Abstract Background and Aims Distal renal tubular acidosis (dRTA) is a rare disease, either inherited or acquired, characterized by an hyperchloremic metabolic acidosis leading to negative effects on growth, bone metabolism and kidney function, and hearing impairment. Sibnayal®, an oral twice-daily fixed and prolonged-release combination of potassium bicarbonate and potassium citrate3, is registered in the indication of dRTA, whatever the genetic or acquired form, in patients aged 1 year and older. Both efficacy and good tolerability profile of Sibnayal® versus alkali Standard of Care (SoC) were demonstrated in the short-term in children and adults dRTA patients (B21CS study1). B22CS study2 is the long-term follow-up study with safety profile as main objective and evaluation of the impact on the long-term complications as secondary or exploratory objectives. Method Thirty patients with genetic dRTA, previously enrolled in B21CS study, were followed-up for six years on average in a multicenter open-label extension trial (B22CS) to evaluate long-term impact of Sibnayal® on safety and efficacy on metabolic acidosis control, renal function, bone remodeling and growth. Tubular damages and kidney function were assessed by bicarbonatemia, kalemia, eGFR (CKiDU25 formula), nephrocalcinosis (paired-t-test) and urinary pH (UpH) (symmetry test). Bone remodeling was assessed with spine bone mineral density (BMD) Z-score (paired t-test, McNemar-test) from baseline to end of follow-up (EoF) and bone alkaline phosphatase (bALP) until M48. Growth was assessed by Z-score of height, weight, and body mass index (BMI) (paired t-test). Results Thirty patients (24 children, 6 adults), median age 10.6 (2-21) years, with inherited dRTA were included in B22CS study (mean study duration of 5.8 ± 1.3 years). Only 20% of patients reported at least one treatment related adverse event, mainly of gastro-intestinal type, which resolved without study treatment discontinuation. Bicarbonatemia was maintained stable in the normal range over the study duration (22.0 ± 3.2 mmol/L at baseline and 22.6 ± 2.5 mmol/L at EoF, p = NS). Kalemia was also maintained in the normal range (3.8 ± 0.5 mmol/L at baseline and 3.7 ± 0.4 mmol/L at EoF, p = NS). UpH was maintained between 7 and 8 in 70% of patients and when UpH was superior to 8 there was no impact on ACCP crystals presence (47% of patients at baseline versus 35.3% at EoF, p = NS). Nephrocalcinosis was reported in 89% of patients at baseline and in 93% at EoF (p = NS). Glomerular filtration rate remained stable all over the follow-up, eGFR was 105.2 ± 16.9 mL/min/1.73 m2 at baseline versus 103.9 ± 19.9 mL/min/1.73 m2 at EoF (p = NS). Bone metabolism was improved as spine BMD Z-score significantly increased from baseline (−1.1 ± 1.0) to EoF (−0.8 ± 0.9), p = 0.0053. In addition, 88% of patients had a spine BMD Z-score in the normal range (> -2SD) at EoF versus 71% of patients at baseline (p = NS). bALP Z-score was in normal range at baseline versus M48 (0.9 ± 2.22 at baseline vs 0.7 ± 1.3 at M48, p = NS). Growth was improved as Z-score for height significantly increased from baseline to EoF (p = 0.0323) while both Z-scores for weight and BMI were stable (p = NS). Conclusion These data confirm the long-term good tolerability profile and efficacy of Sibnayal® in the management of metabolic acidosis, in patients with dRTA. Sibnayal® showed a preventive effect on metabolic acidosis long-term complications in this population.