Reversible Acute Renal Failure from Combined Triamterene and Indomethacin

Abstract

As part of a study on the interaction between diuretics and renal prostaglandins, four healthy medical students receiving indomethacin for 8 days were also given triamterene for 3 days. Whereas renal function was initially normal in all four subjects, creatinine clearance decreased in two by 62% and 72% after concomitant administration of the two drugs, and was only restored to normal after 4 weeks. In control periods when triamterene or indomethacin was given alone renal function was preserved in all subjects. Urinary prostaglandin E2 was stimulated by triamterene and inhibited by indomethacin in all four subjects; both changes were more marked in the two sensitive subjects. Thus prostaglandin inhibition by indomethacin may unmask triamterene toxicity and contribute to the pathogenesis of the renal failure observed in sensitive subjects. As alternative therapy is readily available, avoidance of this potentially nephrotoxic association is recommended.

Anuric Renal Failure Precipitated by Indomethacin and Triamterene

“…The latter seems unlikely, however, since Favre et al [6] found only minimal changes in renal function when indomethacin was given with other diuretics, including furosemide. In our patient, renal function did not return to normal soon after the indomethacin and triamterene had been discon tinued, anuria persisting for 11 days, suggesting the pres ence of a true structural renal lesion as well.…”

“…A recent clinical study of the humoral effects of triam terene may offer an explanation for the renal failure in our patient [6]. When normal human volunteers were given triamterene, plasma renin activity became elevated and increased quantities of prostaglandins were excreted in the urine.…”

“…Recently, Favre et al [6] found that several normal human volunteers developed renal insufficiency when given combinations of indomethacin and triamterene, and we now report the first clinical example of this phenomenon.…”

Irreversible Renal Failure Associated with Triamterene

“…Reddish-brown crystals and casts, an increase in hyaline casts and a 54% incidence of urinary birefringent triamterene crystals have been re ported [3,4], Triamterene has also been implicated in radiolucent kidney stone formation in 0.07% of triam terene users [5], The presence of uric acid or calcium oxalate monohydrate in the urine along with triamterene and hydroxy-triamterene sulfate increases the likelihood of urinary stones [6], Reversible renal failure has been reported to occur with the association triamterene-indomethacin in healthy subjects [7] and in hypertensive patients [8]. Triamterene, like other diuretics that cause volume de pletion, can lead to acute renal failure in elderly patients [9], Triamterene may also cause acute interstitial nephri tis [10]; in the patients reported, renal function im proved upon cessation of triamterene.…”

Network Analysis of Adverse Drug Interactions

“…We illustrated Figure 2 as an example of the association between interaction mechanisms and pharmacological/chemical subgroups, and Figure 3A shows another example of the associations. D00386 (Triamterene) interacts 8 different drugs, of which 6 drugs are classified "Acetic acid derivatives" subgroup, and these interactions cause acute renal failure [9,10]. Figure 3B illustrates the case of D00089 (Oxytocin), and these interactions result in the enhancement effect of both drugs and lead to serious events [11].…”