Diuretic resistance: mechanisms and therapeutic strategies.

The mechanism(s) responsible for diuretic resistance differ in different clinical conditions. Renal insufficiency is a prototype of a pharmacokinetic mechanism wherein the disease causes decreased delivery of diuretic to its urinary site of action. Hepatic cirrhosis, on the other hand, is a prototype of a pharmacodynamic mechanism wherein normal amounts of diuretic reach the site of action but nephron response is subnormal. The mechanism of this effect is unknown. In congestive heart failure and in nephrotic syndrome, both pharmacokinetic and pharmacodynamic mechanisms occur. The different mechanisms of diuretic resistance in these various diseases dictate specific therapeutic strategies for each clinical condition.