Centre de Référence des Maladies Rénales Rares - Néphrogones - Hôpital Femme Mère Enfant, Hospices Civils de Lyon - Filière ORKiD, Bron, France.
Advicenne, Nîmes, France.
Nefrologia (Engl Ed). 2023 Jul-Aug;43(4):458-466. doi: 10.1016/j.nefroe.2022.02.012. Epub 2022 Dec 16.
ADV7103 is a new prolonged-release treatment for distal renal tubular acidosis (dRTA), containing potassium citrate and potassium bicarbonate. Since acidosis may affect bone mineral contents, the effects of ADV7103 on bone mineral density (BMD) and growth in patients with dRTA over 24 months were evaluated.
Thirty patients (24 paediatric patients and 6 adults) were included in an open-label extension study after a phase II/III trial. BMD, measured by densitometry, was assessed at baseline and at 24 months. Growth was evaluated throughout the study. Plasma bicarbonate, parathyroid hormone, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, bone alkaline phosphatase, calciuria and citraturia, were also determined. Safety and treatment compliance were evaluated as well.
After 24 months of treatment with ADV7103, mean spine BMD z-score values significantly increased as compared with baseline (p=0.024). In adults, spine and whole-body densitometry z-scores showed a significant correlation with plasma bicarbonate levels (r=0.82 and r=0.97, respectively, p<0.005). There was an increase>0.5 units in z-scores for height and weight in 18% and 36% of the paediatric patients, respectively. With treatment, plasma bicarbonate concentration and calciuria at the different visits were normal in 69-86% and 93-96% patients, respectively. Only nine treatment-related gastrointestinal AEs of mild/moderate severity, were reported in five patients.
Two years of ADV7103 treatment improved growth and increased spine BMD. These results suggest that control of acidosis by ADV7103 treatment improves bone parameters.
ADV7103 是一种新的用于治疗远端肾小管酸中毒（dRTA）的缓释制剂，包含枸橼酸钾和碳酸氢钾。由于酸中毒可能会影响骨矿物质含量，因此评估 ADV7103 对 dRTA 患者 24 个月时的骨密度（BMD）和生长的影响。
在一项 II/III 期试验后，30 名患者（24 名儿科患者和 6 名成年患者）参加了一项开放性扩展研究。通过密度测定法在基线和 24 个月时评估 BMD。整个研究期间评估生长情况。还测定了血浆碳酸氢盐、甲状旁腺激素、25-羟维生素 D、1,25-二羟维生素 D、骨碱性磷酸酶、尿钙和枸橼酸盐排泄。还评估了安全性和治疗依从性。
在接受 ADV7103 治疗 24 个月后，与基线相比，平均脊柱 BMD z 评分显著增加（p=0.024）。在成年患者中，脊柱和全身骨密度 z 评分与血浆碳酸氢盐水平呈显著相关性（r=0.82 和 r=0.97，分别为 p<0.005）。在 18%和 36%的儿科患者中，身高和体重的 z 评分分别增加了>0.5 个单位。在 69-86%和 93-96%的患者中，分别有 93-96%和 93-96%的患者在不同时间点的血浆碳酸氢盐浓度和尿钙正常。在 5 名患者中，仅报告了 9 例与治疗相关的胃肠道轻度/中度不良事件。
ADV7103 治疗两年可改善生长并增加脊柱 BMD。这些结果表明，ADV7103 治疗通过控制酸中毒可改善骨参数。
