Intermittent Hypoxemia and Acute Kidney Injury Study (IHAKI Study)

BACKGROUND:

Preterm birth is a major health care concern and although survival of premature infants has improved, the incidence of neonatal morbidities has slightly decreased especially in cases of extreme prematurity. Apnea of prematurity (immature respiratory control) is a major complication in Neonatal Intensive Care Units occurring in virtually all infants born before 28 weeks gestation. Intermittent Hypoxemia (IH), episodic oxygen desaturation events, is generally attributed to apnea of prematurity often superimposed upon suboptimal lung function. Intermittent hypoxemia events are common in preterm infants and may lead to both short-term and long-term morbidities. Typically, the incidence of intermittent hypoxemia (IH) increases over the first 4 weeks of life before plateauing at weeks 6-8. In addition to inducing oxidative stress by increasing production of reactive oxygen species, this hypoxemia/reoxygenation cycle is thought to induce a pro-inflammatory cascade of transcription factors that promotes activation of inflammatory cells resulting in multisystem morbidity. These morbidities include retinopathy of prematurity, cardiorespiratory instability, and poor neurodevelopmental outcomes. A potential morbidity that has yet to be investigated is acute kidney injury (AKI).

AKI is associated with morbidity and mortality in critically ill neonates. The risk of AKI is higher in very low birth weight infants requiring assisted ventilation and ionotropic support, and in infants with congenital heart disease. Additionally, AKI occurs more frequently in infants who suffered severe birth asphyxia. While it has been established that end-stage kidney disease (ESKD) is associated with worsening sleep apnea in adults, it has been proposed that sleep apnea and nocturnal hypoxemia may contribute to kidney injury, the development of chronic kidney disease (CKD), and the progression to kidney failure. Proposed mechanisms of kidney disease via intermittent nocturnal hypoxemia include 1: direct intrarenal hypoxemia (resulting in tubulointerstitial injury) 2: an increase in oxidative stress, inflammatory cytokines, and systemic blood pressure (via activation of the renin-angiotensin system). Hence It is plausible that IH may modulate AKI in preterm neonates. The investigators goal is to test the hypothesis that intermittent hypoxemia is associated with Acute Kidney Injury in preterm infants. Investigation of relationship between IH and AKI may provide further insight into onset and prevention given the recent advancements in the detection and characterization of AKI in this vulnerable population.

SPECIFIC AIMS:

AIM 1: Test the hypothesis that intermittent hypoxemia is associated kidney injury in preterm infants, as reflected by a rise in serum creatinine.