Influence of sodium intake on Amphotericin B-induced nephrotoxicity among extremely premature infants.

UNLABELLED: Amphotericin B (AmphoB) remains the preferred therapy for invasive fungal infections despite many side effects, such as nephrotoxicity and electrolyte imbalance. Our previous study suggested that high sodium (Na) intake >4 mEq/kg per day may be associated with lower nephrotoxicity in extremely premature infants treated with AmphoB. Subsequently, it became a standard of care in our unit to administer Na >4 mEq/kg per day to extremely premature infants treated with AmphoB. The purpose of this study was to evaluate the effect of high Na intake > 4 mEq/kg per day on the incidence of AmphoB-induced nephrotoxicity among extremely premature infants with birth weight <1250 gm. All extremely premature infants with birth weight <1250 gm born between 1992 and 2004 and treated with AmphoB for systemic fungal infections were included in the study. The study infants were divided into two groups: a control (CL) group (1/1992-12/1999, n = 21) consisting of extremely premature infants given a maintenance Na intake during AmphoB therapy, and a high sodium intake (High Na) group (1/2000-12/2004, n = 16) consisting of extremely premature infants given a high Na intake >4 mEq/kg per day during AmphoB therapy. Nephrotoxicity was defined as serum creatinine levels >1 mg/dl, urinary output (UOP) < 1 ml/kg per hour or a decrease in UOP of 50%, compared with the previous 2 days, and persisting for at least 2 days. Invasive fungal infection was diagnosed in 5.7% of the infants (44/763 infants). Thirty-seven infants were eligible for the study and seven were excluded. There were no differences between the two groups in gestational age, birth weight, age at fungal infection diagnosis, length of AmphoB therapy, daily fluid intake or hyponatremia. Nephrotoxicity was significantly higher in the CL group than in the High Na group (13/21 vs. 3/16; P = 0.02). In the CL group, nephrotoxicity occurred at (mean +/- SD) 1.9 +/- 3.2 days after the initiation of AmphoB treatment and lasted for 5.5 +/- 4.7 days. In this group, nephrotoxicity occurred in two of the 13 infants before the initiation of AmphoB therapy. In the High Na group, nephrotoxicity occurred before the start of AmphoB therapy in two of the three infants. In the third infant, nephrotoxicity lasted for 1 day. Mean Na intake was not different between the two groups during the 4-day period prior to AmphoB therapy. Mean Na intake during the first 10-day period of AmphoB therapy was significantly lower in the CL group (3.7 vs 6.2; P < 0.001). CONCLUSION: High Na intake was associated with a reduction in the incidence of AmphoB-induced nephrotoxicity in extremely premature infants with birth weight <1250 gm. We recommend the use of a high Na intake of >4 mEq/kg per day for extremely premature infants during Amphotericin B therapy.

Effects of fluid and electrolyte management on amphotericin B-induced nephrotoxicity among extremely low birth weight infants.

OBJECTIVE: Greater use of invasive procedures and aggressive antimicrobial therapy predispose extremely low birth weight (ELBW) infants to systemic fungal sepsis. Despite its adverse effects (including renal and electrolyte disturbances), amphotericin B (amphoB) remains the preferred drug for fungal therapy. Multiple studies have indicated that sodium loading may prevent renal toxicity among animals and human adults. The effects of fluid and electrolyte management on amphoB-induced nephrotoxicity among ELBW infants have not been evaluated extensively. The purpose of this study was to examine the effects of fluid and electrolyte management on amphoB-induced nephrotoxicity among ELBW infants. DESIGN/METHODS: The medical records were reviewed for all ELBW infants (birth weights of < or =1250 g) who developed systemic fungal sepsis, requiring amphoB therapy, between January 1992 and December 2000. Demographic, clinical, and laboratory data were collected from the medical records for each patient. RESULTS: Fungal sepsis requiring amphoB treatment developed for 4.4% of ELBW infants (25 of 573 infants), with a gestational age of 25 +/- 1 weeks and a birth weight of 738 +/- 37 g, at a postnatal age of 16 +/- 2 days. Renal compromise, as manifested by low urine output and high creatinine levels, occurred for 44% of those infants (11 of 25 infants). There was no difference between the infants who developed renal compromise (renal compromise group [RCG], n = 11) and those who did not (no-renal-compromise group [NCG], n = 14) with respect to birth weight, gestational age, and risk factors predisposing the infants to fungal sepsis. The RCG demonstrated a decrease in urine output by 3.4 +/- 2 days and an increase in serum creatinine levels by 3.9 +/- 2 days after the initiation of amphoB therapy. Infants in the RCG had a significantly higher incidence of hyponatremia, compared with infants in the NCG (7 of 11 infants vs 0 of 14 infants), with no significant difference in the incidences of hypokalemia (2 of 11 infants vs 0 of 14 infants). Infants in the RCG, compared with infants in the NCG, had significantly lower mean daily sodium intakes in the 4 days before the initiation of amphoB therapy (2.6-2.9 mEq/kg per day vs 4.2-4.7 mEq/kg per day) and in the first 4 days of amphoB treatment (2.7-3.1 mEq/kg per day vs 4.5-5.6 mEq/kg per day). Mean daily sodium intakes were not statistically significantly different between the 2 groups between day 5 and day 10 of amphoB therapy. Infants in the RCG tended to have lower mean daily potassium intakes in the 4 days before the initiation of amphoB therapy and during the first 4 days of amphoB therapy. Subsequently, the mean daily potassium intakes remained not statistically significantly different between the groups. Mean daily fluid intakes were not different between the groups. CONCLUSIONS: Conventional amphoB combined with adequate hydration and higher sodium intakes of >4 mEq/kg per day may provide effective protection against amphoB-induced nephrotoxicity among ELBW infants. Our data confirm the published results of animal and human adult studies and suggest that higher sodium intakes may prevent renal compromise during amphoB therapy among ELBW infants.