Article Dans Une Revue Kidney International Reports Année : 2025

Furosemide and Serum Protein-Bound Uremic Toxin Concentrations in Patients With CKD

Dorothée Cannet
  • Fonction : Collaborateur
Christian Combe
Aghilès Hamroun
Yves-Edouard Herpe
  • Fonction : Collaborateur
Christian Jacquelinet
  • Fonction : Collaborateur
Pascal Morel
  • Fonction : Collaborateur
Christophe Pascal
Roberto Pecoits-Filho
  • Fonction : Collaborateur
Joost Schanstra
Bénédicte Stengel
  • Fonction : Directeur de publication
Céline Lange
  • Fonction : Auteur
Oriane Lambert
  • Fonction : Collaborateur
Marie Metzger
  • Fonction : Collaborateur

Résumé

Introduction: Furosemide is commonly prescribed to patients with chronic kidney disease (CKD) but may impair the kidney's excretion of protein-bound uremic toxins (PBUTs) via the organic anion transporters 1 and 3 (OAT1 and OAT3). We evaluated the association between furosemide prescription (status and dose level) and the serum concentrations of free OAT1/3-inhibiting uremic toxins (UTs) in patients with CKD. Methods: We included 2342 patients with CKD (stages 2-5) from the CKD-Renal Epidemiology and Information Network (CKD-REIN) cohort and with centralized serum UT assay data at baseline. The UTs were assayed using liquid chromatography - tandem mass spectrometry. The OAT1/3-inhibiting UTs identified in a literature review included indoxyl sulphate (IS), kynurenine (Kyn), p-cresyl sulphate (PCS), and indole-3-acetic acid (IAA). Multiple linear regression was used to assess each PBUT or their sum ( ΣUTs free) as the dependent variable. Results: Patients prescribed furosemide (n = 799, 34%) were older and had a lower estimated glomerular filtration rate (eGFR), a higher C-reactive protein (CRP) concentration, more comorbidities, and more concomitant medications than patients not prescribed furosemide. After adjustment for potential confounders, patients prescribed > 120 mg furosemide had significantly higher serum concentrations of ΣUTs free (+19.1%), IS (+31.9%), Kyn (+9.3%), PCS (+29.3%), and IAA (+162.9%) than patients not prescribed furosemide. Using a smooth function to model the association between the furosemide dose level and PBUTs, we observed (for ΣUTs free and each free UT) a steep increase between 80 and 100 mg and then a high plateau. Conclusion: In patients with CKD, furosemide (particularly at a dose level > 120 mg) is independently associated with higher serum free PBUT concentrations. Our findings suggest that drug-UT competition contributes to PBUT accumulation.

Dates et versions

hal-05185285 , version 1 (24-07-2025)

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Citer

Margaux Costes-Albrespic, Natalia Alencar de Pinho, Islam Amine Larabi, Carolla El Chamieh, Solène Laville, et al.. Furosemide and Serum Protein-Bound Uremic Toxin Concentrations in Patients With CKD. Kidney International Reports, 2025, 10 (7), pp.2165-2177. ⟨10.1016/j.ekir.2025.04.040⟩. ⟨hal-05185285⟩
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