Acetazolamide-induced nephrolithiasis: implications for neuromuscular disorders. Neurology 43:1105-1106

Neuromuscular Disease Center, University of Rochester School of Medicine and Dentistry, NY 14642.
Neurology (Impact Factor: 8.29). 07/1993; 43(6):1105-6. DOI: 10.1212/WNL.43.6.1105
Source: PubMed


Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use.

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    • "Only $ 50% of patients have a beneficial response (Matthews et al., 2011), and patients with HypoPP with NaV1.4 mutations may have worsening of symptoms on acetazolamide (Torres et al., 1981; Sternberg et al., 2001). Moreover, chronic administration of acetazolamide carries a 15% risk of developing nephrolithiasis (Tawil et al., 1993 ). Our comparative studies of acetazolamide and bumetanide in mouse models of HypoPP suggest bumetanide is as effective (Fig. 5) or may even be superior to acetazolamide (Fig. 3). "
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    ABSTRACT: Transient attacks of weakness in hypokalaemic periodic paralysis are caused by reduced fibre excitability from paradoxical depolarization of the resting potential in low potassium. Mutations of calcium channel and sodium channel genes have been identified as the underlying molecular defects that cause instability of the resting potential. Despite these scientific advances, therapeutic options remain limited. In a mouse model of hypokalaemic periodic paralysis from a sodium channel mutation (NaV1.4-R669H), we recently showed that inhibition of chloride influx with bumetanide reduced the susceptibility to attacks of weakness, in vitro. The R528H mutation in the calcium channel gene (CACNA1S encoding CaV1.1) is the most common cause of hypokalaemic periodic paralysis. We developed a CaV1.1-R528H knock-in mouse model of hypokalaemic periodic paralysis and show herein that bumetanide protects against both muscle weakness from low K(+) challenge in vitro and loss of muscle excitability in vivo from a glucose plus insulin infusion. This work demonstrates the critical role of the chloride gradient in modulating the susceptibility to ictal weakness and establishes bumetanide as a potential therapy for hypokalaemic periodic paralysis arising from either NaV1.4 or CaV1.1 mutations.
    Full-text · Article · Oct 2013 · Brain
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    • "The renal compensation for metabolic acidosis generates hypocitraturia which further augments the risk of crystalluria (Lamb et al., 2004; Go, 2005; Welch et al., 2006). TPM and ZNS monotherapy have been associated with rates of urolithiasis ranging from 1.5 to 3.7% (Leppik et al., 1993; Shorvon, 1996; Leppik, 1999; Wroe, 2007), whereas the stronger CA-I activity of AZM may account for its substantially higher rate of associated stone disease (reported as high as 15% (Tawil et al., 1993)). "
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    ABSTRACT: 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.
    Full-text · Article · Jun 2010 · Epilepsy research
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    • "Others complain of paresthesias and cognitive impairment (described by patients as mental dullness, fogginess, inability to concentrate, or confusion) from acetazolamide. Acetazolamide-induced nephrolithiasis (calcium phosphate stones) is not uncommon [7,8] and can often be controlled with dose reduction and appropriate hydration under consultation with a urologist. "
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    ABSTRACT: Management considerations in hypokalemic periodic paralysis include accurate diagnosis, potassium dosage for acute attacks, choice of diuretic for prophylaxis, identification of triggers, creating a safe physical environment, peri-operative measures, and issues in pregnancy. A positive genetic test in the context of symptoms is the gold standard for diagnosis. Potassium chloride is the favored potassium salt given at 0.5-1.0 mEq/kg for acute attacks. The oral route is favored, but if necessary, a mannitol solvent can be used for intravenous administration. Avoidance of or potassium prophylaxis for common triggers, such as rest after exercise, high carbohydrate meals, and sodium, can prevent attacks. Chronically, acetazolamide, dichlorphenamide, or potassium-sparing diuretics decrease attack frequency and severity but are of little value acutely. Potassium, water, and a telephone should always be at a patient's bedside, regardless of the presence of weakness. Perioperatively, the patient's clinical status should be checked frequently. Firm data on the management of periodic paralysis during pregnancy is lacking. Patient support can be found at
    Full-text · Article · Feb 2008 · Journal of Translational Medicine
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