topiramate and Urolithiasis

Topiramate is an effective anti-epileptic drug and can be associated with increased risk for urolithiasis because of its effects on acid-base profile. Evidences that supported an association of topiramate and urolithiasis were limited to case reports or series. We investigated the association of topiramate and urolithiasis in a nationwide population-based cohort study.. We analyzed 1377 patients receiving topiramate and 1377 age- and gender-matched control patients (not receiving topiramate) between 1997 and 2008. The risk of urolithiasis was analyzed using Kaplan-Meier analysis, followed by Cox proportional hazard regression.. Of the 2754 patients, 79 (2.9%) patients developed urolithiasis in two (interquartile range: 1.2-4.2) years. The proportion of patients who developed urolithiasis in the patients receiving topiramate was not different from that of the control patients (p=0.138, χ(2) test). The urolithiasis free survival was not different between the patients receiving topiramate and the control patients (p=0.168) in Cox proportional hazard regression. The duration and total dosage of topiramate were not associated with risk of urolithiasis in patients receiving topiramate (p=0.482 and p=0.751).. Topiramate may not increase the risk of urolithiasis. The duration and the total dosage of topiramate were not associated with urolithiasis risks.

Topics: Adult; Age Factors; Anticonvulsants; Arthritis, Gouty; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Fructose; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Proportional Hazards Models; Sex Factors; Taiwan; Time Factors; Topiramate; Urolithiasis

Pediatric patients who are fed primarily via gastrostomy tube (G-tube) may be at increased risk for urolithiasis, but no studies have specifically examined risk factors for stones in this population. We aimed to determine clinical differences between G-tube fed (GTF) patients with and without stones, in hopes of identifying modifiable factors associated with increased risk of urolithiasis.. We conducted a retrospective case-control study, matching GTF patients with urolithiasis (cases) to GTF children without urolithiasis (controls) based on age (±1 year) and gender. Bivariate comparisons and matched logistic regression modeling were used to determine the unadjusted and adjusted associations between relevant clinical factors and urolithiasis.. Forty-one cases and 80 matched controls (mean age 12.0 ± 6.5 years) were included. On bivariate analysis, factors associated with stone formation included: white race, urinary tract infection (UTI), topiramate administration, vitamin D use, malabsorption, dehydration, 2-year duration with G-tube, and whether goal free water intake was documented in the patient chart. On regression analysis, the following factors remained significant: topiramate administration (odds ratio [OR]: 6.58 [95% confidence interval (CI): 1.76-24.59]), UTI (OR: 7.70 [95% CI: 1.59-37.17]), and <2 years with a G-tube (OR: 8.78 [95% CI: 1.27-52.50]).. Our findings provide a preliminary risk profile for the development of urolithiasis in GTF children. Important associations identified include UTI, topiramate administration, and shorter G-tube duration, which may reflect subclinical chronic dehydration. Of these, topiramate use represents the most promising target for risk reduction.

Topics: Adolescent; Age Factors; Anticonvulsants; Case-Control Studies; Child; Child, Preschool; Chronic Disease; Cohort Studies; Enteral Nutrition; Female; Fructose; Gastrostomy; Humans; Male; Retrospective Studies; Risk Factors; Sex Factors; Topiramate; Urolithiasis

To determine the effect of topiramate (TPM) on 24-hour urinary parameters in stone formers. TPM is frequently prescribed for epilepsy, migraine headaches, and eating disorders.. Twelve stone-forming patients who were prescribed TPM between 2003 and 2008 were identified from our stone clinic. Of these, 9 patients (M:F, 4:5; 47 ± 7.1 y SEM) underwent a full metabolic workup (UroRisk Diagnostic Profile, Mission Pharmacal Reference Laboratory, San Antonio, TX) and were included for review. Parameters examined include duration and dose of the drug, 24-hour urine calcium, oxalate, citrate, volume, and pH. If available, urine parameters before taking TPM and after either stopping it or receiving potassium citrate therapy were recorded.. Mean duration taking TPM was 17 ± 5.2 months (range, 3-43) months and median dose was 100 mg (range, 25-300) daily. Mean urinary citrate excretion was 136 ± 29 mg/d (range, 30-280) in all patients taking the drug. Three patients were either taken off the drug or placed on potassium citrate, resulting in a mean increase in urinary citrate of 374 mg/d (65%). TPM dosage correlated inversely with urinary citrate excretion (Pearson correlation coefficient = -0.73).. TPM therapy is associated with a profound, dose-dependent decrease in urinary citrate, leading to increased lithogenic risk. This hypocitraturia persists even after long periods of taking the drug. Urologists should be aware of the stone-forming risk of this medication. Strategies to maintain therapeutic urinary citrate concentrations in patients on TPM are needed.

Topics: Anticonvulsants; Citric Acid; Female; Fructose; Humans; Kidney Calculi; Male; Metabolic Diseases; Retrospective Studies; Topiramate; Urolithiasis

Topics: Carbonic Anhydrase Inhibitors; Fructose; Humans; Migraine Disorders; Risk Factors; Topiramate; Urolithiasis

Topiramate is an antiepileptic medicine that has been used adjunctively in the treatment of refractory seizures in Japan since 2007. Topiramate has been shown to inhibit specific carbonic anhydrase activity in the kidney and may induce a distal type of renal tubular acidosis. Case 1 : A 22-year-old male was referred to our hospital after complaining of left flank pain. He developed a seizure disorder and had been using topiramate for 4 months. Drip infusion pyelography showed a left ureteral stone. Case 2 : A 7-year-old boy presented with gross hematuria. He developed West syndrome and had been using topiramate for 6 months. A computed tomographic scan showed a right kidney stone.

Topics: Anticonvulsants; Child; Epilepsy; Fructose; Humans; Infant; Kidney Calculi; Male; Spasms, Infantile; Topiramate; Urolithiasis; Young Adult

Children with refractory epilepsy who are co-treated with the ketogenic diet (KD) and carbonic anhydrase inhibitor (CA-I) anti-epileptic medications including topiramate (TPM) and zonisamide (ZNS) are at risk for urolithiasis. Retrospective chart review of all children treated with ketogenic therapy at our institution was performed in order to estimate the minimal risk of developing signs or symptoms of stone disease. Children (N=93) were classified into groups according to KD+/-CA-I co-therapy. Fourteen patients had occult hematuria or worse, including 6 with radiologically confirmed stones. Three of 6 calculi developed in the KD+ZNS group of 17 patients who were co-treated for a cumulative total of 97 months (3.1 stones per 100 patient months). One confirmed stone was in the KD+TPM group of 22 children who were co-treated for a cumulative total of 263 months (0.4 stones per 100 patient months). All six patients had at least three of five biochemical risk factors including metabolic acidosis, concentrated urine, acid urine, hypercalciuria and hypocitraturia. Standard of care interventions to minimize hypercalciuria, crystalluria and stone formation used routinely by pediatric nephrologists should also be prescribed by neurologists treating patients with combination anti-epileptic therapy. Non-fasting KD initiation, fluid liberalization, potassium citrate prophylaxis as well as regular laboratory surveillance are indicated in this high risk population.

Topics: Anticonvulsants; Child; Child, Preschool; Combined Modality Therapy; Diet, Ketogenic; Epilepsy; Female; Fructose; Humans; Infant; Isoxazoles; Male; Retrospective Studies; Risk Factors; Topiramate; Urolithiasis; Zonisamide

Urolithiasis occurs infrequently in the pediatric population, where metabolic factors play a primary role in the pathogenesis of stone formation. Topiramate, an antiepileptic drug, is associated with a kidney stone in 1.5% of patients in published clinical trials. However, this risk may be much higher in certain populations with multiple preexisting risk factors. We performed a retrospective review of all nonambulatory and neurologically impaired individuals in a long-term care facility. Three groups were involved: those with no exposure to antiepileptic drugs, those on antiepileptic drugs other than topiramate, and those who had been treated with topiramate. Thirteen of 24 (54%) individuals on topiramate monotherapy or polytherapy developed clinical evidence of urolithiasis after a mean duration of 36.4 months. Our results suggest that nonambulatory and neurologically impaired individuals in a long-term care facility appear to be at higher risk of developing kidney stones with topiramate than previously reported.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Citrates; Developmental Disabilities; Female; Fructose; Humans; Intellectual Disability; Male; Middle Aged; Retrospective Studies; Topiramate; Urolithiasis; Young Adult