topiramate and Kidney-Calculi

Topics: Adult; Anticonvulsants; Female; Fructose; Humans; Isoxazoles; Kidney Calculi; Migraine Disorders; Pseudotumor Cerebri; Topiramate; Zonisamide

The use of topiramate, which is prescribed for the management of epilepsy, for migraine headache prophylaxis and as a weight-loss agent, has been associated with the development of metabolic acidosis, hypokalaemia and renal stone disease. We systematically reviewed all the literature.. The systematic review of the literature was realized using the principles underlying the UK Economic and Social Research Council guidance on the conduct of narrative synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.. Fourty-seven reports published between 1996 and 2013 were retained for the final analysis. Five case-control studies and six longitudinal studies addressed the effect of topiramate on acid-base and potassium balance. A significant tendency towards mild-to-moderate hyperchloraemic metabolic acidosis (with bicarbonate ≤21.0 mmol l(-1) in approximately every third case) and mild hypokalaemia (with potassium ≤3.5 mmol l(-1) in 10% of the cases) was noted on treatment with topiramate, which was similar in children and adults. A single study observed that topiramate causes mild hyperuricaemia in male adults. A tendency towards hypocitraturia, a recognized promoter of renal stone formation, was noted in all patients on topiramate.. Increasing evidence supports the use of topiramate. Topiramate is generally well tolerated, and serious adverse events are rare. Nonetheless, the present systematic review of the literature indicates that its use is linked with the development of acidosis, hypokalaemia, hyperuricaemia and hypocitraturia.

Topics: Acidosis; Female; Fructose; Humans; Hypokalemia; Kidney Calculi; Male; Topiramate

Topiramate (TPM) is a neuromodulatory agent that was initially approved as an antiepileptic drug and is increasingly used in the treatment of a number of neurological and metabolic disorders. Among its various pharmacological actions, TPM has been shown to inhibit the activity of specific carbonic anhydrase enzymes in the kidney. This action is associated with the development of metabolic acidosis, hypocitraturia, hypercalciuria and elevated urine pH, leading to an increased risk of kidney stone disease. Despite the cautionary note in the package insert of TPM, the extent of these complications has not been fully explored. Few prescribing physicians are aware of these complications, underscoring the need for improved surveillance. Because the drug is among the most frequently prescribed agents in the US, more controlled studies are required to determine the prevalence of kidney stone disease among TPM users, and the optimal approach to prevent and treat nephrolithiasis in these individuals.

Topics: Animals; Calcium Phosphates; Fructose; Humans; Kidney Calculi; Risk Factors; Topiramate

To date, 1,809 individuals have been exposed to topiramate (TPM), primarily adults with partial-onset seizures. Of this total, 665 patients have been treated for more than 1 year, 177 for more than 3 years, and 67 for more than 5 years. The profile of treatment-emergent adverse reactions (TEAEs) observed with TPM at various dosages is based primarily on data from five double-blind, placebo-controlled trials in which 360 patients received TPM at target doses of 200-1,000 mg/day. Long-term safety is assessed on the basis of 1,001 patients treated with TPM in controlled and open trials for up to 5.3 years. Most of the commonly reported TEAEs were related to the central nervous system and were observed with greater frequency at dosages above the 200-600-mg/day range found to be optimal in dose ranging trials. Nephrolithiasis not requiring surgery was seen in 1.5% of patients, and mild, dose-related weight loss was associated with TPM therapy. No clinically significant treatment-related abnormalities were observed in clinical laboratory parameters or in neurologic, electrocardiographic, ophthalmologic, or audiologic tests.

Topics: Adult; Anticonvulsants; Controlled Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Fructose; Humans; Incidence; Kidney Calculi; Male; Middle Aged; Multicenter Studies as Topic; Topiramate; Treatment Outcome; Weight Loss

To determine the prevalence of renal calculi in patients treated with zonisamide during randomized, controlled and open-label clinical trials, and from post-marketing surveillance data.. Reports of renal calculi from four placebo-controlled double-blind trials of zonisamide, their long-term open-label treatment extension phases, and the US/European zonisamide clinical trial programme were reviewed. One double-blind study and its extension included routine ultrasound screening to identify asymptomatic calculi. Post-marketing surveillance data were also investigated, as was concomitant treatment with topiramate.. No symptomatic renal calculi were reported during four randomized double-blind, placebo-controlled trials involving 848 subjects (including 498 zonisamide recipients) treated for up to 3 months. In long-term extension studies with treatment for up to 24 months, symptomatic renal calculi were reported in 9/626 (1.4%) patients. Pooled safety data from all US/European clinical trials identified 15/1296 (1.2%) patients with symptomatic renal calculi during treatment for up to 8.7 years. Post-marketing surveillance revealed nine cases from 59 667 patient-years of exposure in the USA, and 14 from 709 294 patient-years of exposure in Japan; only one case occurred during concomitant topiramate and zonisamide treatment. No imbalance in electrolyte levels was found from 35 patients receiving such co-treatment in clinical trials.. The available data suggest that the risk of developing renal calculi during zonisamide treatment is low. Data are insufficient to determine whether concomitant treatment with topiramate increases the risk of renal stones.

Topics: Adolescent; Adult; Anticonvulsants; Child; Double-Blind Method; Epilepsy; Female; Fructose; Humans; Isoxazoles; Kidney Calculi; Male; Middle Aged; Placebos; Product Surveillance, Postmarketing; Topiramate; Ultrasonography; Zonisamide

Topiramate is a novel neuromodulatory agent commonly prescribed for the treatment of seizure disorders and for migraine headache prophylaxis. Calcium phosphate kidney stones have been observed with topiramate treatment, but a comprehensive elucidation of stone-risk profile was not reported previously. This study explores the relationship between topiramate treatment and propensity for kidney stone formation.. Thirty-two topiramate-treated subjects and 50 healthy volunteers participated in a cross-sectional study in which serum chemistry test and 24-hour urine collection results were evaluated for stone risk. Furthermore, a short-term longitudinal study was conducted in 7 patients to assess stone risk before and 3 months after topiramate treatment.. Serum bicarbonate levels were lower with topiramate treatment. Urinary pH, urinary bicarbonate excretion, and fractional excretion of bicarbonate increased, whereas urinary citrate excretion was significantly lower (737 +/- 329 versus 278 +/- 226 mg/d; P < 0.001). Net acid excretion did not change. The relative saturation ratio for brushite increased with topiramate treatment (3.14 +/- 1.69 versus 1.27 +/- 1.26; P < 0.001) because of urinary alkalinization and decreased urinary citrate levels. Urinary saturation of undissociated uric acid decreased (41 +/- 52 versus 76 +/- 60 mg/d; P < 0.001).. Treatment with topiramate causes systemic metabolic acidosis, markedly lower urinary citrate excretion, and increased urinary pH. These changes increase the propensity to form calcium phosphate stones.

Topics: Acid-Base Equilibrium; Acidosis; Adult; Bicarbonates; Calcium Phosphates; Citrates; Cross-Sectional Studies; Female; Fructose; Humans; Hydrogen-Ion Concentration; Kidney Calculi; Longitudinal Studies; Male; Middle Aged; Neuroprotective Agents; Topiramate

To understand the metabolic disturbances of stone formers currently taking topiramate and to examine the reversibility of these disturbances with cessation of the medication.. All progress notes written by 5 endourologists from a single academic center were retrospectively reviewed from January 2010 to July 2020 containing the words "topiramate" or "topamax." Inclusion criteria were age >18 and presence of either a 24-hour urine sample or stone analysis while on topiramate. In addition, a subgroup of 18 patients with 24-hour urine samples before and after stopping topiramate were identified.. A total of 93 patients were identified and included for final analysis. Twenty-four hour urine samples were available in 67 patients and showed mean citrate excretion of 331 ± 322 mg/d, mean pH of 6.6 ± 0.5, and mean calcium phosphate supersaturation of 1.9 ± 1.1. In the subgroup analysis urinary citrate excretion increased from 225 mg/d to 614 mg/d (P <.01) and pH decreased from 6.59 ± 0.54 to 6.33 ± 0.47 (P = .06) after stopping topiramate. In addition, 114 stone events occurred in 73 distinct patients, with 50% of stones either pure or majority (≥50%) calcium phosphate by composition.. Hypocitraturia and elevated pH is seen during topiramate use with resultant higher rate of calcium phosphate stone formation compared to the general population. Stopping topiramate leads to significant increase in citrate excretion and normalization of pH. These metabolic disturbances appear to be reversible with medication cessation.

Topics: Calcium; Calcium Phosphates; Citrates; Citric Acid; Humans; Kidney Calculi; Retrospective Studies; Topiramate

Isolated hyperglycinuria is a rare disorder that is associated with osteoporosis and renal calculi. We report findings in a middle-aged, black woman who presented for renal function evaluation with a history of transient hypobicarbonataemia associated with topiramate therapy. She displayed the full triad of high urinary glycine, early-onset osteopenia despite normal reproductive hormones, and renal calculus with high urinary oxalate, phosphate and uric acid. Parathyroid hormone and fibroblast growth factor 23 were both normal. Formal genetic testing did not reveal mutations in SLC6A20, SLC6A18, SLC6A19, SLC36A2, the known genes associated with glycinuria; however, black individuals are poorly represented in the genetic databases. It may well be that otherwise unidentified mutations may be present or that topiramate may result in a lingering proximal tubule defect even after cessation of the drug.

Topics: Amino Acid Metabolism, Inborn Errors; Female; Humans; Kidney Calculi; Membrane Transport Proteins; Middle Aged; Parathyroid Hormone; Topiramate; Uric Acid

This study was aimed to assess the accurate incidence of renal stones in severely disabled children treated with topiramate (TPM).. We reviewed the medical records of severely disabled children with epilepsy under 15 years old who underwent radiological examinations to investigate urinary stones. The study enrolled 26 patients who were divided into two groups. One group had been treated with TPM for at least 1 year and the other had not been treated with TPM, zonisamide, acetazolamide, or other diuretic drugs. We collected parameters from the medical records and compared the groups.. There is a high incidence of renal stone formation in severely disabled children treated with TPM.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Disabled Children; Epilepsy; Female; Humans; Incidence; Kidney Calculi; Male; Retrospective Studies; Severity of Illness Index; Topiramate

The aim of this study is to present a case of 44 years old woman with topiramate induced metabolic acidosis and kidney stones.. The laboratory features of topiramate caused renal tubular acidosis in blood and urine during topiramate treatment, with correction of metabolic acidosis by potassium citrate, and after topiramate withdrawal are presented. Differential diagnosis of all possible causes of metabolic acidosis is discussed.. This study has shown that long-term topiramate administration could induce metabolic acidosis and consequently urholithiasis. Thus, we could recommend testing blood acid base balance, urinary pH and citrates in patients taking topiramate and suffering from kidney stones.

Topics: Acidosis; Adult; Anticonvulsants; Female; Fructose; Humans; Kidney Calculi; Migraine Disorders; Topiramate; Withholding Treatment

Topics: Adolescent; Anticonvulsants; Child; Child Health; Child, Preschool; Epilepsy; Female; Hong Kong; Humans; Infant; Kidney Calculi; Male; Retrospective Studies; Topiramate

The aims of this study were to assess (1) the magnitude and temporality of decreased urinary citrate excretion in patients just starting topiramate and (2) the effect of alkali replacement on topiramate-induced hypocitraturia.. Study 1 was a prospective, non-intervention study in which patients starting topiramate for headache remediation provided pre- and post-topiramate 24 h urine collections for measurement of urine citrate. Study 2 was a clinical comparative effectiveness study in which patients reporting to our stone clinic for kidney stones and who were treated with topiramate were prescribed alkali therapy. Pre- and post-alkali 24 h urinary citrate excretion was compared.. Data for 12 and 22 patients (studies 1 and 2 respectively) were evaluated. After starting topiramate, urinary citrate excretion dropped significantly by 30 days (P = 0.016) and 62% of patients had hypocitraturia (citrate <320 mg day(-1) ). At 60 days, urine citrate was even lower than at baseline (P = 0.0032) and 86% of patients had developed hypocitraturia. After starting alkali, urine citrate increased in stone-forming patients on topiramate (198 ± 120 to 408 ± 274 mg day(-1) ; P = 0.042 for difference). 85% of patients were hypocitraturic on topiramate alone vs. 40% after adding alkali. The increase in urinary citrate was greater in patients provided ≥ 90 mEq potassium citrate.. Our study is the first to provide clinical evidence that alkali therapy can raise urinary citrate excretion in patients who form kidney stones while being treated with topiramate. Clinicians should consider alkali therapy for reducing the kidney stone risk of patients benefitting from topiramate treatment for migraine headaches or other conditions.

Topics: Adult; Alkalies; Citric Acid; Female; Fructose; Humans; Kidney Calculi; Male; Middle Aged; Migraine Disorders; Potassium Citrate; Prospective Studies; Topiramate

Topiramate is an approved drug to treat seizures, but its indications have been extended to other diseases of the nervous system and as an adjuvant to chronic pain. We present four cases of topiramate-induced nephrolithiasis from 2006-2012 in women whose treatment was prescribed for pain control and as a mood stabilizer at doses of 250-300 mg/day. In two cases, the lithiasis was caused by calcium phosphate (patite) and in the other two cases by oxalate and calcium phosphate. The most common metabolic alteration was an alkaline pH, followed by hypocitraturia. The drug was discontinued in two patient; it was reduced in one and was maintained in the fourth. An increase in fluid and potassium citrate intake was prescribed. In patients starting treatment with topiramate, an adequate control and prevention of nephrolithiasis should be performed due to the risk of mixed tubular acidosis and hypocitraturia. to the risk of mixed tubular acidosis and hypocitraturia.

Topics: Adult; Aged; Analgesics; Calcium Oxalate; Calcium Phosphates; Chronic Pain; Citric Acid; Female; Fructose; Humans; Hypercalciuria; Kidney Calculi; Middle Aged; Nephrolithiasis; Personality Disorders; Potassium Citrate; Psychotropic Drugs; Topiramate

Topiramate (TPM), an anti-epileptic drug with >4 million users, increases renal stones in adults. We screened outpatient TPM-treated children without history of stones to estimate the prevalence of renal stones and to characterize urine stone-risk profiles.. Children taking TPM ≥1 month underwent an interview, renal ultrasound, and spot urine testing in this prospective study. Normal spot urine values were defined as: calcium/creatinine ratio ≤0.20 mg/mg (>12 months) or ≤0.60 mg/mg (≤12 months), citrate/creatinine ratio >0.50 mg/mg, and pH ≤ 6.7.. Of 41 patients with average age of 9.2 years (range 0.5-18.7), mean TPM dose of 8.0 mg/kg/day (range 1.4-23.6), and mean treatment duration of 27 months (range 1-112), two (4.9%) had renal stones. The majority of children taking TPM had lithogenic abnormalities on spot urine testing, including 21 (51%) with hypercalciuria, 38 (93%) with hypocitraturia, and 28 (68%) with pH ≥ 6.7. Hypercalciuria and hypocitraturia were independent of TPM dose and duration; urine pH increased with dose. 24-h urine parameters improved in 1 stone-former once TPM was weaned.. Asymptomatic stones were found in 2/41 (4.8%) children taking TPM. Risk factors for stones were present in the spot urine of most children, including hypocitraturia (93%) and hypercalciuria (51%), independent of TPM dose and duration. High urine pH, found in 68%, correlated with TPM dose. Pediatric specialists should be aware of increased risks for stones, hypercalciuria, hypocitraturia, and alkaline urine in children taking TPM.

Topics: Adolescent; Alkalies; Anticonvulsants; Calcium; Child; Child, Preschool; Citric Acid; Creatinine; Epilepsy; Female; Fructose; Humans; Hypercalciuria; Infant; Kidney Calculi; Male; Prevalence; Prospective Studies; Risk Factors; Topiramate

A 42-year old woman was referred for a metabolic evaluation after two episodes of kidney stones. Her laboratory results revealed a normal anion-gap metabolic acidosis, a marked hypocitraturia (0,6 mmol/24h; norm 1,6-4,5) and a urinary pH of 7,0 confirming renal tubular acidosis (RTA). We identified topiramate, our patient's medication for migraine, as the cause of the RTA. Topiramate, a carboanhydrase inhibitor leads to RTA of a mixed (proximal and distal) type and thus significantly increases the risk for kidney stones.

Topics: Acidosis; Acidosis, Renal Tubular; Adult; Anticonvulsants; Citric Acid; Diagnosis, Differential; Female; Fructose; Humans; Kidney Calculi; Migraine Disorders; Renal Colic; Topiramate

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

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

We ran this study to assess the incidence of nephrolithiasis in a group of children on topiramate (TPM) therapy for at least 1 year.. In this retrospective observational surveillance study, we reviewed the medical charts of children on TPM for at least 1 year seen at the pediatric neurology department during the period from 2005 to 2010 at King Fahad Medical City. Children with a normal baseline ultrasound report were included. Follow-up ultrasound reports after at least 1 year were collected. However, patients with any evidence of chronic illness or medications that may affect the kidney functions in addition to those who are not compliant with the prescribed dose were excluded. Family history of renal stones, symptoms suggestive of urologic disorders, and comorbidities were recorded.. Medical charts of 96 children on TPM with a mean age of 6.9 (±3.8) years were reviewed; 52 (54.2%) of the children were male. The follow-up ultrasound showed that five children (5.2%) had developed kidney stones. The occurrence of kidney stones was found in four female patients (80%) versus one male (20%) (p > 0.05).. Long-term use of TPM may result in increased incidence of asymptomatic kidney stones in the pediatric population. Hence, routine baseline and follow-up ultrasound of the urinary system should be recommended during the use of TPM in children.

Topics: Age Factors; Anticonvulsants; Child; Epilepsy; Female; Fructose; Humans; Incidence; Kaplan-Meier Estimate; Kidney Calculi; Male; Retrospective Studies; Sex Factors; Topiramate

The incidence of renal stone disease in patients receiving topiramate (Topamax) is 2-4 times that expected in the background population. This has been attributed to a weak carbonic anhydrase inhibitor effect, but published data are scant. Following three cases of renal stones in patients receiving topiramate, we evaluated biochemical risk for nephrolithiasis in eight further unselected patients. Most patients demonstrated inadequate urinary acidification and hypocitraturia; in some cases citrate was undetectable. Several patients also had other risk factors for nephrolithiasis, including increased urinary sodium, calcium and oxalate excretion. The biochemical changes induced by topiramate appear highly penetrant. Experience with this drug is relatively short-lived and it is being prescribed for long-term use in (often) relatively young patients. This report highlights the significantly increased metabolic risk of stone formation in patients receiving topiramate.

Topics: Adult; Calcium; Citric Acid; Epilepsies, Partial; Female; Fructose; Humans; Hydrogen-Ion Concentration; Kidney Calculi; Male; Middle Aged; Neuroprotective Agents; Oxalates; Risk Factors; Sodium; Topiramate

Topiramate is a recently developed antiepileptic medication that is becoming more widely prescribed because of its efficacy in treating refractory seizures. Urologists should be aware that this medication can cause metabolic acidosis in patients secondary to inhibition of carbonic anhydrase. In addition, a distal tubular acidification defect may result, thus impairing the normal compensatory drop in urine pH. These factors can lead to the development of calcium phosphate nephrolithiasis. We report the first two cases of topiramate-induced nephrolithiasis in the urologic literature.

Topics: Acids; Adult; Anticonvulsants; Female; Fructose; Humans; Kidney Calculi; Kidney Tubules; Topiramate

Topics: Anticonvulsants; Epilepsy; Female; Fructose; Humans; Kidney Calculi; Middle Aged; Topiramate