Emerging data suggest that acute kidney injury (AKI) occurs in approximately 30% of hospitalized neonates. Furthermore, single-center data suggest that the majority of neonates who have experienced one or more episodes of AKI will be discharged from the neonatal intensive care unit (NICU) without nephrology follow-up.
AKI can be clinically described as a sudden decline in renal function that results in abnormalities in fluid balance and electrolytes and accumulation of waste products. Defining neonatal AKI has been difficult, secondary to numerous changes in renal physiology after birth. Thus, the diagnosis of neonatal AKI may be challenging due to the frequent subtle changes in serum creatinine or urine output that may be overlooked, resulting in delayed recognition of a progressive renal injury.

Mechanistically, AKI in neonates has important implications on postnatal renal development. Injury can result in loss of final nephron number or mass. Loss of nephron mass may lead to hyperfiltration (seen as paradoxically increased glomerular filtration rate initially) that can progress to glomerular sclerosis, interstitial fibrosis and tubular atrophy — the pathological hallmarks of chronic kidney disease (CKD).
Pediatric and adult data, as well as limited neonatal data, demonstrate that the presence of AKI heightens not only the risk for increased length of hospital stay and mortality rate, but increased risk for the development of CKD. Unfortunately, there are sparse data documenting interventions that can prevent or reverse AKI once it is established in at-risk patients. Severe cases of AKI may lead to the necessity for renal replacement therapy, which while necessary, may result in safety risks (e.g., fluid imbalance, infection) for this vulnerable population.
Implications for general pediatric care
Single-center data suggest that many neonates who experience an AKI may not be given a clear diagnosis within the neonatal discharge summary. As such, and knowing that approximately 30% of neonates experience AKI, the presence of AKI risk factors listed within a hospital discharge summary (e.g., sepsis, nephrotoxin exposure, congenital heart disease, extracorporeal membrane oxygenation requirement, umbilical lines) should prompt the pediatrician to consider it plausible that the patient may have experienced some degree of renal injury during the neonatal period and perform appropriate follow-up.
Recognizing the long-term implications of AKI, clinical practice guidelines (http://kdigo.org/home/) recommend that all adult and pediatric patients who experience AKI be evaluated within three months of AKI for signs of CKD.
No firm data are available to guide formal surveillance and monitoring of children with a history of neonatal AKI; however, emerging data suggest an increased risk for development of CKD within three years following neonatal AKI. Thus, particularly in areas where a nephrologist is not available, well-child care should include evaluation of renal function, including careful assessment of growth, urinalysis and blood pressure measurement.
The primary pediatrician also may obtain laboratory assessment (including electrolytes, creatinine and acid-base status) if a pediatric nephrologist is not available to provide consultation. Frequency of laboratory testing should be based on the clinical history of severity of AKI and growth patterns, blood pressure assessment and urinalysis results.
In this population, a manual blood pressure should be assessed at all outpatient well-child visits beginning after NICU discharge, rather than waiting to begin routine assessment at age 3 years. Evaluation must be performed using resting, manual measurement with an appropriately fitted cuff for age and size, and blood pressures should be compared to age-appropriate normative data. If offices do not have infant blood pressure cuffs, collaboration with the discharging NICU or regional hospitals can facilitate intermittent blood pressure measurement.
In 2007, the Academy recommended against general use of routine screening urinalysis (UA) in healthy, asymptomatic children due to low diagnostic yield. In some populations, including those with any history of AKI, targeted and thoughtful UA screening can have an important role.
If performing a targeted screening urinalysis for a child with a history of neonatal AKI, a first morning, fresh urine sample should be tested if possible. The sample should be evaluated for dipstick and microscopic properties to assess for the presence of hematuria and proteinuria, as well as urine protein to urine creatinine ratio to quantify the degree of proteinuria in appropriate patients.
Concern for proteinuria (as found on an elevated urine protein/urine creatinine ratio greater than 0.4 in infants/toddlers and 0.2 in school-age children), hypertension or evidence of abnormal creatinine for age should prompt a referral to a pediatric nephrologist to evaluate potential CKD status and provide medical counseling to the family.
Risk factors for neonatal acute kidney injury
- Extremely low or very low birthweight
- Sepsis
- Hypoxic ischemic encephalopathy
- Extracorporeal membranous oxygenation
- Nephrotoxin exposure: gentamicin, indomethacin, vancomycin, acyclovir, amphotericin
- Congenital heart disease requiring cardiopulmonary bypass
Dr. Harshman is a training fellow liaison to the AAP Section on Nephrology Executive Committee.