HEMODIALYSIS FOR CHILDREN WITH CHRONIC KIDNEY DISEASE

Author:Lesley Rees, MD, FRCPCHSection Editor:Tej K Mattoo, MD, DCH, FRCPDeputy

Editor:Melanie S Kim, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.Literature review current through: Aug 2021. | This topic last updated: Sep 30, 2020.

INTRODUCTION

Chronic hemodialysis (HD) is technically feasible in children of all ages and even in very small
neonates [1]. Although the principles of HD are similar for adults and children, there are technical
aspects of the procedure and complications that are unique to the pediatric population. It is
crucial that these differences are recognized and addressed in order to effectively and safely
perform pediatric HD, thereby reducing complications in children who are facing a lifetime of
kidney replacement therapy (KRTKRT).

HD in children with chronic kidney disease (CKD), including discussions on types of vascular access
and dialyzers, dialysis prescription, and complications, will be reviewed here. Overviews on the
management of pediatric CKD and KRT are discussed separately. (See "Chronic kidney disease in
children: Overview of management" and "Overview of renal replacement therapy (RRT) for
children with chronic kidney disease".)

OVERVIEW

The goals of pediatric HD are the same as those in adults undergoing HD: effective and safe
clearance of uremic toxins and removal of excess fluid, with the additional need for preservation
of blood vessels to allow for a lifetime of kidney replacement therapy (KRT). The general principles
of HD and a description of HD apparatus are discussed separately. (See "Overview of the
hemodialysis apparatus".)

The following technical aspects of HD may differ in adults and children and need to be considered
and addressed in order to effectively and safely perform pediatric HD:

●Vascular access
●Extracorporeal circuit (eg, size and volume of tubing and dialyzer)
●Choice of dialyzer and machines
●Dialysis prescription particularly blood flows
●Complications and outcome measures

Multidisciplinary team — Successful management of the child on HD is not possible without input
and care from a multidisciplinary team. The team meets routinely to review and monitor the care
for the individual child and is available for any acute issue.
Key members of the team include:
●Nephrologists, nurses, and surgeons with expertise in caring for children receiving HD
●Dieticians who understand the implications of CKD and HD on nutrition and growth in affected
children
●Radiologists with expertise in pediatric vascular access imaging and intervention
●Play therapists who can prepare the child for dialysis and provide distraction therapy when
acquiring vascular access
●Social workers and psychologists to support both the patient and family
●School teachers/tutors, particularly for patients whose schooling is interrupted by center-based
dialysis sessions
VASCULAR ACCESS
Good vascular access is one of the most important factors for successful HD. The three forms of
vascular access in children are:
●Native arteriovenous (AV) fistulas – Preferred chronic access if feasible
●Subcutaneously tunneled central venous catheters (CVCs) – Used when temporary access is
needed
●Synthetic AV grafts – Used whenever other access(es) have failed
We suggest initiating HD through an AV fistula in pediatric patients in whom it is technically
feasible, who are likely to remain on HD and are expected to wait more than one year for a kidney
transplant, and who tolerate needling of the AV fistula [2,3]. AV fistulas are the most reliable long-
term HD access with the lowest mortality and complication rate [4]. A tunneled CVC is typically
used in children when HD access is required for a short duration of time.

AV fistula — AV fistula is the preferred vascular access for chronic HD because AV fistulas are
associated with fewer complications (eg, infection, decreased hospitalization and time spent in
hospital) and provide more reliable access over time than percutaneous CVCs or AV grafts [5-12].
They preserve veins above intravascular catheters for a longer time, thereby reducing damage and
subsequent vascular stenosis and collateral vessels. Over two-thirds of AV fistulas remain
functional after five years, whereas the survival of tunneled CVCs vary from 30 to 85 percent at
one year [5,7,13]. These results and reported excellent outcome from tertiary pediatric centers
regarding the use of AV fistulas for long-term pediatric HD has led to the "Fistula First" initiative,
which is focused on increasing the utilization of AV fistulas for pediatric patients [3,10,14-16].

Nevertheless, there are challenges to using AV fistulas at the time of initiation of HD:

●Early planning is required because AV fistulas require time to mature (ie, several weeks to
months) [17].
●Creating AV fistulas in small children (weight <15 kg) is technically difficult. Successful AV fistula
creation in infants and young children (weight <15 kg) has been reported in tertiary centers using
microsurgical techniques [14,18].
●Patient preparation is required for needling of the access.
Technique — AV fistulas are typically constructed with an end-to-side, vein-to-artery anastomosis.
Pre-surgery ultrasound assessment of vascular anatomy and size provides information in selecting
the vessels with the best chance of success. The preferred site is anastomosis of the radial artery
and cephalic vein (radiocephalic or wrist fistula) so that vessels further up the arm are available in
the event of fistula failure. In smaller children, anastomosis of the brachial artery and cephalic vein
(brachiocephalic or upper arm fistula) may be the better option due to size constraints [17]. A two-
stage basilic vein transposition (BVT) may also be used in small patients: in which, the arterialized
vein is moved to a more superficial position approximately two months after the anastomosis has
been created making access easier. In a report from a single US tertiary center, the primary
patency rates of BVT in 46 children between 3 and 18 years of age were 78 and 72 percent at two-
and four-year follow-up [17,19]. The use of regular ultrasound assessment of volume flow through
the AV fistula monitors AV fistula patency and need for intervention, such as angioplasty or
vascular surgery [16,20].

Central venous catheters — A tunneled CVC is typically used in children when HD access is
required for a short duration of time (eg, child awaiting living-related kidney transplantation).
When a CVC is used initially, the subclavian vein is not recommended as a site because it may
preclude successful subsequent creation of an AV fistula.

Globally, CVC is used in the majority of children when HD is initiated:

●The United States Renal Data System (USRDS) reported that the use of CVC as the vascular access
at the time of HD initiation has remained constant (range 78 to 83 percent) since 2006.
●Data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) from 2010
to 2014 showed that CVC was the initial vascular access in the majority of children between 0 and
17 years of age.
●International collaborative registries have reported CVC as the initial choice for vascular access in
55 percent of the cohort registered in the European Society for Paediatric Nephrology
(ESPN)/European Renal Association-European Dialysis and Transplant Association (ERA-EDTA)
Registry and 73 percent of patients registered in the International Pediatric Hemodialysis Network
(IPHN) Registry [12,21].
The reasons for the high prevalence of CVCs include [6,7]:
●It is technically more difficult to create AV fistulas, especially in small children
●Anticipation of a short and temporary dialysis course prior to kidney transplantation.
●Avoidance of needling accesses in children especially in young children or those with behavioral
problems.
Placement — Catheters are most commonly placed in the internal jugular vein and tunneled
superficially to exit on the upper anterior chest. The catheter tip should be located at the junction
of the superior vena cava (SVC) and right atrium, or in the right atrium to provide adequate blood
flow for dialysis. Catheters located in the SVC may have inadequate blood flow because the entry
and exit sites often seal off as they abut up against the vessel wall. In a small child, positioning of a
catheter can be difficult due to their size and is best undertaken using ultrasound guidance by a
skilled operator. In neonates, the femoral vein can be used as a temporary access, but this should
be avoided if possible, as damage to the inferior venal cava may make future transplantation more
difficult. The subclavian vein should be avoided if at all possible, as stenosis may prevent
successful fistula formation in the future.

Catheter selection — Catheter sizes range from 6.5 to 14 Fr and are chosen according to the vessel
size based on the weight of the child (table 1). Increasing the gauge of the vascular access will
allow for higher blood flow rates. However, too large a catheter can lead to obstruction of vessels,
resulting in reduced venous return and therefore poor flow through the dialysis circuit. Catheters
are available in different lengths based on the gauge (table 1).

In children undergoing chronic HD, cuffed CVCs commonly used are double-lumen catheters
composed of silicone or polyurethane composites. However, in small children (weight between 5
to 10 kg), the distance between the arterial and venous ends of the catheter in double-lumen
catheters may be too far apart to allow successful positioning of both lumens. In this setting, split
catheters (two catheters of equal length joined proximally but separated distally) (picture 1) or the
use of two separate single-lumen catheter systems (inserted in the same vein with different exit
sites or in different veins altogether) can be used.

In infants (body weight <5 kg), single-lumen access may be more appropriate because a larger
catheter can be inserted, remembering that flow is proportional to the fourth power of the radius.
In order to obtain two directional blood flows with a single-lumen line, single-needle HD without
an expansion chamber is used (click-clack). This can be achieved by using the single-pump method,
where the blood pump turns intermittently, using gravity to let blood flow back into the child.
These children typically require priming of the external circuit with donor blood, as the blood
circuit exceeds 10 percent of their total circulating volume. Of note, there is a larger degree of
recirculation with this system.(See 'Extracorporeal circuit' below.)

Complications — Poor function due to catheter malposition is the most frequent complication,
which is increasingly more common as the size of the child decreases.

Infection is a frequent complication and is linked to malpositioning because repeated

disconnection and flushing of the line to improve flow increases the chances of introduction of
pathogens. Infection causes subsequent vessel damage and stenosis, furthering the problem of
poor flows and impairing future successful fistula creation. Strict catheter management using a
rigorous protocol of handwashing and sterile technique for personnel and catheter decreases the
risk of infection [9].

AV grafts — Arteriovenous (AV) grafts are made from a synthetic, inert material that can be used
to join an artery to a vein. AV grafts can be used in young children (<15 kg) in whom an AV fistula is
technically not feasible or when other access options have been exhausted. Complications such as
stenosis, thrombosis, and infection are more common in AV grafts than AV fistula leading to a
shorter vascular access survival time.

HD EQUIPMENT
Equipment for HD includes:

●Tubing●Dialyzer●Dialysis machine

Extracorporeal circuit — The extracorporeal circuit is composed of the arterial (inflow) and venous
(outflow) lines (tubing) and the dialyzer. The volume of this circuit is restricted by the upper safe
limit for extracorporeal blood volume that is dependent on the total blood volume of the patient.
A child can tolerate up to a maximum of 10 percent of his or her total blood volume in the
extracorporeal circuit, and a safe volume of the circuit is targeted at 8 percent of total blood
volume of the child. As an example, the upper safe limit for a child who weighs 10 kg (total blood
volume of 800 mL) would be 64 up to a maximum of 80 mL.

Commercially available tubing that varies in volume should be matched to the size of the patient
based on the upper safe limit of extracorporeal blood volume (table 2).

However, in some infants, even the smallest circuit may exceed the safe limit of extracorporeal
volume. In this setting, the circuit must be primed with donated blood. However, this increases the
risk of HLA (human leukocyte antigen) sensitization, with its consequent difficulties for
transplantation, and is one reason for choosing peritoneal dialysis (PD) in infants. If the lines are
primed, blood in the lines is not given back into the infant at the completion of HD unless a
transfusion is required, because this would be the equivalent of giving additional blood equal to
the volume of the lines to the child.

Dialyzer — The type of dialyzer generally used in children is a hollow fiber design that minimizes
blood volume, and provides reliable and predictable solute clearance and ultrafiltration
coefficients. A wide variety of hollow fiber dialyzers with different blood volumes is commercially
available, and the dialyzer is selected on the basis of the size of the child (ie, surface area of the
child) and the type of HD (eg, standard or hemodiafiltration [HDF]).

The size of the dialyzer is calculated by its surface area. The surface area should be as large as
possible to optimize clearances but should not exceed that of the child's body surface. At present,
most centers have dialyzers with surface areas ranging from 0.25 m2 up to 1.7 m2 and above.
Dialyzers for the new Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) and
Newcastle Infant Dialysis and Ultrafiltration System (NIDUS) machines are smaller. (See 'Small
infants' below.)

A discussion of the different types of dialyzers is presented separately. (See "Overview of the
hemodialysis apparatus", section on 'Dialyzer types'.)

HD machine — Components of the HD machine include a blood pump to move blood between the
patient and dialyzer, a delivery system to transport dialysis solution, and monitoring devices.
Pressure monitors located proximal to the blood pump and distal to the dialyzer guard against
excessive suction of blood from and excessive resistance to blood return to the patient's vascular
access site. Modern machines are able to combine diffusive and convective transport
(hemodiafiltration [HDF]) and generate ultrapure dialysis and infusion fluids online. (See
"Overview of the hemodialysis apparatus", section on 'Dialysis machines'.)

In addition, HD machines used in children, especially small children and infants, must have the
following characteristics:

●A volumetric fluid removal system that can directly measure ultrafiltrate (UF) volume (volume
removed during the dialysis treatment) and is capable of removing very small amounts of fluid.
●Ability to use low blood flow speeds. (See 'Blood flows' below.)
●Ability to use lines of varying blood volumes. (See 'Extracorporeal circuit' above.)
Small infants — CARPEDIEM and the NIDUS machines are much smaller dialyzers and are capable
of hemodialysing infants as small as 800 g [22-24].
●For the CARPEDIEM machine, double-lumen catheters as small as 4 to 4.5 Fr can be used along
with line volumes as low as 27 mL. Dialyzer surface areas range from 0.075 to 0.25 m2, and
miniature roller pumps deliver flow rates of 5 to 50 mL/min. In April 2020, the US Food and Drug
Administration approved the use of CARPEDIEM [25].
●For the NIDUS machine, a single-lumen catheter allows for better flows with an extracorporeal
circuit volume of less than 10 mL. Blood is aspirated and is then passed repeatedly through a high-
flux polysulfone 0.045 m2 hollow-fiber hemofilter before being returned to the patient.

Home HD — New portable HD machines for home use include the NxStage System One [26,27].
Dialysate can be prepared from tap water or be purchased as pre-prepared 5-liter bags. This offers
families the freedom of a portable machine that does not rely on plumbing of the home water
supply.

DIALYSIS PRESCRIPTION

For each patient, a dialysis prescription is developed so that there is adequate solute clearance
and removal of excess fluid. (See "Prescribing and assessing adequate hemodialysis".)

The components of the prescription include:

●Selection of the dialyzer

●HD or hemodiafiltration (HDF)
●Tubing selection (table 2)
●Blood flow rate
●Length and frequency of dialysis sessions
●Determination of fluid removal amount
●Dialysate composition
●Heparinization
Dialyzer — Each center typically picks one type of commercially available dialyzer for their unit,
although more than one type may be necessary depending on the sizes of dialyzer required and
whether the child is treated with conventional HD or HDF.
Each type of dialyzer has an ultrafiltration coefficient (KUf), which describes its ability to remove
water. KUf depends on the surface area of the dialyzer and its membrane characteristics. Dialyzers
with KUfs of less than 10 mL/hour are referred to as low flux, and those with a rate of 15 to 60
mL/hour per mmHg are called high flux.

High-flux dialyzers offer improved permeability for middle and larger molecules. They are
particularly needed for HDF. However, even with HD, there is some back diffusion, leading to
unquantified convective clearance. These types of filters, therefore, require the use of ultra-pure
water.

Blood flows — The speed at which the blood is pumped out of the child and around the circuit is
an important determinant of solute clearance. Although higher blood flows increase solute
clearance by optimizing diffusion and convection, excessive blood flows can compromise
cardiovascular stability. Blood flow speed has to be adjusted to the size of the child and should not
exceed his or her maximum extracorporeal volume in mL/min (ie, up to body weight [kg] x 8
mL/min) in order to safely maintain his or her cardiovascular status.

Length of dialysis and frequency of sessions

Conventional dialysis — Conventional HD is generally performed three times a week with the
duration of the session depending on the predetermined amount and rate of solute clearance and
fluid removal. Individual sessions are rarely less than four hours. However, this provides adequate
rather than optimum clearance [28].

Intensified dialysis — Solute clearance is greater with increasing dialysis time (intensified dialysis),
and data have suggested that in children, the longer the dialysis time, the better the outcomes.
Intensified dialysis compared with conventional dialysis resulted in better phosphate and blood
pressure (BP) control, improved appetite and growth, and, despite increased time spent on
dialysis, improved quality of life [29-35]. Additional support is based on the evidence of an
increased rate of hospitalization for fluid overload and hypertension during the longer interdialytic
break in children maintained on three times a week HD [29].

Schedules for intensified HD include intermittent sessions a week with longer dialysis time,
including a nocturnal schedule (length of single session ranges from six hours to overnight), more
frequent short daytime sessions (two to three hours five to seven times per week), or daily
nocturnal HD [30,35].

Although all children are likely to benefit from intensified dialysis, children who benefit the most
include patients:

●Who remain on HD long-term

●Who have chronic fluid overload, hyperphosphatemia, and/or poor growth
●Who have genetic metabolic disorders such as methylmalonic acidemia (MMA) or hyperoxaluria
(see "Organic acidemias: An overview and specific defects", section on 'Methylmalonic acidemia'
and "Primary hyperoxaluria")
●Who are infants, whose predominantly liquid diet requires removal of relatively large fluid
volumes.
However, the availability of longer hours of HD at dialysis centers is limited by resources [35,36].
Therefore, in many institutions, increasing dialysis frequency (ie, time) is reserved for infants in
whom fluid balance is difficult to control with conventional thrice weekly dialysis.

The use of intensified home HD (HHD) is increasing with the development of simpler new dialysis
machines [26,27] and is an option for children who have adequate housing and a family member
who is able and accepts the responsibility of performing HHD. HHD can be performed in smaller
children with the availability of circuits to dialyze children with weights from 12 kg.

HDF is also beginning to be used more widely in pediatrics as filters and lines are becoming
available for smaller children [37]. HDF is a combination of conventional hemodialysis with the
addition of hemofiltration, which utilizes increased transmembrane pressure to remove fluid and
solutes that can be cleared across the membrane. As a result, HDF raises the convective clearance
rate and thereby increases the solute clearance. HDF may be better tolerated in patients who are
hemodynamically unstable [38], and there is preliminary observational evidence that chronic HDF
may be associated with better outcome with growth and blood pressure control [39]. However,
clinical trials are needed to confirm these findings. (See "Alternative renal replacement therapies
in end-stage kidney disease", section on 'Hemofiltration and hemodiafiltration' and 'Small infants'
above and 'Home HD' above.)

Fluid removal — The amount of fluid removal per session is dependent on the difference between
the predialytic weight and the optimal weight of the patient, and whether the child has residual
kidney function. In some cases, children with adequate urine volume will not need fluid removal
during dialysis. However, in the majority of patients, fluid removal is necessary. Although the
amount of fluid that a child will tolerate losing per hour varies, a generally safe starting point is
approximately 10 mL/kg per hour. Removal of more than 5 percent of body weight in one session,
or 0.2 mL/kg per minute (12 mL/kg per hour), is very likely to result in symptomatic hypovolemia
(intradialytic hypotension). In children who weigh more than 40 kg, typically 600 mL/hour can be
removed without significant symptoms in patients who are consistently volume-overloaded as
they become tolerant of larger fluid shifts.

In some patients, attainment of optimum weight with conventional HD performed three times a
week can be challenging. This includes in infants who are maintained on a liquid diet and children
who have difficulty in complying with interdialytic fluid restriction. In these patients, high
interdialytic weight gains due to excess fluid retention require large ultrafiltration (UF) volumes
during each dialysis session that exceed the upper safe limit, resulting in symptomatic
hypovolemia. As a result, children with recurrent high interdialytic weight gains need more
frequent dialysis sessions (intensified dialysis) [27,40-43]. (See 'Length of dialysis and frequency of
sessions' above.)
Blood volume monitoring during dialysis — Ongoing technologic advances have made it feasible to
monitor intradialytic changes in blood volume resulting in more accurate fluid removal, thereby
avoiding excessive volume depletion or overload [38]. Blood volume monitoring is conducted
through a feedback loop that adjusts ultrafiltration rate and/or dialysate sodium concentration, or
hemoglobin monitoring using new built-in dialyzer systems that measure hematocrit. Clinicians
can set parameters for each dialysis session, which can be adjusted based on feedback from
ongoing intradialytic monitoring.

Residual kidney function — Intradialytic hypovolemia has been linked to loss of residual kidney
function (RKF) and cardiac injury (myocardial stunning) [44] (see 'Cardiovascular disease' below).
Maintaining RKF is important because RKF clears uremic toxins that are not removed by
conventional dialysis (eg, protein-bound molecules). Patients with RKF also have better volume
control, better phosphate and potassium clearance, lower requirements for erythropoietin, and
better quality of life and survival [15]. (See 'Length of dialysis and frequency of sessions' above.)

Estimation of optimum weight — Because of growth, estimation of optimum weight requires

regular ongoing assessment, and the frequency of monitoring depends on the age of the patient.
For example, in an infant, who should gain 200 g per week, assessment is needed every week,
whereas in a school-age child, weight can be assessed once a month.

At the end of each dialysis session, the child should be at his or her target/optimum weight,
defined as the weight below which the child will become symptomatically hypotensive. Target
weight can only be determined by careful but persistent fluid removal to achieve a normal BP for
age after dialysis. The child who is always hypertensive is likely to be above his or her target
weight; antihypertensive medications are usually unnecessary when optimum weight is achieved.

Bioimpedance spectroscopy and echocardiographic measurements of inferior vena cava

dimensions have been used to assess optimum weight [45,46]. However, reports of their reliability
are variable, and they are not used routinely. Lung ultrasound assessing B lines (image 1) alongside
clinical examination and blood pressure measurement is being evaluated as a tool to accurately
detect hypervolemia [47]. (See "Bedside pleural ultrasonography: Equipment, technique, and the
identification of pleural effusion and pneumothorax".)

Anticoagulation — Unfractionated heparin is the standard anticoagulant used during HD. It can be
infused slowly and continuously throughout the session to prevent blood clotting within the
circuit. It is administered at a rate of 5 to 50 units/kg per hour through the arterial side of the
circuit. Some units use low molecular weight heparin, given as a bolus at the beginning of the
dialysis session, particularly for patients on HHD. (See "Anticoagulation for the hemodialysis
procedure".)

Dialysate composition — Although the principals of selecting electrolyte composition of the

dialysate are similar to those of adults, specific pediatric issues include the following:
●Children with residual kidney function and proximal renal tubular acidosis may have ongoing
large urinary losses of bicarbonate, which need to be replaced using a high concentration of
dialysate bicarbonate.
●The normal range for calcium is higher in the first 12 months of life, and particularly in the first 6
months. As a result, the selection of dialysate calcium concentration is dependent on the plasma
calcium level and whether calcium influx or removal is required.
PROVISION AND ASSESSMENT OF HD

The provision of optimal pediatric dialysis is based on fulfilling the following [15]:
●Create and maintain a well-functioning and long-lasting vascular access:
•Proactive creation of an AV fistula ("Fistula First" policy) (see 'Vascular access' above)
•Use of optimal access technique to minimize infection and access failure
●If possible, maintain residual kidney function (RKF), as RKF clears uremic toxins that are not
removed by conventional dialysis; provides better volume control, phosphate and potassium
clearance, erythropoiesis; and reduces the need for fluid removal during dialysis (eg, avoiding
intradialytic hypovolemia). RKF preservation includes avoiding nephrotoxic medications and
intradialytic hypotension. Assessment of RKF includes regular monitoring of urine output.
●Obtain optimum weight at the end of each dialysis session, which results in normal blood
pressure and avoids antihypertensive medications.
●Provide adequate dialysis clearance. (See 'Adequate dialysis clearance' below.)
●Avoid pain and hypotension during and after dialysis – Pain (eg, cramps and headaches) and
hypotension are most often due to high ultrafiltration (UF) rates (UF rates >13 mL/kg per hour)
used when there is large interdialytic weight gain.
●Maintain adequate hematocrit, metabolic bone metabolism, nutrition, and growth. (See
"Pediatric chronic kidney disease-mineral and bone disorder (CKD-MBD)", section on
'Management' and "Chronic kidney disease in children: Complications", section on 'Target
hemoglobin goals' and "Chronic kidney disease in children: Complications", section on 'Fluid and
electrolyte abnormalities'.)
●Provide psychosocial and educational support, including promoting good school attendance.
Optimal care is provided by a multidisciplinary team that manages dialysis treatment and
nutrition, ensures effective vascular access, and provides psychosocial support. The team meets
routinely to review and monitor the care of the individual patient and is available for any acute
issue. (See 'Multidisciplinary team' above.)
Adequate dialysis clearance — In our center, assessment of adequate HD is performed once a
month for children who receive chronic HD and includes measures of dialyzer clearance of urea
(Kt/V), protein catabolic rate (PCR), and growth. Our target goals include Kt/V between 1.2 to 1.4,
PCR between 1 to 1.4 g/kg, and adequate growth.

Although measures of HD dialyzer clearance in children have not been studied, consensus
standards propose that they should be equal to or better than adult measures [7,48]. Measures
include:
●Dialyzer clearance of urea (Kt/V), where K is the clearance coefficient for urea of the dialyzer
measured as mL/min, t is duration of the of dialysis treatment measured in minutes, and V is the
distribution of urea in the body measure in mL. (See "Prescribing and assessing adequate
hemodialysis", section on 'Kt/V'.)

●Urea reduction ratio (URR) defined by the following formula (1 - [postdialysis blood urea nitrogen
(BUN) ÷ predialysis BUN]). (See "Prescribing and assessing adequate hemodialysis", section on
'Alternatives to Kt/V'.)
In children, it has been proposed that adequate clearance be defined as >1.2 for Kt/V and >65
percent for URR [7]. One pediatric study found an improvement in hospitalization rates when
using a Kt/V of 1.4 as a standard for HD adequacy, but above this level there was no further
improvement [48]. Other data suggest that daily or frequent short HD results in higher Kt/V, which
was associated with improvement in all aspects of patient well-being [27,40-43]. Measure of
middle molecule clearance includes assessing the clearance of phosphate or beta-2 microglobulin
but is not used clinically.

PCR, also called the protein equivalent of nitrogen appearance (PNA), is used to assess dietary
protein intake in patients who are in a steady state, and varies directly with Kt/V. It is used in
conjunction with Kt/V to determine whether a desirably low predialysis BUN represents a well-
nourished patient who is adequately dialyzed or a patient with a suboptimal protein intake and
inadequate dialysis. It is more sensitive and specific than albumin as a marker of nutritional status
because many processes unrelated to nutrition can affect albumin concentrations [49]. In children
who receive chronic HD, PCR should be measured at least monthly with a goal of 1 to 1.4 g/kg
along with an adequate Kt/V level to ensure adequate nutrition and dialysis clearance. Studies in
adults have shown that adequate dialysis clearance and nutrition are associated with lower
morbidity and mortality. (See "Protein intake in maintenance hemodialysis patients" and
"Prescribing and assessing adequate hemodialysis".)

Adequate growth is the ultimate goal for adequate management of children on chronic HD. It does
require adequate dialysis clearance but is also dependent on adequate nutritional intake as
discussed below. (See 'Growth' below.)

COMPLICATIONS

Complications of HD seen in children include malnutrition, poor growth, mineral and bone
disorders, increased risk of neurodevelopmental and psychosocial impairment, and cardiovascular
disease.

Inadequate nutrition — Inadequate nutrition is common in children receiving chronic HD, and is
associated with an increased risk of poor growth and death. The risk of death increases with a
decrease in serum albumin and when height standard deviation score (SDS) is more than one
below normal height standard deviation score (SDS) below normal and is highest for children with
a height SDS <2.5 [50-53].
In children on HD, guidelines from both the United Kingdom [54] and United States [55]
recommend a normal carbohydrate intake and an increase in the recommended protein intake for
an age-matched population. The increase in protein intake is recommended to be 0.1 g/kg per day
(but may need to be more in very small children) to allow for losses of amino acids into the
dialysate [55].

Since it may be difficult to achieve an adequate dietary intake, either oral or enteral
supplementation may be needed. Intradialytic parenteral nutrition has been used during HD in
children, but patient numbers are small, so it is difficult to draw conclusions about its effectiveness
as a nutrition supplement [56].

Growth — Growth is poor for children (defined as less than the 3rd percentile for age) with end-
stage kidney disease (ESKD), including those who undergo HD [57]. As an example, data from the
North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) demonstrated that
height SDS decreased after one year of dialysis [58].

It appears that early and more intensive nutrition is able to maintain or even improve height SDS
[59-63]. However, a sizable proportion of children at initiation of kidney replacement are
overweight or obese, suggesting that nutritional support alone is not enough to restore normal
growth [57]. In this setting, growth hormone treatment may be useful. (See "Prevention and
management of growth failure in children with chronic kidney disease", section on 'Nutrition' and
"Growth hormone treatment in children with chronic kidney disease and postkidney
transplantation", section on 'Dialysis' and 'Intensified dialysis' above.)

Neuropsychological outcome — Infants and children with chronic kidney disease (CKD) have a
higher incidence of neurodevelopmental and psychosocial impairment compared with the general
pediatric population [56,64,65]. It appears that the longer the duration of dialysis, the more likely
there will be cognitive and learning impairment [65].

In one study of children who initiated HD before 18 months, 42 percent had significant
neuropsychological impairment, of which 25 percent required special education and 13 percent
were severely handicapped, requiring residential care; the remaining 58 percent attended regular
school [56].

Another study reported more encouraging results; children with CKD stage 5 had mild deficits of
IQ and fine motor coordination in comparison with their siblings, but there were no differences in
measures of academic achievement, memory, behavior, or self-esteem [64].

Mineral and bone disorder — Abnormal mineral metabolism, and altered bone structure and
composition are almost universal in children on dialysis, and result in bone and joint pain,
fractures (the most common disability in young adults) [66], and vascular calcifications [67].
Careful management utilizing plasma calcium, phosphate, parathyroid, and alkaline phosphate
measurements can minimize these problems. The management of mineral and bone disorder in
children with CKD is discussed separately. (See "Pediatric chronic kidney disease-mineral and bone
disorder (CKD-MBD)".)

Cardiovascular disease — Children on HD are at risk for cardiovascular disease and myocardial
stunning:

●Cardiac arrest – In the Annual United States Renal Data System (USRDS) report, cardiac arrest of
unknown cause was one of the most common causes of death in children with ESKD.
●Markers of cardiovascular disease (CVD), including abnormal endothelial function and pulse wave
velocity, increased carotid intima media thickness, and vascular calcification, have been observed
in children on dialysis [67-70]. Left ventricular (LV) remodelling and LV hypertrophy have also been
reported in 30 to 80 percent of pediatric dialysis patients, with a higher incidence in HD than
peritoneal dialysis (PD) patients [71].
●Hypertension is the most important and prevalent CVD risk factor. In one case series of 624
children on HD, hypertension was present in 79 percent, with 62 percent receiving
antihypertensive medication [72]. As discussed above, hypertension is primarily due to excess fluid
and can best be prevented by increasing dialysis time. (See 'Length of dialysis and frequency of
sessions' above and 'Fluid removal' above and "Overview of risk factors for development of
atherosclerosis and early cardiovascular disease in childhood", section on 'Atherosclerotic changes
in childhood' and "Chronic kidney disease in children: Complications", section on 'Risk for
cardiovascular disease'.)
●Obesity or overweight, another CVD risk factor, is observed in a sizable proportion of children at
initiation of kidney replacement [57].
●Myocardial stunning (defined as abnormal regional left ventricular wall motion) is associated
with intradialytic hypotension, which often is a result of increased intradialytic weight gain and the
need for large fluid removal during dialysis. Pediatric patients are at risk because of the
predominantly liquid diet in infants, noncompliance with fluid restriction in older children, and the
challenge of determining and attaining optimum weight [73]. Intradialytic weight gain is also
associated with left ventricular hypertrophy, particularly if weight gain is more than 4 percent [74].
Repeated episodes of myocardial stunning can lead to permanent myocardial damage. (See
"Pathophysiology of stunned or hibernating myocardium" and "Overview of screening and
diagnosis of heart disease in dialysis patients", section on 'Diagnosis of heart failure'.)
Anemia — Anemia is a frequent finding in children undergoing dialysis and is associated with an
increased risk for mortality, LV hypertrophy, and/or decreased exercise capacity. In the United
Kingdom, 47 percent of the pediatric dialysis population had a hemoglobin <11 g/dL [75]. Anemia
as a complication of CKD in children and its management are discussed separately. (See "Chronic
kidney disease in children: Complications", section on 'Anemia'.)

LONG-TERM OUTCOME
Mortality rate — The mortality risk for children on dialysis is >30 times higher than age and
gender-matched normal children [76,77]. Mortality increases with decreasing age and the highest
mortality rate is in children less than two years of age [78]. In the United States Renal Data System
report, the one-year adjusted all-cause mortality rate for pediatric patients (0 to 21 years) for
children receiving hemodialysis has continued to improve (figure 1). The five-year survival during
the time period between 2006 and 2010 was lowest for patients on HD (approximately 81 percent)
followed by those on peritoneal dialysis and was the highest for patients who underwent kidney
transplantation (figure 2). The overall five-year survival rate in European children initiating dialysis
between 2005 and 2010 was 89.5 percent [79].

In an analysis of data from the United States Renal Data System (USRDS), the risk of death was
higher in children with elevated body mass index (BMI) and those with short stature [80].

Causes of death — In the United States Renal Data System report, the leading causes of death for
all children with end-stage kidney disease (ESKD) including those on HD are cardiac arrest from
unknown cause, followed by withdrawal from dialysis and sepsis. Causes of death were similar
across all age groups.

Factors influencing survival — Factors that have been shown to influence patient survival include
age at onset of ESKD, presence of comorbidities, access to transplantation, kidney replacement
therapy (KRT) modality, and macroeconomics [7,14].

Era of dialysis — Changes in survival rates based on era of treatment are conflicting. This is not
surprising because it is challenging to compare survival rates over time with changes in the
population treated, as children with potentially poorer outcome have been increasingly accepted
for KRT. These include young infants with CKD and those with severe comorbidities. Acceptance
rates for such children vary, affecting not only outcome data over time, but also results from
different parts of the world, because centers and countries will have different acceptance criteria.

Despite these issues, the United States Renal Data System reported a decrease of 20 percent in
the one-year adjusted all-cause mortality over the last decade between 2006 to 2010 and 2011 to
2016 (figure 1) [81]. The greatest improvement in mortality regardless of modalities between
these time periods was observed in children between zero and four years of age, especially those
less than two years of age at onset of ESKD.

Comorbidity — Comorbidities (eg, multi-organ involvement with cardiac, gastrointestinal, and

metabolic disorders) are common, occurring in approximately 30 percent of infants and young
children who receive HD, and increase the risk of death. The effect of comorbidity on survival
extends into adulthood as childhood survivors of dialysis with comorbidity have a significantly
higher risk of death compared with those with only primary kidney disease [59,82].

In particular, pulmonary hypoplasia associated with fetal oligoanuria increases mortality [83,84].
For example, autosomal recessive polycystic kidney disease, which is often associated with
pulmonary hypoplasia, has an increased mortality odds ratio of 20 compared with other genetic or
congenital causes of CKD [85].

Age at start of dialysis — Globally, the highest mortality is seen in young children and infants. This
group also has the highest incidence of comorbid conditions.

●Data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) showed a
lower five-year survival for patients with ESKD under one year of age compared with the overall
cohort (73 versus 86 percent), and there was a fourfold increased risk of death for infants
compared with children ages 15 to 19 years [76].

●The North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry also
reported lower survival rates for children who began HD before one year of age with survival rates
of 82, 73, and 65 percent at one, two, and three years after initiation of HD, respectively [86].
Most deaths occur in the first year of life [59,83,85]. For infants without a comorbid condition,
there are no differences in rates of survival as compared with other age groups [59], and those
starting dialysis within the first month of life do as well as those starting later in infancy [87].

Modality of dialysis — Amongst different KRT modalities, data show HD has the poorest survival
rate. However, these are observational data, and differences in patient populations likely
contribute to differences in mortality.

In the report from the USRDS report, the five-year survival is lower for children who undergo HD
compared with both PD and kidney transplantation (figure 2).

A study of 6473 children on dialysis (both HD and peritoneal dialysis [PD]) from 36 European
countries from 2000 to 2013, which reported an overall five-year survival rate of 90 percent,
reported a higher mortality for children selected to start on HD compared with those on PD
(adjusted hazard ratio [HR] 1.39, 95% CI 1.06-1.82).

Long-term quality of life — Overall, children with ESKD, especially those on dialysis, have lower
health-related quality of life scores (HRQOL) than healthy controls [88,89]. In addition, children on
dialysis have poor outcomes in regards to adult employment. A Dutch study reported that young
adult survivors of prolonged dialysis during childhood were twice as likely to be unemployed than
an age-matched population [88].

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links: Chronic kidney disease in
children".)

SUMMARY AND RECOMMENDATIONS

Although the principles of hemodialysis (HD) are similar for adults and children, there are
differences that need to be addressed in order to effectively and safely perform pediatric HD and
reduce potential complications, thereby improving life expectancy and quality of life for patients
who face a lifetime of kidney replacement therapy (KRT). Optimal care is provided by a
multidisciplinary team that manages dialysis treatment and nutrition, ensures effective vascular
access, and provides psychosocial support. The team meets routinely to review the care for the
individual and is available for any acute issue. (See 'Overview' above.)
●Good vascular access is essential for successful HD. We suggest placement of an arteriovenous
(AV) fistula for initiation of HD in children if technically feasible, who will remain on HD for >12
months, and are tolerant of access needling (Grade 2C). AV fistulas provide the most reliable
access over time with the lowest complication rate. (See 'AV fistula' above.)
●HD is most often initiated through a central venous catheter (CVC) in children because creating
AV fistulas in small children (weight <15 kg) is technically difficult, time is needed for AV fistula
maturation, and CVC avoids needling for access. The type, size, and length of the catheter is
determined by the size of the child and his or her vessels based on his/her body weight (table 1).
(See 'Central venous catheters' above.)
●The HD equipment must be modified for pediatric patients, particularly infants and small
children, as follows:
•Selection of the HD tubing and dialyzer to ensure that the volume of the extracorporeal circuit
does not exceed the upper limit of safety, which is 8 to 10 percent of their total blood volume
(table 2). (See 'Extracorporeal circuit' above.)
•The size of the dialyzer is dependent on the size of the child and should match his or her body
surface area. (See 'Dialyzer' above.)
•The dialysis machine used in children should have the capabilities to remove small amounts of
fluid, directly measure the volume removed, and use low blood flow rates and lines of varying
blood volumes. (See 'HD machine' above.)
●The dialysis prescription for each patient includes the chosen dialyzer (including size), blood flow
rates, length and frequency of dialysis sessions, and the amount of fluid to be removed each
session based on the estimation of the optimum weight. (See 'Dialysis prescription' above.)
●We suggest that evaluation of the adequacy of dialysis using measures of dialyzer clearance of
urea (Kt/V), protein catabolic rate, and growth be performed once a month in children who
receive chronic HD (Grade 2C). (See 'Adequate dialysis clearance' above.)

●Complications seen in children who receive chronic HD include malnutrition, poor growth,
mineral and bone disorders, anemia, increased risk of neurodevelopmental and psychosocial
impairment, and cardiovascular disease. (See 'Complications' above.)
●Mortality is 30 times higher in children on dialysis compared with gender-matched normal
children. The major causes of death are cardiac arrest, withdrawal from dialysis, and sepsis. Risk
factors that increase mortality include the presence of comorbid conditions (eg, pulmonary
hypoplasia) and initiation of dialysis before one year of age. (See 'Mortality rate' above.)
●In general, long-term quality of life is lower in children on dialysis compared with normal healthy
controls and children who receive a kidney transplant. (See 'Long-term quality of life' above.)