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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


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

mailto:[email protected]


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


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].


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


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, …


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)


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)


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:


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


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


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)


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.


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.


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


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.


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.


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.