Pentamidine volume depletion

Currently, pentamidine in the form of aerosol is used for the prophylaxis of PCP with apparent success [163-166]. Initially no renal side effects were described with its use. However, two reports of acute renal dysfunction raised the possibility of a systemic absorption of aerosolized pentamidine [167, 168]. One of the patients received a previous large dose of TMP-SMZ and the other appears to have had concomitant volume depletion caused by severe diarrhea while an elevation of serum creatinine occurred. We have been unable to find additional reports of renal toxicity associated with aerosol pentamidine administration[169]. Likewise, no renal side effects were reported with the use of aerosolized pentamidine for the prophylaxis of PCP in patients who received bone marrow, renal or hepatic transplants [165, 166]. Although the use of aerosolized pentamidine may be associated with renal dysfunction, this seems much less frequent compared to the parenteral administration of this drug. 

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. 

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