Renal Response to Furosemide in Very Low Birth Weight Infants during Chronic Administration

Abstract

Renal response to furosemide following initial and chronic doses was investigated in premature infants with bronchopulmonary dysplasia. Seven infants (mean birth weight = 890 ± 216 g, mean gestational age at birth = 27.7 ± 2.6 weeks, mean postnatal age at the start of diuretic therapy = 2.7 ± 0.9 weeks) were studied. Twelve-hour urine collections were performed after the initial dose, and following chronic doses after 1 week and 3 weeks of therapy. Volume of each urine sample was measured and concentrations of furosemide, sodium and creatinine determined. Linear dose-response relationships were found between the logarithm of the urinary furosemide excretion rate and diuretic/natriuretic response (urine output and urinary sodium excretion rate). The furosemide excretion rate required to achieve midrange diuretic and natriuretic responses was significantly greater during chronic dosing than following initial doses, indicating a decrease in renal responsiveness to drug with sustained use. Increasing postconceptional age was associated with a decrease in initial responsiveness to furosemide. These data demonstrate that in premature infants renal sensitivity to furosemide decreases with chronic use as well as with increasing postconceptional age at the start of therapy. The decrease in renal sensitivity to drug with chronic use is of much greater magnitude, and appears to represent renal compensation for drug-induced diuresis and natriuresis.

Urinary Aldosterone Excretion and Renal Function in Extremely-Low-Birth-Weight Infants following Acute Furosemide Therapy

“…Our findings are consistent with those of other studies carried out in preterm or very low-birth-weight infants [18][19][20] . In fact, furosemide has been shown to inhibit active chloride reabsorption in the thick ascending limb of Henle's loop, resulting in decreased passive sodium reabsorption and in increased diuresis.…”

Effects of Furosemide on the Renal Functions of the Unanesthetized Newborn Rat

“…Therefore the use of furosemide in young individuals induces alterations in se rum electrolytes that are not observed in older subjects, and should be considered as a potential risk of the diuretic therapy in neo nates. This is in agreement with the findings reported by Mirochnick et al [19] in very low weight infants after the first week of furosemide administration.…”

Clinical Pharmacology of Furosemide in Neonates: A Review

“…Mirochnick et al [67] observed a relationship between the logarithm of the urinary furosemide excretion rate and both the urinary and sodium excretion rate and urine output following initial and chronic multiple doses. There was a significant increase in the mean furosemide excretion rate associated with the midrange responses after 1 and 3 weeks of therapy compared with the initial dose.…”

“…There was a significant increase in the mean furosemide excretion rate associated with the midrange responses after 1 and 3 weeks of therapy compared with the initial dose. The urinary excretion of furosemide was 219 ± 130 (week 1), 959 ± 381 (week 2) and 738 ± 323 µg/kg/12 h (week 3) [67]. …”