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- Title
Kidney tubular injury induced by valproic acid: systematic literature review.
- Authors
Anguissola, Giulia; Leu, Dennis; Simonetti, Giacomo D.; Simonetti, Barbara Goeggel; Lava, Sebastiano A. G.; Milani, Gregorio P.; Bianchetti, Mario G.; Scoglio, Martin
- Abstract
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.
- Subjects
META-analysis; GLYCOSURIA; BIOPSY; MEDICAL information storage &; retrieval systems; SYSTEMATIC reviews; MIGRAINE; KIDNEY tubules; NATIONAL Library of Medicine (U.S.); METABOLIC disorders; RESEARCH funding; PROTEINURIA; HYPOPHOSPHATEMIA; HYPOCALCEMIA; HYPOKALEMIA; FANCONI syndrome; VALPROIC acid; BIPOLAR disorder; DISEASE risk factors
- Publication
Pediatric Nephrology, 2023, Vol 38, Issue 6, p1725
- ISSN
0931-041X
- Publication type
Article
- DOI
10.1007/s00467-022-05869-8