topiramate and Urinary-Calculi

Kidney stones are increasing in the pediatric and adult populations; similarly osteoporosis is increasingly recognized in children. While kidney stone formers are known to suffer from low bone density, metabolic bone patients have not been considered a high risk population for kidney stones. Retrospective chart review of Nationwide Children's Hospital Metabolic Bone Clinic patients from October 2009-2013. Patients were identified by ICD 9 codes for osteoporosis, osteopenia, low bone density and kidney stones. Only patients with radiologic evidence of both diseases were included.Twenty-six of 889 patients met criteria; this is equivalent to an incidence of 30 per 100,000 patients. Osteoporosis was the most frequent bone diagnosis. Males were the majority (68%). Most common secondary diagnoses: seizure (52%) and cerebral palsy (44%).. calcium (48%), vitamin D (40%), bisphosphonates (48%). The majority (75%) were non-ambulatory. Most frequent lithogenic medications: Topiramate (42%) and corticosteroids (27%). This is one of the first studies to consider metabolic bone patients as high risk for urinary stone disease. We found a higher rate of kidney stones in pediatric metabolic bone patients compared to data available for the general pediatric kidney stone population. The most common risk factor for bone and stone disease was nonambulatory status. Males were more frequently affected than females; this is the reverse of general adolescent kidney stone population. The predominance of cerebral palsy and seizure patients can be attributed to their frequency of non-ambulatory status and lithogenic medications such as Topiramate.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Bone Density; Bone Diseases, Metabolic; Child; Female; Fructose; Humans; Incidence; Male; Retrospective Studies; Risk Factors; Sex Factors; Topiramate; Urinary Calculi; Young Adult

To provide prospective, longitudinal evidence of the effects of topiramate, an antiepileptic medication prescribed for migraine headaches, on stone-risk factors, specifically as pertaining to dosing and rapidity of onset.. Patients scheduled to begin topiramate therapy were recruited to participate in the study. Enrolled subjects collected a pretreatment 24-hour urine specimen with subsequent 24-hour urine specimens collected 5 days after beginning topiramate and after each dose escalation.. Six subjects enrolled in the study, 4 of whom completed two additional urine collections after initiating topiramate therapy. The pretreatment urine collections of the 4 subjects with additional samples revealed the following mean (range) values: urine volume 1550 (1300 to 1900) mL, pH 6.75 (6 to 7), creatinine 1436.3 (1196 to 1590) mg/day, calcium 305.8 (209 to 423) mg/day, and citrate 606.8 (290 to 860) mg/day. Five days after initiation of topiramate, mean calcium decreased to 211.5 mg/day (31% decrease), and mean citrate decreased to 398 (99 to 804) mg/day, an average decrease of 39.8% (6.5% to 65.9%) per patient. After a dose escalation, calcium increased to 286.8 mg/day, but citrate decreased further to 209 (119 to 353) mg/day, an average decrease of 65.1% (57.9% to 71.7%) per patient from pretreatment levels.. Topiramate therapy induces a profound decrease in urinary citrate levels, equivalent to the levels seen in distal renal tubular acidosis. Citrate levels decrease quickly after the start of topiramate therapy and continue to decrease with escalating doses.

Topics: Adult; Anticonvulsants; Calcium; Citric Acid; Creatinine; Dose-Response Relationship, Drug; Female; Fructose; Humans; Middle Aged; Migraine Disorders; Topiramate; Urinary Calculi

Topiramate (TPM) is widely used as add-on therapy for epilepsy. TPM inhibits carbonic anhydrase, which may result in metabolic acidosis from decreased serum bicarbonate. The ketogenic diet (KGD) predisposes patients to metabolic acidosis, especially during induction. In children with refractory epilepsy, cotreatment with TPM and KGD may be considered, but special attention should be paid to the combined risks for metabolic acidosis and nephrolithiasis. We report our experience in 14 children cotreated with TPM and the KGD.. Medical records of 14 children cotreated with the KGD and TPM for medically refractory epilepsy were reviewed retrospectively. Bicarbonate levels were analyzed and correlated with clinical profiles, including duration of cotreatment, TPM dose, KGD ratio, and seizure control.. Nine children had a <20% decrease in bicarbonate levels, from 5.3 to 12.3 mEq/L (mean, 7.6 mEq/L). Cotreatment was continued in all patients for duration of 33 to 544 days (seven had remained on cotreatment at the end of the study period), although two children required bicarbonate supplements to continue the KGD. No patient had nephrolithiasis.. Although a large decrease in bicarbonate level occurred in the majority of children, the decrease appeared mostly at the time of KGD induction when added to prior TPM therapy. Bicarbonate levels should be monitored carefully with TPM and KGD cotreatment, and bicarbonate supplements given when symptomatic.

Topics: Acidosis; Adolescent; Age Factors; Anticonvulsants; Bicarbonates; Child; Child, Preschool; Combined Modality Therapy; Epilepsy; Female; Fructose; Humans; Infant; Ketosis; Male; Retrospective Studies; Topiramate; Treatment Outcome; Urinary Calculi