Adverse events associated with currently used medical treatments for cystinuria and treatment goals: results from a series of 442 patients in France.


Journal

BJU international
ISSN: 1464-410X
Titre abrégé: BJU Int
Pays: England
ID NLM: 100886721

Informations de publication

Date de publication:
11 2019
Historique:
pubmed: 26 2 2019
medline: 2 6 2020
entrez: 26 2 2019
Statut: ppublish

Résumé

To evaluate medical treatments, in terms of adverse events (AEs) and therapeutic goals, in a large series of patients with cystinuria. Data from 442 patients with cystinuria were recorded retrospectively. Crystalluria was studied in 89 patients. A mixed-effects logistic regression model was used to estimate how urine pH, specific gravity and cysteine-binding thiols (CBT) correlate with risk of cystine crystalluria. Alkalizing agents and CBT agents were given to 88.8% (n = 381) and 55.3% (n = 238) of patients, respectively. Gastrointestinal AEs were reported in 12.3%, 10.4% and 2.6% of patients treated with potassium bicarbonate, potassium citrate and sodium bicarbonate, respectively (P = 0.008). The percentages of patients who experienced at least one AE with tiopronin (24.6%) and with D-penicillamine (29.5%) were similar (P = 0.45). Increasing urine pH and decreasing urine specific gravity significantly reduced the risk of cystine crystalluria, whereas D-penicillamine and tiopronin treatments did not reduce this risk (odds ratio [OR] 1 for pH ≤6.5; OR 0.52 [95% confidence interval {95% CI} 0.28-0.95] for 7.0 <pH ≤7.5, P = 0.03; OR 0.26 [95% CI 0.13-0.53] for 7.5 < pH ≤8.0, P <0.001; OR 1 for specific gravity ≤1.005 OR 5.76 [95% CI 1.45-22.85] for 1.006 ≤ specific gravity ≤1.010, P = 0.01; and OR 11.06 [95% CI 2.76-44.26] for 1.011 ≤ specific gravity ≤ 1.014, P < 0.001). Increased urine pH significantly increased the risk of calcium phosphate crystalluria (OR 1 for pH≤ 6.5; OR 6.09 [95% CI 2.15-17.25] for pH >8.0, P <0.001). Adverse events were frequent with D-penicillamine and tiopronin. Alkaline hyperdiuresis was well tolerated and reduced cystine crystalluria. Urine specific gravity ≤1.005 and urine pH >7.5, while warning about calcium-phosphate crystallization, should be the goals of medical therapy.

Identifiants

pubmed: 30801923
doi: 10.1111/bju.14721
doi:

Substances chimiques

Sodium Bicarbonate 8MDF5V39QO
Tiopronin C5W04GO61S
Penicillamine GNN1DV99GX

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

849-861

Informations de copyright

© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.

Références

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Auteurs

Caroline Prot-Bertoye (C)

Department of Physiology, Functional Renal Explorations Department, AP-HP (Public Assistance Hospitals of Paris), Georges Pompidou European Hospital, Paris Descartes University, Paris, France.
INSERM UMRS 1138, Paris, France.

Saïd Lebbah (S)

Department of Biostatistics, AP-HP, Necker Hospital for Sick Children, Paris Descartes University, Medicine, Paris, France.

Michel Daudon (M)

Department of Physiology, Functional Renal Explorations Department, AP-HP, Tenon Hospital Pierre and Marie Curie University, INSERM UMR S 1155, Paris, France.

Isabelle Tostivint (I)

Department of Nephrology, AP-HP, Pitié-Salpétrière Hospital, Paris, France.

Jean-Philippe Jais (JP)

Department of Biostatistics, AP-HP, Necker Hospital for Sick Children, Paris Descartes University, Paris, France.
Inserm UMRS 1138 team 22, Paris, France.

Agnés Lillo-Le Louët (A)

Department of Pharmacovigilance, AP-HP, Georges Pompidou European Hospital, Paris, France.

Clément Pontoizeau (C)

Functional Unit of Metabolomics, Functional Explorations Department, APHP, Necker Hospital for Sick Children, Paris Descartes University, Paris, France.

Pierre Cochat (P)

Department of Pediatrics, Hospices Civils de Lyon, Centre de Référence des Maladies Rénales Rares Néphrogones, Lyon, France.

Pierre Bataille (P)

Department of Nephrology, Boulogne-sur-Mer Hospital, Boulogne sur Mer, France.

Franck Bridoux (F)

Department of Neprhology, Poitiers University Hospital, Poitiers University, Poitiers, France.

Pierre Brignon (P)

Department of Nephrology, Pasteur Hospital, Colmar, France.

Christian Choquenet (C)

Department of Urology, Princesse Grace Hospital, Monaco, France.

Christian Combe (C)

Department of Nephrology, Bordeaux University Hospital, Bordeaux University, Bordeaux, France.

Pierre Conort (P)

Department of Urology, AP-HP, Pitié-Salpétrière Hospital, Paris, France.

Stéphane Decramer (S)

Department of Nephrology and Internal Medicine, Toulouse University Children Hospital, Toulouse, France.
INSERM U1048, Toulouse, France.

Bertrand Doré (B)

Department of Urology, Poitiers University Hospital, Poitiers University, Poitiers, France.

Bertrand Dussol (B)

Department of Nephrology, AP-HM (Public Assistance Hospitals of Marseille), Conception Hospital, Aix-Marseille University, Marseille, France.

Marie Essig (M)

Department of Nephrology, Dialysis and Transplantation, Limoges University Hospital, Limoges University, Limoges, France.
INSERM UMR-S850, Limoges, France.

Marie Frimat (M)

Department of Nephrology, Claude Huriez University Hospital, Lille, France.

Nicolas Gaunez (N)

Department of Urology, Niort Hospital, Niort, France.

Dominique Joly (D)

Department of Nephrology, AP-HP, Necker Hospital for Sick Children, Paris Descartes University, Medicine, Paris, France.

Sophie Le Toquin-Bernard (S)

Department of Urology, Private Saint-Martin Hospital, Caen, France.

Arnaud Méjean (A)

Department of Urology, AP-HP, Georges Pompidou European Hospital, Paris Descartes University, Medicine, Paris, France.

Paul Meria (P)

Department of Urology, AP-HP, Saint-Louis Hospital, Paris, France.

Denis Morin (D)

Department of Pediatrics (Pediatric Nephrology and Diabetology), Montpellier University Hospital, Montpellier, France.
CNRS, UMR 5203-INSERM U661, Montpellier, France.

Hung V N'Guyen (HV)

Department of Urology, AP-HP, Saint-Louis Hospital, Paris, France.

Michel Normand (M)

Department of Nephrology, Private Saint-Martin Hospital, Pessac, France.

Michel Pietak (M)

Department of Urology, AP-HP, Georges Pompidou European Hospital, Paris, France.

Pierre Ronco (P)

Department of Nephrology and Dialysis, AP-HP, Tenon Hospital, Pierre and Marie Curie University, Paris, France.
INSERM Unit 702, Paris, France.

Christian Saussine (C)

Department of Urology, Strasbourg University Hospital, Strasbourg University, Strasbourg, France.

Michel Tsimaratos (M)

Department of Pediatrics, AP-HM, La Timone Hospital, Aix-Marseille University, Marseille, France.

Gérard Friedlander (G)

Department of Physiology, Functional Renal Explorations Department, AP-HP (Public Assistance Hospitals of Paris), Georges Pompidou European Hospital, Paris Descartes University, Paris, France.
INSERM U1151, Paris, France.

Olivier Traxer (O)

Department of Urology, AP-HP, Tenon Hospital, Pierre and Marie Curie University, Paris, France.

Bertrand Knebelmann (B)

Department of Nephrology, AP-HP, Necker Hospital for Sick Children, Paris Descartes University, Medicine, Paris, France.

Marie Courbebaisse (M)

Department of Physiology, Functional Renal Explorations Department, AP-HP (Public Assistance Hospitals of Paris), Georges Pompidou European Hospital, Paris Descartes University, Paris, France.
INSERM U1151, Paris, France.

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