Diuretic complications.
BACKGROUND
Diuretics are widely used and generally safe, but like any therapeutic agents, they may cause side effects.


METHODS
A review of recent literature pertaining to diuretic usage was performed, with emphasis on specific reports of side effects. Reports of large-scale hypertension trials employing diuretics were also examined for descriptions of diuretic-related complications.


RESULTS
All diuretics promote excretion of sodium. Depending upon the site and mode of action, some diuretics increase excretion of potassium, chloride, calcium, bicarbonate, or magnesium. Some can reduce renal excretion of electrolyte-free water, calcium, potassium, or protons. Consequently, electrolyte and acid-base disorders commonly accompany diuretic use. Except for the mildly natriuretic collecting duct agents, which are used mainly to limit potassium excretion, all diuretics can cause volume depletion with prerenal azotemia. Loop agents and distal convoluted tubule agents, such as the thiazides, produce hypokalemic, hypochloremic, metabolic alkalosis that responds to potassium chloride replacement. Carbonic anhydrase inhibitors produce less hypokalemia and volume depletion but commonly induce metabolic acidosis that is often symptomatic. The potassium-sparing agents also limit proton excretion, and spironolactone may produce metabolic acidosis. Hyperkalemia is a leading complication of the potassium-sparing agents, especially in patients with an underlying tendency for hyperkalemia. Thiazide diuretics, in particular, have been linked to glucose intolerance, which may be an effect of hypokalemia rather than the diuretic itself. Whether diuretic-induced hypokalemia increases cardiovascular risk is controversial. Loop agents and thiazides may lead to hyponatremia, which, in the case of thiazides, may cause permanent neurologic damage. Dose-related reversible or irreversible ototoxicity may complicate treatment with loop agents. Nephrocalcinosis, nephrolithiasis, hypomagnesemia, and hyperuricemia can potentially complicate treatment with some diuretic agents. Reported idiosyncratic reactions to diuretics include interstitial nephritis, noncardiogenic pulmonary edema, pancreatitis, and myalgias.


CONCLUSIONS
Potential side effects of a diuretic can often be anticipated from its mode of action on the kidney. These complications may be mitigated with careful monitoring, dosage adjustment, and replacement of electrolyte losses. Other side effects are idiosyncratic and cannot be prevented.
Greenberg
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Division of Nephrology, Duke University Medical Center, Durham, North Carolina 27710, USA. green107@mc.duke.edu
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000959:Antihypertensive Agents / Q000009:adverse effects*; D001539:Bendroflumethiazide / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000209:etiology; D004232:Diuretics / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D007008:Hypokalemia / Q000139:chemically induced; D007010:Hyponatremia / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D011188:Potassium / Q000097:blood / Q000378:metabolism; D012964:Sodium / Q000097:blood / Q000378:metabolism
D000959:Antihypertensive Agents; D004232:Diuretics; D008055:Lipids; D001539:Bendroflumethiazide; D012964:Sodium; D011188:Potassium