Triamterene nephrotoxicity

INTRODUCTION — Triamterene is a potassium-sparing diuretic that is commonly used in the treatment of hypertension in combination with a thiazide diuretic. It is not widely appreciated, however, that triamterene is a potential nephrotoxin, occasionally inducing crystalluria and cast formation, and rarely causing stone formation or reversible acute kidney injury [1,2].

The evaluation, diagnosis, and acute management of kidney stones and the general management of acute kidney injury in adults is discussed separately:

●(See "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis".)

●(See "Overview of the management of acute kidney injury (AKI) in adults".)

CRYSTALLURIA AND CAST FORMATION — Triamterene can induce the formation of both triamterene crystals (which are usually brown in color, spherical, and appear as a "Maltese cross" under polarized light) and granular casts (which can look identical to brown pigmented casts), at least when used in higher doses (eg, 50 to 100 mg daily). The following studies illustrate this effect:

●In a study of 20 healthy adults who ingested 100 mg of triamterene, all 20 excreted triamterene crystals, and 17 out of 20 excreted granular casts, which were present within 11 hours of taking the drug [3]. Alkalinization of the urine to a pH of 7.5 or higher prevented the appearance of crystals.

●In a study of 26 hypertensive patients given 50 mg of triamterene, crystals and casts were seen in 14 (54 percent) [4].

Whether crystals and casts commonly occur with 37.5 mg of triamterene (a more typical dose) is unknown. The mechanism responsible for the cast formation is unclear but appears to be specific to triamterene, as this finding is not seen with amiloride, another potassium-sparing diuretic [3,4].

TRIAMTERENE STONES — Stone formation is an uncommon complication of triamterene therapy [2,5-7]. One study, for example, found that triamterene was present in 1 in every 200 to 250 stones [6,8]. Most of these stones contained both triamterene and calcium oxalate or uric acid, although pure triamterene stones did occur [6,9]. Of course, the proportion of all stones containing triamterene will depend upon how commonly triamterene is used in the general population. In addition, the incidence of triamterene-containing stones may be decreasing [10].

Patients who form triamterene-containing stones are more likely to have a prior history of stone disease, suggesting that metabolic predisposition is an important risk factor [5,6]. (See "Kidney stones in adults: Epidemiology and risk factors".)

Triamterene stones are faintly opaque on radiograph examination and, like other stones, are easily seen with non-contrasted computed tomography. (See "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis", section on 'Diagnostic imaging'.)

Early studies suggested no relation with urine pH, but later studies found that triamterene crystals are not seen when the urine pH is 7.5 or higher. If triamterene crystals are seen, the medication should be stopped. Amiloride is an alternative potassium-sparing agent that does not form crystals in the urine.

Triamterene stones cannot be dissolved by raising the urine pH and should be treated by conventional urologic techniques [11]. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones".)

ACUTE KIDNEY INJURY — Reversible acute kidney injury is another rare problem with triamterene (but not other potassium-sparing diuretics). Two different mechanisms have been described: intratubular obstruction by crystals and concurrent therapy with a nonsteroidal antiinflammatory drug (NSAID) [12-14]. Why triamterene seems to make the patient more sensitive to NSAIDs than other diuretics is not clear. (See "NSAIDs: Acute kidney injury".)

SUMMARY

●Triamterene, a commonly used potassium-sparing diuretic, may produce crystalluria and granular casts in as many as one-half of patients taking higher doses, sometimes leading to nephrolithiasis or acute kidney injury. The risk with the more typical dose of 37.5 mg of triamterene is unknown.

●In patients taking triamterene, the medication should be discontinued if crystals or casts are seen in the urine or if triamterene is reported as a component of a stone. Amiloride is a safe alternative.