Bertholet-Thomas Aurélia, De Mul Aurélie, Bernardor Julie, Roussey-Kesler Gwenaëlle, Podracka Ludmila, Novo Robert, Nobili François, Knebelmann Bertrand, Harambat Jérôme, Golubovic Emilija, Boyer Olivia, Di Maio Massimo, Cailliez Mathilde, Baudouin Véronique, Chidler Laure, Leblanc Véronique, Bacchetta Justine
Centre de Référence des Maladies Rénales Rares- MAREGE- Hôpital Femme Mère Enfant, Hospices Civils de Lyon- Filière ORKID (Orphan Kidney Diseases), ERK-Net (The European Rare Kidney Disease Network), Lyon, France.
Hôpital l'Archet, Service de Rhumatologie Pédiatrique et Médecine Interne de l'enfant, CHU de Nice, Nice, France.
Orphanet J Rare Dis. 2025 Aug 13;20(1):431. doi: 10.1186/s13023-025-03953-4.
Distal renal tubular acidosis (dRTA) is a rare disease characterized by hyperchloremic metabolic acidosis affecting growth, bone and kidney health.
The aim of B22CS study was to evaluate long-term safety and efficacy (anthropometric/pubertal, tubular damages/kidney function, bone biomarkers, compliance assessments) of Sibnayal, a prolonged-release alkalinizing formulation with twice daily dosing, in children and adults with dRTA. All patients were previously included in the pivotal B21CS study, so were already receiving Sibnayal when included in B22CS open-label follow-up study.
A total of 30 patients with primary dRTA (mean age:10.6 ± 6.0 years) entered this long-term study (average of 6 years). At inclusion, most patients had adequate metabolic control, normal kidney function and height. Sibnayal was well tolerated over the study duration.The most frequent adverse event was hypovitaminosis D (13 patients). Causality to treatment was reported for only 4% of all TEAEs (6 patients) and were mostly gastrointestinal. All adverse events resolved without treatment discontinuation. Sibnayal allowed a sustained control of metabolic acidosis as plasma bicarbonate level was 22.0 ± 3.2 mmol/L at baseline versus 22.6 ± 2.5 mmol/L at the End of Follow-up (EoF), p = NS. From baseline to EoF, mean Z-score height significantly increased (-0.6 ± 1.0 to -0.3 ± 1.0, p = 0.03), without significant change in weight and body mass index. Kidney function remained stable from baseline to EoF: estimated glomerular filtration rate = 105 ± 17 and 104 ± 20 mL/min/1.73m, respectively, p = NS. Urinary ratios: Calcium/Creatinine (UCa/UCr), Citrate/Creatinine (UCi/UCr), Calcium/Citrate (UCa/UCi) were not significantly different between baseline and EoF (p = NS). Mean lumbar bone mineral density Z-score significantly increased from baseline (-1.1 ± 1.0) to EoF (-0.8 ± 1.0), p = 0.005, with significant improvement between baseline and EoF in pre- and post-pubertal patients (p = 0.035 and p < 0.001, respectively), whilst it was maintained in pubertal patients (p = NS).
Long-term data support the good safety and efficacy profile of Sibnayal in the treatment of dRTA with adequate control of metabolic acidosis, stable kidney function and significant positive long-term clinical outcomes.
远端肾小管酸中毒（dRTA）是一种罕见疾病，其特征为高氯性代谢性酸中毒，会影响生长、骨骼和肾脏健康。
B22CS研究的目的是评估西布奈亚尔（Sibnayal），一种每日给药两次的缓释碱化制剂，在儿童和成人dRTA患者中的长期安全性和疗效（人体测量/青春期发育、肾小管损伤/肾功能、骨生物标志物、依从性评估）。所有患者之前均纳入了关键的B21CS研究，因此在纳入B22CS开放标签随访研究时已在接受西布奈亚尔治疗。
共有30例原发性dRTA患者（平均年龄：10.6±6.0岁）进入了这项长期研究（平均6年）。入组时，大多数患者代谢控制良好，肾功能和身高正常。在研究期间，西布奈亚尔耐受性良好。最常见的不良事件是维生素D缺乏症（13例患者）。所有治疗中出现的不良事件（TEAE）中只有4%（共6例患者）报告与治疗有因果关系，且大多为胃肠道事件。所有不良事件均在未停药的情况下得到缓解。西布奈亚尔能够持续控制代谢性酸中毒，基线时血浆碳酸氢盐水平为22.0±3.2 mmol/L，随访结束时（EoF）为22.6±2.5 mmol/L，p=无统计学意义。从基线到EoF，平均身高Z评分显著增加（从-0.6±1.0增至-0.3±1.0，p=0.03），体重和体重指数无显著变化。从基线到EoF，肾功能保持稳定：估计肾小球滤过率分别为105±17和104±20 mL/min/1.73m²，p=无统计学意义。尿比值：钙/肌酐（UCa/UCr）、柠檬酸盐/肌酐（UCi/UCr）、钙/柠檬酸盐（UCa/UCi）在基线和EoF之间无显著差异（p=无统计学意义）。平均腰椎骨密度Z评分从基线时的-1.1±1.0显著增加至EoF时的-0.8±1.0，p=0.005，青春期前和青春期后患者在基线和EoF之间有显著改善（分别为p=0.035和p<0.001），而青春期患者则保持稳定（p=无统计学意义）。
长期数据支持西布奈亚尔在治疗dRTA方面具有良好的安全性和疗效，能够充分控制代谢性酸中毒，肾功能稳定，长期临床结局显著为阳性。
