Kidney Health Monitoring in Neonatal Intensive Care Unit Graduates: A Modified Delphi Consensus Statement.

Importance: Kidney disease is common in infants admitted to the neonatal intensive care unit (NICU). Despite the risk of chronic kidney disease (CKD) in infants discharged from the NICU, neither evidence- nor expert-based recommendations exist to guide clinical care after discharge. Objective: To develop recommendations for risk stratification and kidney health monitoring among infants after discharge from the NICU. Evidence Review: At the National Institute of Health-supported Consensus Workshop to Address Kidney Health in Neonatal Intensive Care Unit Graduates meeting conducted in February 2024, a panel of 51 neonatal nephrology experts focused on 3 at-risk groups: (1) preterm infants, (2) critically ill infants with acute kidney injury (AKI), and (3) infants with critical cardiac disease. Using established modified Delphi processes, workgroups derived consensus recommendations. Findings: In this modified Delphi consensus statement, the panel developed 10 consensus recommendations, identified gaps in knowledge, and prioritized areas of future research. Principal suggestions include risk stratification at time of hospital discharge, family and clinician education and counseling for subsequent kidney health follow-up, and blood pressure assessment as part of outpatient care. Conclusions and Relevance: Preterm infants, critically ill infants with AKI, and infants with critical cardiac disease are at increased risk of CKD. We recommend (1) risk assessment at the time of discharge, (2) clinician and family education, and (3) kidney health assessments based on the degree of risk. Future work should focus on improved risk stratification, identification of early kidney dysfunction, and development of interventions to improve long-term kidney health.

Acute kidney injury decreases pulmonary vascular growth and alveolarization in neonatal rat pups.

BACKGROUND: Acute kidney injury (AKI) is common in sick neonates and associated with poor pulmonary outcomes, however, the mechanisms responsible remain unknown. We present two novel neonatal rodent models of AKI to investigate the pulmonary effects of AKI. METHODS: In rat pups, AKI was induced surgically via bilateral ischemia-reperfusion injury (bIRI) or pharmacologically using aristolochic acid (AA). AKI was confirmed with plasma blood urea nitrogen and creatinine measurements and kidney injury molecule-1 staining on renal immunohistochemistry. Lung morphometrics were quantified with radial alveolar count and mean linear intercept, and angiogenesis investigated by pulmonary vessel density (PVD) and vascular endothelial growth factor (VEGF) protein expression. For the surgical model, bIRI, sham, and non-surgical pups were compared. For the pharmacologic model, AA pups were compared to vehicle controls. RESULTS: AKI occurred in bIRI and AA pups, and they demonstrated decreased alveolarization, PVD, and VEGF protein expression compared controls. Sham pups did not experience AKI, however, demonstrated decreased alveolarization, PVD, and VEGF protein expression compared to controls. CONCLUSION: Pharmacologic AKI and surgery in neonatal rat pups, with or without AKI, decreased alveolarization and angiogenesis, producing a bronchopulmonary dysplasia phenotype. These models provide a framework for elucidating the relationship between AKI and adverse pulmonary outcomes. IMPACT: There are no published neonatal rodent models investigating the pulmonary effects after neonatal acute kidney injury, despite known clinical associations. We present two novel neonatal rodent models of acute kidney injury to study the impact of acute kidney injury on the developing lung. We demonstrate the pulmonary effects of both ischemia-reperfusion injury and nephrotoxin-induced AKI on the developing lung, with decreased alveolarization and angiogenesis, mimicking the lung phenotype of bronchopulmonary dysplasia. Neonatal rodent models of acute kidney injury provide opportunities to study mechanisms of kidney-lung crosstalk and novel therapeutics in the context of acute kidney injury in a premature infant.

Risk factors for acute kidney injury in neonates with congenital diaphragmatic hernia.

OBJECTIVE: To examine incidence of acute kidney injury (AKI), antenatal and postnatal predictors, and impact of AKI on outcomes in infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: Single center retrospective study of 90 CDH infants from 2009-2017. Baseline characteristics, CDH severity, possible AKI predictors, and clinical outcomes were compared between infants with and without AKI. RESULT: In total, 38% of infants developed AKI, 44% stage 1, 29% stage 2, 27% stage 3. Lower antenatal lung volumes and liver herniation were associated with AKI. Extracorporeal life support (ECLS), diuretics, abdominal closure surgery, hypotension, and elevated plasma free hemoglobin were associated with AKI. Overall survival was 79%, 47% with AKI, and 35% with AKI on ECLS. AKI is associated with increased mechanical ventilation duration and length of stay. CONCLUSION: AKI is common among CDH infants and associated with adverse outcomes. Standardized care bundles addressing AKI risk factors may reduce AKI incidence and severity.