continuous therapies: UF = … mL/kg/h
o Other:
o How is body weight assessed for Kt/V, mL/kg/h
Page 11
E Hoste, PEACE protocol draft version 1.9, 05December 2014 11
Actual, estimated, at time of hosp admission, at time of ICU admission,
…
Net fluid removal:
o Prescribed
o Actual net fluid removal
Anticoagulation strategy (you can tick more than 1)
o Unfractionated Heparin
Monitoring:
ACT
APTT
antiXa
None
o LMWH
Monitoring
antiXa
none
o Citrate
Monitoring
Ca-i patient
Total calcium patient
Ca-i circuit
none
o Saline flushes
o Prostaglandin
o None
o Other …
Vascular access:
o Double lumen catheter
o Single lumen catheter
o … French/gauge
Page 12
E Hoste, PEACE protocol draft version 1.9, 05December 2014 12
o Length
Catheter insertion site:
o Jugular vein L/R
o Subclavian vein L/R
o Femoral vein L/R
Organ dysfunction according to SOFA at time of meeting AKI-3 criteria (when no AKI-RRT)
and at time AKI-RRT
Serum bilirubin
Lowest mean blood pressure
Highest dose of vaso-active therapy (NOR-ADR-DOPA-VASO-DOBU)
Worst SOFA resp score
Mechanical ventilation / non invasive mech vent
Serum creatinine, 24 h urine output, serum urea/BUN, diuretic therapy
Thrombocytes
GCS
Sedation
Outcomes for all patients included in the study (present at time of the index date)
a) For all patients included in the study:
At time of ICU discharge, or when ICU stay is longer than 60-d after the index study date,
at time of index study date +60:
Date and status of ICU discharge (alive/death).
RRT at time of ICU discharge (Y/N)
Creatinine at time of ICU discharge(this allows also calculation of eGFR)
Date and status of Hospital discharge (alive/death),
RRT at time of hospital discharge (Y/N)
Creatinine at time of hospital discharge(this allows also calculation of eGFR)
Status at time of index study date +30 (alive/death, RRT Y/N)
Page 13
E Hoste, PEACE protocol draft version 1.9, 05December 2014 13
Creatinine at time of index study date +30
Status at time of index study date +60 (alive/death, RRT Y/N)
Creatinine at time of index study date +60
The combination of these data will also allow reporting on Major Adverse Kidney Events
(MAKE) at time 30 and 60 days (MAKE30/60).
Publication policy
Publications
Several papers will be published from this dataset:
Primary paper on the primary aim
Secondary papers on the secondary aims
Tertiary papers on analyses proposed by investigators
o Investigators who adequately fulfilled study obligations may propose such an
analysis to the steering committee, which will judge on this.
Authorship
Requirements for authorship will follow AMA guidelines
Writing committees: formed on basis of contribution (enrolment, intellectual
contribution etc.)
Group authorship – the PEACE study group – includes all investigators who
adequately fulfilled study obligations.
Page 14
E Hoste, PEACE protocol draft version 1.9, 05December 2014 14
References
1. Metnitz PG, Krenn CG, Steltzer H, Lang T, Ploder J, Lenz K, Le Gall JR, Druml W: Effect of
acute renal failure requiring renal replacement therapy on outcome in critically ill
patients. Crit Care Med 2002, 30: 2051 - 2058.
2. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I,
Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C: Acute renal failure in critically ill
patients: a multinational, multicenter study. JAMA 2005, 294: 813-818.
3. Hoste EAJ, Schurgers M: Epidemiology of AKI: How big is the problem?Crit Care Med
2008, 36: S1-4.
4. Hoste EAJ, J.A. K, group TAKI-EPIs: The epidemiology of acute kidney injury -
Preliminary results of the multicenter international AKI-EPI study. Intensive Care Med
2011, 37: S207.
5. Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, La Greca G: Effects of
different doses in continuous venovenous haemofiltration on outcomes of acute
renal failure: a prospective randomised trial. Lancet 2000, 356: 26 - 30.
6. Schiffl H, Lang SM, Fischer R: Daily hemodialysis and the outcome of acute renal
failure. N Engl J Med 2002, 346: 305-310.
7. Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, Zandstra DF, Kesecioglu J: Effects
of early high-volume continuous venovenous hemofiltration on survival and recovery
of renal function in intensive care patients with acute renal failure: a prospective,
randomized trial. Crit Care Med 2002, 30: 2205-2211.
8. Palevsky PM, Zhang JH, O'Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K,
Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM, Thompson BT, Vijayan A,
Watnick S, Star RA, Peduzzi P: Intensity of renal support in critically ill patients with
acute kidney injury. N Engl J Med 2008, 359: 7-20.
9. Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S,
Myburgh J, Norton R, Scheinkestel C, Su S: Intensity of continuous renal-replacement
therapy in critically ill patients. N Engl J Med 2009, 361: 1627-1638.
Page 15
E Hoste, PEACE protocol draft version 1.9, 05December 2014 15
10. Forni L, Hilton P: Continuous hemofiltration in the treatment of acute renal failure. N
Engl J Med 1997, 336: 1303 - 1309.
11. Mehta RL, McDonald B, Gabbai FB, Pahl M, Pascual MTA, Farkas A, Kaplan RM, for the
Collaborative Group for the Treatment of ARF in the ICU: A randomized clinical trial of
continuous versus intermittent dialysis for acute renal failure. Kidney Int 2001, 60:
1154-1163.
12. Vinsonneau C, Camus C, Combes A, Costa de Beauregard MA, Klouche K, Boulain T,
Pallot J-L, Chiche J-D, Taupin P, Landais P: Continuous venovenous haemodiafiltration
versus intermittent haemodialysis for acute renal failure in patients with multiple-
organ dysfunction syndrome: a multicentre randomised trial. The Lancet 2006, 368:
379-385.
13. Lins RL, Elseviers MM, Van der Niepen P, Hoste E, Malbrain ML, Damas P, Devriendt J:
Intermittent versus continuous renal replacement therapy for acute kidney injury
patients admitted to the intensive care unit: results of a randomized clinical trial.
Nephrol Dial Transplant 2009, 24: 512-518.
14. Uehlinger DE, Jakob SM, Ferrari P, Eichelberger M, Huynh-Do U, Marti HP, Mohaupt
MG, Vogt B, Rothen HU, Regli B, Takala J, Frey FJ: Comparison of continuous and
intermittent renal replacement therapy for acute renal failure. Nephrol Dial
Transplant 2005, 20: 1630-1637.
15. Bagshaw SM, Berthiaume LR, Delaney A, Bellomo R: Continuous versus intermittent
renal replacement therapy for critically ill patients with acute kidney injury: a meta-
analysis. Crit Care Med 2008, 36: 610-617.
16. Pannu N, Klarenbach S, Wiebe N, Manns B, Tonelli M: Renal replacement therapy in
patients with acute renal failure: a systematic review. JAMA 2008, 299: 793-805.
17. Bell M, Granath F, Schon S, Lofberg E, Ekbom A, Martling CR: End-stage renal disease
patients on renal replacement therapy in the intensive care unit: short- and long-
term outcome. Crit Care Med 2008, 36: 2773-2778.
18. Bell M, Granath F, Schon S, Ekbom A, Martling CR: Continuous renal replacement
therapy is associated with less chronic renal failure than intermittent haemodialysis
after acute renal failure. Intensive Care Med 2007, 33: 773-780.
19. Uchino S, Bellomo R, Kellum JA, Morimatsu H, Morgera S, Schetz MR, Tan I, Bouman C,
Macedo E, Gibney N, Tolwani A, Oudemans-Van Straaten HM, Ronco C: Patient and
Page 16
E Hoste, PEACE protocol draft version 1.9, 05December 2014 16
kidney survival by dialysis modality in critically ill patients with acute kidney injury.
Int J Artif Organs 2007, 30: 281-292.
20. Ricci Z, Ronco C, D'Amico G, De Felice R, Rossi S, Bolgan I, Bonello M, Zamperetti N,
Petras D, Salvatori G, Dan M, Piccinni P: Practice patterns in the management of acute
renal failure in the critically ill patient: an international survey. Nephrol Dial
Transplant 2006, 21: 690-696.
21. Gibney N, Hoste E, Burdmann EA, Bunchman T, Kher V, Viswanathan R, Mehta RL,
Ronco C: Timing of initiation and discontinuation of renal replacement therapy in
AKI: unanswered key questions. Clin J Am Soc Nephrol 2008, 3: 876-880.
22. Section 5: Dialysis Interventions for Treatment of AKI. Kidney Int Supp 2012, 2: 89-115.
23. Ostermann M, Chang R: Correlation between parameters at initiation of renal
replacement therapy and outcome in patients with acute kidney injury. Critical Care
2009, 13: R175.
24. De Corte W, Vanholder R, Dhondt AW, De Waele JJ, Decruyenaere J, Danneels C, Claus
S, Hoste EA: Serum urea concentration is probably not related to outcome in ICU
patients with AKI and renal replacement therapy. Nephrol Dial Transplant 2011, 26:
3211-3218.
25. Bouman C, Forni L: Initiation of renal replacement therapy: is timing
everything?Critical Care 2010, 14: 107.
26. Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman
C, Macedo E, Gibney N, Tolwani A, Oudemans-van Straaten HM, Ronco C, Kellum JA:
Timing of renal replacement therapy and clinical outcomes in critically ill patients
with severe acute kidney injury. J Crit Care 2009, 24: 129 - 140.
27. Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BL: Timing of renal
replacement therapy initiation in acute renal failure: a meta-analysis. Am J Kidney Dis
2008, 52: 272-284.
28. Elseviers MM, Lins RL, Van der Niepen P, Hoste E, Malbrain ML, Damas P, Devriendt J,
Sharf Investigators SH: Renal replacement therapy is an independent risk factor for
mortality in critically ill patients with acute kidney injury. Crit Care 2010, 14: R221.
29. Vinsonneau C, Monchi M: Too early initiation of renal replacement therapy may be
harmful. Crit Care 2011, 15: 112.
Page 17
E Hoste, PEACE protocol draft version 1.9, 05December 2014 17
30. Legrand M, Darmon M, Joannidis M, Payen D: Management of renal replacement
therapy in ICU patients: an international survey. Intensive Care Med 2012,
31. Bell M, Liljestam E, Granath F, Fryckstedt J, Ekbom A, Martling CR: Optimal follow-up
time after continuous renal replacement therapy in actual renal failure patients
stratified with the RIFLE criteria. Nephrol Dial Transplant 2005, 20: 354-360.
32. Ronco C, Ricci Z, Bellomo R: Current worldwide practice of dialysis dose prescription
in acute renal failure. Curr Opin Crit Care 2006, 12: 551-556.
33. Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E,
Gibney N, Tolwani A, Oudemans-van Straaten H, Ronco C, Kellum JA: 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.
34. Mehta RL, Pascual MT, Soroko S, Savage BR, Himmelfarb J, Ikizler A, Paganini EP,
Chertow GM, for the Program of Improve Care in Acute Renal D: Spectrum of acute
renal failure in the intensive care unit: the PICARD experience. Kidney Int 2004, 66:
1613 - 1621.
35. Schneider J, Khemani R, Grushkin C, Bart R: Serum creatinine as stratified in the RIFLE
score for acute kidney injury is associated with mortality and length of stay for
children in the pediatric intensive care unit. Crit Care Med 2010, 38: 933-939.
36. Kellum JA, Mehta RL, Levin A, Molitoris BA, Warnock DG, Shah SV, Joannidis M, Ronco
C: Development of a clinical research agenda for acute kidney injury using an
international, interdisciplinary, three-step modified Delphi process. Clin J Am Soc
Nephrol 2008, 3: 887-894.
37. Cerda J, Lameire N, Eggers P, Pannu N, Uchino S, Wang H, Bagga A, Levin A:
Epidemiology of acute kidney injury. Clin J Am Soc Nephrol 2008, 3: 881-886.
38. Section 2: AKI Definition. Kidney Int Supp 2012, 2: 19-36.
39. Vaara ST, Korhonen A-M, Kaukonen K-M, Nisula S, Inkinen O, Hoppu S, Laurila JJ, Mildh
L, Reinikainen M, Lund V, Parviainen I, Pettila V, Finnaki Sg: Fluid overload is
associated with an increased risk for 90-day mortality in critically ill patients with
renal replacement therapy: data from the prospective FINNAKI study. Crit Care 2012,
16: R197.
Page 18
E Hoste, PEACE protocol draft version 1.9, 05December 2014 18
40. Wiedermann CJ, Wiedermann W, Joannidis M: Hypoalbuminemia and acute kidney
injury: a meta-analysis of observational clinical studies. Intensive Care Med 2010, 36:
1657-1665.