Association between potassium supplementation and the occurrence of acute kidney injury in patients with hypokalemia administered liposomal amphotericin B: a nationwide observational study

Abstract

Background Hypokalemia and acute kidney injury (AKI) occur in patients administered liposomal amphotericin B (L-AMB), a wide-spectrum anti-fungicidal drug. However, the association between potassium supplementation and the occurrence of AKI in patients with hypokalemia who were administered L-AMB is not well understood. Methods Using nationwide claims data and laboratory data, the occurrence of AKI during L-AMB treatment was retrospectively compared between patients with hypokalemia who were or were not supplemented with potassium and between those adequately or inadequately supplemented with potassium (serum potassium levels corrected to ≥3.5 mEq/L or remained < 3.5 mEq/L, respectively) before or after L-AMB treatment initiation. Results We identified 118 patients who developed hypokalemia before L-AMB treatment initiation (43 received potassium supplementation [25 adequate and 18 inadequate supplementation] and 75 did not receive potassium supplementation), and 117 patients who developed hypokalemia after L-AMB initiation (79 received potassium supplementation [including 23 adequate and 15 inadequate supplementation] and 38 did not receive potassium supplementation). The occurrence of any stage of AKI was similar between patients with hypokalemia, regardless of potassium supplementation (i.e., before L-AMB treatment initiation [supplementation, 51%; non-supplementation, 45%; P = 0.570] or after L-AMB initiation [supplementation, 28%; non-supplementation, 32%; P = 0.671]). After adjusting for confounding factors, we found that the occurrence of any stage of AKI was not associated with potassium supplementation before L-AMB initiation (odds ratio [OR]: 1.291, 95% confidence interval [CI]: 0.584–2.852, P = 0.528) or after L-AMB initiation (OR: 0.954, 95% CI: 0.400–2.275, P = 0.915). The occurrence of any stage of AKI tended to decline in patients with hypokalemia who were adequately supplemented with potassium (44%) before, but not after, L-AMB initiation relative to that in patients inadequately supplemented with potassium (61%), however this result was not significant (P = 0.358). Conclusion Potassium supplementation was not associated with any stage of AKI in patients with hypokalemia who were administered L-AMB.

Association between the hypokalaemia index based on area over the serum potassium concentration curve and occurrence of acute kidney injury in patients administered liposomal amphotericin B

“…Clinical evidence as to whether transient acute hypokalaemia causes AKI in patients with AMB therapy is scarce. Indeed, K supplementation was not associated with the prevention of any stage of AKI in patients with hypokalaemia who were administered L‐AMB, although K administration before the start of L‐AMB therapy reduced the risk of hypokalaemia, which would cause other type of adverse effects such as arrhythmia 16 …”

“…The incidences of a greater than 50% increase in serum creatinine concentration and a K concentration less than 3.0 were significantly higher in patients receiving L-AMB than voriconazole (19.0% vs. 10.4% and 31.0% vs. 16.4%, respectively). 10 The incidence of nephrotoxicity in patients receiving L-AMB was also significantly higher than those on caspofungin (11.5% vs. 2.6%), and a decrease in serum K concentration was observed in 11.8% of patients on L-AMB therapy compared with 7.3% on caspofungin therapy.…”

“…Indeed, K supplementation was not associated with the prevention of any stage of AKI in patients with hypokalaemia who were administered L-AMB, although K administration before the start of L-AMB therapy reduced the risk of hypokalaemia, which would cause other type of adverse effects such as arrhythmia. 16 Anecdotal studies reported that chronic hypokalaemia caused pathophysiological changes in the kidneys of patients with chronic severe diarrhoea or those who abused medications including diuretics, laxatives, phenacetin containing analgesics, barbiturates, or benzodiazepines. Menahem et al 17 reported AKI arising in a patient with hypokalaemia for 5 years secondary to laxative abuse.…”

Amphotericin B in the Era of New Antifungals: Where Will It Stand?

“…It seems that the combination of sodium bicarbonate and normal saline compared to normal saline alone appears to have no superiority in preventing or attenuating different studied aspects of AmB nephrotoxicity [34]. The potential effect of a decrease does occur at the cost of electrolyte disturbances, mainly potassium; however, requirement of long-term supplementation in these patients is not associated with acute kidney injury [35].…”