Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium metabolism and its response to citrate were examined in 51 patients with glaucoma receiving carbonic anhydrase inhibitors (acetazolamide or methazolamide). Metabolic acidosis, hypocitraturia and increased incidence of nephrolithiasis were induced by both drugs. However, the acidosis was milder with methazolamide administration. Normocalciuria was observed in 29 patients and was shown to be a result of low filtered calcium. Renal hypercalciuria in 16 patients was associated with elevated parathyroid hormone but nephrogenic cyclic adenosine monophosphate remained within normal limits. Citrate in the form of potassium citrate (4.3 mmol.) and sodium citrate (4.0 mmol.) did not correct the metabolic acidosis or hypocitraturia but consistently decreased fasting and 24-hour urinary calcium excretion in patients with renal hypercalciuria. This event did not occur in patients with normocalciuria or absorptive hypercalciuria. These results suggest that a small amount of citrate could reverse renal hypercalciuria without correcting the metabolic acidosis.
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PMID:Calcium metabolism in acidotic patients induced by carbonic anhydrase inhibitors: responses to citrate. 201 6

We report a case of a 33 years old female with a history of paroxystic hemidystonia treated by acetazolamide, a carbonic anhydrase inhibitor (CAI), and who developed two years after the initiation of this treatment bilateral radio-opaque stones. Laboratory tests revealed a hyperchloremic acidosis, an elevated urinary pH, a hypercalciuria, a severe hypocitraturia and numerous granulations of amorphous carbonated calcium phosphates and brushite crystals on urinary microscopic examination, the whole suggests a diagnosis of acetazolamide-induced nephrolithiasis. We discuss in this article the lithogenetic process and the usual composition of the stones induced by CAI, and specific risk factors for developing drug-induced lithiasis which should be taken into consideration when prescribing long-term drug regimens.
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PMID:[Carbonic anhydrase inhibitors and calcium phosphate stones]. 1545 90

Chronic metabolic acidosis results in renal Ca2+ and Mg2+ wasting, whereas chronic metabolic alkalosis is known to exert the reverse effects. It was hypothesized that these adaptations are mediated at least in part by the renal Ca2+ and Mg2+ transport proteins. The aim of this study, therefore, was to determine the effect of systemic acid-base status on renal expression of the epithelial Ca2+ channel TRPV5, the Ca2+-binding protein calbindin-D28K, and the epithelial Mg2+ channel TRPM6 in relation to Ca2+ and Mg2+ excretion. Chronic metabolic acidosis that was induced by NH4Cl loading or administration of the carbonic anhydrase inhibitor acetazolamide for 6 d enhanced calciuresis accompanied by decreased renal TRPV5 and calbindin-D28K mRNA and protein abundance in wild-type mice. In contrast, metabolic acidosis did not affect Ca2+ excretion in TRPV5 knockout (TRPV5-/-) mice, in which active Ca2+ reabsorption is effectively abolished. This demonstrates that downregulation of renal Ca2+ transport proteins is responsible for the hypercalciuria. Conversely, chronic metabolic alkalosis that was induced by NaHCO3 administration for 6 d increased the expression of Ca2+ transport proteins accompanied by diminished urine Ca2+ excretion in wild-type mice. However, this Ca2+-sparing action persisted in TRPV5-/- mice, suggesting that additional mechanisms apart from upregulation of active Ca2+ transport contribute to the hypocalciuria. Furthermore, chronic metabolic acidosis decreased renal TRPM6 expression, increased Mg2+ excretion, and decreased serum Mg2+ concentration, whereas chronic metabolic alkalosis resulted in the exact opposite effects. In conclusion, these data suggest that regulation of Ca2+ and Mg2+ transport proteins contributes importantly to the effects of acid-base status on renal divalent handling.
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PMID:Acid-base status determines the renal expression of Ca2+ and Mg2+ transport proteins. 1642 Dec 27

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.
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PMID:Increased propensity for calcium phosphate kidney stones with topiramate use. 1787 42

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.
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PMID:Urolithiasis on the ketogenic diet with concurrent topiramate or zonisamide therapy. 2046 20

Topiramate is an anticonvulsant that is being increasingly used for a number of different off-label indications. Its inhibition of carbonic anhydrase isoenzymes can lead to metabolic acidosis, elevated urine pH, reduced urine citrate, and hypercalciuria, thereby creating a milieu that is ripe for calcium phosphate stone formation. In this review, we describe a case of topiramate-induced metabolic acidosis. We review the frequency of metabolic acidosis among children and adults, as well as the mechanism of hyperchloremic metabolic acidosis and renal tubular acidosis in topiramate users. Finally, we describe the long-term effects of topiramate-induced metabolic acidosis, including nephrolithiasis, nephrocalcinosis, and bone degradation. Patients who are prescribed topiramate should be carefully monitored for metabolic derangements, and they may benefit from alkali supplementation, or in extreme cases, discontinuation of the drug altogether.
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PMID:Topiramate and metabolic acidosis: an evolving story. 2882 86