Pentamidine hyperkalemia with

Pentamidine is structurally similar to amiloride and can cause severe hyperkalemia if co-prescribed with potassium-sparing diuretics (10). This is a particularly important interaction in patients with AIDS. 

The exact mechanism of the pentamidine-induced hyperkalemia has not yet been defined. Many different mechanisms can impair the renal handling of potassium and thus favor hyperkalemia in patients with AIDS. These include decreased renal function secondary to volume depletion, presence of under-lying renal disease, including tubular dysfunction with the possibility of hyporeninemic hypoaldos-teronism, hypoadrenalism, and the administration of drugs with potential for impairing renal potassium excretion (nonsteroidal anti-inflammatory agents, ACE inhibitors, potassium-sparing diuretics. 

In summary, parenteral pentamidine administration for the treatment of PCP can be associated with the development of usually mild, reversible acute kidney injury. Compounding risk factors, of which volume depletion is the most important, are found in the majority of cases of pentamidine nephrotoxicity. There is no convincing evidence that the aerosol route of pentamidine administration for PCP prophylaxis results in nephrotoxicity. Hypocalcemia and hypomagnesemia with renal magnesium wasting, and particularly, hyperkalemia are seen with pentamidine therapy. 

Lachaal M, Venuto RC. Nephrotoxicity and hyperkalemia in patients with acquired immunodeficiency syndrome treated with pentamidine.The American journal of medicine. 1989 Sep 87(3) 260-3. 

Pentamidine therapy for Pneumocystis carinii infections is also limited by nephrotoxicity. Prospective studies have shown azotemia in 60% to 90% of treated patients. Hyperkalemia, metabolic acidosis, hypomagnesemia, and hypocalcemia may also occur. Toxicity is more frequent in patients with the acquired immunodeficiency syndrome (AIDS) than in patients without this immune deficiency, and may... 

Perturbations in mono- and divalent cation renal handling have been reported in association with pentamidine administration. Several reports of hyperkalemia in association with pentamidine therapy have been recently published [132,134,136,137,167,168]. Lachaal and Venuto [132] in a retrospective review reported a very high incidence of hyperkalemia (5.1 to 8.7 mEq/ L) in 19 of 20 patients (95%). This incidence was greater than the 5% reported earlier [123], or the 24% reported subsequently [134] in 37 patients with AIDS, and was challenged as a possible overestimation [169]. The hyperkalemia usually correlates with the presence of decreased GFR [132,134]. In our clinical study [133] the mean serum potassium concentration tended to be higher in the AIDS patients that developed pentamidine nephrotoxicity than in those that did not (5.0+0.3 vs 4.3+0.2, respectively, p <0.055). No patient, however, had a serum potassium concentration higher than 6.0 mEq/L. Hyperkalemia induced-arrhythmias occur [170], and rarely may include cardiac arrest [171]. The hyperkalemia usually reversed on discontinuation of pentamidine, and although most patients required only conservative measures, occasionally dialysis was necessary [132]. 

Briceland LL, Bailie GR. Pentamidine-associated nephrotoxicity and hyperkalemia in patients with AIDS. DICP, Ann Pharmacother 1991 25 1171-1174. 

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