Critical Care Medicine

Renal replacement in pediatric AKI

Renal replacement in pediatric AKI

Synonyms

Dialysis, hemodialysis, peritoneal dialysis, continuous renal replacement therapy

Acute Renal Failure, Acute Kidney Injury, Fluid Overload.

1. Description of the problem

Renal replacement therapy for pediatric AKI represents a wide spectrum of modalities that must be tailored to the individual patient based on

  • Underlying medical condition leading to AKI

  • Patient hemodynamic stability

  • Patient size

  • Institutional resources and nursing expertise to provide the specific therapy

Clinical features

The key acute kidney injury features leading to the need for pediatric renal replacement therapy include:

  • Oliguria with resultant positive fluid overload resulting in:

    • hypertension

    • pulmonary compromise and pulmonary edema

    • abdominal compartment syndrome

  • Metabolic derangements which include:

    • Hyperkalemia

    • Acidosis

    • Hyponatremia

    • Uremia

    • Hypocalcemia

    • Hyperphosphatemia

  • Non-acute kidney injury related indications for renal replacement therapy techniques include:

    • Inborn errors of metabolisms resulting in hyperammonemia or other endogenous neurologic toxins

    • Exogenous toxin ingestions that are amenable to dialytic removal:

      • Low protein binding

      • Molecular weight less than 15-30 kilodaltons

      • Low volume of distribution

Key management points

Pediatric renal replacement therapy for acute kidney injury has become more commonplace over the past two decades. Three modalities are available and should be individualized for each patient and their clinical situation.

  1. Intermittent hemodialysis is usually most appropriate for patients who are hemodynamically stable and larger than 10 kg.

  2. Peritoneal dialysis is usually most appropriate for patients who are hemodynamically stable, smaller than 10 kg, who have not had major abdominal surgery and infants after congenital heart surgery.

  3. Continuous renal replacement therapy is usually most appropriate for patients who are hemodynamically unstable and of any size.

2. Emergency Management

The emergency management indications for initiating acute renal replacement therapy in children include immediate life-threatening, or severe complications of acute kidney injury that are refractory to medical/pharmacological therapy:

  • Hyper- or hyponatremia with neurologic compromise:

    • Coma

    • Somnolence

    • Seizures

  • Hyperkalemia:

    • Associated with electrocardiogram changes

      • Peaked T-waves

      • Widened QRS complexes

  • Hypokalemia:

    • U-waves on ECG

    • Paralysis

  • Hypocalcemia:

    • Tetany

  • Hyperphosphatemia:

    • Gross hematuria with calcium-phosphate crystals in urine

  • Hyperuricemia:

    • Gross hematuria with uric acid crystals in urine

  • Volume overload:

    • Pulmonary edema

    • Respiratory distress

Management points not to be missed

The key points to remember in providing emergent renal replacement therapy include:

  • Expeditious placement of an appropriate access

    • Hemodialysis or CRRT catheters can be placed at the bedside

      • A dual or triple lumen venous hemodialysis catheter can be placed in any large vein:

        • The femoral or internal jugular veins are used most commonly

        • Avoid the subclavian if possible as patients may develop subclavian vein stenosis which can preclude chronic arteriovenous access placement in that limb if the patient develops End-Stage Renal Disease

        • The catheter size (French) and length should be matched to the patient size to allow for adequate flow while minimizing vessel trauma

        • Catheter placement should be checked prior to using catheter

          • Internal jugular or subclavian vein catheters should have tip in right atrium

          • Femoral vein catheters should be free of kinking

        • A trained dialysis nurse or technician should test the flow of the catheter prior to initiating therapy - see Table I.

Table I.

Hemodialysis/CRRT patient and catheter sizes
Patient size Catheter Size
< 3 kg 7 French dual or triple lumen
3-6 kg 7 or 8 French dual lumen
6-10 kg 8 French dual lumen
10-20 kg 9 French dual lumen
20-30 kg 10 French dual lumen
30-40 kg 11 French dual lumen
> 40 kg 11 French dual lumen of 12 French triple lumen
  • Peritoneal dialysis

    • Acute peritoneal dialysis catheters can be placed at the bedside. The catheter tip should be positioned in the left lower quadrant if possible

      • Both cuffed and uncuffed catheters are available

      • A suture should not be placed at the exit site

      • The peritoneal dialysis catheter can be placed through the thoracotomy site in patients who receive peritoneal dialysis catheters in the OR at the time of cardiopulmonary bypass

Drugs and dosages

A number of pharmacological issues must be considered with respect to renal replacement therapy provision:

  • Anticoagulation of the dialysis circuit for hemodialysis or continuous renal replacement therapy:

    • Hemodialysis

      • Usually performed with unfractionated heparin anticoagulation:

        • Bolus dose of 50 units/kg

        • Continuous infusion of 25 units/kg/hour

        • Check activated clotting times to keep in 180-240 second range

      • Saline flushes or tight heparin anticoagulation (activated clotting time range 120-160 second range)

      • Continuous renal replacement therapy:

        • Heparin anticoagulation:

          • Keep activated clotting time between 180-240 seconds

          • Measured every 1-4 hours

        • Regional citrate anticoagulation (numerous protocols):

          • Citrate infused in access line to circuit to keep circuit ionized calcium between 0.2-0.4 mmol/L

          • Calcium chloride infused systemically to keep patient ionized calcium between 1-1.2

          • Monitor for citrate lock which results from incomplete metabolism, clearance of citrate:

            • Increasing systemic patient total calcium concentration

            • Decreasing systemic patient ionized calcium

            • Treatment: stop citrate for 2-4 hours, restart at 50% of previous rate once patient systemic ionized calcium has normalized

  • Dialysis/Replacement fluids:

    • Industry standard grade pre-made solutions are available and safer than extemporaneously made pharmacy solutions

    • Fluid rates should equal a minimum small solute clearance of 2000 ml/hr/1.73m2 body surface area which is equivalent to 30 ml/kg/hour for a 70 kg male

  • Blood priming of the dialysis circuit is required for small children where extracorporeal circuit volume >1015% of patient total blood volume:

    • Interaction of blood with certain CRRT membranes can lead to bradykinin release syndrome:

      • hypotension

      • bronchospasm

      • multiple protocols to prevent this syndrome:

        • Bypass procedure where the patient receives packed cells but the prime is discarded

        • Zero-balance ultrafiltration procedure where the blood is dialyzed in via the CRRT circuit placed in recirculation

  • Peritoneal dialysis:

    • Solutions are generally made of 1.5%, 2.5% or 4.25% complexed dextrose solution to achieve fluid removal (ultrafiltration)

    • A low volume (Gesco®) set-up is required to minimize the dead space for smaller patients

    • A continuous cycler can be used for patients larger than 5 kg

    • Initial acute peritoneal dialysis prescription guideline:

      • 1.5% solution

      • 10 ml/kg dwell volume

      • 5 minute fill time

      • 45 minute dwell time

      • 10 minute drain time

      • Continuous 24 hours per day

      • Potassium (up to 4 meq/L) and phosphorus (up to 2 mmol/L) added as needed

3. Diagnosis

The diagnosis for renal replacement therapy requirement in children with acute kidney injury requires a complex clinical and laboratory assessment of the patient's current status, ongoing needs and predicted future course. There is no hard and fast rule for initiating renal replacement therapy.

Current status assessment

If the patient has any of the following, then an assessment of ongoing needs and predicted future course must be undertaken to determine if renal replacement therapy should be initiated.

  • Patient vital signs and respiratory status:

    • Hypertension leading to fluid overload?

    • Pulmonary edema and respiratory compromise secondary to fluid overload?

    • Anasarca with abdominal compartment syndrome/infection risk secondary to fluid overload?

  • Laboratory assessment:

    • The normal serum electrolyte and creatinine ranges vary by pediatric age as a function of tubular maturation and increase in muscle mass during growth and development. The following table lists the general ranges based on patient age. These values should serve only as one piece of data to inform clinical decision making as many electrolyte concentrations can be affected by dietary and other non-kidney function related factors.

    • See Emergency Management section for associated clinical conditions that require immediate renal replacement therapy initiation - see Table II.

Table II.

Pediatric Electrolyte and Creatinine Ranges based on Age
Infant Child Adolescent
Sodium (meq/L) 130-140 133-146 133-146
Potassium (meq/L) 3.7-5.9 3.4-5.7 3.5-5.1
Chloride (meq/L) 98-113 98-107 98-107
Bicarbonate (meq/L) 16-24 22-26 22-26
Blood Urea Nitrogen (mg/dL) < 20 < 20 < 20
Creatinine (mg/dL) 0.2-0.4 0.3-0.7 0.5-1.0
Calcium (mg/dL) 9.0-11.0 8.8-10.8 8.6-10.0
Phosphorus (mg/dL) 4.5-6.7 4.5-5.5 2.7-4.5
Uric Acid (mg/dL) 2.4-6.4 2.4-5.9 2.4-7.2

Ongoing needs assessment

An assessment of the patient's fluid and associated electrolyte needs should be made at least daily. If the volume and solute load required for the day would likely lead to worsening clinical status from the sequelae of acute kidney injury, then assessment of the patient's predicted future course must be undertaken to determine if renal replacement therapy should be initiated.

  • Fluid volume needed:

    • Nutrition (TPN + enteral feeds)

    • Medication volumes

    • Blood product requirements

  • Solute burden:

    • Nutrition (TPN + enteral feeds)

    • Medications (sodium is prevalent in many antibiotics)

    • Blood products (sodium and potassium are present in blood products)

Predicted future course

A realistic assessment of the patient's resolution of acute kidney injury with resumption of adequate urine output and electrolyte homeostasis must be undertaken at least daily.

If the patient already has signs and symptoms of the sequelae of acute kidney injury with volume overload and electrolyte imbalance, and/or if the daily ongoing needs to for nutrition/blood products/medication would put the patient a risk for worsening sequelae, and the kidney function is not expected to improve in the next 24 hours, renal replacement therapy initiation should be strongly considered.

The clinical criteria to diagnose when a patient needs renal replacement therapy is guided by the principles discussed in the previous section. In addition, recent pediatric data suggest patients with acute kidney injury and a relative intensive care unit fluid accumulation of > 10-20% of their intensive care unit admission body weight are at increased risk for mortality.

Data from a multicenter pediatric continuous renal replacement therapy consortium (the Prospective Pediatric CRRT Registry) listed the following averages for CRRT initiation in terms of estimated glomerular filtration rate and blood urea nitrogen levels.

  • eGFR - 42.8 ml/min/1.73 m2

  • BUN - 64 mg/dL

The diagnostic approach to the pediatric patient with acute kidney injury who may need renal replacement therapy involves:

  • Assessment of the underlying condition leading to acute kidney injury

  • Assessment of the patient's current clinical and laboratory status (previous sections)

  • Assessment of the patient's ongoing needs

  • Assessment of the patient's likely recovery of kidney function in the next 12-24 hours.

Pathophysiology

The pathophysiology of severe acute kidney results from the complete or partial dysregulation of fluid, electrolyte and potentially relevant hormonal homeostatic mechanisms

Fluid dysregulation characteristics

  • Anasarca:

    • Increased infection risk

    • Impact on surgical wound healing

  • Abdominal compartment syndrome:

    • Decreased hepatic and renal perfusion

    • Decreased venous return and cardiac preload

  • Pulmonary edema:

    • Decreased oxygenation

    • Increased pulmonary wedge pressure with right sided heart failure

  • Intravascular fluid overload:

    • Systemic hypertension

    • Increased afterload and with left sided heart failure

Electrolyte dysregulation characteristics

  • Uremia:

    • Platelet dysfunction

    • Central nervous system depression

    • Immunoparalysis

    • Pericarditis

  • Hyperkalemia:

    • Dysrhythmias

  • Hypokalemia:

    • Dysrhythmias

    • Muscle weakness or paralysis

  • Hypocalcemia:

    • Tetany

    • Seizures

Hormonal dysregulation characteristics

Patients with prolonged acute kidney injury requiring renal replacement therapy may develop many of the hormonal imbalances seen in patients with chronic kidney disease including:

  • Secondary hyperparathyroidism

  • Anemia from erythropoietin deficiency and/or resistance.

Epidemiology

The epidemiology of pediatric patients who receive renal replacement therapy parallels the changes in epidemiology observed in pediatric acute kidney injury.

  • Pediatric patients receiving acute renal replacement therapy do so as a result of another system illness or its treatment and not primary kidney disease

  • Continuous renal replacement therapy has become the most common modality to support children with acute kidney injury, with the exception that continuous peritoneal dialysis is preferred in smaller children less than 8 kg

  • CRRT has proven effective across the span of pediatric age range (0-25 years) and sizes (2-200kg), but requires special technical expertise in small children.

Prognosis

The prognosis for children receiving acute renal replacement therapy is related to a number of clinical and demographic variables

Patient characteristics

  • Children receiving CRRT less than 1 year of age or 10 kg have a lower survival rate than older/larger patients (43% vs 63%)

  • Children receiving CRRT with another major system illness have lower survival than patients with less complex disease:

    • Liver transplant/disease - 31%

    • Bone marrow transplant - 45%

    • Pulmonary disease/transplant - 45%

    • Malignancy - 48%

    • Cardiac disease/transplant - 51%

    • Sepsis - 59%

    • Shock - 68%

    • Renal disease - 84%

Clinical variables

  • Multiple single- and multi-center studies show that ICU fluid accumulation at CRRT initiation is independently associated with increased risk of mortality, although to date, no randomized trial as assessed the impact of fluid accumulation on outcome

    • Six studies comprising 750 patients demonstrate an independent increased risk of mortality for CRRT patients at > 10-20% fluid overload - see Table III.

Table III.

Fluid Overload and Outcomes in Children Receiving CRRT
Author Fluid Overload Threshold Mortality
Gillespie 10% OR 3.02 for > 10% FO
Foland 10% increment OR 1.78 for each 10% increment
Goldstein 20% < 20% FO - 42%; > 20% FO - 60%
Hayes 20% OR 6 for > 20% FO
Sutherland < 10%, 10-20%, > 20% < 10% FO - 29%, 10-20% FO -43%, > 20% FO - 66%

Survival Rates by CRRT Duration in Children Receiving CRRT

  • 1-7 days - 65%

  • 8-14 days -55%

  • 15-21 days - 53%

  • 22-28 days - 43%

  • > 28 days - 35%

Discontinuation

No pediatric study has determined precise criteria for terminating renal replacement therapy in the acute setting. The following serve as general principles:

  • Increase in urine output to tolerate daily fluid requirements

  • Improvement in kidney function to tolerate daily solute load

In clinical practice, patients are usually trialed off renal replacement therapy with close monitoring of fluid balance and electrolyte homeostasis.

Special considerations for nursing and allied health professionals.

NA

What's the evidence?

Emergency management

Symons, JM, Picca, S. "Acute kidney injury and dialysis in children: illustrative cases". Semin Nephrol. vol. 28. 2008. pp. 431-5.

Brophy, PD. "Renal supportive therapy for pediatric acute kidney injury in the setting of multi-organ dysfunction syndrome/sepsis". Semin Nephrol. vol. 28. 2008. pp. 457-69.

Bunchman, TE, Brophy, PD, Goldstein, SL. "Technical considerations for renal replacement therapy in children". Semin Nephrol. vol. 28. 2008. pp. 488-92.

Picca, S, Ricci, Z, Picardo, S. "Acute kidney injury in an infant after cardiopulmonary bypass". Semin Nephrol. vol. 28. 2008. pp. 470-6.

(This issue of Seminars in Nephrology is completely dedicated to pediatric acute kidney injury. The cases presented in these articles form the basis for renal replacement therapy management in children including timing and technical considerations.)

Hackbarth, R, Bunchman, TE, Chua, AN. "The effect of vascular access location and size on circuit survival in pediatric continuous renal replacement therapy: a report from the PPCRRT registry". Int J Artif Organs. vol. 30. 2007. pp. 1116-21.

(This article deals with technical aspects of CRRT catheter placement and performance.)

Diagnosis

Goldstein, SL, Somers, MJ, Brophy, PD. "The Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry: design, development and data assessed". Int J Artif Organs. vol. 27. 2004. pp. 9-14.

(This article describes the ppCRRT Registry format.)

Goldstein, SL, Currier, H, Graf, C, Cosio, CC, Brewer, ED, Sachdeva, R. "Outcome in children receiving continuous venovenous hemofiltration". Pediatrics. vol. 107. 2001. pp. 1309-12.

Gillespie, RS, Seidel, K, Symons, JM. "Effect of fluid overload and dose of replacement fluid on survival in hemofiltration". Pediatr Nephrol. vol. 19. 2004. pp. 1394-9.

Goldstein, SL, Somers, MJ, Baum, MA. "Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy". Kidney Int. vol. 67. 2005. pp. 653-8.

Foland, JA, Fortenberry, JD, Warshaw, BL. "Fluid overload before continuous hemofiltration and survival in critically ill children: a retrospective analysis". Crit Care Med. vol. 32. 2004. pp. 1771-6.

Hayes, LW, Oster, RA, Tofil, NM, Tolwani, AJ. "Outcomes of critically ill children requiring continuous renal replacement therapy". J Crit Care. vol. 24. 2009. pp. 394-400.

Sutherland, SM, Zappitelli, M, Alexander, SR. "Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry". Am J Kidney Dis. vol. 55. 2010. pp. 316-25.

(These articles comprise the current assessment of the association between fluid overload and patient outcome in children receiving CRRT.)

Sorof, JM, Stromberg, D, Brewer, ED, Feltes, TF, Fraser, CD. "Early initiation of peritoneal dialysis after surgical repair of congenital heart disease". Pediatr Nephrol. vol. 13. 1999. pp. 641-5.

Picca, S, Principato, F, Mazzera, E. "Risks of acute renal failure after cardiopulmonary bypass surgery in children: a retrospective 10-year case-control study". Nephrol Dial Transplant. vol. 10. 1995. pp. 630-6.

Bokesch, PM, Kapural, MB, Mossad, EB. "Do peritoneal catheters remove pro-inflammatory cytokines after cardiopulmonary bypass in neonates?". Ann Thorac Surg. vol. 70. 2000. pp. 639-43.

(These articles detail the use of peritoneal dialysis in the setting of congenital heart surgery.)

Epidemiology

Hui-Stickle, S, Brewer, ED, Goldstein, SL. "Pediatric ARF epidemiology at a tertiary care center from 1999 to 2001". Am J Kidney Dis. vol. 45. 2005. pp. 96-101.

(This paper details the most current pediatric AKI epidemiology in the hospital setting.)

Akcan-Arikan, A, Zappitelli, M, Loftis, LL, Washburn, KK, Jefferson, LS, Goldstein, SL. "Modified RIFLE criteria in critically ill children with acute kidney injury". Kidney Int. vol. 71. 2007. pp. 1028-35.

Bailey, D, Phan, V, Litalien, C. "Risk factors of acute renal failure in critically ill children: A prospective descriptive epidemiological study". Pediatr Crit Care Med. vol. 8. 2007. pp. 29-35.

Plotz, FB, Bouma, AB, van Wijk, JA, Kneyber, MC, Bokenkamp, A. "Pediatric acute kidney injury in the ICU: an independent evaluation of pRIFLE criteria". Intensive Care Med. vol. 34. 2008. pp. 1713-7.

Schneider, J, Khemani, R, Grushkin, C, Bart, R. "Serum creatinine as stratified in the RIFLE score for acute kidney injury is associated with mortality and length of stay for children in the pediatric intensive care unit". Crit Care Med. vol. 38. 2010. pp. 933-9.

(These articles detail AKI epidemiology in the pediatric ICU setting.)

Flores, FX, Brophy, PD, Symons, JM. "Continuous renal replacement therapy (CRRT) after stem cell transplantation. A report from the prospective pediatric CRRT Registry Group". Pediatr Nephrol. vol. 23. 2008. pp. 625-30.

(This article details epidemiology and outcomes in pediatric stem cell transplant recipients who receive CRRT.)

Symons, JM, Chua, AN, Somers, MJ. "Demographic characteristics of pediatric continuous renal replacement therapy: a report of the prospective pediatric continuous renal replacement therapy registry". Clin J Am Soc Nephrol. vol. 2. 2007. pp. 732-8.

(This study comprises the largest pediatric CRRT cohort reported, detailing outcomes, patient size and co-morbid condition effects on mortality.)

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