Peruzzi Licia, Leporati Marta
Pediatric Nephrology Unit, Regina Margherita Children's Hospital, AOU Città della Salute e Della Scienza di Torino, Piazza Polonia 94, 10126, Turin, Italy.
European Reference Network for Rare Kidney Diseases (ERKNet) Center, Turin, Italy.
J Nephrol. 2025 Jul 9. doi: 10.1007/s40620-025-02325-2.
Lumasiran, an RNA interference therapeutic, demonstrated effectiveness in clinical trials, leading to approval for primary hyperoxaluria type 1 management in all age groups. To date, little is known about its use in newborns. This study assesses, for the first time, the oxalate and glycolate metabolism in a newborn affected by primary hyperoxaluria type 1 treated at birth. His older brother, also affected by primary hyperoxaluria type 1, experienced severe disease progression and significant comorbidities. These challenges informed the decision to initiate immediate treatment for the younger sibling. The child was treated at 6 h of life with lumasiran 6 mg/kg subcutaneously, in combination with pyridoxin 10 mg/kg/day. Lumasiran 6 mg/kg was repeated at 30 and 60 days, then was reduced to 3 mg/kg every month. Intravenous hyperhydration (240 mL/kg/day) was maintained for 16 days, together with oral water and potassium citrate (500 mg in 500 mL/day) in addition to breastfeeding. Although gycolate oxidase inhibition was started immediately after birth in the absence of previous deposits, it showed a latency of at least 15 days. Over this period of time, dangerous levels of blood and urinary oxalate were reached, due to the physiological low glomerular filtration rate in the perinatal period, as demonstrated by the increasing levels of endogenous oxalate production until day 6. Blood oxalate supersaturation 30 days after the first dose of treatment was never reached again. No adverse events occurred. In this report, early treatment with lumasiran, coupled with hyperhydration and supportive therapy, was able to ensure the absence of primary hyperoxaluria type 1 symptoms throughout the 24 months of follow-up.
鲁马西拉（Lumasiran）是一种RNA干扰疗法药物，在临床试验中显示出有效性，已获批用于各年龄组原发性高草酸尿症1型的治疗。迄今为止，关于其在新生儿中的应用知之甚少。本研究首次评估了一名出生时即接受治疗的原发性高草酸尿症1型新生儿的草酸盐和乙醇酸盐代谢情况。他的哥哥也患有原发性高草酸尿症1型，经历了严重的疾病进展和显著的合并症。这些情况促使决定对弟弟立即进行治疗。该患儿在出生后6小时接受了皮下注射6mg/kg的鲁马西拉治疗，并联合每天10mg/kg的吡哆醇治疗。在30天和60天时重复给予6mg/kg的鲁马西拉，之后每月减至3mg/kg。静脉补液（240mL/kg/天）维持16天，除母乳喂养外，还口服水和枸橼酸钾（500mg溶于500mL/天）。尽管在出生后立即开始抑制乙醇酸氧化酶时并无先前的沉积物，但显示出至少15天的潜伏期。在此期间，由于围产期生理性低肾小球滤过率，血液和尿液中的草酸盐达到了危险水平，直到第6天内源性草酸盐生成水平不断升高就证明了这一点。首次给药治疗30天后，血液草酸盐过饱和状态再也未出现。未发生不良事件。在本报告中，早期使用鲁马西拉治疗，再加上补液和支持治疗，能够确保在24个月的随访期间未出现原发性高草酸尿症1型症状。
