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Hemodialysis for children with chronic kidney disease

Hemodialysis for children with chronic kidney disease
Literature review current through: Jan 2024.
This topic last updated: Jul 11, 2023.

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 to effectively and safely perform pediatric HD, thereby reducing complications in children who are facing a lifetime of kidney replacement therapy (KRT).

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 kidney replacement therapy for children with chronic kidney disease".)

OVERVIEW

Goals — 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".)

Pediatric-specific technical issues — The following technical aspects of HD may differ in adults and children and need to be considered and addressed to effectively and safely perform pediatric HD:

Vascular access (see 'Vascular access' below)

Extracorporeal circuit (eg, size and volume of tubing and dialyzer) (see 'Extracorporeal circuit' below)

Choice of dialyzer and machines (see 'Dialyzer' below and 'Hemodialysis machine' below)

Dialysis prescription particularly blood flows (see 'Dialysis prescription' below)

Complications and outcome measures (see 'Complications' below and 'Long-term outcome' below)

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

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

Additionally, involving radiologists who have expertise in pediatric vascular access imaging and intervention is essential.

Physiology of hemodialysis — All dialysis modalities operate under physical principles related to the movement of molecules in aqueous solutions across semipermeable membranes. Understanding these basic principles allows full recognition of the processes engaged in dialysis therapies and gives the operator more control over the prescription and the procedure. These processes, which include diffusion, convection, and ultrafiltration (ie, fluid removal), are discussed in detail separately. (See "Overview of the hemodialysis apparatus", section on 'General principles of dialysis'.)

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

Arteriovenous fistula

Preferred for chronic vascular acccess — 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]. A tunneled CVC is typically used in children when HD access is required for a short duration of time. (See 'Central venous catheters' below.)

AV fistula is the preferred vascular access for chronic HD because AV fistulas are the most reliable long-term HD access; they are also associated with a lower mortality rate and fewer complications (eg, infection, decreased hospitalization and time spent in hospital) than percutaneous CVCs or AV grafts [4-12]. 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 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 United States tertiary center, the primary patency rates of basilic vein transposition 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

Frequent use as temporizing access — 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 from 2014 to 2018 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/European Renal Association-European Dialysis and Transplant Association Registry and 73 percent of patients registered in the International Pediatric Hemodialysis Network 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 and right atrium, or in the right atrium to provide adequate blood flow for dialysis. Catheters located in the superior vena cava 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. 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 blood flow 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 multiple factors, including catheter 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].

Arteriovenous grafts — 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.

HEMODIALYSIS 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 (table 3). (See 'Small infants' below.)

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

Hemodialysis 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 (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 — Improvements in dialysis technology have ignored the needs for the youngest and most vulnerable patients [22]. Available maintenance HD devices require an extracorporeal volume that is too high for children weighing <10 kg and do not meet the stringent criteria for ultrafiltration accuracy that is critical for the smallest children.

CARPEDIEM and the NIDUS machines are much smaller dialyzers and are able to perform CVVH in infants as small as 800 g [23-26]. They are not recommended for chronic intermittent HD.

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 [27].

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 hemodialysis — New portable HD machines for home use include the NxStage System One [28,29]. 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 (table 3) 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 ultrapure 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] × 8 mL/min) to safely maintain his or her cardiovascular status.

Type, length, and frequency of dialysis 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 [30].

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 [31-37]. 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 [31].

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 [32,37].

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 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 and family disruption [37,38]. 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 is increasing with the development of simpler new dialysis machines [28,29] and is an option for children who have adequate housing and a family member who is able and accepts the responsibility of performing home HD. Home HD can be performed in smaller children with the availability of circuits to dialyze children with weights from 12 kg.

Hemodiafiltration — HDF is a combination of conventional hemodialysis with the addition of hemofiltration, which utilizes increased transmembrane pressure to remove fluid and solutes across the membrane. As a result, HDF raises the convective clearance rate and thereby increases the solute clearance. The general aspects of HDF are discussed in more detail separately. (See "Alternative kidney replacement therapies in end-stage kidney disease", section on 'Hemofiltration and hemodiafiltration' and "Technical aspects of hemodiafiltration".)

Three requirements for performing HDF in children include "ultrapure" water for replacement of convective volume, high-flux dialyzer membranes, and dialysis machines that allow careful regulation of ultrafiltration (UF). Although HDF is being used more widely in pediatrics as filters and lines are becoming available for smaller children, it may be difficult to obtain an HDF machine suitable for use in children, as few manufacturers make them [39].

HDF can be performed in children in pre- or postdilution modes, depending on whether the replacement fluid is infused upstream or downstream of the dialyzer. Currently available dialyzers that perform mid-dilution or mixed dilution HDF are too large for use in most children. Most pediatric centers perform postdilution HDF, although a potential disadvantage is the hemoconcentration and protein concentration with high ultrafiltration rates; these can result in protein deposition on the membrane surface, which can alter membrane permeability and performance and can facilitate clotting of the extracorporeal circuit. Predilution HDF may overcome these limitations but diluting the blood entering the dialyzer may render both the diffusive and convective components less efficient; using higher convective volumes (equal to the blood flow rate) can improve clearance of middle and larger molecular weight toxins. (See "Technical aspects of hemodiafiltration", section on 'Modes of infusion of replacement fluid'.)

When compared with conventional HD, HDF in children is associated with improvements in the following parameters [35,40-44]:

Growth, including catchup growth

Overall cardiovascular risk profile

Anemia control

Blood pressure control

Bone health

Medication burden

Fluid and dietary restrictions

Levels of inflammatory markers

Overall quality of life

In addition, HDF may be better tolerated than conventional HD in patients who are hemodynamically unstable [45].

The benefits of HDF versus HD in children have been reported in several observational studies [40-42,44]. In a multicenter, prospective observational study comparing outcomes in children on HDF or conventional HD (The HDF, Hearts, and Heights [3H] study), HDF was associated with a median annualized increase in height standard deviation score (SDS) versus a static score for those on HD (0.15 for HDF versus -0.01 for HD) [40]. HDF was also associated with improved surrogate markers of preclinical cardiovascular disease compared to HD, including carotid intima-media thickness, beta-2-microglobulin, parathyroid hormone, and high-sensitivity C-reactive protein. In a post hoc analysis from the 3H study, HDF was associated with a consistently lower mean arterial pressure than HD, and this difference persisted beyond the one-year point [42]. Another post hoc analysis from the 3H study reported similar levels of bone formation and resorption biomarkers at baseline in both the HDF and HD groups, but increased levels after 12 months in the HDF group only [44]. Inflammatory markers were also lower in the HDF group than in HD at baseline and at 12 months. Switching to HDF from HD has also been associated with reduced markers of inflammation, oxidative stress, and endothelial dysfunction [43].

Studies in adults have reported improved survival for patients with end-stage kidney disease on HDF versus conventional HD when the convective volume is at least 23 liters/session3 [46,47]. Although similar studies have not yet been done in children, high convective volumes of 12–15 L/m2 body surface area in children (equating to approximately 20–25 L per 1.73m2 per session in adults) were used safely in children in the 3H study [40]. A high convective volume is achieved by optimizing the blood flow and setting a high filtration fraction (up to 33 percent in postdilution HDF) without increasing treatment time [41]. (See "Technical aspects of hemodiafiltration".)

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) [29,48-51]. (See 'Type, length, and frequency of dialysis 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 [45]. 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) [52] (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 'Type, length, and frequency of dialysis 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 [53,54]. However, reports of their reliability are variable, and they are not used routinely. Lung ultrasound assessing B lines alongside clinical examination and blood pressure measurement is being evaluated as a tool to accurately detect hypervolemia [55]. (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. (See "Anticoagulation for the hemodialysis procedure".)

Dialysate composition — Although the principles 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 six 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.

General issues related to dialysis solutions are discussed in detail elsewhere. (See "Overview of the hemodialysis apparatus", section on 'Dialysis solution'.)

PROVISION AND ASSESSMENT OF HEMODIALYSIS

Steps — 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' 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 [7,56]. 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 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 urea reduction ratio [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 [56]. 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 [29,48-51]. 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, 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 [57]. 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 patients on maintenance hemodialysis" 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 [58-61].

In children on HD, guidelines from both the United Kingdom [62] and United States [63] 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 [63].

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 [64].

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 [65]. As an example, data from the North American Pediatric Renal Trials and Collaborative Studies demonstrated that height SDS decreased after one year of dialysis [66].

It appears that early and more intensive nutrition is able to maintain or even improve height SDS [67-71]. 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 [65]. In this setting, growth hormone treatment may be useful.

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 [64,72,73]. It appears that the longer the duration of dialysis, the more likely there will be cognitive and learning impairment [73].

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 [64].

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 [72].

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) [74], and vascular calcifications [75]. 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 [75-78]. Left ventricular (LV) remodeling 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 [79].

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 [80]. As discussed above, hypertension is primarily due to excess fluid and can best be prevented by increasing dialysis time. (See 'Type, length, and frequency of dialysis 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 [65].

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 [81]. Intradialytic weight gain is also associated with left ventricular hypertrophy, particularly if weight gain is more than 4 percent [82]. 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 patients on dialysis", 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 [83]. 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 sex-matched normal children [84,85]. Mortality increases with decreasing age and the highest mortality rate is in children less than two years of age [86]. 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 [87].

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 and those with short stature [88].

Causes of death — In the USRDS 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 USRDS 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) [89]. 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, multiorgan 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 [67,90].

In particular, pulmonary hypoplasia associated with fetal oligoanuria increases mortality [91,92]. 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 [93].

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 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 [84].

The North American Pediatric Renal Trials and Collaborative Studies 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 [94]. Most deaths occur in the first year of life [67,91,93]. For infants without a comorbid condition, there are no differences in rates of survival as compared with other age groups [67], and those starting dialysis within the first month of life do as well as those starting later in infancy [95].

Modality of dialysis — Among 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 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 than healthy controls [96,97]. 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 [96].

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

Goals and issues specific to hemodialysis (HD) in children – The principles of HD are similar for adults and children, but there are some differences in approach to perform pediatric HD effectively and safely. Optimal care is provided by a multidisciplinary team that manages dialysis treatment and nutrition, ensures effective vascular access, and provides psychosocial support. For children on HD and their families/caregivers, a multidisciplinary team manages dialysis treatment and nutrition, ensures effective vascular access, and provides psychosocial support. (See 'Overview' above.)

Vascular access – We suggest placement of an arteriovenous (AV) fistula for initiation of HD in children in whom it is technically feasible, who will remain on HD for >12 months, and who are tolerant of access needling (Grade 2C). AV fistulas provide the most reliable access over time with the lowest complication rate. (See 'Arteriovenous fistula' above.)

We typically use a tunneled central venous catheter (CVC) in children when HD access is required for a short duration of time (table 1). (See 'Central venous catheters' above.)

HD equipment – Pediatric-specific considerations include (table 3):

HD tubing and dialyzer should be selected to ensure that the volume of the extracorporeal circuit does not exceed the upper limit of safety, which is 8 to 10 percent of the total blood volume (table 2). (See 'Extracorporeal circuit' above.)

The size of the dialyzer depends on the size of the child and should match their 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. Available maintenance HD devices do not meet the needs of children <10 kg. (See 'Hemodialysis machine' above.)

Dialysis prescription – The dialysis prescription for each patient includes the chosen dialyzer (including size), blood flow rates, length and frequency of dialysis sessions, and amount of fluid to be removed at each session based on the estimation of the optimum weight. (See 'Dialysis prescription' above.)

Assessing adequate dialysis – We suggest that the adequacy of dialysis be evaluated once a month in children who receive chronic HD using measures of dialyzer clearance of urea (Kt/V), protein catabolic rate (PCR), and growth (Grade 2C). (See 'Adequate dialysis clearance' above.)

Complications – Complications in children who receive chronic HD may include malnutrition, poor growth, mineral and bone disorders, anemia, increased risk of neurodevelopmental and psychosocial impairment, and cardiovascular disease. (See 'Complications' above.)

Mortality rate and risk factors – Mortality is 30 times higher in children on dialysis compared with sex-matched normal children (figure 1 and figure 2). 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.)

Lower long-term quality of life – 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.)

ACKNOWLEDGMENT — We are saddened by the death of Lesley Rees, MD, FRCPCH, who passed away in May 2022. UpToDate acknowledges Dr. Rees's past work as an author for this topic.

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Topic 14562 Version 42.0

References

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