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. 2025 Aug 13;20(1):431.
doi: 10.1186/s13023-025-03953-4.

6-year treatment follow-up with an extended-release alkaline formulation (Sibnayal®) in primary distal renal tubular acidosis

Aurélia Bertholet-Thomas  1 , Aurélie De Mul  2 , Julie Bernardor  3 , Gwenaëlle Roussey-Kesler  4 , Ludmila Podracka  5 , Robert Novo  6 , François Nobili  7 , Bertrand Knebelmann  8 , Jérôme Harambat  9 , Emilija Golubovic  10 , Olivia Boyer  11 , Massimo Di Maio  12 , Mathilde Cailliez  13 , Véronique Baudouin  14 , Laure Chidler  15 , Véronique Leblanc  15 , Justine Bacchetta  16
Affiliations

6-year treatment follow-up with an extended-release alkaline formulation (Sibnayal®) in primary distal renal tubular acidosis

Aurélia Bertholet-Thomas et al. Orphanet J Rare Dis. .

Abstract
in English, German

Background: Distal renal tubular acidosis (dRTA) is a rare disease characterized by hyperchloremic metabolic acidosis affecting growth, bone and kidney health.

Methods: 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.

Results: 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/1.73m2, 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).

Conclusion: 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.

Key learning points: WHAT WAS KNOWN: The medical management of dRTA consists in the correction of metabolic acidosis to prevent long-term complications on growth, bone metabolism and kidney function. Growth and kidney function were shown to be correlated to metabolic control. Only half of patients had adequate metabolic control. More than 80% of adult patients had CKD KDIGO ≥ 2.

This study adds: For the first time, a long-term follow-up study provides safety and efficacy data of Sibnayal®, an alkali medication with long-lasting release allowing 2 intakes per day. This study supports a long-term adequate control of metabolic acidosis with Sibnayal®, along with significant clinical outcomes on growth, kidney function and bone metabolism.

Potential impact: The main challenge for physicians is to prevent long-term complications of dRTA by better controlling metabolic acidosis. Sibnayal® as an innovative prolonged-release alkalinizing formulation with twice daily dosing, adapted for children, contributes to improving current medical management, clinical outcomes and quality of life of dRTA patients.

Trial registration number: Registered as EudraCT 2013-003828-36 on September 03, 2013.

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Conflict of interest statement

Declarations. Ethical approval: The study was approved by regional independent ethics committees (CPP sud-est II; clinical center of niš, ethics committee, Niš; Etická komisia Detská fakultná nemocnica s poliklinikou Bratislava, Bratislava) and national regulatory health authorities and conducted in accordance with Good Clinical Practice and the Declaration of Helsinki. Consent to participate: Written informed consent was obtained from all adult patients, and from the parents or legal guardians of all children. When possible, the assent from pediatric patients themselves was also obtained. Consent for publication: All authors consent for publication. Competing interests: A. Bertholet-Thomas received travel and speaker fees from Advicenne. J. Bacchetta received speaker fees from Advicenne. L. Chidler and V. Leblanc are Advicenne’s employees.

Figures

Fig. 1
Fig. 1
Clinical design of Arena 1 program including B21CS and B22CS studies. The B21CS, Phase II/III study enrolled 37 patients and included three treatment periods: baseline/SoC, Sibnayal® titration period, and fixed-dose Sibnayal® period. A total of 30 patients from B21CS study entered the OLE B22CS study and 27 patients completed the study with an average of 6 years of treatment with Sibnayal® (30 months for Slovakian and Serbian patients). EoS, End of Study; N, number of evaluated patients; OLE, open label extension; SoC, Standard of Care
Fig. 2
Fig. 2
Comparison of mean height Z-score (a), weight Z-score (b), and BMI Z-score (c) data at baseline (M1) and EoF (post-hoc analysis, paired t-test). BMI, body mass index; EoF, End of Follow-up; M, Month
Fig. 3
Fig. 3
Evolution of mean height Z-score in patients with abnormal EAS at baseline (post-hoc analysis, repeated measure model on change adjusted on baseline) (n = 6), p < 0.001). EAS, estimated adult stature; EoS, End of Study; ET, early termination visit; M, month; n, number of evaluated patients
Fig. 4
Fig. 4
Mean plasma bicarbonate levels over time (descriptive analysis) and comparison EoF versus Baseline (post-hoc analysis, paired t-test). EoF, End of Follow-up; EoS, End of Study; M, month; N/n, number of evaluated patients; NS, non-significant; SD, standard deviation
Fig. 5
Fig. 5
Mean plasma potassium levels over time (descriptive analysis) and comparison EoF versus Baseline (post-hoc analysis, paired t-test). EoF, End of Follow-up; EoS, End of Study; M, month; N/n, number of patients; NS, non-significant; SD, standard deviation
Fig. 6
Fig. 6
Evolution of mean lumbar spine BMD Z-score: mean change from baseline in all patients (post-hoc analysis, repeated measure model adjusted on baseline). BMD, bone mineral density; CI, confidence interval; ET, early termination visit; M, month; NS, non-significant; SD, standard deviation
Fig. 7
Fig. 7
Mean lumbar spine BMD Z-score at baseline and EoF by pubertal status according to baseline age (post-hoc analysis, paired t-test). BMD, bone mineral density; EoF, End of Follow-up; n, number of patients
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References

    1. Trepiccione F, Walsh SB, Ariceta G, et al. Distal renal tubular acidosis: erknet/espn clinical practice points. Nephrol Dial Transpl. 2021;36(9):1585–96. 10.1093/ndt/gfab171. - PubMed
    1. Vallés PG, Batlle D. Hypokalemic distal renal tubular acidosis. Adv Chronic Kidney Dis. 2018;25(4):303–20. 10.1053/j.ackd.2018.05.003. - PubMed
    1. Gómez-Conde S, García-Castaño A, Aguirre M, et al. Molecular aspects and long-term outcome of patients with primary distal renal tubular acidosis. Pediatr Nephrol. 2021;36(10):3133–42. 10.1007/s00467-021-05066-z. - PubMed
    1. Forero-Delgadillo JM, Gil-Peña H, Alonso-Varela M, Santos F, RenalTube G. Kidney function in patients with primary distal renal tubular acidosis. Pediatr Nephrol. 2021;36(7):1931–5. 10.1007/s00467-021-05068-x. - PubMed
    1. Lopez-Garcia SC, Emma F, Walsh SB, et al. Treatment and long-term outcome in primary distal renal tubular acidosis. Nephrol Dial Transpl. 2019;34(6):981–91. 10.1093/ndt/gfy409. - PubMed

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