Impact of Gestational Age and Birth Weight on Amikacin Clearance on Day 1 of Life

Abstract

Background and objectives: Intrauterine growth restriction (IUGR) and prematurity are associated with a low nephron endowment. It can therefore be expected that neonates who are born premature and/or after IUGR have a lower GFR. Measurement of GFR in neonates is difficult, but the clearance of amikacin has been proven to be a reliable marker. We hypothesized that amikacin clearance is lower after IUGR or premature birth as a marker of low nephron endowment.Design, setting, participants, & measurements: Amikacin clearance was retrospectively analyzed in 161 neonates who received amikacin within the first 24 h of life. Using the MW/Pharm computer program, a population one-compartment model was calculated. The mean population pharmacokinetic parameters were individualized for each patient according to the maximum a posteriori Bayesian fitting method and provided the amikacin clearance.Results: Our results show that birth weight z score and gestational age are correlated with the clearance of amikacin (partial correlation coefficient 0.159, P ‫؍‬ 0.046, and 0.396, P < 0.001, respectively), after correction for other factors.Conclusions: We conclude that renal clearance on the first day of life is lower in neonates with a lower gestational age and/or birth weight z score. This indicates that both prematurity and IUGR impair GFR on the first day of life.

Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease

“…Indeed, GFR extrapolated from Amikacin clearance on day 1 of life, preceding any compensatory adaptation, was significantly reduced in premature and LBW infants compared to term controls 67 . GFR measured by inulin clearance was significantly lower at age 7.6 years in children who had been premature and had severe growth restriction compared to non growth restricted controls 41 .…”

The Clinical Importance of Nephron Mass

“…119 In longer term follow-up of children with very low birth weight (VLBW; Ͻ1000 g), serum creatinine was higher and GFR lower compared with age-matched NBW children at 6 to 12 years. 120 A stronger association was found using cystatin C in children, suggesting that creatinine-based formulas underestimate the impact of birth weight on GFR.…”

Pharmacokinetic Variability of Amikacin After Once-Daily and Twice-Daily Dosing Regimen in Full-Term Neonates

“…Previous studies indicated that amikacin CL was in the range of 31.3 -91 ml/h·kg, while half-life (t 1/2 ) was in the range of 4 -9.3 h (8, 11 -13, 21). High interindividual variability in amikacin pharmacokinetics was previously observed, and it was described in detail in pre-term neonates (9,11,22). In pre-term neonates, weight and gestational and/or neonatal age significantly contributed to amikacin pharmacokinetic variability (9,10,23).…”