Urine biomarkers of acute kidney injury and association with brain MRI abnormalities in neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: Determine whether urine biomarkers NGAL (neutrophil gelatinase-associated lipocalin), KIM-1 (kidney injury molecule 1) and IL-18 (interleukin-18) are associated with abnormal MRI findings in neonates with hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). STUDY DESIGN: Secondary analysis of a multicenter, prospective study of neonates with HIE requiring TH. Urine biomarkers were obtained at 12 and 24 h of life (HOL). Brain MRI was scored per NICHD criteria. Association between biomarkers and MRI stage was determined. RESULTS: In 57 neonates with HIE, only IL-18 at 24 HOL was significantly increased in neonates with MRI Stage 2B or greater, compared to Stage 2A or less (mean 398.7 vs. 182.9 pg/mL, p = 0.024.) A multivariate model including IL-18 at 24 HOL and 5-min Apgar performed best, with an AUC of 0.84 (SE = 0.07, p = 0.02). CONCLUSIONS: Elevated urine IL-18 at 24 HOL was associated with more severe brain MRI abnormalities among neonates with HIE.

Potential Adjuncts to Therapeutic Hypothermia to Mitigate Multiorgan Injury in Perinatal Hypoxia-Ischemia.

Over the last 2 decades, therapeutic hypothermia has become the standard of care to reduce morbidity and mortality in neonates affected by moderate-to-severe hypoxic-ischemic encephalopathy (HIE). There is a significant interest in improving the neurologic outcomes of neonatal HIE, ranging from adjunctive therapy to therapeutic hypothermia. Importantly, the pathophysiologic mechanisms underlying HIE also affect multiple other organs, contributing to high morbidity and mortality in this patient population. This review focuses on the adjunct therapies currently under investigation to mitigate the impact of hypoxic-ischemic injury on the brain, kidneys, liver, heart, and gastrointestinal system.

Neonatal acute kidney injury during indomethacin therapy: does it predict ductal closure?

BACKGROUND: Preterm newborns are at risk for patent ductus arteriosus, and non-steroidal anti-inflammatory drugs are often used to facilitate patent ductus arteriosus closure. Acute kidney injury is common in critically ill neonates and may be caused by non-steroidal anti-inflammatory drugs. We sought to describe the incidence of acute kidney injury among preterm infants receiving indomethacin and determine whether acute kidney injury during indomethacin therapy is associated with subsequent patent ductus arteriosus closure. METHODS: Retrospective cohort including neonates < 33 weeks gestational age, admitted to two level IIIb neonatal intensive care units between November 2016 and November 2019, who received indomethacin in the first 2 weeks of life. Acute kidney injury in the 7-day period after treatment was defined by neonatal modified Kidney Disease Improving Global Outcomes (KDIGO) criteria. Patent ductus arteriosus closure was defined clinically and/or via echocardiogram. Clinical characteristics were extracted from medical records. Association between acute kidney injury during treatment and successful closure of patent ductus arteriosus was evaluated using chi-square tests and logistic regression. RESULTS: One hundred fifty preterm infants were included; acute kidney injury occurred in 8% (all KDIGO Stage 1). Patent ductus arteriosus closed in 52.9% of the non-acute kidney injury group and 66.7% of the acute kidney injury group (p = 0.55). Serum creatinine was checked a mean of 3.1 times in the acute kidney injury group and 2.2 times in the non-acute kidney injury group. There was no difference in survival. CONCLUSION: We found no association between acute kidney injury during indomethacin therapy and patent ductus arteriosus closure. Paucity of serum creatinine values likely underdiagnosed acute kidney injury. Surveillance of kidney function during indomethacin therapy using more sensitive renal biomarkers may better identify infants who develop acute kidney injury in the context of non-steroidal anti-inflammatory drug use.

The efficacy of calcium carbonate in the treatment of protease inhibitor-induced persistent diarrhea in HIV-infected patients.

BACKGROUND: Although some evidence exists to support the practice of using calcium carbonate to treat nelfinavir-induced diarrhea, there is a lack of data supporting the role of calcium in diarrhea induced by other protease inhibitors (PIs). PURPOSE: The objective of this prospective open-label study is to evaluate the efficacy of calcium carbonate in the treatment of PI-induced persistent diarrhea in HIV-infected patients. METHOD: Along with dietary advice, patients were asked to take oral calcium carbonate 500 mg twice daily for 2 weeks. Visual Analog Scale (VAS) and the National Cancer Institute of Canada (NCIC) scale were used to assess the severity of diarrhea. Data were analyzed using paired t tests to test for differences in VAS and NCIC scores between baseline and 14 days. Pearson correlation was used to explore the relationships between change in diarrhea and patient baseline factors. RESULTS: At day 0, the mean VAS +/- standard deviation was 6.6 +/- 2.1 and decreased to 5.3 +/- 1.9 (p=.01) after 14 days. At day 0, the mean NCIC score was 1.9 +/- 0.8 and decreased to 1.2 +/- 0.9 (p=.005) after 14 days. No baseline patient factors predicted change in NCIC or VAS grade. CONCLUSION: Calcium carbonate is associated with a reduction of diarrhea in individuals with diarrhea induced by PI.