Diagnosis and management of neonatal acute kidney injury

Introduction

Acute kidney injury (AKI) is defined as a decrease in overall kidney function, resulting in reduction of glomerular filtration rate (GFR) and subsequent retention of waste products such as urea. As a result, there is a loss of established electrolyte, acid-base, and fluid balance regulation. AKI is a serious, underrecognized yet common complication that occurs in neonates who receive intensive medical care, and there is a well-documented association with increases in mortality (20%–50%) in the neonate. The loss of vital kidney-mediated compensatory mechanisms prevents critically ill neonates from responding to any number of insults that occur within the prenatal, perinatal, or postnatal periods.

Previously, the characterization of AKI in existing literature was highly variable and lacking in clearly defined standardized practices. This changed upon the publication of defining guidelines set forth by Kidney Disease: Improving Global Outcomes (KDIGO) in 2012, who consider the official definition of AKI to include any one of the following: an increase in serum creatinine (SCr) ≥ 0.3 mg/dL (≥26.5 μmol/L) within 48 hours, increase in SCr to ≥ 1.5 times baseline (known or presumed to have occurred within the prior 7 days), or urine volume < 0.5 mL/kg per hour for 6 hours. The modified neonatal KDIGO criteria is summarized in Table 3.1 . Utilization of these criteria have changed perceptions of AKI in the literature, with many newer studies disproving previously held beliefs regarding the reversibility of AKI and challenging the use of renal replacement therapy as the sole gold standard for treatment. As the field of AKI continues to evolve with newly standardized practices, the question of whether these findings can be applied to neonates has remained largely unclear. AKI is one of the most prevalent disease processes that occurs in critically ill neonates, with the reported incidence of AKI in neonatal intensive care unit (NICU) admissions reported to be 56% by Shalaby et al. In this chapter, we aim to present the latest knowledge of the epidemiology, pertinent risk factors, clinical outcomes, assessment, preventative measures, and treatments associated with neonatal AKI.

Epidemiology and risk factors

Fetal kidney development begins with formation of the nephron around 5 weeks of gestation, followed by urine production at 9–10 weeks. Passage of urine in the fetal period is essential for lung development and contributes to production and composition of amniotic fluid. Nephrogenesis continues until anywhere from 34 to 36 weeks of gestation, with up to 60% estimated to be completed within the third trimester. Previous literature has found that each additional kilogram of fetal weight produces about 200,000 nephrons, which further demonstrates the detrimental effects of compromised fetal growth. For these reasons, extremely low birth weight (ELBW) (classified as any neonate < 1000 g) is one of the most significant predisposing conditions to developmentally immature kidney formation, AKI, and chronic kidney disease (CKD). The causes of ELBW are multifactorial, but most often go hand in hand with prematurity and low gestational age. Other pertinent risk factors include low APGAR score, intubation, asphyxia, and hypoxia secondary to neonatal respiratory distress syndrome.

In 2017, a large multicenter, multinational observational cohort study known as the AWAKEN study sought to strengthen the findings of multiple smaller-sample, single-center research analyses that associated neonatal AKI with worsened clinical outcomes. In this work, the incidence of AKI among varying gestational age demonstrated a U-shaped distribution, with the highest rates occurring in neonates aged > 36 weeks (37%) and those between 22 and < 29 weeks (48%). Neonates within the middle group (29–36 weeks’ gestation) had a rate of 18%. These data suggest that infants at either extreme of gestational age, due to the various prenatal and perinatal complications associated with each end, are more likely to become critically ill with subsequent organ dysfunction. Common insults to these neonates include respiratory failure, sepsis, necrotizing enterocolitis, and hypoxic ischemic encephalopathy (HIE) in the preterm group and maternal infection, meconium-stained fluid, and HIE in those over 36 weeks.

When evaluating an AKI, the underlying cause may fall within any one of the following categories: prerenal, intrinsic, and postrenal. In a study by Timovska et al. seeking to evaluate the most prevalent of these etiologies in a group of 50 patients, 78.5% were prerenal, 19.5% intrinsic renal, and 2.0% postrenal. Causes of neonatal prerenal AKI are those that compromise the perfusion of kidney parenchyma, most commonly due to hemodynamic instability, poor volume status, shunt-forming congenital heart defects such as patent ductus arteriosus, and ischemic injury. Other neonates who are at risk for prerenal insults are those who require central vascular access for nutrition, medication delivery, and clinical monitoring due to significantly increased risk for renal vein and artery thrombosis. Another mechanism of injury is the vicious cycle created by polyuria that results from functionally immature kidneys that cannot properly concentrate urine. As increased free water losses create a hypovolemic state, subsequent hypotension prevents adequate perfusion and further weakens the ability of the kidneys to effectively compensate for volume losses.

Intrinsic renal injury is a frequent complication of nephrotoxic medication administration, which are often necessary for lifesaving medical treatment. An investigation by Rhone et al. showed 87% of all neonates included in the study were exposed to nephrotoxic medications for 14 days on average. Some of the most common offenders in the prenatal and perinatal period include maternal use of angiotensin-converting enzyme inhibitors, indomethacin for tocolysis, and antenatal steroids used for respiratory maturation. Neonates with infections requiring antibiotics, antivirals, and antifungal medications are also predisposed to intrinsic insults. This is especially true in those administered vancomycin, aminoglycosides, amphotericin, and acyclovir. Nonsteroidal antiinflammatory drugs are another well-known nephrotoxic therapy used for patent ductus arteriosus closure or intraventricular hemorrhage prophylaxis. Sepsis, acquired congenital kidney malformations, and acute tubular necrosis are other processes implicated in intrinsic renal injury. Obstructive uropathy due to lesions such as posterior urethral valves can cause prenatal and postnatal renal injury. Risk factors associated with AKI according to various studies are summarized in Table 3.2 .