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

Abstract

OBJECTIVE:

To evaluate medical treatments, in terms of adverse events (AEs) and therapeutic goals, in a large series of patients with cystinuria.

PATIENTS AND METHODS:

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.

RESULTS:

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).

CONCLUSION:

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.

• Authors: Caroline Prot-Bertoye, Saïd Lebbah, Michel Daudon, Isabelle Tostivint, Jean-Philippe Jais, Agnés Lillo-Le Louët, Clément Pontoizeau, Pierre Cochat, Pierre Bataille, Franck Bridoux, Pierre Brignon, Christian Choquenet, Christian Combe, Pierre Conort, Stéphane Decramer, Bertrand Doré, Bertrand Dussol, Marie Essig, Marie Frimat, Nicolas Gaunez, Dominique Joly, Sophie Le Toquin-Bernard, Arnaud Méjean, Paul Meria, Denis Morin, Hung V N'Guyen, Michel Normand, Michel Pietak, Pierre Ronco, Christian Saussine, Michel Tsimaratos, Gérard Friedlander, Olivier Traxer, Bertrand Knebelmann, Marie Courbebaisse, French Cystinuria Group
• Journal: BJU international (BJU Int) Vol. 124 Issue 5 Pg. 849-861 (11 2019) ISSN: 1464-410X [Electronic] England
• PMID: 30801923 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.

Chemical References

• Sodium Bicarbonate
• Tiopronin
• Penicillamine

Topics

• Adolescent
• Adult
• Aged
• Child
• Child, Preschool
• Cystinuria (drug therapy, prevention & control)
• Drug-Related Side Effects and Adverse Reactions
• Female
• France
• Humans
• Hydrogen-Ion Concentration
• Infant
• Male
• Middle Aged
• Penicillamine (adverse effects, therapeutic use)
• Retrospective Studies
• Sodium Bicarbonate (adverse effects, therapeutic use)
• Tiopronin (adverse effects, therapeutic use)
• Treatment Outcome
• Urinalysis
• Young Adult