Acute kidney injury in the infant/child; Pediatric acute renal failure, pediatric acute kidney failure

1. Description of the problem

What every clinician needs to know

Acute kidney injury in the child/newborn is defined as an abrupt cessation or diminution of kidney function. The time frame for pediatric AKI is now considered to be less than 48 hours. Multi-dimensional pediatric AKI definitions include the pediatric modified RIFLE criteria (pRIFLE: Risk, Injury, Failure, Loss, End-stage kidney disease) and the Acute Kidney Injury Network (AKIN criteria).

Clinical features

The clinical features of AKI include:

Oliguria

Hyperkalemia

Acidosis

Volume overload

Hypertension

Hyperphosphatemia

Uremia

Hypocalcemia

Key management points

The key management points for pediatric AKI include, in order of importance:

Treat life-threatening features of pediatric AKI with medical management or renal replacement therapy (dialysis). These include:

Hyperkalemia with evidence of electrocardiographic changes (peaked T-waves, widened QRS interval).

Hypocalcemia with evidence of tetany.

Volume overload with evidence of pulmonary edema.

Prevent worsening clinical sequelae (electrolyte imbalance or increasing fluid accumulation) of pediatric AKI with medical management and/or renal replacement therapy (dialysis), while allowing for appropriate critical care management, which includes:

Nutrition administration in the form of enteral feeds or total parenteral nutrition.

Blood product administration.

Medication administration.

2. Emergency Management

Stabilizing the patient

The emergency management steps for pediatric AKI are listed below and focus on each clinical feature of pediatric AKI.

Hyperkalemia

Sodium polystyrene sulfonate (Kayexalate®): 1 g/kg body weight by mouth or if contraindicated, per rectum. This dose should decrease serum potassium concentration by 1 meq/L (PO) or 0.5 meq/L (PR).

For widened QRS complexes or peaked T-waves.

Sodium bicarbonate 1 meq/kg intravenously to cause intracellular shift of potassium; this maneuver does not reduce total body potassium stores.

Insulin and glucose intravenously; this maneuver does not reduce total body potassium stores.

Infants and children: 0.5-1 gm/kg dextrose (using D25 or D50), combine with 1 unit of regular insulin for each 4-5 grams of dextrose given

Adolescents: 25-50 grams of D10W (250-500 ml) combined with 10 units of regular insulin

Calcium chloride 20 mg/kg intravenously; this maneuver stabilizes the cardiac myocyte membrane and prevents dysrhythmias
Hypocalcemia

Calcium chloride 10-20 mg/kg per dose, may repeat as necessary.
Volume overload

Furosemide 1 mg/kg IV with repeated doses as necessary.

Renal replacement therapy (dialysis) for patients refractory to furosemide.

3. Diagnosis

Diagnostic criteria and tests

The diagnosis of AKI is based on increases in serum creatinine or decreases in urine output. Until recently, multiple diagnostic criteria were used, which confounded analysis. Recent validation of the pediatric modified RIFLE (pRIFLE) criteria has standardized the definition and diagnosis of AKI presence and severity.

pRIFLE creatinine-based AKI criteria: Serum creatinine values are used to calculate an estimated creatinine clearance (eCCl) by the Schwartz formula:

eCCl (ml/min/1.73m2) = k * patient height (cm)/serum creatinine (mg/dl), where k is a constant based on patient’s gender and age

k values: low birth weight less than 1 year (0.33); full term less than 1 year (0.45); 2-12 years of age (0.55); 13-21 year old female (0.55); 13-21 year old male (0.70).

Use baseline and current serum creatinine to calculate a change in eCCl.

If no baseline serum creatinine is available for 3 months prior to current value, assume eCCl = 120 ml/min/1.73m2.

pRIFLE AKI strata: eCCl change: less than 25% (no AKI); 25-49% (pRIFLE-R); 50-74% (pRIFLE-I); greater than or equal to 75% or eCCl below 35 ml/min/1.73m2 (pRIFLE-F).
pRIFLE urine output-based criteria: At least 8 hours of recorded UOP is required to diagnose AKI with the pRIFLE UOP-based criteria.

pRIFLE AKI strata: less than 0.5 ml/kg/hour for 8 hours (pRIFLE-R); less than 0.5 ml/kg/hour for 16 hours (pRIFLE-I); less than 0.3 ml/kg/hour for 24 hours or anuric for 12 hours (pRIFLE-F).

Normal lab values

The normal serum electrolyte and creatinine ranges vary by pediatric patient age as a result of nephron tubular maturation. Table I lists the general ranges based on patient age. These 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.

Table 1.

	Infant	Child	Adolescent
Sodium (meq/L)	130-140	133-146	133-146
Potassium (meq/L)	3.7-5.9	3.4-4.7	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
Magnesium (mg/dL)	1.3-2.0	1.3-2.0	1.3-2.0
Uric acid (mg/dl)	2.4-6.4	2.4-5.9	2.4-7.2

Urine output

Typically, urine output is reported in terms of ml/kg of patient body weight/hour, with a value greater than 1 ml/kg/hour considered to be “normal.”

In AKI, the 1ml/kg/hour threshold does not apply as patients may have a “relative oliguria” if they have received large fluid volumes, which would require sufficiently greater urine volumes to maintain euvolemia.

Thus, matching intake to output and assessing daily weight and edema status are crucial to determine if urine output is really “normal”.

Establishing a diagnosis

You know that the patient has AKI if he/she has sustained periods of oligo-anuria and/or some of the metabolic derangements noted above.

The pRIFLE diagnostic criteria serve as a guideline to detect AKI and to determine its severity in children.

Other possible diagnoses

The differential diagnosis for pediatric AKI mainly focuses on the potential cause of AKI. These causes have classically been characterized as pre-renal, intrinsic renal and post-renal.

Pre-renal disease: Results from decreased renal blood flow leading to the kidney appropriately conserving volume.

Pre-renal azotemia has been recently retermed as fluid-responsive AKI and is suggested by the following lab assessments:

BUN/Cr ratio above 20

Fractional excretion of sodium [FeNa = (urine sodium/serum sodium)/(urine creatinine/serum creatinine) * 100%] below 1%.

This test is not valid in patients receiving loop diuretics, which lead to tubular sodium wasting.

Fractional excretion of urea [FeUrea = (urine urea nitrogen/blood urea nitrogen)/(urine creatinine/serum creatinine) * 100%] below 35%.

Causes

Dehydration.

Blood loss.

Abdominal compartment syndrome.
Intrinsic renal disease: results from direct damage to the kidneys.

Acute tubular necrosis (ATN)/ischemia-reperfusion injury has recently been termed fluid-non-responsive and is suggested by the following lab assessment:

Fractional excretion of sodium [FeNa = (urine sodium/serum sodium)/(urine creatinine/serum creatinine) * 100%] below 3%.

This test is not valid in patients receiving loop diuretics. which lead to tubular sodium wasting.

Fractional excretion of urea [FeUrea = (urine urea nitrogen/blood urea nitrogen)/(urine creatinine/serum creatinine) * 100%] below 35%.

Causes

Glomerulonephritides.

Hemolytic uremic syndrome (HUS)/Thrombotic thrombocytopenic purpura (TTP) complex.

Prolonged distributive shock.

Cardiogenic shock.

Nephrotoxic medications or other toxins.

Urinary tract infection/pyelonephritis.

Hemolytic uremic syndrome.

Rhabdomyolysis.

Tumor lysis syndrome.

Interstitial nephritis.

Renal arterial thrombosis (bilateral).

Renal vein thrombosis (bilateral).

Trauma.
Post-renal disease: Results from obstruction to urinary flow from the level of the renal pelvis to the urethra. These entities can be congenital or acquired. The obstruction usually must be bilateral (above the level of the urethra) to cause kidney failure.
Causes

Congenital

Posterior urethral valves (males only).

Ureteral-vesical junction obstruction.

Ureteral-pelvic junction obstruction.

Severe vesico-ureteral reflux.

Eagle-Barrett (prune-belly) syndrome.

Acquired

Trauma.

Oncologic lesions (neuroblastoma, Wilms’ tumor most common).

Nephrolithiasis with obstructing stones.

Ureteral/urethral/bladder clots.

Confirmatory tests

The following lab and radiologic tests should be considered in patients with suspected acute kidney injury:

Serum electrolytes, BUN, creatinine, calcium, phosphorus, magnesium, uric acid.

Urinalysis with microscopy.

Urinary electrolytes (sodium, potassium, chloride), creatinine and urea nitrogen (if patient is receiving a loop diuretic) to calculate FeNa or FeUrea.

Urine culture (if patient has signs/symptoms of a urinary tract infection).

Urine for eosinophils (if patient is receiving a medication with potential to cause interstitial nephritis).

Renal ultrasound to include the kidneys and bladder.

Creatine phosphokinase (if rhabdomyolysis is suspected).

Renal biopsy in cases of suspected rapidly progressive glomerulonephritis or if AKI cause is uncertain in setting of rapidly rising creatinine.

Anti-nuclear antibody, anti-double-stranded DNA, C3, C4, anti-nuclear cytoplasmic antibody (ANCA), anti-glomerular basement membrane antibody (if patient has history, signs and symptoms consistent with a glomerulonephritis).

ADAMTS-13 activity/antibody (if TTP is suspected).

Stool for enteropathogenic E. coli (if HUS is suspected in children with bloody diarrhea).

Abdominal computed tomography scan or ultrasound (if trauma or abdominal mass is suspected).

Spiral computed tomography scan (if nephrolithiasis is suspected).

24-hour urine for calcium, oxalate, citrate, cystine, uric acid (in patients with confirmed nephrolithiasis).

4. Specific Treatment

First-line therapies

Therapy should be directed at the suspected underlying cause of AKI in the child. Currently, therapy is supportive for most causes of AKI.

Pre-renal disease

Fluid resuscitation

Crystalloid (normal saline – 20 ml/kg time three doses, then reassess).

Colloid (including blood or 5% albumin based on cause).

Paracentesis for abdominal compartment syndrome.
Intrinsic renal disease

Acute tubular necrosis (ATN)

Supportive treatment

Restore blood pressure with fluid resuscitation and vasoactive medications.

Prevent severe fluid overload once blood pressure and end-organ perfusion are restored.

Avoid unnecessary nephrotoxins.

Initiate renal replacement therapy/extracorporeal membrane oxygenation if:

ATN course is expected to be prolonged AND

Administration of nutrition, blood products and medications would lead to worsening severe positive fluid accumulation

Glomerulonephritides: Consider the following in cases of rapidly progressive (crescentic GN)

Corticosteroids

Cyclophosphamide

Plasma exchange

HUS/TTP Complex

HUS

Supportive care only (fluid, electrolyte restrictions, renal replacement therapy in severe cases).

TTP

Supportive care (fluid, electrolyte restrictions, renal replacement therapy in severe cases).

Plasma exchange (daily until platelet count above 150K for 3 consecutive days).

Shock

Address underlying cause of shock.

Fluid resuscitation.

Vasoactive medications.

Inotropes.

Nephrotoxic medications and other toxins

Discontinue the suspected nephrotoxic medication.

Extracorporeal removal by renal replacement therapy or hemoperfusion if:

Sustained elevated concentrations are life-threatening or could lead to permanent kidney damage AND

Compound is removable by extracorporeal therapies.

Urinary tract infections/pyelonephritis

Treat with appropriate antimicrobial agent(s).

Rhabdomyolysis

Hydrate with 2-3 times maintenance fluid (as long as patient is non-oliguric).

Alkalinize urine with sodium bicarbonate in maintenance fluid to achieve urine pH above 7.

Tumor lysis syndrome

Hydrate with 2-3 times maintenance fluid (as long as patient is non-oliguric).

Alkalinize urine with sodium bicarbonate in maintenance fluid to achieve urine pH above 7.

Prescribe oral phosphorus binders.

Prescribe urate oxidase.

Renal replacement therapy for patients with hyperuricemia, hypocalcemia and/or hyperphosphatemia refractory to medical management.

Interstitial nephritis

Corticosteroids.

Renal artery thrombosis

Systemic and/or direct anticoagulation.

Vascular surgical thrombectomy.

Renal vein thrombosis (bilateral)

Systemic anticoagulation

Trauma

Surgical exploration as warranted.
Post-renal disease

Congenital conditions

Posterior urethral valves

Place indwelling urethral catheter.

Consult pediatric urologist to fulgurate valves.

Upper obstructive lesions

Consult pediatric urologist for urinary diversion or surgical correction.

Drugs and dosages

The drug dosages listed here are for guidance only as few randomized trials have compared efficacy of different regimens in children. For doses of vasoactive and inotropic medications, please refer to the chapter on “Septic Shock” in this section.

Corticosteroids

Methylprednisolone: 10-30 mg /kg body weight pulse IV (maximum 1000 mg) daily or alternate day for 6 doses.

Prednisone: 2 mg/kg body weight po (maximum 60-80 mg) daily.
Cyclophosphamide

IV: 500-1000 mg/m2 BSA pulse monthly for 6 months.

Oral: 2-3 mg/kg body weight daily for total cumulative dose of 160-200 mg/kg body weight.
Phosphorus binders

Calcium carbonate (many formulations).

Aluminum hydroxide.

Children: 30 mg/kg body weight divided 4 times daily (maximum dose 3000 mg/day).

Adolescents/adults: 300-600 mg 4 times per day.

Currently, there is no specific treatment for acute kidney injury once it has developed other than treating the underlying cause and preventing the known sequelae of acute kidney injury.

5. Disease monitoring, follow-up and disposition

2/3 of children who develop acute kidney injury and survive to hospital discharge will recover kidney function.
30% of children will be discharged with decreased kidney function.
5% of children will be discharged on dialysis.
Mortality for children with acute kidney injury increases with:

increasing pRIFLE strata.

increasing patient severity of illness.

younger age (patients under1 year of age with higher mortality rates).
1/3 of patients who survive an acute kidney injury episode will have signs or symptoms of chronic kidney disease 3-5 years later.
Death or ESRD occurs in 12% of children with HUS.
25% of children who survive an HUS episode will have signs and symptoms of chronic kidney disease.

Incorrect diagnosis

The diagnosis of acute kidney injury is very straightforward. The differential diagnoses arise in determining the cause of pediatric acute kidney injury.

Follow-up

Children who survive an acute kidney injury episode should be followed periodically for:

Resolution of acute kidney injury.

Development of signs and symptoms of chronic kidney disease, which include:

Proteinuria.

Decreased glomerular filtration rate.

Hypertension.

The frequency of the follow-up will depend on:

The severity of the acute kidney injury.

The resolution of acute kidney injury.

The presence of signs and symptoms of chronic kidney disease.

Pathophysiology

The pathophysiology of acute kidney injury is often multifactorial and is similar to that seen in adult patients. In general, most pediatric acute kidney injury cases result from:

A hypoxic-ischemic-reperfusion injury caused by prolonged hypotension and decreased renal blood flow.

Direct toxic effect to the proximal tubules by an exogenous or endogenous toxin.

In either case, damage to the proximal tubule can lead to tubule cell sloughing into the proximal lumen, with obstruction to urinary flow and backleak though the tubules and into the glomerulus. Once the injury has subsided, the proximal tubules must regenerate their integrity and polarity to resume normal function.

Epidemiology

The epidemiology of pediatric acute kidney injury has changed from the 1990s on from primary kidney disease to another system illness or its treatment.

Only 7% of pediatric acute kidney injury cases result from a primary kidney disease in the tertiary hospitalized setting. In the intensive care setting, multi-organ dysfunction syndrome, with primary cardiac, hepatic, hematological or pulmonary diagnoses, is the most common. Pediatric acute kidney injury affects the entire pediatric age spectrum, from premature neonates to young adults.

Prognosis

The prognosis for pediatric acute kidney injury varies with patient age, severity of illness and underlying diagnosis.

Children below 1 year of age have worse survival rates.
Children admitted to an ICU have worse survival rates than those who are not.
Critically ill children receiving invasive mechanical intubation and on vasoactive medication have an independent increased risk of mortality if they experience pRIFLE-I or pRIFLE-F acute kidney injury compared to no acute kidney injury or pRIFLE-R AKI.
Children with acute decompensated heart failure have an independent increased risk of death or requirement for a cardiac mechanical assist device if they experience a serum creatinine rise greater than or equal to 0.3 mg/dl.

Special considerations for nursing and allied health professionals.

N/A

What's the evidence?

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Critical Care Medicine