#6649 significant clinical improvement of paediatric and adult patients with distal renal tubular acidosis after 6 years of treatment with sibnayal®

Abstract Background and Aims Distal renal tubular acidosis (dRTA) is a rare disease, inherited or acquired, characterized by hyperchloremic metabolic acidosis leading to negative effects on growth, bone and kidney, with growth retardation, rickets in children and osteomalacia in adults, nephrolithiasis and chronic kidney disease. No alkalizing treatment, necessary to control the metabolic acidosis and its consequences in growth, bone and kidney, has been shown, to date, to control the disease in the long term. The aim of this clinical study is to describe a cohort of adult and pediatric dRTA patients treated during 6 years by Sibnayal®, a new prolonged-release alkalizing formulation, in term of metabolic control, growth and long-term complications on bone mineralization and kidney function. Method Thirty patients with genetic dRTA taking Sibnayal®, previously treated with alkalizing standard of care and enrolled in the short-term B21CS study, were followed up for six years on average in a multicenter open-label extension trial (B22CS) to evaluate long-term impact of treatment on standard deviation score (SDS) of height, SDS weight, body mass index (BMI), Z-score spine bone mineral density (BMD), phosphocalcic metabolism (up to 4 years). glomerular filtration rate (GFR), nephrolithiasis, metabolic acidosis control, safety and compliance were also evaluated. Paired t-tests were done from baseline to end of study (EoS) when appropriate. The covariance ANCOVA test was performed to analyze spine BMD Z-score. Data are presented as mean ± standard error of mean. Results Clinical observations in this cohort, after an average of six years of treatment with Sibnayal®, confirmed the adequate control of metabolic acidosis (plasma bicarbonate from 22.0±0;6 mmol/L at baseline to 22.8±0.56 mmol/L at study end). The phosphocalcic metabolism analysis, from baseline to Month 48, demonstrated no significant change on Z-score for age of blood bone alkaline phosphatases, and a significant decrease of Z-score for age of blood phosphorus level (from to -0.5±0.7 to -1.3±1.0, p = 0.03). From baseline to EoS, SDS of height and weight increased significantly (-0.6±1.0 to -0.3±0.9 p = 0.04 and 0.2±1.5 to 0.7±1.4 p = 0.03, respectively), without significant difference in BMI. The spine BMD Z-score, relevant skeletal area for both pediatric and adult patients, underwent a continuous and significant increase of the change from baseline values over 6 years of treatment (difference [95% CI] = 0.404 [0.170; 0.639]). At EoS, spine BMD Z-score was improved in pre- and post-pubertal patients (mean 0.76±0.54 and 0.56±0.22 respectively), while it was stabilized in pubertal patients (mean -0.01±0.39). There was no significant variation of GFR between baseline and EoS. Nephrolithiasis increased slightly according to the increased age of the patient, without surgical intervention for stones removal. Safety and adherence to treatment remained good throughout the study. Conclusion Our data show the positive effect of the long-term treatment with Sibnayal® on growth and spine BMD, nicely improved, in the dRTA patients who participated to this long-term follow-up clinical study. The kidney function is also stabilized in these patients during the follow-up. This is the first report describing the prevention effect on the long-term complications of the distal Renal Tubular Acidosis patients under 6 years of Sibnayal® treatment.