Basics
Description
- Acute kidney injury (AKI) is defined as an abrupt (within 48 hours) reduction in kidney function with an absolute increase in serum creatinine of more than or equal to 0.3 mg/dL, or a 1.5-fold increase from baseline or a reduction in urine output (documented oliguria of less than 0.5 mL/kg per hour for more than 6 hours).
- The pediatric modified RIFLE (risk, injury, failure, loss, and end-stage renal disease) system classifies the degree of renal insult by changes in serum creatinine and/or the duration of oliguria.
- In AKI, the urine output is variable: anuria, oliguria and, in some cases, polyuria can all be observed at presentation.
Epidemiology
- The epidemiology of AKI has changed over the recent years from primary kidney disease to a syndrome secondary to other systemic illness.
- AKI may be seen in up to 10% of all hospitalized children. The incidence is higher in ICU admissions and with increasing multiorgan disease severity.
Pathophysiology
The pathogenesis of AKI is multifactorial. It may be initiated by ischemia or toxins, and the subsequent injury involves a complex interplay between vasoconstriction, leukostasis, vascular congestion, cell death, and abnormal immune modulators.
Etiology
Previously, AKI was subcategorized into 3 groups: prerenal, renal, and postrenal. The differentiation between "prerenal"ť and "renal"ť causes can be difficult because renal hypoperfusion may coexist with any stage of AKI.
- Prerenal azotemia (functional)
- Decreased glomerular filtration rate (GFR) resulting from renal hypoperfusion in a structurally intact kidney
- Often rapidly reversible when the underlying cause is corrected
- Intrinsic (structural)
- Disorders that directly affect the kidney
- Acute tubular necrosis (ATN) was used in the past to describe a form of intrinsic AKI from severe and persistent hypoperfusion of the kidneys. However, the histologic diagnosis of tubular necrosis is rarely confirmed by biopsy.
- Glomerular disorders include the various forms of acute glomerulonephritis (AGN) (e.g., postinfectious, rapidly progressive [crescentic]).
- Vascular lesions compromise glomerular blood flow. Hemolytic uremic syndrome (HUS) is the most common vascular disorder that causes intrinsic AKI in children.
- Acute interstitial nephritis (AIN) most often occurs as a result of exposure to medications such as NSAIDs. It may also be associated with infections (e.g., pyelonephritis), systemic diseases, or tumor infiltrates.
- Postrenal
- Obstructive process (either structural or functional)
- Obstruction can be in the lower tract or bilaterally in the upper tracts (unless the patient has a single kidney).
- More common in newborns
Diagnosis
History
- Previous infection, neurogenic bladder, single kidney
- Exposure to nonsteroidal anti-inflammatory agents, β-lactam antibiotics, acyclovir, aminoglycosides, amphotericin B, cisplatin
- Gross hematuria: AGN (tea colored), renal calculi (bright red blood)
- Trauma: crush injury
- Signs and symptoms: fever, rash bloody diarrhea, pallor, severe vomiting or diarrhea, abdominal pain hemorrhage, shock, anuria, polyuria
Physical Exam
- General: weight and hydration status; shock, edema (calculation of percent fluid overload), jaundice
- Lungs: rales
- Heart: gallop
- Abdomen/pelvis: mass
- Skin: rash, petechiae
- Joints: arthritis
Diagnostic Tests & Interpretation
Lab
- All patients with AKI should have a urinalysis with microscopic exam, serum chemistries, and a CBC:
- Urinalysis: specific gravity (>1.020 suggests prerenal AKI), proteinuria (>3+ intrinsic, glomerular AKI), eosinophiluria (AIN), pyuria (pyelonephritis), granular casts (prerenal, ATN), pigmenturia (ATN), erythrocyte casts (glomerulonephritis, AIN, ATN)
- Serum chemistries: hyponatremia, acidosis, hyperkalemia, hypocalcemia, hyperphosphatemia
- CBC: microangiopathic hemolytic anemia, thrombocytopenia (i.e., HUS), eosinophilia (i.e., AIN)
- Selected patients require further studies, including serologies, urine electrolytes, imaging, and renal biopsy:
- Serologies: hypocomplementemia, antineutrophil cytoplasmic antibodies, antinuclear antibodies (AGN)
- The fractional excretion of sodium (FENa)
- Can be useful to assess tubular function. FENa = [(UNa/PNa)/(Ucreat/Pcreat)] — 100.
- The FENa should not be obtained after diuretics are administered. FENa >2: ATN; FENa <1: AGN, prerenal
- FENa can be <1% despite ATN in case of radiocontrast nephropathy or pigment nephropathy.
- Fractional excretion of urea (FEUrea)
- Less affected by diuretics
- FEUrea = [(UUrea/PUrea)/(Ucreat/Pcreat)] — 100
- FEUrea <35: prerenal AKI; FEUrea >50: ATN
Imaging
- Chest radiograph: cardiomegaly or pulmonary edema (fluid overload)
- Renal US: hydronephrosis, trabeculated bladder (i.e., obstruction), increased echogenicity (i.e., ATN, AIN, AGN, HUS), abnormal Doppler study (renal venous thrombosis)
Diagnostic Procedures/Other
Renal biopsy: indicated in patients with prolonged, unexplained AKI or suspicion for crescentic glomerulonephritis
Differential Diagnosis
- Chronic kidney disease: insidious, associated with poor growth, normocytic anemia, hyperparathyroidism
- Azotemia (elevated BUN): hypercatabolic states including corticosteroid therapy or upper GI bleeding
- Elevated creatinine: caused by rhabdomyolysis, drugs (trimethoprim-sulfamethoxazole, cimetidine)
Treatment
Medication
- Clearance of many medications is impaired in AKI. Careful monitoring of drug dosing and levels can minimize toxicity.
- Low-dose (renal dose) dopamine is ineffective in improving kidney function in AKI. Loop diuretics (furosemide) and osmotic diuretics (mannitol) do not affect the progression or outcome of AKI and may be harmful.
- Bicarbonate may be useful to treat AKI in rhabdomyolysis.
- N-acetylcysteine and bicarbonate, used prophylactically, may prevent contrast nephropathy.
Additional Therapies
- Supportive
- Avoid nephrotoxic medications when possible.
- Monitor electrolytes closely. Avoid drugs, fluids, or foods containing potassium in patients with oliguria or anuria.
- Hyponatremia is usually due to free water excess and should be managed with fluid restriction. Hypertonic saline should be used only if CNS symptoms are present.
- Fluid management
- Can be divided into 3 phases based on the clinical status
- Fluid resuscitation/repletion: The goal is to restore end-organ perfusion.
- Fluid balance maintenance: After initial resuscitation, the patient's ongoing fluid needs (blood products, medications, nutrition) should be balanced with the output (urine and insensible losses). Fluid restriction may be needed to avoid worsening fluid overload. Increasing degrees of fluid overload (%FO) at initiation of renal replacement therapy (RRT) are independently associated with mortality.
- Fluid overload may be calculated as:
- %FO = (Fluid Input [L] - Fluid Output [L])/Patient ICU admission weight (kg) —100
- Fluid removal/recovery: If the fluid conservative strategy does not work, RRT may be needed to remove the volumes associated with patient needs.
- RRT is indicated for fluid overload, refractory acidosis, severe hyperkalemia, and uremic symptoms (e.g., pericarditis, lethargy, bleeding diathesis). The modality of RRT (hemodialysis or continuous RRT) depends on the hemodynamic status of the patient.
- Provision of adequate nutrition is essential due to the high prevalence of malnutrition in this group and the associated morbidity and mortality. Protein restriction with the aim of delaying RRT is not recommended.
- Specific treatment based on etiology: Each cause of AKI may necessitate specific treatment, such as fluid resuscitation (i.e., prerenal), urologic intervention (i.e., obstruction), and corticosteroids (i.e., AIN, some forms of AGN).
Inpatient Considerations
Admission Criteria
- If hypovolemic, rapidly establish euvolemia with 0.9% NS or balanced solution boluses.
- If urine output remains low after euvolemia is established, begin fluid restriction (insensible losses and urine output).
- In severe hyperkalemia (>6.5 mEq/L), consider the following:
- Calcium gluconate (100 mg Ca gluconate salt/kg IV) over 5-10 minutes if symptomatic
- Glucose (0.5 g/kg) and insulin (0.1 U/kg) IV over 30 minutes
- Sodium bicarbonate (1-2 mEq/kg) IV over 10-30 minutes if acidotic
- When administering sodium bicarbonate, monitor serum calcium carefully because the hypocalcemia may worsen.
- Kayexalate (1 g/kg) PO or PR in sorbitol
- Furosemide (1-2 mg/kg) if renal function is adequate
- RRT
Ongoing Care
Follow-up Recommendations
- The likelihood of recovery from AKI depends on the underlying cause.
- AKI may result in full recovery or incomplete recovery leading to chronic kidney disease. In severe cases, nonrecovery may lead to end-stage renal disease.
- Long-term follow-up to monitor renal function is recommended.
Prognosis
The mortality rate increases in patients with multisystem organ failure despite good supportive care. AKI is independently associated with increased mortality in ICU patients.
Complications
- A significant postobstructive diuresis can be seen after treatment for obstructive AKI.
- Fluid overload, resulting in congestive heart failure, hypertension, or hyponatremia
- Hyperkalemia, affecting cardiac function by causing arrhythmias
- Uremia, manifest by mental status changes, increased risk of bleeding, and infection
- Metabolic acidosis
- Hypocalcemia, causing tetany
Additional Reading
- Fortenberry JD, Paden ML, Goldstein SL. Acute kidney injury in children: an update on diagnosis and treatment. Pediatr Clin North Am. 2013;60(3):669-688. [View Abstract]
- KDIGO AKI Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2(1):1-138.
- Singri N, Ahya SN, Levin ML. Acute renal failure. JAMA. 2003;289(6):747-751. [View Abstract]
- Zappitelli M. Epidemiology and diagnosis of acute kidney injury. Semin Nephrol. 2008;28(5):436-446. [View Abstract]
Codes
ICD09
- 584.9 Acute kidney failure, unspecified
- 584.5 Acute kidney failure with lesion of tubular necrosis
- 580.9 Acute glomerulonephritis with unspecified pathological lesion in kidney
- 580.89 Acute glomerulonephritis with other specified pathological lesion in kidney
- 866.00 Injury to kidney without mention of open wound into cavity, unspecified injury
- 283.11 Hemolytic-uremic syndrome
ICD10
- N17.9 Acute kidney failure, unspecified
- N17.0 Acute kidney failure with tubular necrosis
- N00.9 Acute nephritic syndrome with unsp morphologic changes
- N10 Acute tubulo-interstitial nephritis
- S37.009S Unspecified injury of unspecified kidney, sequela
- S37.009D Unspecified injury of unspecified kidney, subs encntr
- S37.009A Unspecified injury of unspecified kidney, initial encounter
- D59.3 Hemolytic-uremic syndrome
SNOMED
- 14669001 Acute renal failure syndrome (disorder)
- 35455006 Acute tubular necrosis (disorder)
- 19351000 Acute glomerulonephritis (disorder)
- 28637003 Acute interstitial nephritis (disorder)
- 111407006 Hemolytic uremic syndrome (disorder)
FAQ
- Q: What is the expected recovery time in patients with AKI who present with anuria?
- A: Recovery time depends on the etiology of the AKI. Children with HUS may recover in days to weeks. In severe HUS or AKI requiring RRT, ongoing recovery to new, baseline renal function occurs over several months. Those with ATN recover days after treatment for the cause. Children with AKI secondary to an obstructive process usually recover as soon as the obstruction is removed.
- Q: When should renal function return to normal?
- A: Renal function may never return to normal in patients with long-standing anuria. In other cases, after recovery occurs, serum creatinine levels return to normal within weeks.
- Q: Which indices should be observed after a patient recovers from AKI?
- A: Patients recovering from AKI should have renal function (serum creatinine and cystatin C), BP, and urinalysis for proteinuria monitored regularly.