Fanconi Syndrome Secondary to Sodium Valproate Therapy: Experience and Literature Review

Álvarez, Daniela Andrea Sturla; Marcos, Elena Sánchez; Collantes, Carmen de Lucas; Extremera, Verónica Cantarín; Insuga, V. Soto; López, Cristina Aparicio

doi:10.1016/j.pediatrneurol.2022.03.001

Cited by 5 publications

(4 citation statements)

References 15 publications

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“…1 . For the overt kidney tubular injury study, we retained 28 articles [ 4 , 13 – 39 ] documenting individuals presenting with three or more laboratory features consistent with a kidney tubular injury. We also found 8 reports [ 40 – 47 ] addressing the possible existence of a pauci-symptomatic kidney tubular damage.…”

Section: Resultsmentioning

confidence: 99%

“…Three or more otherwise unexplained laboratory abnormalities consistent with an overt kidney tubular injury were found in 48 epileptic subjects on valproic acid for 7 months or more [ 4 , 13 – 39 ]. No patient on treatment with valproic acid because of a bipolar disorder or a migraine headache was reported to have otherwise unexplained laboratory abnormalities.…”

Section: Resultsmentioning

confidence: 99%

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Kidney tubular injury induced by valproic acid: systematic literature review

et al. 2023

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Background Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular injury. Methods We undertook a review of the literature to characterize the biochemical and histopathological features of the overt kidney tubular injury and to evaluate the possible existence of a pauci-symptomatic injury. The pre-registered review (CRD42022360357) was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were conducted in Excerpta Medica, the National Library of Medicine, and Web of Science. The gray literature was also considered. Results For the final analysis, we retained 36 articles: 28 case reports documented 48 individuals with epilepsy on valproic acid for 7 months or more and presenting with features consistent with an overt kidney tubular injury. The following disturbances were noted: hypophosphatemia (N = 46), normoglycemic glycosuria (N = 46), total proteinuria (N = 45), metabolic acidosis (N = 36), hypouricemia (N = 27), tubular proteinuria (N = 27), hypokalemia (N = 23), and hypocalcemia (N = 8). A biopsy, obtained in six cases, disclosed altered proximal tubular cells with giant and dysmorphic mitochondria. Eight case series addressed the existence of a pauci- or even asymptomatic kidney injury. In the reported 285 subjects on valproic acid for 7 months or more, an isolated tubular proteinuria, mostly N-acetyl-β-glucosaminidase, was often noted. Conclusions Valproic acid may induce an overt kidney tubular injury, which is associated with a proximal tubular mitochondrial toxicity. Treatment for 7 months or more is often associated with a pauci- or oligosymptomatic kidney tubular injury. Graphical abstract

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Kidney tubular injury induced by valproic acid: systematic literature review

et al. 2023

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“…Te prevalence rate of this disease in children is high, and most of them need to take antiepileptic drugs for a long time to control or prevent seizures [2]. Sodium valproate, as a broad-spectrum antiepileptic drug commonly used in the clinic, is the frstline therapeutic drug for the treatment of major seizures, minor seizures, and myoclonic seizures in children with epilepsy, and it has a remarkable curative efect [3,4]. However, the blood concentration of valproate should be maintained within the efective therapeutic range (50-100 μg/mL).…”

Section: Introductionmentioning

confidence: 99%

Development and Internal Validation of Machine Learning Algorithms for Determining Sodium Valproate Concentrations below the Standard Level Using a Risk Prediction Model of Children with Epilepsy

Yao,

Zhao,

Wang

et al. 2023

Journal of Clinical Pharmacy and Therapeutics

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Background. There is a narrow therapeutic window for sodium valproate, and the blood concentration is too low to control epilepsy, while it is easy to poison the body if the concentration is too high. It is therefore necessary to monitor drug concentration reasonably in order to control epilepsy. The purpose of this study was to establish a model for predicting concentrations of sodium valproate below 50 μg/mL in children with epilepsy. Methods. The clinical data and biochemical examination results of children with epilepsy treated in the pediatric outpatient department of our hospital from June 2019 to March 2022 were retrospectively collected and divided into a development group and a validation group according to a patient ratio of 8 to 2. Five machine learning algorithms were used to identify the key variable factors, and a risk prediction model for sodium valproate blood concentrations lower than the standard concentration was established. The area under the curve (AUC), calibration curve, GiViTi calibration band, and clinical influence curve were used to evaluate the diagnostic efficacy and clinical application value of the model. Results. A total of 525 children with epilepsy were enrolled. In the development group, the random forest algorithm performed best in predicting that the blood concentration of sodium valproate was lower than the standard concentration, showing the highest AUC (1.00). Six factors were determined as a nomogram to predict the incidence of low concentrations. In the validation group and the development group, the calibration curve, GiViTi calibration band, and clinical influence curve all performed well in the evaluation of the diagnostic efficacy and clinical application value of the model. Conclusions. This finding highlights the importance of examining biochemical indices in patients when data regarding the blood concentration of sodium valproate are lacking.

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“…When it does occur in adults, it is usually associated with multiple myeloma or medications such as tenofovir. There are multiple case reports of valproic acid causing Fanconi syndrome in children usually after chronic exposure 3–9. But, in a recent PubMed literature search, valproic acid has been associated with Fanconi syndrome in adults in only one case report dating from 2011 10.…”

Section: Introductionmentioning

confidence: 99%

Valproic acid as an adjuvant analgesic: adult Fanconi syndrome

Maybach

Baro

Kachurka

et al. 2022

BMJ Support Palliat Care

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We report an 80-year-old woman who developed severe hypophosphataemia and elevated urinary phosphate levels while started on valproic acid. This occurred within 1–2 days of starting valproic acid. There are rare single-patient reports of the association of valproic acid with adult Fanconi syndrome. This generally occurs after long-term exposure to valproate. This is the first reported experience of Fanconi’s syndrome in an adult with acute exposure to valproic acid. Clinicians should be aware of the possible association.

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Fanconi Syndrome Secondary to Sodium Valproate Therapy: Experience and Literature Review

Cited by 5 publications

References 15 publications

Kidney tubular injury induced by valproic acid: systematic literature review

Kidney tubular injury induced by valproic acid: systematic literature review

Development and Internal Validation of Machine Learning Algorithms for Determining Sodium Valproate Concentrations below the Standard Level Using a Risk Prediction Model of Children with Epilepsy

Valproic acid as an adjuvant analgesic: adult Fanconi syndrome

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