The Association of Intraventricular Hemorrhage and Acute Kidney Injury in Premature Infants from the Assessment of the Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) Study

Abstract

<b><i>Background:</i></b> Acute kidney injury (AKI) and intraventricular hemorrhage (IVH) are common in premature infants. We previously demonstrated that infants with AKI have a higher hazards ratio to develop grade ≥2 IVH when controlling for confounders. However, that single-center study was unable to show an overall association. <b><i>Objectives:</i></b> To test the hypothesis that infants diagnosed with AKI have an increased risk of IVH independent of variables associated with both AKI and IVH, we performed a study on 825 infants from the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study (a 24-center multinational retrospective cohort). <b><i>Method:</i></b> A neonatal modified KDIGO definition of AKI was used based on serum creatinine (SCr) and/or urine output criteria. Baseline SCr was defined as the lowest previous value. IVH was diagnosed with head ultrasounds. <b><i>Results:</i></b> AKI was documented in 22.2% (183/825) of infants and IVH in 14.3% (118/825). Infants with AKI (<i>n</i> = 183) were more likely to have IVH (26.8%, 49/183) than those without AKI (<i>n</i>= 642) who had IVH (10.7%, 69/642, <i>p</i> < 0.0001). After controlling for 5-min Apgar score, vasopressor support within the first week of age, and gestational age, infants with AKI had 1.6 times higher adjusted odds to develop any grade IVH (95% CI 1.04–2.56). Furthermore, infants of gestational age of 22–28 weeks had 1.9 times higher adjusted odds to develop IVH (OR 1.87, 95% CI 1.08–3.23). <b><i>Conclusions:</i></b> We present the first multicenter evaluation of the association between AKI and IVH in premature infants showing a significant independent association between AKI and IVH. Development of strategies to reduce AKI may also reduce IVH.

Changes in Serum Creatinine Levels and Natural Evolution of Acute Kidney Injury with Conservative Management of Hemodynamically Significant Patent Ductus Arteriosus in Extremely Preterm Infants at 23–26 Weeks of Gestation

“…In contrast, while sepsis rate was more elevated in AKI stage 3 than in stage 0-2, only in EPT at gestation of 25-26 but not of 23-24 weeks, neither the presence nor the prolonged duration of AKI stage 3 was associated with elevated mortality or any morbidities rates including BPD and IVH. The reasons for our results, which are contradictory to other studies showing increased mortality and/or morbidities [2,11,[17][18][19][20][21][22][23][24], are difficult to explain. Few data are available for the peri-viable EPT of 23-24 week's gestation, and actively treated with pharmacologic agents for HS PDA could be cofounders in other studies.…”

“…Although AKI in premature infants has been known to be related to raised mortality [11,[17][18][19][20][21] and morbidity rates, including BPD [2,22,23] and IVH [24], evidence supporting their direct causal relationships are lacking. In contrast, while sepsis rate was more elevated in AKI stage 3 than in stage 0-2, only in EPT at gestation of 25-26 but not of 23-24 weeks, neither the presence nor the prolonged duration of AKI stage 3 was associated with elevated mortality or any morbidities rates including BPD and IVH.…”

“…AKI in premature infants are known to be related to increased mortality [11,[17][18][19][20][21] and morbidities, which includes bronchopulmonary dysplasia (BPD) [2,22,23] and intraventricular hemorrhage (IVH) [24]. However, these associations have not been well reported and elucidated in EPT, although J. Clin.…”

AWAKEN-Ing a New Frontier in Neonatal Nephrology

“…In a manuscript published in JAMA-Peds, we show that despite the fact that infants who received caffeine (commonly done to keep infants from needing to get intubated) were sicker, those who received caffeine had a much lower adjusted odds of developing AKI than those who were not exposed to caffeine (number needed to treat = 4.3) (29). Other ancillary studies include a report the association of AKI and Hypertension (30), a study showing the association between AKI and mortality in those with severe neonatal encephalopathy (31), the association of AKI and Intra-ventricular hemorrhage (32), the association of AKI and Chronic Lung Disease in premature (33) and near term/term infants (34).…”

Patent Ductus Arteriosus-Dependent Cardiovascular Compromise as a Potential Link between Acute Kidney Injury and Intraventricular Hemorrhage in Very Low Birth Weight Infants

“…Stoops et al [1] documented a rate of acute kidney injury (AKI) of 22.2% (183/825) in very low birth weight infants (VLBW), and a rate of intraventricular hemorrhage (IVH) in 14.3% (118/825). Infants with AKI ( n = 183) were more likely to have IVH (26.8%, 49/183) than those without AKI (10.7%, 69/642, p < 0.0001).…”