Examining the role of biologic sex on kidney outcomes in preterm neonates: A secondary analysis of the PENUT/REPAIReD study

BACKGROUND: Biological sex plays a crucial role in the pathophysiology of morbidities related to preterm birth. Studies specifically investigating the role of biological sex in neonatal kidney disease are lacking. This study aimed to determine the association between biological sex and kidney outcomes in preterm infants. We hypothesized that male infants would be more likely to have poor kidney outcomes, including acute kidney injury (AKI), hypertension and chronic kidney disease. Given data on the relationship between sex, AKI and lung disease, we also evaluated lung disease as a secondary outcome. METHODS: Retrospective analysis of the Preterm Erythropoietin Neuroprotection Trial data. For adjusted models, we used covariates associated with adverse outcomes a priori (gestational age, SGA status) and a lasso regression. AKI was defined using creatinine only neonatal modified KDIGO criteria and bronchopulmonary dysplasia (BPD) by Neonatal Research Network criteria. RESULTS: Of the 923 infants included, 479 (51.8%) were male. AKI was more common among males (aOR 1.31, 95%CI 1.00-1.74). Hypertension was nearly twice as common in males (66.4% vs. 51.5%, p < 0.001) and remained after adjustment (aOR 1.91, 95%CI 1.32-2.77). Severe BPD was more common in males (33.4% vs. 24.3%, p = 0.0024), which persisted after adjustment (aOR 1.65, 95%CI 1.22-2.23). This association was not fully mitigated by AKI exposure. CONCLUSIONS: We describe differences in kidney outcomes and BPD by sex. Male sex is associated with an increased risk of AKI and hypertension. Research efforts focused on the mechanisms underlying sex-specific differences are needed for the identification of novel therapies that benefit both sexes.