Beharry Kay D, Cai Charles L, Soontarapornchai Kultida, Ahmad Taimur, Valencia Gloria B, Aranda Jacob V
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, USA; Department of Ophthalmology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA; SUNY Eye Institute, New York, NY, USA.
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, USA.
Prostaglandins Other Lipid Mediat. 2018 Jan;134:57-65. doi: 10.1016/j.prostaglandins.2017.10.004. Epub 2017 Oct 26.
Caffeine, one of the most commonly prescribed drugs in preterm neonates, is given in standard or suprapharmacologic doses. Although known as a diuretic, its effects in the neonatal kidneys are not well studied. We tested the hypothesis that neonatal intermittent hypoxia (IH) and high caffeine doses (HCD) alter renal regulators of vasomotor tone and water balance. Newborn rats were randomized to room air, hyperoxia, or IH and treated with standard or high caffeine doses; or placebo saline. Renal prostanoids; histopathology; and cyclooxygenase (COX), prostanoid receptor, and aquaporin (AQP) immunoreactivity were determined. HCD in IH caused severe pathological changes in the glomeruli and proximal tubules, consistent with acute kidney injury. This was associated with reductions in anthropometric growth, PGI and IP, DP, and AQP-4 immunoreactivity, well as a robust increase in COX-2, suggesting that the use of HCD should be avoided in preterm infants who experience frequent IH episodes.
咖啡因是早产儿最常用的处方药之一，以标准剂量或超药理剂量给药。尽管咖啡因被认为是一种利尿剂，但其对新生儿肾脏的影响尚未得到充分研究。我们检验了这样一个假设，即新生儿间歇性缺氧（IH）和高咖啡因剂量（HCD）会改变肾血管舒缩张力和水平衡的调节因子。新生大鼠被随机分为常氧、高氧或间歇性缺氧组，并接受标准或高咖啡因剂量治疗；或给予安慰剂生理盐水。测定了肾脏前列腺素、组织病理学以及环氧化酶（COX）、前列腺素受体和水通道蛋白（AQP）的免疫反应性。间歇性缺氧状态下的高咖啡因剂量导致肾小球和近端小管出现严重病理变化，符合急性肾损伤。这与人体测量生长指标、前列环素I2（PGI）和前列环素（IP）、前列腺素D2（DP）以及水通道蛋白4（AQP-4）免疫反应性降低有关，同时环氧化酶-2（COX-2）显著增加，这表明对于频繁经历间歇性缺氧发作的早产儿应避免使用高咖啡因剂量。
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