Pediatric acute kidney injury (AKI): Indications, timing, and choice of modality for kidney replacement therapy (KRT)

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Pediatric acute kidney injury (AKI): Indications, timing,

and choice of modality for kidney replacement
therapy (KRT)
Authors: Patrick D Brophy, MD, Melissa Muff-Luett, MD
Section Editor: Tej K Mattoo, MD, DCH, FRCP
Deputy Editor: Laurie Wilkie, MD, MS

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jan 2023. | This topic last updated: Oct 22, 2021.

Introduction

Critically ill children with acute kidney injury (AKI) are at greater risk for mortality than
those without AKI due to associated complications, including symptomatic uremia,
metabolic and electrolyte abnormalities, and fluid overload. The management of children
with AKI is supportive, with kidney replacement therapy (KRT) indicated in patients with
severe kidney injury. (See "Prevention and management of acute kidney injury (acute renal
failure) in children", section on 'Management of acute kidney injury'.)

The indications, timing, and modalities for KRT for children with AKI will be reviewed here.
KRT in adults with AKI is discussed separately. (See "Kidney replacement therapy (dialysis)
in acute kidney injury in adults: Indications, timing, and dialysis dose".)

Definitions

● Acute kidney injury (AKI) is characterized by a sudden decrease in the ability of the
kidneys to maintain adequate electrolyte, acid-base, and fluid homeostasis along with
a reduction in glomerular filtration rate (GFR) [1-3]. Clinically, AKI is manifested by
increases in nitrogenous waste products (blood urea nitrogen [BUN]) and serum
creatinine (SCr) and, in many cases, a concomitant reduction in urine output (less
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Pediatric acute kidney injury (AKI): Indications, timing, and choice of modality for kidney replacement therapy (KRT)

than 0.5 to 1 mL/kg per hour) that may be refractory to diuretic therapy [1-3]. In
severe AKI, a change in urine output may be identified before any change in serum
creatinine; thus it has been proposed that both urine output and creatinine must be
used to identify and stage AKI [4,5].

Several published criteria are used clinically to manage pediatric AKI [5,6]. This topic
uses the Kidney Disease Improving Global Outcomes (KDIGO) definition and staging
based on consensus of pediatric nephrology experts following a systematic review of
the literature ( table 1). Other definitions used to guide clinical care include pRIFLE
(Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease) ( table 2) and AKIN
(Acute Kidney Injury Network) and are discussed separately. (See "Acute kidney injury
in children: Clinical features, etiology, evaluation, and diagnosis", section on
'Definition'.)

● Kidney replacement therapy (KRT) is treatment that replaces the normal blood-
filtering function of the kidneys. Several different modalities of KRT are used in
children with AKI, including intermittent hemodialysis (HD), peritoneal dialysis,
continuous KRT therapy (ie, continuous venovenous HD, continuous venovenous
hemofiltration, continuous venovenous hemodiafiltration) and modified
aquapheresis. (See 'Modality' below.)

AKI and mortality: Potential role of KRT

AKI and fluid overload are associated with greater morbidity and mortality in pediatric
patients [5,7-9]. Mortality is highest in critically ill children especially infants and those with
multiorgan failure, and significant fluid overload [5,7,9-16]. Kidney replacement therapy
(KRT) prevents and corrects the adverse and potentially life-threatening complications of
AKI including symptomatic uremia, metabolic and electrolyte imbalance, and severe fluid
overload. Early initiation and effective administration of KRT in AKI is generally believed to
improve survival in critically ill pediatric patients [17]. Nevertheless, there continues to be a
lack of robust evidence-based guidelines regarding the indications for and timing of
initiation of kidney replacement therapy (KRT) in children, as well as the most appropriate
KRT modality for pediatric use in various settings.

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Pediatric acute kidney injury (AKI): Indications, timing, and choice of modality for kidney replacement therapy (KRT)

Indication and timing for KRT

The decision to begin KRT is based on the severity and complications of AKI and the
urgency of the clinical setting.

Urgent indications — Urgent indications include the following:

● Clinically significant fluid overload with evidence of escalating ventilatory support due
to pulmonary edema and/or congestive cardiac failure, which is unresponsive to
diuretic therapy and fluid restriction (typically seen in patients with >15 percent fluid
overload). (See 'Fluid overload' below.)

● Presence of uremic complications such as pericarditis, uremic encephalopathy or

unexplained change in mental status, and bleeding. (See "Acute toxic-metabolic
encephalopathy in adults", section on 'Uremic encephalopathy' and "Uremic platelet
dysfunction".)

● Life-threatening metabolic derangements that are refractory to medical

management:

• Severe persistent hyperkalemia – Values typically >6.5 mEq/L that are refractory to
medical management, or whenever there are associated electrocardiographic
changes. (See "Causes, clinical manifestations, diagnosis, and evaluation of
hyperkalemia in children", section on 'Symptomatic patients' and "Causes, clinical
manifestations, diagnosis, and evaluation of hyperkalemia in children", section on
'Cardiac conduction abnormalities' and "Management of hyperkalemia in
children", section on 'Dialysis'.)

• Severe metabolic acidosis (pH <7.1) refractory to medical therapy – (See "Approach
to the child with metabolic acidosis", section on 'Acute metabolic acidosis' and
"Approach to the child with metabolic acidosis", section on 'Renal replacement
therapy'.)

• Severe persistent hyponatremia is a rare indication for KRT but mainly when
associated with fluid overload.

● Removal of toxins or drugs, which are dialyzable, including alcohols, lithium,

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salicylates, and other drugs. (See "Ethanol intoxication in children: Clinical features,
evaluation, and management", section on 'Extracorporeal removal' and "Lithium
poisoning", section on 'Role of extracorporeal removal' and "Salicylate poisoning in
children and adolescents", section on 'Hemodialysis'.)

● Other metabolic derangements including tumor lysis syndrome and

hyperammonemia. (See "Enhanced elimination of poisons", section on
'Extracorporeal removal' and "Tumor lysis syndrome: Prevention and treatment",
section on 'Indications for renal replacement therapy' and "Urea cycle disorders:
Management", section on 'Hemodialysis'.)

Non-urgent indications — For some patients with severe AKI but without one of the
conditions listed above, dialysis may be warranted to prevent worsening complications
and/or further deterioration of the patient's clinical status. In these cases, the decision to
initiate KRT is based primarily on the judgement of clinicians in evaluating the level of
impairment, patient factors (age/size, illness acuity, comorbidities, and ongoing needs),
and organizational resources including availability of necessary equipment and trained,
experienced staff. Nonurgent indications include:

● Potential risk for clinically significant fluid overload – For patients with:

• Reduced or fixed urine output (ie, oligoanuria), with high-volume requirement for
administration of nutrition, medications, and/or blood products with evidence of
continued deterioration of renal function.

• Impending fluid overload with tachycardia, hypertension, or escalating ventilatory

requirement.

● Refractory electrolytes and acid-base disturbances – Deteriorating electrolyte and

acid-base anomalies not responding to supportive management (eg, refractory
severe hyperkalemia) but not yet meeting life-threatening values (noted above).

● Elevated blood urea nitrogen (BUN) – In our practice, we consider the use of KRT
when the BUN reaches a level between 80 and 100 mg/dL in the context of oliguria
without response to diuretics, worsening electrolyte abnormalities, and nutritional
need. However, data from adult studies suggest that early initiation of KRT is not
beneficial as the use of BUN as an indicator for KRT is limited by several nonrenal

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factors that affect BUN measurements. These include gastrointestinal bleeding,

steroid use, diuretic use, catabolism, and nutritional intake. (See "Kidney replacement
therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis
dose", section on 'Timing of elective initiation'.)

● Serum creatinine (SCr) – Elevated serum creatinine by itself is not an indication for
KRT. Increases in SCr often occur late in the course of AKI and thus, SCr is an
imperfect marker to determine the appropriate timing of KRT [18,19]. SCr is also
affected by muscle mass that varies according to the size, nutritional status, and
underlying medical comorbidities of the child. Given the limitations associated with
serum creatinine as a kidney function biomarker, decisions regarding initiation of KRT
should take into account the multiple patient factors and not be based solely on
changes in SCr or a cut-off SCr level.

Evidence for KRT initiation and timing — In children, there are sufficient data to provide
guidelines to initiate KRT for fluid overload. However, data remain inadequate to support
evidence-based guidelines for quantifiable values for uremia and metabolic disturbances.
Nevertheless, most pediatric intensivists and nephrologists, including the authors,
advocate for earlier implementation of KRT to avoid these late manifestations of AKI.

Fluid overload — Fluid overload is associated with increased mortality, increased length

of mechanical ventilation for mechanically ventilated children, increased organ
dysfunction, and prolonged intensive care unit (ICU) and hospital stay when controlled for
severity of illness in both single center and multicenter pediatric studies [9,20-22].
Observational data suggest that early initiation of KRT is beneficial in children with
multiorgan dysfunction and fluid overload [23].

Based on these findings, the American College of Critical Care Medicine Clinical Guidelines
for Hemodynamic Support of Neonates and Children with Septic Shock suggest that KRT
be considered in pediatric patients with septic shock at risk for worsening significant fluid
overload [24]. Once hemodynamic stability is achieved, diuretics or KRT can be used to
remove fluid in patients who are >10 percent fluid overloaded and are unable to maintain
fluid balance with their native urine output and/or extrarenal losses. The patient's fluid
status is evaluated by determining the percent fluid overload (FO) using the following
equation:

Percent FO at KRT initiation = [fluid in (liters) – fluid out (liters)]/admission weight (kg)
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X 100

or

Percent FO at KRT initiation = [current weight (kg) – admission weight (kg)]/admission

weight (kg) X 100

KRT also may be used to maintain the fluid status of critically ill children who remain
oliguric, but require high volumes of intravenous fluids, including parenteral nutrition and
medications and /or blood products. In this setting, KRT is not used to remove fluid but to
prevent further fluid overload, which may lead to worsening respiratory status and cardiac
function. Once the patient has achieved a satisfactory level of hemodynamic stability, the
process of fluid removal can commence.

Severe AKI — Although data from adult studies have been inconclusive about the
benefits of early KRT, we recommend elective initiation of KRT in pediatric patients with AKI
when their renal injury is severe or unlikely to quickly resolve. The definitions and staging
criteria of AKI are based on the degree of GFR reduction or change in serum creatinine
(SCr) in addition to the urine output. However, as stated previously SCr is not the ideal
biomarker for renal injury and even with AKI severity staging, the likely duration of AKI is
difficult to predict. (See "Acute kidney injury in children: Clinical features, etiology,
evaluation, and diagnosis", section on 'Risk stratification system to predict severe AKI' and
"Acute kidney injury in children: Clinical features, etiology, evaluation, and diagnosis",
section on 'Serum creatinine'.)

Several investigational tools are being studied to see if they can predict the severity of AKI
in children and whether KRT should be initiated. However, these tools have not been
conclusively validated in the clinical setting and as a result are not used routinely in
managing pediatric AKI.

● Novel biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), insulin-

like growth-factor binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinases
(TIMP-2), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) show promise in
both their diagnostic and prognostic utility in the setting of AKI and may allow for
early intervention prior to the onset of SCr rise, severe metabolic derangements, and
fluid overload. These biomarkers and their role in predicting AKI are discussed
separately [25-29]. (See "Acute kidney injury in children: Clinical features, etiology,
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evaluation, and diagnosis", section on 'Biomarkers of AKI' and "Investigational

biomarkers and the evaluation of acute kidney injury", section on 'Diagnostic
biomarkers'.)

● Furosemide stress test – Furosemide stress test, which assesses urine output after a
weight-based dose of furosemide, has been reported to predict progression of AKI in
both adults and children. In one study of 166 children who underwent cardiac
surgery, the furosemide stress test was predicative of AKI with lower mean urine flow
rate for patients with AKI compared with those without AKI at two hours (2.9 versus 5
mL/kg/hour) and at six hours (2.4 versus 4 mL/kg/hour) [30]. (See "Investigational
biomarkers and the evaluation of acute kidney injury", section on 'Furosemide stress
test'.)

● Combination of clinical factors (renal angina) – The use of a collection of clinical risk
factors and signs of renal disease has been proposed as a method to identify patients
most at risk for developing AKI, analogous to assessing myocardial infarction [31].
The risk of AKI (referred to as renal angina) would be based on the presence of
established risk factors (eg, mechanical ventilation, history of cardiopulmonary
bypass, bone marrow transplantation) and evidence of renal disease (fluid overload
and changes in serum creatinine) [32]. The proposed renal angina criteria stratify
patients into moderate-risk, high-risk, and very high-risk patients according to their
underlying clinical condition. For each level of preexisting risk factors, there is a
threshold of evidence of injury that a patient must meet to be considered to have
renal angina ( table 3) [32-36].

Modality

Available pediatric modalities — The following modalities are available for the provision
of KRT in the pediatric patient with AKI [37-39]:

● Peritoneal dialysis (PD)

● Intermittent hemodialysis (HD)

● Continuous kidney replacement therapies (CKRT), including:

• Continuous venovenous hemodialysis (CVVHD)

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• Continuous venovenous hemofiltration (CVVH)

• Continuous venovenous hemodiafiltration (CVVHDF)

● Prolonged intermittent kidney replacement therapy (PIKRT)

Factors in modality selection — All dialysis modalities can remove fluid and clear solutes.
For the pediatric patients with AKI, selection of modality is typically based upon local
expertise and availability of staff and equipment. However, in selected patients, other
factors may need to be considered.

● Size of the patient – This is a major consideration for dialysis modality selection as
HD and CKRT may not be feasible in infants and small children <15 kg in weight. Most
CKRT machines and hemodialysis machines used in the United States are only
approved for patients weighing more than 15 or 20 kg. As a result, machines must be
used off-label to dialyze patients who fall below this cut-off. In addition, the
extracorporeal volume of these circuits typically exceeds 10 percent of the blood
volume of small patients <10 to 120 kg. For these children, packed red blood cells are
required to prime the extracorporeal circuit to prevent hemodynamic instability
leading to exposure to donated blood [40]. Smaller dialyzers and extracorporeal
circuits have been developed but are not universally available. As a result, PD remains
the most common modality used for infants and small children who require KRT. (See
"Hemodialysis for children with chronic kidney disease", section on 'Dialyzer' and
"Hemodialysis for children with chronic kidney disease", section on 'Extracorporeal
circuit' and "Hemodialysis for children with chronic kidney disease", section on 'Small
infants'.)

● Dialysis access – Hemodialysis and CKRT require placement of a large-bore dual

lumen central catheter, which is often not an option in small children or infants or
those with compromised vasculature.

● Hemodynamic instability – Intermittent HD may be difficult to perform in

hemodynamically unstable patients. In these patients, CKRT or PD allow for more
gradual and sustained solute and fluid removal and less perturbations on the
intravascular circulation than intermittent HD.

● Abdominal or diaphragmatic pathology

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• Abdominal defects may preclude the use of PD due to changes in clearance and
filtration across a compromised peritoneal membrane.
• Leakage of peritoneal solution used in dialysis may occur in patients with
diaphragmatic defects.

● Anticipated duration of KRT – It is important to consider the likely length of KRT. For
example, if a child is likely to require chronic dialysis and is a candidate for home
therapy, PD might be the preferred initial selected mode of dialysis as it may facilitate
transition to chronic KRT.

KRT modalities and clinical considerations — Regardless of the modality choice,

initiating KRT in a critically ill child requires collaboration among the pediatric
nephrologists, intensivists, and other subspecialists. Early discussion and planning will
facilitate the process and allow for more rapid intervention, thereby improving survival
outcomes and reducing morbidity. All acute dialysis programs can be monitored and
assessed through quality improvement programs with specific metrics and outcome
indicators [41]. Quality improvement goals have been outlined for adult programs and
similar quality improvement programs are now recommended in pediatric programs.

The following sections describe the use of currently available KRT modalities in pediatrics,
including their relative advantages and disadvantages.

Peritoneal dialysis — PD provides gradual, continuous solute and water clearance

through diffusion and ultrafiltration, although the ability to separate these components is
limited with this modality.

● General availability – Many centers have a relatively greater experience and comfort
level using PD in pediatric patients compared with the other modalities. PD
historically has provided effective therapy for the management of pediatric AKI and
continues to provide reasonably cost-effective, efficient therapy. PD is widely available
in resource-limited countries because it requires less technological expertise, as it
does not require vascular access, less resource allocation, and is more cost effective
than CKRT or HD. PD is critical in the treatment for any child with AKI especially in
facilities where pediatric HD and CKRT are unavailable [42,43].

● Access – PD does not require vascular access and thus allows critically ill patients to
be dialyzed with preservation of vasculature for patients who may require chronic
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dialysis in the future. Access for PD can be quickly and safely obtained, even in
hemodynamically unstable patients, thus allowing for the rapid institution of therapy.
Typical access includes Tenckhoff catheters, usually placed in the operating room by
pediatric surgeons, or acute PD or adapted PD catheters placed at the bedside
percutaneously by experienced clinicians in patients unable to tolerate a surgical
placement [44,45].

● Components of the PD prescription

• Dialysate composition – The composition of dextrose-based peritoneal dialysate

solutions available in the United States includes sodium (132 mEq/L), magnesium
(0.5 mEq/L), chloride (95 mEq/L), lactate for a bicarbonate source (40 mEq/L), and
two different concentrations of calcium (2.5 and 3.5 mEq/L). Modifications
customized to the needs of individual patients can be prepared by hospital
pharmacies [46,47], although this does increases the risk of prescription errors or
introduction of contaminants [48]. The most common supplementation is the
addition of sodium to increase the standard composition of 130 mEq/L, typically in
hyponatremic or hypotensive infants. Potassium or phosphate which are not
included in standard PD formulations may also be required at times. In addition,
bicarbonate may be used in patients with hepatic dysfunction who are unable to
metabolize lactate.

- Dextrose – Three different dextrose concentrations are available commercially

in the United States: 1.5, 2.5, and 4.25% solutions with respective osmolalities
of 346, 396, and 485 mOsm/L. The dextrose used in PD dialysate can provide
an extra source of carbohydrate nutrition and calories [47,49], but may also
lead to hyperglycemia necessitating insulin correction [50].

- Heparin – Heparin is added to the dialysate when fibrin is present in the

dialysate or during episodes of peritonitis given the possible antiangiogenic
and anti-inflammatory properties [51]. When adding heparin we use the
Pediatric International Society for Peritoneal Dialysis (ISPD) guidelines that
suggest administrating intraperitoneal heparin at 500 to 1000 units per L until
complete resolution of the cloudy effluent to prevent occlusion of the catheter
[52].

Exchange volume – The recommended initial exchange volume in acute pediatric

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• PD is low (10 mL/kg) in order to minimize abdominal pressure that may cause
dialysate leakage around the catheter. The volume can be slowly increased to a
maximum of 35 to 40 mL/kg. As volume increases, the number of exchanges per
day often can be decreased. Strict fluid balance is particularly critical in small
children and infants and the use of buretrols allows for precise measurements of
in- and outflow when operating a manual and gravity-based system used for these
small patients [53].

• Dwell time – The time allowed for exchange of molecules and fluid is often short
in pediatric patients. Initial standard dwell time is between 40 and 60 minutes,
which is then adjusted based on the patient's fluid status, rate of ultrafiltration
(fluid removal), and clinical course. Shorter dwell times can be utilized to increase
ultrafiltration (fluid removal), but this may reduce clearance.

• Number of daily exchanges – Number of exchanges per 24 hours depends on

the duration of time required for the inflow, dwell, and outflow of dialysate for
each exchange. Typically, on initiation, acute PD runs over the entire 24-hour day,
but as the exchange volume is increased or the patient is stabilized the amount of
time on dialysis can be reduced.

● Specific clinical settings

• Multiorgan failure – Retrospective pediatric data show that PD can be performed

successfully in the setting of multisystem organ failure, including cardiovascular
instability requiring vasopressor support [54,55]. However, the ability to provide
adequate dosing of dialysis in the AKI setting is problematic when using PD in the
most critically ill patients. These patients, who may have severe fluid overload,
lactic acidosis, and hypotension, require precise fluid balance with controlled
ultrafiltration, but may not have adequate blood flow (cardiac output) to the
peritoneum to allow for efficient solute and fluid removal. Pressor agents may
alter peritoneal blood flow in septic patients, further diminishing these processes.
Thus, in patients with sepsis-induced AKI the beneficial aspects of slow solute
clearance and ultrafiltration provided by PD also limit its effectiveness. Patients
with preload-dependent cardiac physiology may become unstable with filling and
draining [54,56], necessitating the use of tidal PD prescriptions or an alternative
modality such as CKRT. Patients with pulmonary compromise may worsen with

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increased abdominal dialysate volumes that may prevent full diaphragmatic

excursion.

• Other settings – PD can be used to support patients with ventriculoperitoneal

shunts, prune-belly syndrome, abdominal surgeries, and ventilation via the high-
frequency oscillator, though these situations may present some technical
challenges for catheter placement (eg, thin abdominal wall in patients with prune-
belly syndrome) and come with higher risk of catheter malfunctions [57].

● Contraindications – PD is absolutely contraindicated in patients with diaphragmatic

defects due to leakage of peritoneal fluid into the pleural cavity.

● Complications – Complications of PD include:

• Peritonitis – The risk of peritonitis increases when using a PD catheter acutely due
to the risk of dialysate leak and thus PD initiation is often delayed, if possible, for
48 to 72 hours or longer to allow for healing and lower the risk of infection and
the other PD complications. Peritonitis can enhance dialysate protein loss,
compromise nutrition, and permanently damage the peritoneal membrane.

• Catheter malfunction – PD catheter malfunctions are common and can include

failure to fill and drain completely and quickly and leakage of peritoneal fluid at
the exit site.

• Electrolyte abnormalities – Patients may have significant losses of sodium and

other electrolytes especially in infants and children who only receive formula or
breast milk feeds. In such cases, where sodium deficit is present, significant
hypotension may result. PD is also associated with hyperglycemia and an increase
incidence of hypokalemia and hypophosphatemia if these are not added to the
dialysate [58].

• Protein loss – Patients on PD also require increased protein intake due to amino
acid losses with PD, and they also lose immunoglobulins in the dialysate, making
them more susceptible to infection.

• Hydrothorax due to dialysate leakage into the pleural space.

• Hernia due to fluid in the peritoneal space and increased abdominal pressures.
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Intermittent hemodialysis — Intermittent HD provides the most efficient solute

clearance and ultrafiltration compared with other KRT modalities. However, for children,
especially critically ill patients and small children, management should be undertaken by a
team (nephrologist and dialysis nurses) with expertise in administrating HD to children
because of specific pediatric issues regarding obtaining vascular access, catheter selection
and placement, and dialysis prescription. For small children, centers should have policies
for utilizing hemodialysis equipment as the majority of the hemodialysis machines
available on the market are only approved for patients greater than 15 or 20 kg.

● Advantages – In the hemodynamically stable patient, no other modality is better

suited for rapid and accurate small solute reduction with or without ultrafiltration.
Thus, this therapy is particularly important in the pediatric population for the
treatment of acute and life-threatening electrolyte abnormalities (eg, hyperkalemia),
ingestions (eg, lithium, aspirin), drug toxicity (eg, vancomycin), tumor lysis syndrome,
and hyperammonemia [38,59,60].

● HD access and location – Access is one of the most important components leading
to the satisfactory provision of HD. The placement of acute catheters can be
performed in most children at the bedside by pediatric nephrologists or intensivists.
Placement of semipermanent tunneled catheters and acute catheters in very small
infants is usually done in the operating room by surgeons or interventional
radiologists.

Access site is typically preferred in the right internal jugular vein due to lower risk for
complication compared with other insertion sites, which include lower venous return
pressures and positionality of groin lines. Subclavian veins should be avoided in order
to preserve these vessels for future use as arteriovenous fistulas in patients who may
progress to end-stage kidney disease.

● Catheter selection and line placement – A wide variety of temporary vascular

catheters are available for the pediatric population with different sizes (gauge) and
lengths ( table 4) [61].

• Gauge – 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 4). 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
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therefore poor flow through the dialysis circuit. Pediatric catheters are available in
different lengths based on the gauge. In the United States, the smallest currently
available is a 7 Fr double lumen non-tunneled catheter ( table 5). However, in
preterm infants, even the 7 Fr catheter may be too large, and two smaller single
lumen catheters placed at different access sites, including umbilical veins, may be
the only option for HD.

• Length – Pediatric catheters are available in different lengths based on the gauge.
The selected length is based on optimal line placement of the catheter tip at the
junction of the superior vena cava and the right atrium to optimize flows and limit
recirculation.

● Components of the HD prescription

• Blood flow rate – Blood flow rate is a significant factor in determining solute
clearance in patients as higher flow rates increase diffusive clearance. However, in
acutely ill patients with AKI, the risks of higher blood flow and increased clearance
must be weighed against instability of the patient's hemodynamic status and their
ability to tolerate a higher blood flow rate. The blood flow rate is also dependent
on the size and quality of the dialysis access as larger bore catheters will allow a
higher blood flow rate without collapsing or causing high negative arterial
pressures on the dialysis machine. Typical blood flow rates range from 3 to 10
mL/kg/minute.

• Dialysate flow rate – The rate of dialysate flow also determines clearance in HD but
to a lesser extent than the blood flow rate. The dialysate flow rate should be set at
a rate of at least 1.5 to 2 times the blood flow rate to maximize bidirectional flow
between the blood and dialysate [62].

• Dialysate composition – Dialysate composition is modified based on patient needs

mainly to adjust for sodium, potassium, calcium, and bicarbonate levels.

• Dialyzer and tubing size – The small solute clearance characteristics of the dialyzer
are determined by the surface area of this dialyzer. Typically, a dialyzer is
prescribed with a surface area similar to the patient’s body surface area
( table 6).

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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. For small children
and infants, extracorporeal volume often exceeds 10 percent of the blood volume
of the child and donor red blood cells are used to prime the extracorporeal circuit
to prevent hemodynamic instability. Commercially available tubing that varies in
volume should be matched to the size of the patient ( table 7). For neonates,
tubing volume can be as low as 29 mL.

A dialysis machine developed for infants weighing between 0.8 and 8 kg, which
uses a single-lumen catheter and does not require blood priming, is being
evaluated for efficacy and safety [63].

• Ultrafiltration (fluid removal) – The volume of fluid removal during a short three- to
four-hour dialysis run is often very limited, especially if the patient is not
hemodynamically stable or small in size.

• Length of dialysis treatment – The duration of a dialysis treatment is e determined

on the clearance and/or fluid removal goals.

• Anticoagulation – Unfractionated heparin is the standard anticoagulation method

used for intermittent hemodialysis therapy to prevent loss of the dialysis circuit or
complications with the hemodialysis catheter. A typical dose of unfractionated
heparin is a bolus of 10 to 30 units/kg followed by a continuous infusion at a rate
of 10 to 30 units/kg/hour. During short hemodialysis treatments, treatments can
be successful with no anticoagulation or with the administration of frequent saline
flushes into the circuit.

● Complications

• Line placement complications – During placement of vascular catheters,

complications may include blood vessel sclerosis or thrombosis, air emboli, or
hemorrhage.

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Pediatric acute kidney injury (AKI): Indications, timing, and choice of modality for kidney replacement therapy (KRT)

• Infection – As with all central lines, hemodialysis catheters are a potential source
of infection introduction.

• Hypotension – Rapid fluid removal may lead to episodes of hypotension.

• Neurologic complications (ie, dialysis disequilibrium syndrome) – A range of

neurologic manifestations including headache, nausea, blurred vision,
restlessness, mental status changes, and/or seizures due to cerebral edema is
associated with the initiation of HD (referred to as dialysis disequilibrium
syndrome or DDS) (see "Dialysis disequilibrium syndrome") [64].

● Potential contraindications

• Hemodynamic instability may make PD or CKRT better KRT options than HD. Low
blood pressure (hypotension) in the critically ill patient will limit the capacity for
ultrafiltration and ultimately the ability to provide adequate treatment with HD.

• Large fluid volume requirements – In critically ill patients who are anuric or
oliguric and require large fluid volumes for nutrition and/or medications, it may be
challenging to adequately remove fluid over the short treatment typically used
with HD. As a result, PD or CKRT may be better options for those patients as they
allow greater fluid removal that is continuous and gradual than HD.

Continuous kidney replacement therapy — CKRT, if available, is the preferred primary

modality for KRT in the critically ill, hemodynamically unstable pediatric patient [20]. CKRT
includes dialysis and/or filtration treatments that operate in a continuous mode typically
performed in the pediatric intensive care unit (ICU) setting.

● Modalities –The following modalities of CKRT are used in children.

• Continuous venovenous hemodialysis (CVVHD) – Predominantly diffusion based

solute clearance.

• Continuous venovenous hemofiltration (CVVH) – Predominantly convection based

solute clearance.

• Continuous venovenous hemodiafiltration (CVVHDF) – Provides diffusion and

convection based solute clearance.

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Pediatric acute kidney injury (AKI): Indications, timing, and choice of modality for kidney replacement therapy (KRT)

Ongoing research is trying to determine which modality is better suited for specific
patient conditions. Convective therapies (CVVH and CVVHDF) provide superior middle
molecule clearance compared with diffusive therapy (CVVHD) [65]. These convective
modalities are thought to be superior in clearing proinflammatory cytokines and may
be beneficial in the treatment of patients with sepsis-related AKI. As an example, the
Selective Cytopheretic Device has been shown to deactivate leukocytes within a low
ionized calcium environment as with regional citrate anticoagulation when used in
tandem with a hemodialyzer in CKRT circuits in adults [66,67]. In a small clinical trial,
this device was shown it can be used safely in children with AKI and multiorgan
dysfunction. Further investigation is needed to demonstrate that its use would be
beneficial for treating pediatric patients with systemic inflammatory response
syndrome (SIRS) with AKI.

● Advantages – CKRT mimics native kidney function with its continual ultrafiltration
and solute clearance [68,69] and has several advantages over HD and PD in the
management of patients with AKI.

• CKRT is more precise in delivering the goals of solute clearance and ultrafiltration
than PD. Although PD provides continuous solute clearance and ultrafiltration, the
rates of clearance are variable and dependent on the patient's clinical status. CKRT
can control ultrafiltration separately from solute removal, which PD cannot,
allowing for greater flexibility within the prescription.

• Because ultrafiltration is continuous and can be adjusted to meet the patient's

needs with CKRT, there is usually no need for fluid restriction unlike that required
in patients managed by HD. CKRT allows for administration of all necessary blood
products, large volumes of medications, and adequate nutrition without
compromising the volume status of the patient.

• CKRT provides superior uremia control compared with PD [70,71] or HD [72,73].

● Components of the CKRT prescription – Prescription components are similar to

those used for intermittent HD and many of the same issues apply to both
modalities:

• Blood flow rate – Similar to HD, blood flow rate determines solute clearance with
higher flow rates increasing diffusive clearance. Blood flow is dependent on the
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Pediatric acute kidney injury (AKI): Indications, timing, and choice of modality for kidney replacement therapy (KRT)

size and quality of the dialysis access and catheter. As noted above, the balance of
higher blood flow and increased clearance must be weighed against the patient's
hemodynamics and their ability to tolerate a higher blood flow rate. Typical blood
flow rates also range from 3 to 10 mL/kg/minute.

• Dialysate/replacement flow rate – The dialysate flow rate does determine

clearance provided by CVVHD and CVVH, but the replacement solution plays a
larger role in determining convective clearance in CVVH and CVVHDF. The
standard dose for combined dialysate and replacement rate is 2000
mL/1.73m2/hour or 30 to 50 mL/kg/hour though in some cases (eg,
hyperammonemia and severe tumor lysis) higher rates of 4000 to 8000
mL/1.73m2/hour may be needed [74,75].

• Dialysate composition – Dialysate or replacement fluids come in a variety of

commercially available formulations, but modification based on patient needs is
possible [76]. However, because of potential pharmacy compounding errors when
manually preparing custom solutions, caution needs to be exercised when
performing these alterations [48].

• Size of the dialyzer – Most CKRT machines have an adult and pediatric set for CKRT
with limited options for dialyzer size and extracorporeal blood volume. The
volume of these circuits is often >10 percent of the blood volume for children who
weigh less than 10 kg. Newer devices are available specifically designed for infants
and neonates with smaller dialyzer surface area and blood volume ( table 8).

• Ultrafiltration – CKRT allows for slow, continuous fluid removal which is often
better tolerated in the hemodynamically unstable patients and can be adjusted on
an ongoing basis depending on the fluid intake needed for medication and
nutrition to attain a daily fluid balance goal.

• Anticoagulation – Anticoagulation is typically required with pediatric CKRT due to

the higher risk of clotting due to low blood flow rates through the small caliber
catheters and tubing. In rare cases, anticoagulation may not be required in larger
patients with high blood flow rates or in patients with coagulopathies (ie, liver
failure patients).

Anticoagulation therapy can be provided regionally or systematically. Regional

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Pediatric acute kidney injury (AKI): Indications, timing, and choice of modality for kidney replacement therapy (KRT)

anticoagulation is typically the preferred method of anticoagulation at most

pediatric centers, but this choice is highly dependent on patient characteristics
and the experience of the center and its staff. (See "Anticoagulation for continuous
kidney replacement therapy".)

- Regional anticoagulation – Citrate is the preferred method of regional

anticoagulation in pediatric patients. Regional anticoagulation should be
considered in pediatric patients with significant bleeding risk, especially
central nervous system hemorrhage risk (see "Anticoagulation for continuous
kidney replacement therapy"). There are commercial preparations of sodium
citrate or anticoagulant citrate dextrose solution (ACD-A) designed for CKRT
use. However, citrate anticoagulation has several key requirements which
must be considered including separate central access for calcium infusion,
arterial line for accurate lab draws, dialysate with no calcium and the need to
measure ionized calcium levels frequently. Relative contraindications for
citrate anticoagulation include liver failure, mitochondrial disorders, and
infants as they are at risk of citrate accumulation. Complications with citrate
anticoagulation include hypo- or hypercalcemia, hypernatremia,
hyperglycemia, and metabolic alkalosis. Regional citrate anticoagulation has
shown longer circuit life than heparin in several pediatric studies [77,78].

- Systemic anticoagulation – Unfractionated heparin is the most common form

of systemic anticoagulation for CKRT in pediatric patients. (See
"Anticoagulation for continuous kidney replacement therapy".)

● Challenges – The main disadvantages of CKRT are its complexity and expense, which
limit its general availability. While it is an established therapy at many tertiary care
hospitals in resource-rich countries, CKRT requires significant technological expertise
and resource allocation, including trained ICU nurses to monitor and adjust CKRT,
and pediatric pharmacy support for modification of dialysate composition [39,79].

Other challenges include:

• Central line access – Like HD, adequate vascular access is essential. An additional
central line may also be required for the administration of calcium chloride as part
of regional citrate anticoagulation protocols.

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Pediatric acute kidney injury (AKI): Indications, timing, and choice of modality for kidney replacement therapy (KRT)

• Limitations for small infants and neonates – For small infants and neonates,
limitations are based on dialyzer and tubing size. In many cases, similar to
intermittent HD, donor blood is needed to prime the extracorporeal circuit, which
may expose these infants to transfusion risks and hypotension [80,81].

The development of dialyzers specifically designed for neonates and small infants
that require lower priming volumes of blood and are able to run accurately at low
blood flows between 5 and 50 mL/min via smaller-sized dialysis catheters have
increased the feasibility of providing CKRT to critically ill infants ( table 8) [82,83].
The CARPEDIEM machine is now approved in several countries, including the
United States, for CKRT in patients weighing between 2 to 10 kg [82,84]. This
system has two dialyzer cartridges which have priming volumes of 32 and 41 mL.
They have successfully utilized small-bore dialysis catheters (4 to 7 Fr) with blood
flow rates as low as 5 mL/min. However, the experience using this system in
critically ill patients has been limited to a few tertiary centers.

A multicenter study reported the successful use of an ultrafiltration device

(Aquadex FlexFlow System) in critically ill infants and children, including neonates,
which had been initially designed for adult-sized patients [81]. Although this
device has a small extracorporeal volume of 33 mL, a blood prime was still needed
for patients weighing <4 kg.

• Effect on medications – Careful attention must be paid to medications that a

patient is receiving because CKRT may alter the clearance of these drugs,
especially those that are of lower molecular weight, water soluble, and not highly
protein bound. Close collaboration with a pharmacist knowledgeable about drug
dosing is a key component for the care of children receiving CKRT.

Prolonged intermittent kidney replacement therapy (PIKRT) — PIKRT is defined as

intermittent KRT performed over a prolonged time period (6 to 12 hours) using
conventional HD machines. Adult trials have shown PIKRT to be more cost effective and
have similar efficacy as CKRT. Pediatric studies are limited to one small case series of four
patients that reported the use of lower ultrafiltration and blood flow rates with excellent
survival [85]. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults:
Indications, timing, and dialysis dose", section on 'Prolonged intermittent kidney
replacement therapy'.)

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Pediatric acute kidney injury (AKI): Indications, timing, and choice of modality for kidney replacement therapy (KRT)

Comparisons of modalities — There have been no prospective clinical trials comparing

the three modalities (PD, HD, and CKRT) for treatment of children with AKI. Several trials in
adults have demonstrated no difference in survival between CKRT and HD. (See "Kidney
replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and
dialysis dose".)

Observational data in children with AKI include the following:

● A retrospective population-based study from the United Kingdom of children who

received KRT from 2005 to 2012 reported improved survival with PD compared with
CKRT [86].

● In a multicenter retrospective study of 226 children who received KRT from 1992 to
1998, survival rates were 40, 49, and 81 percent for hemofiltration (HF), PD, and HD,
respectively [87]. However, in this cohort, the use of inotropic pressors was the most
important factor for survival, and its use was greatest in children on HF and larger
patients were selected for HD.

● In a retrospective study of 42 children following congenital heart disease repair, there

was no difference in mortality between patients who were treated with PD and CKRT
[71]. However, CKRT was superior to PD in terms of fluid balance, solute clearance,
and ability to provide adequate nutrition.

However, available evidence for the optimal treatment is limited by the lack of control for
confounding factors, such as severity of illness and underlying etiology of AKI. This lack of
data has left unresolved the persistent debate on whether initiation of CKRT contributes to
kidney injury by reducing renal blood flow.

Although an alternate medical approach to treat pediatric AKI has been proposed, which
uses a regimen of high-dose diuretics and/or medications to augment renal blood flow (eg,
dopamine) [88], this approach increases the metabolic demand of the kidneys, which has
the potential to be more harmful than CKRT. This approach would also seem to require an
already damaged organ to work even harder in a critical environment. As a result, further
research is needed to determine the best approach to treat pediatric AKI. In particular,
randomized trials that compare regimens of early initiation of CKRT, AKI medical
management (eg, diuretics), and current standard care would be useful in guiding clinical
decision making in children with AKI.
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Pediatric acute kidney injury (AKI): Indications, timing, and choice of modality for kidney replacement therapy (KRT)

Discontinuation

The factors determining when or how KRT should be discontinued (or transitioned to
another modality) are even less well described than the factors determining initiation. No
clear approach for dialysis step down or discontinuation has been defined for patients with
AKI. Just as with initiation, KRT cessation or modality change is influenced by multiple
factors such as urine output (including response to diuretic therapy), hemodynamic
stability, respiratory, nutritional and volume status, and changes in underlying disease and
overall prognosis. Other considerations may include ongoing resource use, staff
availability, family/caregiver wishes, and long-term patient needs. For example, if a patient
with multiorgan failure has improved and is at the point of extubation, it may be
reasonable to change the patient from a continuous therapy to intermittent HD to facilitate
patient rehabilitation and transfer from the pediatric intensive care unit (PICU) to the ward.

Guidelines or strategies have not been published regarding transitioning patients off of
KRT. Unlike mechanical ventilation weaning, which has been studied extensively, the
approach to tapering and discontinuation of KRT is an area ripe for investigation.

Outcomes

Retrospective data demonstrate that the overall survival rates range between 50 and 75
percent in children with AKI who received KRT [9,86,87,89-91]. Factors that increase
mortality include:

● Underlying diseases that cause secondary kidney failure, including bone marrow
failure, hepatic failure, oncohematologic and severe pulmonary disease. In addition,
stem cell and solid organ transplantation (eg, lung and liver) are associated with
poorer survival [9,86,89,92].

● Hypotension at the onset of KRT [87].

● Use of inotropic agents anytime during the course of KRT [87,91].

● Degree of fluid overload present on initiation of KRT [9,21,91].

● Patients under one year of age [86].

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Pediatric acute kidney injury (AKI): Indications, timing, and choice of modality for kidney replacement therapy (KRT)

Additional studies are needed to determine whether other measures including chronic
kidney disease, hypertension, and proteinuria during and after KRT are predictive for long-
term outcome.

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: Acute
kidney injury in children".)

Summary and recommendations

● Acute kidney injury (AKI) and role of kidney replacement therapy (KRT) – For
infants and children, AKI is an independent predictor of morbidity and mortality,
especially in critically ill patients. KRT may prevent and correct the adverse and
potentially life-threatening complications and improve survival. (See 'AKI and
mortality: Potential role of KRT' above.)

● Indications

• Urgent indications for KRT include (see 'Urgent indications' above):

- Children with clinically significant fluid overload with evidence of escalating

ventilatory requirements (typically seen in patients with >15 percent fluid
overload). (See 'Fluid overload' above.)

- Critically ill children with persistent hyperkalemia (eg, potassium level >6.5
mEq/L) that is refractory to medical management as they are at risk for life-
threatening cardiac conductin abnormalities due to hypokalemia. (See
"Causes, clinical manifestations, diagnosis, and evaluation of hyperkalemia in
children", section on 'Cardiac conduction abnormalities'.)

- Critically ill children with persistent metabolic acidosis that is refractory to

medical management.

- Children with complications due to uremia, including pericarditis,

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Pediatric acute kidney injury (AKI): Indications, timing, and choice of modality for kidney replacement therapy (KRT)

encephalopathy, or unexplained change in mental status and bleeding.

- Children with exposure to either endogenous or exogenous toxins, which are

dialyzable, that are inadequately excreted by the kidney.

• Nonurgent indications include (see 'Non-urgent indications' above):

- Although there are insufficient data to support evidence-based guidelines that

include quantifiable values for uremia, we suggest that KRT should be
initiated early based on a serum blood urea nitrogen level between 80 and
100 mg/dL prior to the development of significant signs and symptoms of
acute kidney failure rather than delaying dialysis until the child is symptomatic
(Grade 2C). (See 'Severe AKI' above.)

- For patients who remain oliguric despite diuretic therapy with high volume
requirements (eg, nutrition, medications, and/or blood products) for their
care.

● Modalities – Several KRT modalities, including peritoneal dialysis, intermittent

hemodialysis, and continuous KRT, are available to manage pediatric patients with
AKI. PD is the most common modality utilized in pediatric dialysis, particularly in the
smallest children. Data are insufficient to recommend one modality over another.
Thus, the selection of modality of KRT is based on patient factors (size, underlying
illness, ability to obtain access), local expertise and experience, and available
resources. (See 'Modality' above.)

● Multidisciplinary team – Initiating KRT in a critically ill child requires collaboration

among the nephrologists, intensivists, and other subspecialists caring for the child.
Early discussion and planning will facilitate the process and allow for more rapid
intervention, thereby improving survival outcomes. (See 'KRT modalities and clinical
considerations' above.)

● Outcome – Retrospective data demonstrate the overall survival rates range between
50 and 75 percent in children with AKI who received KRT. Risk factors for mortality
include the underlying disease, hypotension, and significant fluid overload at the
start of KRT, use of inotropic therapy during KRT, and patients less than one year of
age. (See 'Outcomes' above.)

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