PDF(Pubmed)
Abstract：
Background: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate, ultimately responsible for kidney stones, kidney failure and systemic oxalosis. Lumasiran, is a liver-directed RNA interference therapeutic agent. It has been shown to reduce hepatic oxalate production by targeting glycolate oxidase, and to dramatically reduce oxalate excretion. Care Report: We present the case of a teenager patient affected by PH1, who entered in the lumasiran compassionate use program. The patient had a rapid and sustained decrease in urinary oxalate/creatinine ratio, with a mean reduction after lumasiran administration of about 70%. During the 18 months long follow-up, urinary oxalate remained low, reaching nearly normal values. Plasma oxalate also decreased dramatically. Normal levels were reached immediately after the first dose and remained consistently low thereafter. During the same follow-up period, eGFR remained stable at about 60 ml/min/1.73 m2, but no new kidney stones were observed. Existing kidney stones did not increase in size. The patient did not suffer renal colic events and did not require further urological interventions. Conclusion: In our severely affected PH1 patient, lumasiran proved to be very effective in rapidly and consistently reducing plasma oxalate and urinary excretion to normal and near-normal levels, respectively. In the 18 months long follow-up post-lumasiran, the eGFR remained stable and the patient showed clinical improvements. As far as we know, this report covers the longest observation period after initiation of this novel RNAi therapy.
摘要：
背景：原发性高草酸尿症1型（PH1）是一种罕见的遗传性疾病，由肝脏过量生产的草酸盐，最终导致肾结石，肾功能衰竭和全身性氧化中毒。Lumasiran,是针对肝脏的RNA干扰治疗剂。它已被证明可以通过靶向乙醇酸氧化酶来减少肝草酸盐的产生，并显著减少草酸盐的排泄。护理报告：我们介绍了一名受PH1影响的青少年患者的情况，该患者进入了lumasiran同情使用计划。患者的尿草酸盐/肌酐比值快速持续下降，lumasiran给药后平均减少约70％。在长达18个月的随访中，尿草酸盐仍然很低，达到接近正常值。血浆草酸盐也显著降低。在第一次给药后立即达到正常水平，此后始终保持低水平。在同一随访期间，eGFR稳定在约60ml/min/1.73m2,但未观察到新的肾结石。现有的肾结石没有增加。患者没有发生肾绞痛事件，也不需要进一步的泌尿外科干预。结论：在我们严重受影响的PH1患者中，lumasiran被证明是非常有效的快速和持续减少血浆草酸盐和尿排泄到正常和接近正常水平，分别。在lumasiran术后18个月的随访中，eGFR保持稳定,患者临床症状改善.据我们所知,本报告涵盖了这种新型RNAi治疗开始后最长的观察期.
