CJASN ePress. Published on August 28, 2019 as doi: 10.2215/CJN.

03240319
Article

Kidney Support in Children using an Ultrafiltration

Device
A Multicenter, Retrospective Study

Shina Menon,1 John Broderick,2,3 Raj Munshi,1 Lynn Dill,4 Bradley DePaoli,2 Sahar Fathallah-Shaykh,4 Donna Claes,2,3
Stuart L. Goldstein,2,3 and David J. Askenazi4
1
Division of Pediatric
Abstract Nephrology, Seattle
Background and objectives Provision of kidney replacement therapy (KRT) to manage kidney injury and volume Children’s Hospital,
overload in critically ill neonates and small children is technically challenging. The use of machines designed University of
Washington, Seattle,
for adult-sized patients, necessitates large catheters, a high extracorporeal volume relative to patient size, and
Washington; 2Center
need for blood priming. The Aquadex FlexFlow System (CHF Solutions Inc., Eden Prairie, MN) is an ultrafiltration for Acute Care
device designed for fluid removal in adults with diuretic resistant heart failure. It has an extracorporeal volume of Nephrology,
33 ml, which can potentially mitigate some complications seen at onset of KRT in smaller infants. Cincinnati Children’s
Hospital Medical
Center, Cincinnati,
Design, setting, participants, & measurements In this multicenter, retrospective case series of children who Ohio; 3Department of
received KRT with an ultrafiltration device (n=119 admissions, 884 circuits), we report demographics, circuit Pediatrics, University
characteristics, complications, and short- and long-term outcomes. Patients were grouped according to weight (,10, of Cincinnati College
10–20, and .20 kg), and received one of three modalities: slow continuous ultrafiltration, continuous venovenous of Medicine,
Cincinnati, Ohio; and
hemofiltration (CVVH), or prolonged intermittent KRT. Our primary outcome was survival to end of KRT. 4
Division of Pediatric
Nephrology,
Results Treatment patterns and outcomes varied between the groups. In patients who weighed ,10 kg, the primary University of Alabama
indication was AKI in 40%, volume overload in 46%, and ESKD in 14%. These patients primarily received CVVH at Birmingham,
(66%, n=48) and prolonged intermittent KRT (21%, n=15). In the group weighing .20 kg, volume overload was Birmingham, Alabama
the primary indication in 91% and slow continuous ultrafiltration was the most common modality. Patients ,10 kg
Correspondence:
had lower KRT survival than those .20 kg (60% versus 97%), more volume overload at onset, and received
Dr. Shina Menon,
KRT for a longer duration. Cardiovascular complications at initiation were seen in 3% of treatments and none were Division of Pediatric
severe. Complications during therapy were seen in 15% treatments and most were vascular access–related. Nephrology, Seattle
Children’s Hospital,
Conclusions We report the first pediatric experience using an ultrafiltration device to provide a range of Seattle, WA 98145-
5005. Email: shina.
therapies, including CVVH, prolonged intermittent KRT, and slow continuous ultrafiltration. We were able to menon@
initiate KRT with minimal complications, particularly in critically ill neonates. There is an unmet need for seattlechildrens.org
devices specifically designed for younger patients. Having size-appropriate machines will improve the care
of smaller children who require kidney support.
CJASN 14: ccc–ccc, 2019. doi: https://doi.org/10.2215/CJN.03240319

Introduction States, there are no CRRT machines approved by the

AKI and volume overload are common and are
associated with morbidity and mortality in critically
ill neonates and children (1–3). In recent years,
continuous renal replacement therapy (CRRT) has
emerged as the preferred modality to provide kidney
support to such children (4). CRRT is used sparingly in
neonates and is associated with worse outcomes
compared with larger children (5,6).
The main reasons for the lower use of CRRT in
infants are that it is technically challenging and has
higher risk of complications than in older and larger
children (weighing .10 kg). Machines designed for
adult-sized patients require larger catheters, tubing,
and filters, which result in a high extracorporeal
volume relative to patient size (6,7). In the United
US Food and Drug Administration (FDA) for use in
children ,20 kg; nevertheless, existing CRRT ma-
chines approved for use in older children are used off-
label in small children. To reduce the complications at
KRT initiation from large extracorporeal volume,
most centers prime the circuit with blood when the
extracorporeal volume is .10% of total blood volume.
Although blood primes are generally safe, they can
result in hypocalcemia, hyperkalemia, acidosis,
thrombocytopenia, and coagulopathy around initia-
tion. A recent single study evaluation of hemody-
namic stability in neonates (eight patients, 70 sessions)
after CRRT initiation showed that 55% of sessions had
intradialytic hypotension, most of which occurred
shortly after CRRT initiation (8).

www.cjasn.org Vol 14 October, 2019 Copyright © 2019 by the American Society of Nephrology 1
2 CJASN
Furthermore, dialysis machines with smaller extracor-
poreal volume may provide an option for KRT to neonates
with ESKD who are unable to initiate peritoneal dialysis
(PD) because of their small size, recent abdominal surgery,
or abdominal wall defect.
Novel machines designed for neonates are used in a
few centers in Europe, but are not currently available in
the United States (9,10). The Aquadex FlexFlow System
(Aquadex; CHF Solutions Inc., Eden Prairie, MN) is FDA-
approved for isolated ultrafiltration (UF) in adults with
diuretic-resistant congestive heart failure (11,12). With an
extracorporeal volume of 33 ml, it can mitigate some
complications seen at CRRT initiation in smaller infants.
Askenazi et al. (7) published a case series of continuous
venovenous hemofiltration (CVVH) in 12 infants and small
children by adapting the device. They were able to initiate
CVVH with minimal complications (7).
Volume overload is common in critically ill children
(13,14). Although volume overload and AKI are often
interrelated and have similar deleterious effects, they
may not always occur together. Volume overload may be
seen without significant kidney dysfunction, as in patients
with congestive heart failure or nephrotic syndrome. These
children are often managed conservatively with diuretics and
an ultrafiltration device has not been widely used (15). Given
that volume overload, with or without AKI, is a common
indication for kidney support in children, the paucity of data
on its use in pediatrics is surprising.
We performed a multicenter study to report the charac-
teristics of children who received kidney support with
Aquadex. We describe demographics and short- and long-
term outcomes in these patients. We also report differences
in KRT modality (slow continuous ultrafiltration versus
CVVH versus prolonged intermittent kidney replace-
ment therapy), circuit characteristics, and complications
during KRT.
Materials and Methods
Study Design and Population
This is a multicenter, descriptive, retrospective case
series of children aged 0–20 years, who received KRT
with an ultrafiltration device from January 2012 to March
2018 at three United States pediatric hospitals (Seattle
Children’s Hospital [SCH], Seattle, WA; Children’s of
Alabama [COA], Birmingham, AL, and Cincinnati Child-
ren’s Hospital Medical Center [CCHMC], Cincinnati, OH).
Patients were included from the intensive care units,
inpatient floors, and chronic dialysis units. For each pa-
tient, the decision to initiate KRT and the modality pre-
scribed was per clinician discretion, after reviewing the
options of care with the primary team and family. Clin-
ical informed caregiver consent for KRT was obtained in
accordance with policies for all acute KRT procedures
(hemodialysis, PD, CRRT) at each institution. Local insti-
tutional review boards at each center approved the study,
with a waiver of informed research consent.
Demographic, clinical, and circuit data were collected
through medical record review, and from institutional
CRRT clinical quality improvement databases. Data in-
cluded sex, age/weight at admission, primary indication
for KRT (AKI, electrolyte abnormalities, volume overload,
and ESKD), percent fluid overload (volume overload%),
and catheter location and size.
Volume overload% was calculated with the formula
described by Selewski et al. (16):
Volume overload% ¼ ½CRRT initiation weight ðkgÞ  –
Hospital admission weight ðkgÞ=
Hospital admission weight ðkgÞ 3 100%:
Circuit data included maximal blood pump flow rate,
complications at initiation and during therapy, and anti-
coagulation method. We looked at overall circuit life and
the proportion of CVVH circuits that survived to 60 hours.
For the latter metric, we censored circuits that were dis-
connected for procedures or other patient-related issues as
has been described previously by the Prospective Pediatric
CRRT (ppCRRT) registry (17).
The primary outcome was patient survival to end of KRT
using the ultrafiltration device, i.e., the patient no longer
needed KRT or was transitioned to another modality.
Secondary outcomes included survival and kidney func-
tion at 1 year or last follow up.
Patients were grouped by weight (,10, 10–20, and .20 kg)
for analyses. We chose these categories on the basis of previ-
ous studies that have looked at CRRT in patients ,10 kg,
and because CRRT machines are FDA-approved for
children .20 kg (5,6,18).
Treatment Modality
Kidney support modalities included CVVH, prolonged
intermittent KRT, or slow continuous ultrafiltration (Sup-
plemental Table 1). The three centers differed in their choice
of therapy. CVVH was primarily used at SCH and COA,
prolonged intermittent KRT was primarily used at
CCHMC, and slow continuous ultrafiltration was per-
formed at all three.
CVVH was provided using replacement fluids as pre-
viously described (7). Briefly, this device uses the UF 500
filter set, which has a polysulfone membrane with a 0.12 m2
surface area and a 33 ml ECV. The set has pre- and postfilter
pigtail ports, an air detector, and a blood-leak detector. The
blood pump can run at 10–40 ml/min (at intervals of five).
The effluent dose used for CVVH was 24 ml/kg per h (at
COA) or 2000 ml/1.73 m2 per hour (at SCH and CCHMC),
which is within the maximum UF rate of the device. The UF
pump has a range of 0–500 ml/h (at intervals of 10 ml/h)
and an accuracy of 610% of setting.
Pre- or postfilter replacement fluid was infused with an
Alaris (Becton, Dickinson and Company, Franklin Lakes,
NJ) fluid infusion system via the proximal or distal pigtail,
respectively. Prismasol or phoxillum (Gambro Renal Prod-
ucts, Inc., Daytona Beach, FL) was used as replacement
fluid. UF rates were on the basis of the hourly fluid intake
and overall desired fluid balance. CVVH circuits were
changed at least every 72 hours per manufacturer protocol.
During CVVH or prolonged intermittent KRT, heparin anti-
coagulation was infused through a y-connector on the
withdrawal (access) line. Laboratory analysis to assess
anticoagulation was drawn from the postfilter pigtail. A
blood warmer (AstoFlo Plus Stihler Electronic; Stuttgart,
Germany or HOTLINE Blood and Fluid Warmer; Smiths
CJASN 14: ccc–ccc, October, 2019
Medical, Dublin, OH) was placed on the infusion line if
required.
Slow continuous ultrafiltration was used to treat isolated
volume overload. This did not involve provision of re-
placement fluid and the duration of therapy was typically
6 hours. Therapy was labeled as prolonged intermittent
KRT when hemofiltration (similar to CVVH above) was
performed for an extended period of 6–8 hours, either daily
or multiple times per week. The dose used for prolonged
intermittent KRT was 2000 ml/1.73 m2 per hour for 6–8 hours.
The typical blood pump speed (Qb) was 30–40 ml/min.
Circuits were primed with packed red blood cells
(pRBCs) or crystalloid. Crystalloid primes were used if
the extracorporeal volume was ,10% of total blood
volume, and the patient was clinically stable. If extracor-
poreal volume $10% of total blood volume, the circuit was
primed with pRBCs per each institution’s protocol. At
SCH, pRBCs are mixed 1:1 with 5% albumin for the prime.
At COA, prime includes pRBCs and sodium bicarbonate
in equal parts, and CCHMC uses pRBCs only. Calcium
gluconate was given for all initiations at COA, and at SCH
and CCHMC was given per clinician decision. If a blood
primed circuit was undergoing a planned circuit change,
the new circuit was crossprimed with blood from the
expiring circuit, when possible.
Statistics
The Shapiro–Wilk test was used to check for normal
distribution. Data were not normally distributed, so con-
tinuous variables are reported as median (with inter-
quartile range [IQR]). Categorical variables are reported
as number and percentage. For analysis, R program was
used (R Core Team, 2018; https://www.R-project.org/.)
Results
Patient Characteristics
We present data on 117 unique patients (Figure 1).
Patients were divided into three groups by weight (,10 kg,
n=72; 10–20 kg, n=13; .20 kg, n=32). Two patients in the
.20 kg group had a repeat admission requiring KRT with
the ultrafiltration device .12 months after the first admis-
sion; thus there were a total of 119 separate hospital
encounters (Table 1). For the short-term outcomes, we
evaluated all 119 encounters individually; for long-term
outcomes, we looked at 117 patients and considered the
first encounter.
The median age and weight at onset of KRT are shown in
Table 1. In the ,10 kg group, 44 (61%) were ,30 days old
and 58 (82%) weighed ,5 kg.
Most patients had an underlying kidney or cardiac
disease; however, the indication for KRT was different
between the groups. In ,10 kg group, the primary indi-
cation was AKI and electrolyte abnormalities in 25%,
volume overload in 46%, AKI and volume overload in
15%, and ESKD (with relative or absolute contraindica-
tion for PD) in 14%. These patients primarily received
CVVH (66%, n=48) and prolonged intermittent KRT
(21%, n=15). In patients weighing .20 kg, volume overload
was the primary indication in most (91%, n=31) and slow
continuous ultrafiltration was the most common modality
(94%, n=32).
Pediatric KRT using an Ultrafiltration Device, Menon et al. 3
Primary Outcome
Of the 72 patients ,10 kg, 43 (60%) patients survived to
end of KRT with the ultrafiltration device or transitioned to
another modality of kidney support, and 23 (32%) survived
to hospital discharge. Among patients .20 kg, 33 (97%)
survived to KRT discontinuation and 23 (68%) survived to
hospital discharge.
Secondary Outcomes
We looked at survival and kidney outcomes at last
follow-up for patients who were discharged from the
hospital (Table 2). In the ,10 kg group, of the 23 who
survived to hospital discharge, two were transferred to
another facility and 12 survived to last follow-up. The
median follow-up duration was 13 months (IQR, 12–24)
and age at last follow-up was 16 months (IQR, 12–25). In
this group, five patients had ESKD, including two who
subsequently received a kidney transplant. Of those, three
patients had initiated KRT for underlying CKD and two
progressed to ESKD from AKI. After excluding those with
ESKD, median eGFR at follow-up was 111 ml/min per
1.73 m2 (IQR, 102–131).
In the entire cohort, hypertension was present in 15
(60%) patients and proteinuria (.0.2 mg protein/mg
creatinine on a spot sample) was seen in six patients at
last follow-up.
Circuit Characteristics and Outcomes
We report on 884 circuits used over 2338 days. Of these,
157 circuits were for slow continuous ultrafiltration, 190
for prolonged intermittent KRT, and 537 for CVVH (Supple-
mental Table 2). We looked at complications at initiation
and during KRT, according to weight (Table 3).
The right internal jugular vein was the most common
location for vascular access, followed by the femoral vein.
Heparin was used in .80% circuits (n=731). No antico-
agulation was used in 126 circuits (14%). Citrate anti-
coagulation was attempted in one patient (two circuits).
However, it was not successful because of the need for
multiple lines and a nonintegrated system.
The median circuit life for the 537 CVVH circuits was
66 hours (IQR, 30–71). Of the CVVH circuits, 71 out of 537
(13%) were discontinued because of patient issues (with-
drawal of cardiopulmonary support, elective therapeutic
plasmapheresis, radiologic and/or surgical procedures,
or improvement in patient condition and trial off CVVH)
and ten out of 537 (2%) circuits underwent planned
change before 60 hours for staff scheduling reasons.
After censoring circuits that were changed because of
patient issues or scheduling, we evaluated the remaining
456 out of 537 (85%) circuits and found that 309 (68%) of
these circuits lasted for $60 hours, whereas 147 out of
309 (32%) had circuit loss, defined as unplanned, early
termination at ,60 hours. The reasons for early termi-
nation include clot in the circuit (98 out of 147, 67%),
problems with vascular access (32 out of 147, 22%),
machine malfunction (14 out of 147, 9%), and unknown
(three out of 147, 2.0%).
Overall, only 28 out of 884 (3%) circuit initiations
required an increase in cardiovascular support, and most
(24 out of 28, 86%) were in the group weighing #10 kg
(Table 3). In this group, the interventions included extra
4 CJASN

Children who received KRT

using an ultrafiltration device
N=117

Weight 10 kg, Weight 10-20 kg, Weight > 20 kg,

N=72 N=13 N=32*

Treatment Modality

SCUF 9
SCUF 5 SCUF 30*
Prolonged intermittent
CVVH 8 CVVH 2
KRT 15
CVVH 48

Hospital Mortality

49 died: 2 died: 11 died:

29 on KRT Came off KRT, but died 1 on KRT
20 came off KRT, but died prior to discharge 10 came off KRT, but died
prior to discharge prior to discharge

Survival and Kidney

Outcome at Discharge

N=23 N=11 N=21

Normal kidney function=10 Normal kidney function=3 Normal kidney function=4
Acute Kidney Disease=1 Chronic Kidney Disease=8 Acute Kidney Disease=7
Chronic Kidney Disease=11 Chronic Kidney Disease=10
Not known=1

9: died after discharge 2: died after discharge 7: died after discharge

2: Transferred 1: Transferred

Survival and Kidney

Outcome at Follow up

N=12 N=8 N=14

Normal kidney function=5 Normal kidney function=4 Normal kidney function=3
Chronic Kidney Disease=2 Chronic Kidney Disease=1 Chronic Kidney Disease=6
Dialysis=3 Dialysis=1 Kidney transplant=4
Kidney transplant=2 Kidney transplant=2 Unknown=1

Figure 1. | Flow diagram of all children who initiated kidney replacement therapy using an ultrafiltration device, according to their weight at
initiation, through hospital discharge and follow-up. *Two patients had two admissions .12 months apart. For this figure, their first admission
was used. KRT, kidney replacement therapy; SCUF, slow continuous ultrafiltration; CVVH, continuous venovenous hemofiltration.

volume of saline, 5% albumin, or pRBCs in 17 out of
24 (70%), and a new inotrope or an increase in dose of
inotropes in eight patients. Four patients in the group
weighing 10–20 kg had cardiorespiratory complications at
circuit initiation. No complications at circuit initiation were
seen in the .20 kg group (Table 3). None had severe
decompensation associated with circuit initiation.
Overall, complications during therapy were seen in 132
out of 884 treatments (15%). In the group weighing ,10 kg,
complications were seen in 106 treatments (15%) and were
CJASN 14: ccc–ccc, October, 2019 Pediatric KRT using an Ultrafiltration Device, Menon et al. 5

Table 1. Patient characteristics

Group 1 (Weight ,10 kgs) Group 2 (Weight 10–20 kgs) Group 3 (Weight .20 kgs)
Characteristic
n=72 n=13 n=34a

Age at first KRT 19 (7, 87) d 26 (17, 38) mo 190 (158, 258) mo
Patient location
Neonatal ICU 46 (64) 1 (8) 0
Cardiac ICU 13 (18) 3 (23) 12 (35)
Pediatric ICU 12 (17) 8 (62) 16 (47)
Dialysis unit 1 (1) 1 (8) 4 (12)
Inpatient floor 0 0 2 (6)
Base weight, kg 3.2 (2.6, 4.3) 12.3 (11.5, 13.7) 58.7 (37.1, 77)
Weight at onset of therapy, kg 4.1 (3.1, 5.6) 15.1 (12.9, 15.9) 60.1 (38.2, 79.2)
Female 34 (47) 3 (23) 20 (59)
Primary disease
Cardiac 21 (29) 2 (15) 13 (38)
Kidney 31 (43) 7 (54) 8 (24)
Other 20 (28) 4 (31) 13 (38)
Primary indication
Volume overload 33 (46) 7 (54) 31 (91)
AKI and electrolyte abnormalities 18 (25) 2 (15) 0
AKI and volume overload 11 (15) 1(8) 2 (6)
ESKD 10 (14) 3 (23) 1 (3)
Treatment modality
Slow continuous ultrafiltration 9 (12) 5 (38) 32 (94)
Prolonged intermittent KRT 15 (21) 0 0
CVVH 48 (67) 8 (62) 2 (6)
Volume overload at onset of KRT (%) 20 (5, 40) 20 (8, 23) 7 (3, 11)
Days in hospital before KRT 13 (3, 28) 21 (7, 88) 11 (3, 35)
Days in ICU before KRT 12 (2, 23) 11 (3, 97) 6 (2, 20)
Days on Ultrafiltration Device 9 (3, 33) 7 (5, 14) 1 (1, 3)
Number of circuits 4 (2, 10) 3 (2, 6) 2 (1, 3)
Initial catheter site
Right internal jugular 46 (64) 6 (46) 19 (56)
Femoral 19 (26) 3 (23) 7 (21)
Other 7 (10) 4 (31) 8 (24)
Initial catheter size
6 Fr 25 (35) 3 (23) 1 (3)
7–8 Fr 37 (51) 7 (54) 5 (15)
9–10 Fr 5 (7) 2 (15) 8 (23)
12–14 Fr 0 1 (8) 20 (59)
Other 5 (7) 0 0
Treatment course survival 43 (60) 13 (100) 33 (97)
Hospital survival 23 (32) 11 (85) 23 (68)
Kidney outcome at discharge among (n=23) (n=11) n=23
survivors
Normal kidney function 10 3 4
Acute kidney disease 1 0 7
CKD 11 8 12
Not known 1 0 0

Continuous variables are shown as median (interquartile range) and categorical variables as number (percentage). The percentages
may not add up to 100 because of rounding. KRT, kidney replacement therapy; d, days; mo, months; ICU, intensive care unit; CVVH,
continuous venovenous hemofiltration.
a
Two patients had repeat admissions .12 months apart requiring KRT and are counted as separate.

primarily vascular access–related, with a clot in 37 and Discussion

catheter malfunction in 12. Bleeding was seen in 17,
primarily oozing from catheter insertion sites that im-
proved with modification of anticoagulation. None had
known cerebral or pulmonary hemorrhage attributed to
KRT. Hypothermia was seen in four treatments in this
group. Clot in the line and hypotension during treatment
were the commonest complications in patients weighing
10–20 kg and .20 kg. Other rare complications (seen in
four or fewer treatments each across the entire cohort)
included thrombocytopenia, seizure, arrhythmias, acidosis,
and hypomagnesemia.
We report a three-center experience with an ultrafiltra-
tion device, in children. We used it to provide a range of
kidney supportive therapies, including CVVH, prolonged
intermittent KRT, and slow continuous ultrafiltration. Adapt-
ing this system to provide CVVH allowed us to initiate
KRT with minimal complications in critically ill neonates.
More than 50% of infants weighing ,10 kg survived to
come off KRT with this device or transition to another
modality of kidney support. We were also able to provide
kidney support to neonates with ESKD who were unable
to receive PD. In patients weighing .20 kg, who primarily
6 CJASN

Table 2. Outcomes at last follow-up of unique patients who survived to hospital discharge

Group 1 (Weight ,10 kg), Group 2 (Weight 10–20 kg), Group 3 (Weight .20 kg),
Characteristics
n=23 n=11 n=21a

Outcome at last follow up Expired=9 Expired=2 Expired=7

Alive=12 Alive=8 Alive=14
Transferred=2 Transferred=1 Transferred=1
Age, mo 16 (12, 25) 41 (35, 57) 221 (192, 259)
Median follow-up duration, 13 (12, 24) 20 (19, 26) 27 (22, 46)
months
Kidney outcome n=12 n=8 n=14
eGFR.150 1 0 0
eGFR 90–150 5 4 3
eGFR 60–90 0 1 2
eGFR,60 1 0 4
eGFR,15 3 1 0
Kidney transplant 2 2 4
Unknown 0 0 1
Median eGFR at last follow upb 111 (102, 131) 98 (94, 124) 66 (53, 102)

eGFR, estimated Glomerular Filtration Rate. eGFR is reported in ml/min per 1.73 m2.
a
Two patients had repeat admissions requiring kidney replacement therapy. Follow-up data are from their first admission.
b
After excluding those with eGFR,15.

received slow continuous ultrafiltration, 97% survived to end
of therapy. In addition, we were able to manage a small
group of patients with volume overload in the outpatient
dialysis unit.
Many of our patients who received CVVH were small,
young, and critically ill. Because of the challenges pre-
viously discussed, a majority of these may not have
traditionally received KRT (2,6). The main advantage to
the use of this device is the ability to initiate therapy with
excellent hemodynamic stability. Fewer than 4% treat-
ments had any complications reported at initiation, and
none were serious enough to interrupt initiation. The
incidence of cardiopulmonary complications at circuit
initiation in infants using other machines has not been
widely reported. A recent study reported hypotension at
onset in 55% of CRRT sessions in neonates with 25%
showing recovery within 60 minutes (8).
In addition, use of machines with smaller filters (and
corresponding tubing sets with lower extracorporeal vol-
ume) help reduce the frequent exposure to blood products
for blood prime and allow for smaller vascular access
and lower blood flow rates (18–20). Using the rule that
anyone with extracorporeal volume .10% receives a blood
prime, the smallest available filter most commonly used in
the United States (Prismaflex M60; extracorporeal volume
93 ml) necessitates blood prime for anyone weighing
,11.5 kg. By using the ultrafiltration device, we were able
to avoid blood prime for 23 patients weighing between 4
and 11.5 kg.
Complications during therapy were also infrequent,
and mostly related to vascular access (clot or catheter
malfunction) or minor bleeding at catheter insertion sites.
Hypothermia was reported in four treatments and all
were before the use of an in-line blood warmer. Once
again, there are limited reports on complications of CRRT
in infants.
This ultrafiltration device has not been widely used in
children even for its traditional indication of slow contin-
uous ultrafiltration (15). Although it is FDA-approved in
patients weighing .20 kg, we included these patients in
our study to highlight the clinical use of this device in the
pediatric setting, particularly in patients with congenital
heart disease and cardiomyopathies with associated heart
failure. In our study, 50 patients (40%) underwent 157
treatments for UF only. Of these, six patients were able to
receive treatment in the dialysis unit. The ease of doing
UF and a low rate of complications suggests a promising
role for this therapy in the ambulatory management of
patients with diuretic-resistant volume overload, such as
those with steroid-resistant nephrotic syndrome or con-
gestive heart failure.
Our intensive care unit and hospital survival rate for
patients ,10 kg was 32%, which is lower than some
previous studies. Symons et al. (5) reported 38% survival to
intensive care unit discharge in children ,10 kg; however,
in the #3kg subgroup the survival was only 25%. Data
from the ppCRRT registry reported an intensive care unit
survival rate of 44% in children #5 kg (6). A more recent
study showed a higher intensive care unit survival rate
(57%) in infants ,10 kg receiving CVVH (18). However,
28% of their cohort had inborn errors of metabolism, which
typically has better outcomes. They also did not include
patients with complex cardiac problems who have higher
mortality and the smallest patient weighed 2 kg. The lower
survival in our cohort likely reflects the fact that our
patients were more premature, had lower weight, and more
comorbidity. In our cohort, six patients weighed ,2 kg and
the smallest patient was 1.4 kg. KRT using existing dialysis
machines would have been difficult and they may not have
received KRT without this adapted system.
Our 1-year survival for children ,10 kg was 52%; in
the subset of patients who were #30 days at initiation of
KRT, it was 16%. This low rate was also secondary to
factors mentioned above. Limited data are available on the
long-term outcomes of children who start KRT at a younger
age. In the multinational study by van Stralen et al. (21),
children with ESKD who started KRT in the neonatal
period had an estimated 2-year survival of 81% and 5-year
CJASN 14: ccc–ccc, October, 2019 Pediatric KRT using an Ultrafiltration Device, Menon et al. 7

Table 3. Circuit characteristics by patient weight

Group 1 (Weight Group 2 (Weight Group 3 (Weight

Characteristic
,10 kg), n=711 10–20 kg), n=66 .20 kg), n=107

Blood flow rate, ml/min 40 (30, 40) 40 (30, 40) 40 (40, 40)
Cardiorespiratory support at initiation (or with 24 (3) 4 (7) 0
complications at initiation)
Type of support neededa
Normal saline 4 1 —
Inotrope 8 — —
Calcium chloride 1 2 —
Albumin 8 1 —
Sodium bicarbonate 2 — —
Blood transfusion 5
Circuits with complications during therapy 106 (15) 12 (18) 15 (14)
Type of complicationa
Hypothermia 4 — —
Bleeding 17 — —
Hypotensionb 30 3 4
Clot 37 9 6
Thrombocytopenia 2 — —
Seizure — — 2
Catheter malfunction 12 — —
Other 8 — 3
Anticoagulation
Heparin 616 47 68
Citrate 2 — —
Argatroban 0 11 3
None 91 5 30
Unknown/other 2 3 6

Continuous variables are shown as median (interquartile range) and categorical data as number (%). —, zero.
a
Some patients needed more than one intervention or had multiple complications.
b
Hypotension was defined as needing bolus of fluid, new inotrope requirement, or an increase in rate of existing inotrope infusion.

survival of 76%. They did not include children in whom
kidney support was withheld or withdrawn early because
of various reasons, or those who died shortly after
initiation, thus potentially overestimating their survival
rates. Another study reported 65.3% (32 out of 49) mortality
in neonates who started CRRT in the first 30 days of life
(22). The median age of death was 22 days, with 56% of the
total deaths occurring within the first 30 days of life, and
94% within the first year. The authors did not comment on
long term kidney outcomes (20). Nishimi et al. (8) reported
75% mortality in neonates who underwent CRRT; five out
of eight died within 3 months, and one died at 2 years.
Although we have been able to successfully provide
CVVH using an ultrafiltration device, it has certain limita-
tions. As it was designed for slow continuous ultrafiltration,
it does not have a pump to provide countercurrent dialysis
and can only provide CVVH. The replacement fluid and
heparin infusions have to be given through separate flow
regulators external to the device that are not integrated with
it. This requires extra vigilance on the part of the nursing
staff in case either the CRRT pump or the replacement fluid
flow regulator is not running. The accuracy of the UF pump
is 610% of setting, which can be a clinically significant
volume change for smaller patients. Additionally, although
the extracorporeal volume is low (33 ml), infants weighing
,4 kg will still require a blood prime (for extracorporeal
volume .10%).
The ultrafiltration device has a sensor that allows non-
invasive monitoring of hematocrit and can be used to guide
UF. Changes in hematocrit are inversely proportional to
changes in patient blood volume. A typical setting alerts
the clinician when the patient’s blood volume change
exceeds 10%. This technology has been previously used in
the maintenance hemodialysis setting to reduce intradia-
lytic events related to UF (23,24). There are limited data on
its use in acute KRT. We used noninvasive monitoring in
some of our older patients to guide UF. However, we do
not have data on this.
These problems can be addressed by machines specifi-
cally developed for providing kidney support to small
children. The Cardio-Renal Pediatric Dialysis Emergency
Machine (CARPEDIEM) is a pump-driven machine with
filters available in three sizes (ranging in volume from 27.2
to 41.5 ml) (9). It can be used with catheters as small as
4 Fr to provide blood flow rates of 5–50 ml/min (25). The
Newcastle Infant Dialysis and Ultrafiltration System
(NIDUS) has been designed to provide continuous veno-
venous hemodialysis to infants between 800 g and 8 kg
(10). It is a syringe-driven system (extracorporeal volume
of 10 ml) that withdraws 5–12.5 ml of blood and passes it
through a dialysis filter before returning to the patient.
NIDUS can be used with a 4 Fr single-lumen catheter.
Despite being able to provide kidney support success-
fully to a large cohort, we acknowledge certain limita-
tions in our study. Being a retrospective study, we were
dependent on data available in our quality improvement
database and medical records. In certain cases where the
reason for escalation of inotropic support was not specified,
we assumed it to be secondary to CRRT initiation. Infor-
mation on complications of access placement, including the
8 CJASN
need for multiple catheters was not collected and included
in this analysis. Furthermore, as a retrospective study, the
data are subject to center and patient selection bias.
In conclusion, we report the first large experience in
pediatrics using an ultrafiltration device, both for UF and
for modified CVVH. This study speaks to the unmet need
for devices specifically designed for younger patients. With
the use of a machine with small extracorporeal volume, we
could initiate CRRT safely without significant cardiovas-
cular decompensation. Having more size-appropriate ma-
chines will shift the benefit–risk equation such that small
children can get the benefit of kidney support to a level that
is closer to larger children and older patients.
Disclosures
Dr. Goldstein reports personal fees from and a position as a
consultant to CHF Solutions Inc. which manufactures the Aquadex
device. Dr. Goldstein also consults for Medtronic Inc. (Minneapolis,
MN) which manufactures a CRRT device. Dr. Goldstein receives
grant funding from and serves as a consultant and on a Speaker’s
Bureau for Baxter Healthcare, Inc. (McGaw Park, IL), which manu-
facturers a CRRT device. Dr. Askenazi is on a Speaker’s Bureau
for Baxter Healthcare, Inc. (McGaw Park, IL). Dr. Askenazi is
also a consultant for CHF Solutions Inc. Dr. Askenazi reports
an education grant for neonatal AKI from CHF Solutions Inc.
Dr. Broderick, Dr. Claes, Dr. DePaoli, Ms. Dill, Dr. Menon,
Dr. Munshi, and Dr. Fathallah-Shaykh have nothing to disclose.
Funding
The authors have nothing to disclose.
Supplemental Material
This article contains the following supplemental material online
at http://cjasn.asnjournals.org/lookup/suppl/doi:10.2215/
CJN.03240319/-/DCSupplemental.
Supplemental Table 1. Description of the kidney replacement
therapy modality used.
Supplemental Table 2. Circuit characteristics by treatment
modality.
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Received: March 15, 2019 Accepted: July 17, 2019
S.M. and J.B. contributed equally to this work.
Published online ahead of print. Publication date available at
www.cjasn.org.