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BJU Int. 2019 Nov;124(5):849-861. doi: 10.1111/bju.14721. Epub 2019 Mar 25.

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

Author information

1
Department of Physiology, Functional Renal Explorations Department, AP-HP (Public Assistance Hospitals of Paris), Georges Pompidou European Hospital, Paris Descartes University, Paris, France.
2
INSERM UMRS 1138, Paris, France.
3
Department of Biostatistics, AP-HP, Necker Hospital for Sick Children, Paris Descartes University, Medicine, Paris, France.
4
Department of Physiology, Functional Renal Explorations Department, AP-HP, Tenon Hospital Pierre and Marie Curie University, INSERM UMR S 1155, Paris, France.
5
Department of Nephrology, AP-HP, Pitié-Salpétrière Hospital, Paris, France.
6
Department of Biostatistics, AP-HP, Necker Hospital for Sick Children, Paris Descartes University, Paris, France.
7
Inserm UMRS 1138 team 22, Paris, France.
8
Department of Pharmacovigilance, AP-HP, Georges Pompidou European Hospital, Paris, France.
9
Functional Unit of Metabolomics, Functional Explorations Department, APHP, Necker Hospital for Sick Children, Paris Descartes University, Paris, France.
10
Department of Pediatrics, Hospices Civils de Lyon, Centre de Référence des Maladies Rénales Rares Néphrogones, Lyon, France.
11
Department of Nephrology, Boulogne-sur-Mer Hospital, Boulogne sur Mer, France.
12
Department of Neprhology, Poitiers University Hospital, Poitiers University, Poitiers, France.
13
Department of Nephrology, Pasteur Hospital, Colmar, France.
14
Department of Urology, Princesse Grace Hospital, Monaco, France.
15
Department of Nephrology, Bordeaux University Hospital, Bordeaux University, Bordeaux, France.
16
Department of Urology, AP-HP, Pitié-Salpétrière Hospital, Paris, France.
17
Department of Nephrology and Internal Medicine, Toulouse University Children Hospital, Toulouse, France.
18
INSERM U1048, Toulouse, France.
19
Department of Urology, Poitiers University Hospital, Poitiers University, Poitiers, France.
20
Department of Nephrology, AP-HM (Public Assistance Hospitals of Marseille), Conception Hospital, Aix-Marseille University, Marseille, France.
21
Department of Nephrology, Dialysis and Transplantation, Limoges University Hospital, Limoges University, Limoges, France.
22
INSERM UMR-S850, Limoges, France.
23
Department of Nephrology, Claude Huriez University Hospital, Lille, France.
24
Department of Urology, Niort Hospital, Niort, France.
25
Department of Nephrology, AP-HP, Necker Hospital for Sick Children, Paris Descartes University, Medicine, Paris, France.
26
Department of Urology, Private Saint-Martin Hospital, Caen, France.
27
Department of Urology, AP-HP, Georges Pompidou European Hospital, Paris Descartes University, Medicine, Paris, France.
28
Department of Urology, AP-HP, Saint-Louis Hospital, Paris, France.
29
Department of Pediatrics (Pediatric Nephrology and Diabetology), Montpellier University Hospital, Montpellier, France.
30
CNRS, UMR 5203-INSERM U661, Montpellier, France.
31
Department of Nephrology, Private Saint-Martin Hospital, Pessac, France.
32
Department of Urology, AP-HP, Georges Pompidou European Hospital, Paris, France.
33
Department of Nephrology and Dialysis, AP-HP, Tenon Hospital, Pierre and Marie Curie University, Paris, France.
34
INSERM Unit 702, Paris, France.
35
Department of Urology, Strasbourg University Hospital, Strasbourg University, Strasbourg, France.
36
Department of Pediatrics, AP-HM, La Timone Hospital, Aix-Marseille University, Marseille, France.
37
INSERM U1151, Paris, France.
38
Department of Urology, AP-HP, Tenon Hospital, Pierre and Marie Curie University, Paris, 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.

KEYWORDS:

D-penicillamine; cystinuria; potassium citrate; sodium bicarbonate; tiopronin

PMID:
30801923
DOI:
10.1111/bju.14721

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