Teriflunomide‐associated urolithiasis: a new adverse reaction explained by its uricosuric effect

• Published in: Fundamental & clinical pharmacology Vol. 35; no. 5; pp. 930 - 932
• Main Authors: Largeau, Bérenger, Béra, Frédéric, Vannier, Jacques, Jonville‐Béra, Annie‐Pierre
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.10.2021
• Subjects: Calculi; Citric acid; Clinical trials; Computed tomography; Crotonates - adverse effects; Diagnosis, Differential; Disease control; Humans; Hydroxybutyrates - adverse effects; Immunosuppressive Agents - adverse effects; Kidney stones; Lithiasis; Lithotripsy; Male; Middle Aged; Morphology; Multiple sclerosis; Multiple Sclerosis - drug therapy; Nephrolithiasis; Nitriles - adverse effects; Patients; Pharmacology; pharmacovigilance; Potassium; Reabsorption; Risk analysis; Risk factors; teriflunomide; Toluidines - adverse effects; Uric acid; uricosuric agents; Urolithiasis; Urolithiasis - chemically induced; Urolithiasis - diagnosis; teriflunomide; Nephrolithiasis; pharmacovigilance; uricosuric agents; uric acid; multiple sclerosis
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12647

In clinical trials, few investigations have been conducted to determine the mechanism involved in teriflunomide‐associated kidney stone formation. We report the first case of recurrent teriflunomide‐induced uric acid urolithiasis. A 55‐year‐old man with relapsing‐remitting multiple sclerosis experienced three occurrences of urolithiasis several months after the initiation of teriflunomide. While serum uric acid remained stable at 280 mmol/L, 24‐h urine uric acid was increased to 2195 mmol/24 h. For the third episode, computed tomography showed three bladder stones and one stone in the right calyceal group. Endovesical lithotripsy was used to extract four orange‐colored stones of more than 20 mm. Stone analysis exhibited morphology subtype IIIb with 100% of anhydrous uric acid. Given the disease control, teriflunomide was continued. After urinary alkalinization by potassium citrate, the patient remained asymptomatic at 18 months follow‐up. An inhibitory effect of dihydroorotate and/or teriflunomide on urate tubular reabsorption could explain teriflunomide‐associated uric acid urolithiasis. This case in a patient without risk factors suggests that multiple sclerosis patients may be at greater risk of forming uric acid urinary stones when taking teriflunomide. Alkalinization of the urine may reduce the risk of recurrence, allowing further treatment with teriflunomide.