A Targeted Release Capsule of Lanthanum Carbonate: a New Efficient Cheap Treatment for Primary Hyperoxalurias

Introduction: Primary hyperoxaluria (PH) is a devastating disease in children and adults. Recently, a substantial progress in the treatment of this deadly disease has been made that consists of the introduction of the RNA inhibitors, lumasiran and nedosiran, which deplete the substrate for oxalate s...

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Main Authors: Marc E. De Broe, Marc P. Uytterhoeven, Jan De Causmaecker, Yannick De Brucker, Erik D. Snelders, Johan Van De Walle, Koen Van Hoeck, Dominique Trouet, Monique Elseviers
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024924020424
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author Marc E. De Broe
Marc P. Uytterhoeven
Jan De Causmaecker
Yannick De Brucker
Erik D. Snelders
Johan Van De Walle
Koen Van Hoeck
Dominique Trouet
Monique Elseviers
author_facet Marc E. De Broe
Marc P. Uytterhoeven
Jan De Causmaecker
Yannick De Brucker
Erik D. Snelders
Johan Van De Walle
Koen Van Hoeck
Dominique Trouet
Monique Elseviers
author_sort Marc E. De Broe
collection DOAJ
description Introduction: Primary hyperoxaluria (PH) is a devastating disease in children and adults. Recently, a substantial progress in the treatment of this deadly disease has been made that consists of the introduction of the RNA inhibitors, lumasiran and nedosiran, which deplete the substrate for oxalate synthesis. Methods: Lanthanum carbonate (Lanth.Carb., La2[CO3]3) is a powerful phosphate binder having a strong affinity to oxalate. Its use as such in PH is not relevant because patients with normal renal function develop a severe phosphate depletion without a clear effect on oxalate balance. Considering that the absorption of phosphate is in the early gastrointestinal (GI) tract and mainly in the distal part of the GI tract for oxalate, we developed a targeted release capsule (trc) containing 500 mg Lant.Carb. released in the distal part of the GI tract as proven by radiological investigations of the radiopaque trcLanth.Carb. Results: Four patients with PH and estimated glomerular filtration rate > 60 ml/min per 1.73 m2 were treated with trcLanth.Carb., which turned out to decrease the urinary oxalate concentrations clearly < 0.51 mmol/24 h per 1.73 m2,45 mg/24 h per 1.73 m2 (considered as upper limit of normal), after 2.5 months of treatment in 3 patients and 18 months in 1 patient. Calciuria remained normal or decreased slightly. Phosphaturia and phosphatemia remained normal and stable in all 4 cases. Conclusion: trcLanth.Carb. is a promising repurposed, efficient, nontoxic, and cheap drug, lacking serious side effects in the treatment of any type of PH in whatever place in the world. A randomized controlled trial supporting this proof-of-concept is the next step.
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spelling doaj-art-49ac99501ca24a84b2b74dd72ee6cb052025-08-20T02:06:00ZengElsevierKidney International Reports2468-02492025-02-0110250351510.1016/j.ekir.2024.11.020A Targeted Release Capsule of Lanthanum Carbonate: a New Efficient Cheap Treatment for Primary HyperoxaluriasMarc E. De Broe0Marc P. Uytterhoeven1Jan De Causmaecker2Yannick De Brucker3Erik D. Snelders4Johan Van De Walle5Koen Van Hoeck6Dominique Trouet7Monique Elseviers8Laboratory of Pathophysiology, University of Antwerp, Wilrijk, Belgium; Correspondence: Marc E. De Broe, Hillare 12, B-9160 Lokeren, Belgium.Sonic Healthcare Benelux AML, Antwerp, BelgiumPharmacist, Lokeren, BelgiumDepartment of Radiology, Vrije Universiteit Brussels, Ixelles, BelgiumDepartment of Nephrology, Antwerp University Hospital, Edegem, Belgium; Laboratory of Experimental Medicine and Pediatrics (LEMP), University of Antwerp, Wilrijk, BelgiumDepartment Pediatric Nephrology, Ghent University Hospital, Ghent, BelgiumLaboratory of Experimental Medicine and Pediatrics (LEMP), University of Antwerp, Wilrijk, Belgium; Department Pediatric Nephrology, Antwerp University Hospital, Edegem, BelgiumLaboratory of Experimental Medicine and Pediatrics (LEMP), University of Antwerp, Wilrijk, Belgium; Department Pediatric Nephrology, Antwerp University Hospital, Edegem, BelgiumCenter for Research and Innovation in Care, University of Antwerp, Antwerp, BelgiumIntroduction: Primary hyperoxaluria (PH) is a devastating disease in children and adults. Recently, a substantial progress in the treatment of this deadly disease has been made that consists of the introduction of the RNA inhibitors, lumasiran and nedosiran, which deplete the substrate for oxalate synthesis. Methods: Lanthanum carbonate (Lanth.Carb., La2[CO3]3) is a powerful phosphate binder having a strong affinity to oxalate. Its use as such in PH is not relevant because patients with normal renal function develop a severe phosphate depletion without a clear effect on oxalate balance. Considering that the absorption of phosphate is in the early gastrointestinal (GI) tract and mainly in the distal part of the GI tract for oxalate, we developed a targeted release capsule (trc) containing 500 mg Lant.Carb. released in the distal part of the GI tract as proven by radiological investigations of the radiopaque trcLanth.Carb. Results: Four patients with PH and estimated glomerular filtration rate > 60 ml/min per 1.73 m2 were treated with trcLanth.Carb., which turned out to decrease the urinary oxalate concentrations clearly < 0.51 mmol/24 h per 1.73 m2,45 mg/24 h per 1.73 m2 (considered as upper limit of normal), after 2.5 months of treatment in 3 patients and 18 months in 1 patient. Calciuria remained normal or decreased slightly. Phosphaturia and phosphatemia remained normal and stable in all 4 cases. Conclusion: trcLanth.Carb. is a promising repurposed, efficient, nontoxic, and cheap drug, lacking serious side effects in the treatment of any type of PH in whatever place in the world. A randomized controlled trial supporting this proof-of-concept is the next step.http://www.sciencedirect.com/science/article/pii/S2468024924020424primary hyperoxaluriasefficientcheaptreatmenttrc-Lanthanum Carbonate
spellingShingle Marc E. De Broe
Marc P. Uytterhoeven
Jan De Causmaecker
Yannick De Brucker
Erik D. Snelders
Johan Van De Walle
Koen Van Hoeck
Dominique Trouet
Monique Elseviers
A Targeted Release Capsule of Lanthanum Carbonate: a New Efficient Cheap Treatment for Primary Hyperoxalurias
Kidney International Reports
primary hyperoxalurias
efficient
cheap
treatment
trc-Lanthanum Carbonate
title A Targeted Release Capsule of Lanthanum Carbonate: a New Efficient Cheap Treatment for Primary Hyperoxalurias
title_full A Targeted Release Capsule of Lanthanum Carbonate: a New Efficient Cheap Treatment for Primary Hyperoxalurias
title_fullStr A Targeted Release Capsule of Lanthanum Carbonate: a New Efficient Cheap Treatment for Primary Hyperoxalurias
title_full_unstemmed A Targeted Release Capsule of Lanthanum Carbonate: a New Efficient Cheap Treatment for Primary Hyperoxalurias
title_short A Targeted Release Capsule of Lanthanum Carbonate: a New Efficient Cheap Treatment for Primary Hyperoxalurias
title_sort targeted release capsule of lanthanum carbonate a new efficient cheap treatment for primary hyperoxalurias
topic primary hyperoxalurias
efficient
cheap
treatment
trc-Lanthanum Carbonate
url http://www.sciencedirect.com/science/article/pii/S2468024924020424
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