A case of nephrogenic syndrome of inappropriate antidiuresis caused by carbamazepine

Abstract

We report a case of nephrogenic syndrome of inappropriate antidiuresis caused by carbamazepine (CBZ). CBZ, an antiepileptic drug, is known to cause hyponatremia. The mechanism is generally considered to be inappropriate secretion of antidiuretic hormone, whereas an experimental study suggests a direct effect of CBZ on the kidney by stimulating vasopressin receptor. An 18-year-old male with atypical autism and epilepsy has been treated with CBZ and clobazam since age 9 and 10 years, respectively. At age 11, he was found to have asymptomatic hyponatremia. He had the habit of drinking tea approximately 3 L/day. The low plasma osmolality and high urine osmolality and sodium concentration in the presence of normal thyroid and adrenal function were compatible with syndrome of inappropriate excretion of antidiuretic hormone. His plasma vasopressin level, however, was undetectable. Urine cyclic AMP level was higher than expected from urine osmolality despite the suppressed plasma arginine vasopressin. With fluid restriction, hyponatremia improved. CBZ tapering begun later in the course maintained normal serum sodium concentrations with less strict water intake. This case demonstrates the direct effect of CBZ stimulating vasopressin receptor in the kidney leading to nephrogenic syndrome of inappropriate diuresis.

Pharmacokinetic Monitoring of Levetiracetam in Portuguese Refractory Epileptic Patients: Effect of Gender, Weight and Concomitant Therapy

“…However, in addition to gender and weight, we also demonstrated that co-medication with carbamazepine determines the Vd/F. We suggest that hyponatremia, a well-known adverse effect of carbamazepine [54][55][56][57][58][59], may be involved in this drug-drug interaction. Briefly, the increased secretion of the antidiuretic hormone due to carbamazepine stimulation may lead to the syndrome of inappropriate antidiuretic hormone secretion.…”

“…Briefly, the increased secretion of the antidiuretic hormone due to carbamazepine stimulation may lead to the syndrome of inappropriate antidiuretic hormone secretion. In turn, this may cause the direct stimulation of the hormone receptor and nephrogenic syndrome of inappropriate diuresis [ 57 , 60 , 61 ]. High water reabsorption appears to increase body water content with a consequent decrease of plasma sodium concentrations and decrease of blood osmolarity.…”

A genome‐wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine

“…Experimental studies and a recent clinical report suggest that COIH is caused by a direct effect of CBZ/OXC on the kidney by stimulating the vasopressin receptor. 25,26 Mutations in the V2R/AQP2 pathway regulating water reabsorption can cause disorders clinically similar to the syndromes of inappropriate secretion of antidiuresis associated with CBZ/OXC use. Meanwhile thiazide-induced hyponatremia has been associated with polymorphisms in the gene KCNJ1 and a suggestive association with a variant in SLCO2A1, encoding a prostaglandin transporter; these signals did not show even nominal significance in our data.…”

The Role of Vasopressin V2 Receptor in Drug-Induced Hyponatremia

“…The mechanism of anticonvulsant-associate hyponatremia has generally been considered to be inappropriate hypersecretion of AVP (Ashton et al, 1977;Smith et al, 1977), but an experimental study has indicated a direct effect of carbamazepine on the kidney through V2R stimulation without evidence of increased release of endogenous AVP (Meinders et al, 1975). Sekiya et al also reported that 18-year-old male with carbamazepine-associated hyponatremia had features of the SIADH but had an undetectable level of plasma AVP and an elevated urine cyclic AMP excretion (Sekiya and Awazu, 2018). Thus, a human case of carbamazepine-induced NSIAD was demonstrated.…”