It is important to note that, even more than in heart failure, overly aggressive use of diuretics in this setting can be disastrous. Vigorous diuretic therapy can cause marked depletion of intravascular volume, hypokalemia, and metabolic alkalosis. Hepatorenal syndrome and hepatic encephalopathy are the unfortunate consequences of excessive diuretic use in the cirrhotic patient. Vaptans are relatively contraindicated in patients with liver disease because a study of tolvaptan in treating patients with autosomal dominant polycystic kidney disease resulted in increased transaminases in some patients treated with high-dose tolvaptan. Low-dose tolvaptan, however, may prove to be useful in treating some patients with cirrhosis (those who do not have ongoing liver damage) who suffer from hyponatremia or fluid overload.
Idiopathic edema (fluctuating salt retention and edema) is a syndrome found most often in 20to 30-year-old women. Despite intensive study, the pathophysiology remains obscure. Some studies suggest that surreptitious, intermittent diuretic use may actually contribute to the syndrome and should be ruled out before additional therapy is pursued. While spironolactone has been used for idiopathic edema, it should probably be managed with moderate salt restriction alone if possible. Compression stockings have also been used but appear to be of variable benefit.
The diuretic and mild vasodilator actions of the thiazides are useful in treating virtually all patients with essential hypertension and may be sufficient in many (see also Chapter 11). Although hydrochlorothiazide is the most widely used diuretic for hypertension, chlorthalidone may be more effective because of its much longer half-life. Loop diuretics are usually reserved for patients with mild renal insufficiency (GFR < 30–40 mL/min) or heart failure. Moderate restriction of dietary Na+ intake (60–100 mEq/d) has been shown to potentiate the effects of diuretics in essential hypertension and to lessen renal K+ wasting. A K+-sparing diuretic can be added to reduce K+ wasting.
There has been debate about whether thiazides should be used as the initial therapy in the treatment of hypertension. Their modest efficacy sometimes limits their use as monotherapy. However, a very large study of over 30,000 participants has shown that inexpensive diuretics like thiazides result in outcomes that are similar or superior to those found with ACE inhibitor or calcium channel-blocker therapy. This significant result reinforces the importance of thiazide therapy in hypertension.
Although diuretics are often successful as monotherapy, they also play an important role in patients who require multiple drugs to control blood pressure. Diuretics enhance the efficacy of many agents, particularly ACE inhibitors. Patients being treated with powerful vasodilators such as hydralazine or minoxidil usually require simultaneous diuretics because the vasodilators cause significant salt and water retention. There is also growing evidence showing that spironolactone may be the most effective single agent in the therapy of drug-resistant hypertension, and this effect may extend to dialysis patients.