Diuretic-Related Side Effects: Development and Treatment

Domenic A. Sica, MD

In This Article


Hyponatremia is an uncommon, but serious, complication of diuretic therapy.[6,7] Thiazide diuretics are more likely than loop diuretics to cause hyponatremia. Loop diuretics inhibit sodium (Na+) transport in the renal medulla and prevent the generation of a maximal osmotic gradient. Thus, urinary concentrating ability is impaired with loop diuretics. Alternatively, thiazide-type diuretics increase Na+ excretion and preclude maximal urine dilution, while preserving the kidney's innate concentrating capacity. When diuretic-related hyponatremia occurs, it is typically in elderly females and is usual seen shortly after therapy begins (within the first 2 weeks).[8] However, diuretic-related hyponatremia can occur on a delayed basis even after several years of therapy.[7] Multiple factors contribute to the penchant of females to diuretic-related hyponatremia, including age, reduced body mass, exaggerated natriuretic response to a thiazide diuretic, diminished capacity to excrete free water, and self-imposed low-solute intake. Independent of this constellation of risk factors, it has been suggested that the apparent female preponderance of thiazide-induced hyponatremic adverse events is related to overrepresentation of females in thiazide-treated cohorts, rather than intrinsic susceptibility to the electrolyte disturbance.[7]

Mild asymptomatic diuretic-related hyponatremia (typically between 125-135 mmol/L) can be managed in a number of ways (which are not necessarily mutually exclusive), including: restricting free-water intake, replacing potassium (K+) losses, withholding diuretics, or switching to loop diuretic therapy if diuretic therapy remains necessary.[9,10] Severe, symptomatic hyponatremia (generally <125 mmol/L), complicated by seizures or other active neurologic sequelae, represents a true medical emergency. A fall in serum Na+ to this degree calls for intensive therapy; however, this level of symptomatic hyponatremia should not be corrected too rapidly because the osmotic demyelinating syndrome has occurred under these circumstances. The risks of ongoing hyponatremia must be weighed against those of too hasty a correction, and current recommendations are that plasma Na+ should be corrected by no more than 0.5 mmol/h during the first 24 hours of treatment.[11,12] The pace at which hyponatremia is corrected should be slowed once a mildly hyponatremic serum Na+ range has been reached (approximately 125-130 mmol/L). The acuity (≤48 hours) of the hyponatremia also influences the speed with which hyponatremia is corrected. Controversy still surrounds a number of aspects of the therapy of hyponatremia.