{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T13:02:58Z","timestamp":1784206978483,"version":"3.55.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Advicenne"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Nephrol"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A new prolonged-release formulation of potassium citrate and potassium bicarbonate, ADV7103, has been shown to improve metabolic control, palatability, and gastrointestinal safety in patients with distal renal tubular acidosis (dRTA) when compared to standard of care (SoC) treatments. The present work evaluates safety and efficacy of ADV7103 during 24 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty pediatric and adult patients were included in an open-label extension study after a phase II\/III trial. Safety and tolerability were assessed. Plasma bicarbonate and potassium levels, as well as urine parameters, were evaluated over time. Acceptability, adherence, and quality of life were also assessed. The evolution of clinical consequences of dRTA in the cohort was explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were 104 adverse events (AEs) reported, but only 9 gastrointestinal events observed in five patients (17%) were considered to be related to ADV7103 treatment. There were no AEs leading to treatment discontinuation. Plasma bicarbonate and potassium levels were in the normal ranges at the different visits, respectively, in 69\u201386% and 83\u201393% of patients. Overall adherence rates were \u2265 75% throughout the whole study in 79% patients. An average improvement of quality of life of 89% was reported at 24 months of study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Common AEs concerned metabolism and gastrointestinal disorders; the former being related to the disease. Less than half of the gastrointestinal AEs were related to ADV7103 treatment and they were mostly mild in severity. Metabolic parameters were maintained in the normal ranges in most patients. Patient satisfaction was high and adherence to treatment was good and remained stable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p>Registered as EudraCT 2013-003828-36 on the 3rd of September 2013.<\/jats:p><\/jats:sec><jats:sec><jats:title>Graphical Abstract<\/jats:title><\/jats:sec>","DOI":"10.1007\/s00467-020-04873-0","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T16:12:44Z","timestamp":1614355964000},"page":"1765-1774","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Safety, efficacy, and acceptability of ADV7103 during 24 months of treatment: an open-label study in pediatric and adult patients with distal renal tubular acidosis"],"prefix":"10.1007","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4207-824X","authenticated-orcid":false,"given":"Aur\u00e9lia","family":"Bertholet-Thomas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Guittet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5056-9065","authenticated-orcid":false,"given":"Maria A.","family":"Manso-Silv\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Joukoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Navas-Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Baudouin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Cailliez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Di Maio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Gillion-Boyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilija","family":"Golubovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Harambat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Knebelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Nobili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Novo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"Podracka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwena\u00eblle","family":"Roussey-Kesler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4174-2487","authenticated-orcid":false,"given":"Luc-Andr\u00e9","family":"Granier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"4873_CR1","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1007\/s00467-018-3965-8","volume":"33","author":"M Alonso-Varela","year":"2018","unstructured":"Alonso-Varela M, Gil-Pena H, Coto E, G\u00f3mez J, Rodr\u00edguez J, Rodr\u00edguez-Rubio E, Santos F, RenalTube Group (2018) Distal renal tubular acidosis. Clinical manifestations in patients with different underlying gene mutations. Pediatr Nephrol 33:1523\u20131529","journal-title":"Pediatr Nephrol"},{"key":"4873_CR2","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1007\/s00296-014-2993-3","volume":"34","author":"T Both","year":"2014","unstructured":"Both T, Zietse R, Hoorn EJ, van Hagen PM, Dalm VASH, van Laar JAM, van Daele PLA (2014) Everything you need to know about distal renal tubular acidosis in autoimmune disease. Rheumatol Int 34:1037\u20131045","journal-title":"Rheumatol Int"},{"key":"4873_CR3","doi-asserted-by":"publisher","first-page":"181","DOI":"10.2147\/PHMT.S174459","volume":"9","author":"T Watanabe","year":"2018","unstructured":"Watanabe T (2018) Improving outcomes for patients with distal renal tubular acidosis: recent advances and challenges ahead. Pediatric Health Med Ther 9:181\u2013190","journal-title":"Pediatric Health Med Ther"},{"key":"4873_CR4","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1007\/s40620-017-0447-1","volume":"31","author":"N Mohebbi","year":"2018","unstructured":"Mohebbi N, Wagner CA (2018) Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis. J Nephrol 31:511\u2013522","journal-title":"J Nephrol"},{"key":"4873_CR5","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1093\/ndt\/gfy409","volume":"34","author":"SC Lopez-Garcia","year":"2019","unstructured":"Lopez-Garcia SC, Emma F, Walsh SB, Fila M, Hooman N, Zaniew M, Bertholet-Thomas A, Colussi G, Burgmaier K, Levtchenko E, Sharma J, Singhal J, Soliman NA, Ariceta G, Basu B, Murer L, Tasic V, Tsygin A, Decramer S, Gil-Pe\u00f1a H, Koster-Kamphuis L, La Scola C, Gellermann J, Konrad M, Lilien M, Francisco T, Tramma D, Trnka P, Y\u00fcksel S, Caruso MR, Chromek M, Ekinci Z, Gambaro G, Kari JA, K\u00f6nig J, Taroni F, Thumfart J, Trepiccione F, Winding L, W\u00fchl E, A\u011fba\u015f A, Belkevich A, Vargas-Poussou R, Blanchard A, Conti G, Boyer O, Dursun I, P\u0131narba\u015f\u0131 AS, Melek E, Miglinas M, Novo R, Mallett A, Milosevic D, Szczepanska M, Wente S, Cheong HI, Sinha R, Gucev Z, Dufek S, Iancu D, European dRTA Consortium, Kleta R, Schaefer F, Bockenhauer D (2019) Treatment and long-term outcome in primary distal renal tubular acidosis. Nephrol Dial Transplant 34:981\u2013991","journal-title":"Nephrol Dial Transplant"},{"key":"4873_CR6","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1053\/j.ackd.2018.05.003","volume":"25","author":"PG Vall\u00e9s","year":"2018","unstructured":"Vall\u00e9s PG, Batlle D (2018) Hypokalemic distal renal tubular acidosis. Adv Chronic Kidney Dis 25:303\u2013320","journal-title":"Adv Chronic Kidney Dis"},{"key":"4873_CR7","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1007\/s00467-016-3573-4","volume":"32","author":"MTP Besouw","year":"2017","unstructured":"Besouw MTP, Bienias M, Walsh P, Kleta R, Van't Hoff WG, Ashton E, Jenkins L, Bockenhauer D (2017) Clinical and molecular aspects of distal renal tubular acidosis in children. Pediatr Nephrol 32:987\u2013996","journal-title":"Pediatr Nephrol"},{"key":"4873_CR8","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1007\/s00467-020-04685-2","volume":"35","author":"B Atmis","year":"2020","unstructured":"Atmis B, Cevizli D, Melek E, Bisgin A, Unal I, Anarat A, Bayazit AK (2020) Evaluation of phenotypic and genotypic features of children with distal kidney tubular acidosis. Pediatr Nephrol 35:2297\u20132306","journal-title":"Pediatr Nephrol"},{"key":"4873_CR9","doi-asserted-by":"publisher","first-page":"13960","DOI":"10.1038\/s41598-020-70549-2","volume":"10","author":"C Guittet","year":"2020","unstructured":"Guittet C, Roussel-Maupetit C, Manso-Silv\u00e1n MA, Guillaumin F, Vandenhende F, Granier LA (2020) Innovative prolonged-release oral alkalising formulation allowing sustained urine pH increase with twice daily administration: randomised trial in healthy adults. Sci Rep 10:13960","journal-title":"Sci Rep"},{"key":"4873_CR10","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s00467-020-04693-2","volume":"36","author":"A Bertholet-Thomas","year":"2020","unstructured":"Bertholet-Thomas A, Guittet C, Manso-Silv\u00e1n MA, Castang A, Baudouin V, Cailliez M, Di Maio M, Gillion-Boyer O, Golubovic E, Harambat J, Klein A, Knebelmann B, Nobili F, Novo R, Podracka L, Roussey-Kesler G, Stylianou C, Granier LA (2020) Efficacy and safety of an innovative prolonged-release combination drug in patients with distal renal tubular acidosis: an open-label comparative trial versus standard of care treatments. Pediatr Nephrol 36:83\u201391","journal-title":"Pediatr Nephrol"},{"key":"4873_CR11","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/S0022-3476(97)70162-8","volume":"131","author":"V Matos","year":"1997","unstructured":"Matos V, van Melle G, Boulat O, Markert M, Bachmann C, Guignard JP (1997) Urinary phosphate\/creatinine, calcium\/creatinine, and magnesium\/creatinine ratios in a healthy pediatric population. J Pediatr 131:252\u2013257","journal-title":"J Pediatr"},{"key":"4873_CR12","first-page":"13","volume":"59","author":"J Frey","year":"2001","unstructured":"Frey J, Daudon M, Raby N, Augereau C, Dechaux M, Diehl JL, Sicallac P, Bonneau C (2001) Valeur s\u00e9miologique des param\u00e8tres biochimiques urinaires. Ann Biol Clin 59:13\u201325","journal-title":"Ann Biol Clin"},{"key":"4873_CR13","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1007\/s00467-014-2806-7","volume":"29","author":"JK Kirejczyk","year":"2014","unstructured":"Kirejczyk JK, Porowski T, Konstantynowicz J, Kozerska A, Nazarkiewicz A, Hoppe B, Wasilewska A (2014) Urinary citrate excretion in healthy children depends on age and gender. Pediatr Nephrol 29:1575\u20131582","journal-title":"Pediatr Nephrol"},{"key":"4873_CR14","first-page":"1051","volume":"6","author":"XBG Parent","year":"1999","unstructured":"Parent XBG, Brignon P (1999) Lithiase oxalocalcique. Relation entre facteurs de risque biochimiques et phase cristalline du calcul. Prog Urol 6:1051\u20131056","journal-title":"Prog Urol"},{"key":"4873_CR15","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1016\/j.jpeds.2014.02.027","volume":"164","author":"AD Rogol","year":"2014","unstructured":"Rogol AD, Hayden GF (2014) Etiologies and early diagnosis of short stature and growth failure in children and adolescents. J Pediatr 164:S1\u2013S14","journal-title":"J Pediatr"},{"key":"4873_CR16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1651-2227.2006.tb02378.x","volume":"450","author":"WHO multicentre growth reference study group","year":"2006","unstructured":"WHO multicentre growth reference study group (2006) WHO child growth standards based on length\/height, weight and age. Acta Paediatr Suppl 450:76\u201385","journal-title":"Acta Paediatr Suppl"},{"key":"4873_CR17","doi-asserted-by":"publisher","first-page":"660","DOI":"10.2471\/BLT.07.043497","volume":"85","author":"M De Onis","year":"2007","unstructured":"De Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J (2007) Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ 85:660\u2013667","journal-title":"Bull World Health Organ"},{"key":"4873_CR18","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.jocd.2013.08.004","volume":"16","author":"JT Schousboe","year":"2013","unstructured":"Schousboe JT, Shepherd JA, Bilezikian JP, Baim S (2013) Executive summary of the 2013 International Society for Clinical Densitometry Position Development Conference on bone densitometry. J Clin Densitom 16:455\u2013466","journal-title":"J Clin Densitom"},{"key":"4873_CR19","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1097\/01.ASN.0000023430.92674.E5","volume":"13","author":"J Rodriguez Soriano","year":"2002","unstructured":"Rodriguez Soriano J (2002) Renal tubular acidosis: the clinical entity. J Am Soc Nephrol 13:2160\u20132170","journal-title":"J Am Soc Nephrol"},{"key":"4873_CR20","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1146\/annurev.med.52.1.471","volume":"52","author":"D Batlle","year":"2001","unstructured":"Batlle D, Ghanekar H, Jain S, Mitra A (2001) Hereditary distal renal tubular acidosis: new understandings. Annu Rev Med 52:471\u2013484","journal-title":"Annu Rev Med"},{"key":"4873_CR21","doi-asserted-by":"publisher","first-page":"725","DOI":"10.2169\/internalmedicine.54.9421","volume":"54","author":"C Zhang","year":"2015","unstructured":"Zhang C, Ren H, Shen P, Xu Y, Zhang W, Wang W, Li X, Ma Y, Chen N (2015) Clinical evaluation of Chinese patients with primary distal renal tubular acidosis. Intern Med 54:725\u2013730","journal-title":"Intern Med"},{"key":"4873_CR22","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/j.kint.2016.12.017","volume":"91","author":"V Palazzo","year":"2017","unstructured":"Palazzo V, Provenzano A, Becherucci F, Sansavini G, Mazzinghi B, Orlandini V, Giunti L, Roperto RM, Pantaleo M, Artuso R, Andreucci E, Bargiacchi S, Traficante G, Stagi S, Murer L, Benetti E, Emma F, Giordano M, Rivieri F, Colussi G, Penco S, Manfredini E, Caruso MR, Garavelli L, Andrulli S, Vergine G, Miglietti N, Mancini E, Malaventura C, Percesepe A, Grosso E, Materassi M, Romagnani P, Giglio S (2017) The genetic and clinical spectrum of a large cohort of patients with distal renal tubular acidosis. Kidney Int 91:1243\u20131255","journal-title":"Kidney Int"},{"key":"4873_CR23","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1053\/ajkd.2002.30560","volume":"39","author":"S Domrongkitchaiporn","year":"2002","unstructured":"Domrongkitchaiporn S, Khositseth S, Stitchantrakul W, Tapaneya-olarn W, Radinahamed P (2002) Dosage of potassium citrate in the correction of urinary abnormalities in pediatric distal renal tubular acidosis patients. Am J Kidney Dis 39:383\u2013391","journal-title":"Am J Kidney Dis"},{"key":"4873_CR24","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1016\/S0022-3476(72)80124-0","volume":"80","author":"MA Nash","year":"1972","unstructured":"Nash MA, Torrado AD, Greifer I, Spitzer A, Edelmann CM Jr (1972) Renal tubular acidosis in infants and children. Clinical course, response to treatment, and prognosis. J Pediatr 80:738\u2013748","journal-title":"J Pediatr"},{"key":"4873_CR25","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1159\/000478781","volume":"3","author":"F Trepiccione","year":"2017","unstructured":"Trepiccione F, Prosperi F, de la Motte LR, H\u00fcbner CA, Chambrey R, Eladari D, Capasso G (2017) New findings on the pathogenesis of distal renal tubular acidosis. Kidney Dis 3:98\u2013105","journal-title":"Kidney Dis"},{"key":"4873_CR26","doi-asserted-by":"publisher","first-page":"3691","DOI":"10.1093\/ndt\/gfs442","volume":"27","author":"D Batlle","year":"2012","unstructured":"Batlle D, Haque SK (2012) Genetic causes and mechanisms of distal renal tubular acidosis. Nephrol Dial Transplant 27:3691\u20133704","journal-title":"Nephrol Dial Transplant"},{"key":"4873_CR27","first-page":"92","volume":"3","author":"JCM Chan","year":"2007","unstructured":"Chan JCM, Santos F (2007) Renal tubular acidosis in childhood. World J Pediatr 3:92\u201397","journal-title":"World J Pediatr"},{"key":"4873_CR28","first-page":"202","volume":"4","author":"M Sharifian","year":"2010","unstructured":"Sharifian M, Esfandiar N, Mazaheri S, Kariminejad A, Mohkam M, Dalirani R, Esmaili R, Ahmadi M, Hassas-Yeganeh M (2010) Distal renal tubular acidosis and its relationship with hearing loss in children: preliminary report. Iran J Kidney Dis 4:202\u2013206","journal-title":"Iran J Kidney Dis"},{"key":"4873_CR29","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/ki.1981.213","volume":"20","author":"E McSherry","year":"1981","unstructured":"McSherry E (1981) Renal tubular acidosis in childhood. Kidney Int 20:799\u2013809","journal-title":"Kidney Int"}],"container-title":["Pediatric Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00467-020-04873-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00467-020-04873-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00467-020-04873-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,22]],"date-time":"2023-10-22T02:56:48Z","timestamp":1697943408000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00467-020-04873-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,26]]},"references-count":29,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["4873"],"URL":"https:\/\/doi.org\/10.1007\/s00467-020-04873-0","relation":{},"ISSN":["0931-041X","1432-198X"],"issn-type":[{"value":"0931-041X","type":"print"},{"value":"1432-198X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,26]]},"assertion":[{"value":"6 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 February 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"C. Guittet, M.A. Manso-Silv\u00e1n and L.A. Granier are employees of Advicenne and hold stock options or shares in the company. S. Joukoff and V. Navas-Serrano are also employees of Advicenne.A. Bertholet received support from Advicenne for traveling to meetings and\/or funding for lectures.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by regional independent ethics committees and national regulatory health authorities, and conducted in accordance with Good Clinical Practice and the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"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.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}}]}}