Leigh Mark Ettinger, MD, MS
Kenneth Lieberman, MD
BASICS
DESCRIPTION
• A sudden or recently acquired functional impairment of the kidney relative to physiologic demands with or without actual kidney injury (1)
• Causes mild to potentially life-threatening alterations in fluid, electrolyte, acid–base and hormonal homeostasis
• Terminology evolving from acute tubular necrosis (ATN) to acute renal failure (ARF) to acute kidney injury (AKI) of varying grades to standardize reporting, clinical care, and research
• Diagnosed by the Pediatric Modified Risk Injury Failure Loss End Stage Renal Disease (pRIFLE) criteria based on the estimated creatinine clearance (eCCl, based on Schwartz formula) and urine output (UOP) (2)
– Risk: eCCl decrease by 25% and/or UOP <0.5 mL/kg/h for 8 hr
– Injury: eCCl decrease by 50% and/or UOP <0.5 mL/kg/h for 16 hr
– Failure: eCCl decrease by 75% or eCCl <35 mL/min/1.73 m2 and/or UOP <0.3 mL/kg/h for 24 hr or anuric for 12 hr
– Loss: Persistent failure >4 wk
– End stage renal disease (ESRD): Persistent failure >3 mo
• No standardized definition for neonatal AKI
EPIDEMIOLOGY
Incidence
• A difficult assessment since, until recently, there was no unifying criteria to make the diagnosis
– Recent meta-analysis showed reported incidences in hospitalized pediatric population from 1–82% (3)
Prevalence
Unknown
RISK FACTORS
• Chronic kidney disease (CKD) increases the risk for AKI
• Hospitalization, especially in the ICU
• Exposure to potentially nephrotoxic agents, such as nonsteroidal anti-inflammatories (NSAIDs), contrast, aminoglycosides
• Recent surgery, solid organ or marrow transplant, cardiopulmonary bypass
Genetics
• If recurrent rhabdomyolysis, consider an underlying defect in muscle metabolism
• If recurrent hemolytic uremic syndrome (HUS) consider a defect in the complement cascade
• If AKI in the presence of CKD then consider inherited forms of ESRD, such as autosomal recessive polycystic kidney disease
PATHOPHYSIOLOGY
• Prerenal and intrinsic renal injury disrupt the regional perfusion of, and subsequent oxygen delivery to, the kidney (3)
– The natural arterial gradient of oxygen tension from cortex to medulla makes the kidney highly susceptible to hypoxic and oxidative injury during ischemia and reperfusion
– Poorly perfused glomerular endothelial cells release vasoactive substances, proteases, reactive oxygen species, and nitric oxide and activate the coagulation cascade and complement pathways
– Even well-perfused kidneys can develop AKI during sepsis from circulating cytokines, lymphocytes, T cells, and other factors
– When found in the presence of cardiac, pulmonary, or hepatic failure it is likely due to endothelial activation and circulatory aberrations
– Nephrotoxic agents each have their own mechanism of damage, eg, by forming crystals in the microstructures of the kidney
– Rhabdomyolysis causes intrarenal vasoconstriction, direct ischemic tubule injury, and tubular obstruction in acidic urine
• Postrenal injury is due to antegrade urine flow disruption from the kidney
– Must be bilateral to cause pRIFLE findings but can be unilateral if only one kidney is present due to congenital absence, prior nephrectomy, or kidney transplant
• Etiology may be multifactorial, especially in the ICU setting
ASSOCIATED CONDITIONS
CKD increases the risk for AKI
GENERAL PREVENTION
• Prerenal
– Prevent volume depletion (1)[B]
– Maintain cardiac output and oxygenation with vasopressors and blood transfusions as needed (1)[C]
• Intrinsic renal
– Careful dosing and therapeutic drug level monitoring of aminoglycosides or avoidance altogether
– Use lipid formulation of amphotericin B or another antifungal alternative
– Contrast-induced AKI
Avoid the use of contrast
Use either iso- or low-osmolar iodinated contrast media
Intravenous fluid expansion for those patients at risk
– Avoid NSAIDs
– Animal models have shown the potential benefit of vasodilators, growth factors, antioxidants, and anti-inflammatory drugs in preventing AKI
• A single dose of theophylline given to neonates with severe perinatal asphyxia has been shown to significantly reduce the risk of AKI
DIAGNOSIS
HISTORY
• Evaluate for shock, sepsis, bleeding, dehydration, gastrointestinal losses
• Assess recent medication exposure, including natural products
• History of urologic surgery, anatomic problems, or kidney transplantation
• Family history of ESRD, HUS
• Recent trauma, crush injury
• Seek signs of CKD, such as growth delay
• Review recent blood tests to determine baseline serum creatinine (SCr) and onset of AKI
PHYSICAL EXAM
• Assess hydration status, blood pressure, heart rate, and temperature
• Lungs for rales
• Abdomen for masses
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• SCr and blood urea nitrogen will be elevated
• May have hyperkalemia, acidosis
• Hemoglobin will be low if bleeding
• HUS causes thrombocytopenia, increased lactate dehydrogenase
• When muscular damage is the cause creatinine kinase will be elevated and urinary myoglobin will be positive
• Urinalysis to detect red blood cells, proteinuria
• Urine eosinophils indicate interstitial nephritis
• Strict UOP monitoring to assess AKI stage and progression
• Atypical-AKI
– Clinical AKI fails to meet the definition
SCr falsely lowered by dilution due to large volume fluid resuscitation or transfusions, thereby reflecting the blood donors’ kidney function
SCr falsely lowered by muscle wasting or reduced muscle mass due to quadriplegia, cerebral palsy, or other neuromuscular disorders
SCr falsely lowered during sepsis by decreased muscle perfusion
• Real-time markers of AKI are being sought
– Candidates include serum cystatin C, kidney injury molecule-1, interleukin-18, liver fatty acid–binding protein, neutrophil gelatinase-associated lipocalin
Imaging
• Renal ultrasound with Doppler analysis of the renal artery and veins
– Hydronephrosis indicates obstruction
– Increased echogenicity consistent with medical renal disease
– Thrombosis of renal artery or vein
– Small echogenic kidneys, cystic kidneys indicate CKD
• Bladder ultrasound
– Trabeculated, thick-walled bladder may indicate lower urinary tract abnormality such as a neurogenic bladder or obstruction
• Technetium-99m MAG3 renal scan can be used in prolonged AKI to differentiate prolonged ATN from permanent cortical necrosis
Diagnostic Procedures/Surgery
Kidney biopsy rarely necessary but may be indicated to diagnosis prolonged AKI without a clear etiology
Pathologic Findings
Kidney biopsy may reveal ATN, interstitial disease, thrombotic microangiopathy, medication-induced crystal formation, glomerulonephritis
DIFFERENTIAL DIAGNOSIS
• Prerenal
– Intravascular volume depletion
Dehydration, hemorrhage, gastrointestinal losses, burns, pancreatitis, peritonitis
Congestive heart failure, sequestration in interstitial spaces, shock, anaphylaxis
• Intrinsic renal
– ATN, hypoxic/ischemic insults, sepsis/toxin mediated, multiple organ dysfunction syndrome, interstitial nephritis, tumor lysis syndrome, glomerulonephritis, vascular thrombosis, cortical necrosis, HUS, cortical dysplasia or hypoplasia, rhabdomyolysis
– Potentially nephrotoxic agents such as aminoglycoside antibiotics, NSAIDs, radio-opaque contrast, antivirals, antifungals, chemotherapeutic agents
– Chinese herb nephropathy is an acute to chronic interstitial fibrosis caused by Aristolochia fangchi, an herb still available in natural products ordered online
• Postrenal
– Obstruction in the ureter(s) or urethra
– Bilateral nephrolithiasis due to cystinuria has been reported as a cause of pediatric AKI
• Pseudo-AKI
– Always interpret lab data in clinical context to avoid overdiagnosis of AKI
Endogenous chromogens (eg, bilirubin, ascorbic acid, uric acid) and exogenous chromogens (eg, cephalosporins, trimethoprim, cimetidine) may interfere with the creatinine assay and cause falsely elevated results
Weight-based determination of UOP may falsely cause the obese patient to fulfill the criteria without actual AKI
TREATMENT
GENERAL MEASURES
• Reduce risk of dehydration or fluid overload by only replacing calculated insensible fluid losses and measured UOP
– Intravenous fluid should have no potassium
• Maintain renal perfusion and oxygenation (1)[C]
– Renal dilators (dopamine, fenoldopam) have not been shown to improve pediatric AKI
– No studies relating fluid type used in pediatric resuscitation on AKI incidence or outcome
• Continuous renal replacement therapy (CRRT) has not been shown to improve kidney function or mortality, although there is controversy about the timing of initiation, dose, route, and duration (1)[C]
• Hemodialysis or peritoneal dialysis may play a role in supportive care of the patient with AKI
• Discontinue potentially nephrotoxic drugs
• Medications with renal clearance require dosing/timing adjustments/drug level monitoring, when available, to reduce the risk of toxicity
• Nutritional research is limited to observational studies
– Critically ill children should receive 100–130% of their basal energy needs
MEDICATION
First Line
• Diuretics to convert oliguric AKI to nonoliguric AKI have not been shown to affect outcomes (1)[C]
• IV sodium bicarbonate has been administered to correct the acidosis of AKI but has not been studied with randomized controlled trials
• Emerging treatments include apoptosis inhibitors, iron chelators, anti-inflammatory agents, repair agents (eg, stem cells)
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Central venous access may be needed for renal replacement therapy (CRRT or hemodialysis)
• Postrenal AKI may require decompression surgery, nephrostomy tube, or ureteral stent
• Nephrolithiasis may respond to extracorporeal shock wave lithotripsy, endoscopic surgery, or surgery (open, laparoscopic, robotically assisted)
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• With multisystem organ failure the addition of AKI increases mortality from 10–57%
• A 3–5-yr follow-up study after resolution of AKI showed that 40–50% of pediatric patients showed signs of CKD (3)
COMPLICATIONS
• Hyperkalemia, fluid overload, pulmonary edema, hypertension, acidosis, reduced drug excretion, and uremic symptoms
– Overcorrection of any of the above
• Nephrogenic systemic fibrosis (NSF) is a rare but potentially lethal fibrosing disorder of the skin, liver, heart, lungs, diaphragm, and skelet al muscle observed in patients with AKI or CKD who were exposed to gadolinium used in MRI (4)
– 335 cases in the NSF International Registry at the time of writing; some were children
– Gadolinium should be avoided in AKI
• Patients exposed to the Aristolochia fangchi herb are at increased risk for urothelial malignancies
FOLLOW-UP
Patient Monitoring
Monitor SCr, blood pressure, somatic growth, urinalysis for signs of CKD after resolution of AKI
Patient Resources
• American Society of Pediatric Nephrology
– www.aspneph.com/parentpatient.asp
• Kidney & Urology Foundation of America
– www.kidneyurology.org/
• National Kidney Foundation
– www.kidney.org/patients/index.cfm
REFERENCES
1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Inter., Suppl. 2012;2:1–138.
2. Akcan-Arikan A, Zappitelli M, Loftis LL, et al. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Inter. 2007;71:1028–1035.
3. Basu RK, Devarajan P, Wong H, et al. An update and review of acute kidney injury in pediatrics. Pediatr Crit Care Med. 2011;12:339–347.
4. Perazella M. Nephrogenic Systemic Fibrosis, kidney disease, and gadolinium: Is there a link? Clin J Am Soc Nephrol. 2007;2:200–202.
ADDITIONAL READING
N/A
See Also (Topic, Algorithm, Media)
• Acute Kidney Injury, Adult (Renal Failure, Acute)
• Chronic Kidney Disease, Pediatric (Renal Failure, Chronic)
• Pediatric Modified Risk Injury Failure Loss End Stage Renal Disease (pRIFLE)
CODES
ICD9
• 584.5 Acute kidney failure with lesion of tubular necrosis
• 584.9 Acute kidney failure, unspecified
• 728.88 Rhabdomyolysis
ICD10
• M62.82 Rhabdomyolysis
• N17.0 Acute kidney failure with tubular necrosis
• N17.9 Acute kidney failure, unspecified
CLINICAL/SURGICAL PEARLS
• AKI is often multifactorial.
• Seek prerenal, intrinsic renal, and postrenal causes of the AKI.
• Stage AKI with pRIFLE criteria.
• Avoid potentially nephrotoxic drugs and gadolinium during AKI.