Renal Research Institute, New York, NY, USA.
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sci Rep. 2024 Sep 19;14(1):21910. doi: 10.1038/s41598-024-72256-8.
Severe Neonatal Jaundice (SNJ) causes long-term neurocognitive impairment, cerebral palsy, auditory neuropathy, deafness, or death. We developed a mathematical model for allo-hemodialysis as a potential blood purification method for the treatment of SNJ in term or near-term infants. With allo-hemodialysis (allo-HD), the neonate's blood flows through hollow fibers of a miniature 0.075 m hemodialyzer, while the blood of a healthy adult ("buddy") flows counter-currently through the dialysate compartment. We simulated the kinetics of unconjugated bilirubin in allo-hemodialysis with neonate blood flow rates of 12.5 and 15 mL/min (for a 2.5 kg and 3.5 kg neonate, respectively), and 30 mL/min for the buddy. Bilirubin production rates in neonate and buddy were set to 6 and 3 mg/kg/day, respectively. Buddy bilirubin conjugation rate was calculated to obtain normal steady-state bilirubin levels. Albumin levels were set to 1.1, 2.1, 3.1 g/dL for the neonate and 3.3 g/dL for the buddy. Model simulations suggest that a 6-h allo-hemodialysis session could reduce neonatal bilirubin levels by > 35% and that this modality would be particularly effective with low neonatal serum albumin levels. Due to the high bilirubin conjugation capacity of an adult's healthy liver and the larger distribution volume, the buddy's bilirubin level increases only transiently during allo-hemodialysis. Our modelling suggests that a single allo-hemodialysis session may lower neonatal unconjugated bilirubin levels effectively. If corroborated in ex-vivo, animal, and clinical studies, this bilirubin reduction could lower the risks associated with SNJ, especially kernicterus, and possibly avoiding the morbidity associated with exchange transfusions.
严重新生儿黄疸（SNJ）可导致长期神经认知障碍、脑瘫、听神经病、耳聋或死亡。我们开发了一种用于同种异体血液透析的数学模型，作为治疗足月或近足月婴儿 SNJ 的潜在血液净化方法。在同种异体血液透析（allo-HD）中，新生儿的血液流经微型 0.075 m 血液透析器的中空纤维，而健康成人（“供体”）的血液则逆流通过透析液室。我们模拟了新生儿血流量分别为 12.5 和 15 mL/min（分别用于 2.5 kg 和 3.5 kg 的新生儿）以及 30 mL/min 的 allo-HD 中未结合胆红素的动力学，新生儿和供体的胆红素生成率分别设定为 6 和 3 mg/kg/天。计算供体胆红素结合率以获得正常的稳态胆红素水平。新生儿白蛋白水平设定为 1.1、2.1、3.1 g/dL，供体白蛋白水平设定为 3.3 g/dL。模型模拟表明，6 小时的 allo-HD 治疗可使新生儿胆红素水平降低 > 35%，并且对于新生儿血清白蛋白水平较低的情况，这种治疗方式尤其有效。由于成人健康肝脏的胆红素结合能力较高，且分布容积较大，因此在 allo-HD 期间供体的胆红素水平仅短暂升高。我们的模型表明，单次 allo-HD 治疗可能有效降低新生儿未结合胆红素水平。如果在离体、动物和临床研究中得到证实，这种胆红素降低可能会降低与 SNJ 相关的风险，尤其是核黄疸，并可能避免与换血相关的发病率。
