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

Prot-Bertoye, Caroline; Lebbah, Saïd; Daudon, Michel; Tostivint, Isabelle; Jais, Jean-Philippe; Lillo-Le Louët, Agnés; Pontoizeau, Clément; Cochat, Pierre; Bataille, Pierre; Bridoux, Franck; Brignon, Pierre; Choquenet, Christian; Combe, Christian; Conort, Pierre; Decramer, Stéphane; Doré, Bertrand; Dussol, Bertrand; Essig, Marie; Frimat, Marie; Gaunez, Nicolas; Joly, Dominique; Le Toquin-Bernard, Sophie; Méjean, Arnaud; Meria, Paul; Morin, Denis; N'Guyen, Hung V; Normand, Michel; Pietak, Michel; Ronco, Pierre; Saussine, Christian; Tsimaratos, Michel; Friedlander, Gérard; Traxer, Olivier; Knebelmann, Bertrand; Courbebaisse, Marie.
BJU Int; 2019 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-30801923

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 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.
Selo DaSilva