Furosemide-Induced Nephrocalcinosis in Premature Neonates: A Critical Review of Observational Data

TL;DR

Furosemide use in premature infants is linked to kidney calcifications, which can persist with high doses or long-term use, highlighting the need for careful dosing and monitoring.

Contribution

This paper provides a comprehensive review of observational data showing a dose-dependent risk of nephrocalcinosis in preterm infants due to furosemide.

Findings

Furosemide is associated with a dose-related risk of nephrocalcinosis in preterm infants.

Persistent nephrocalcinosis is more likely with prolonged furosemide exposure and renal dysfunction.

Careful dosing (≤2 mg/kg/day for 28 days) may reduce nephrocalcinosis risk without increasing electrolyte disturbances.

Abstract

What are the main findings?
•Furosemide is linked to a dose-related risk of nephrocalcinosis in preterm infants.•Although the condition resolves with discontinuation of medication in most cases, it can persist especially with prolonged exposure.

Furosemide is linked to a dose-related risk of nephrocalcinosis in preterm infants.

Although the condition resolves with discontinuation of medication in most cases, it can persist especially with prolonged exposure.

What is the implication of the main finding?
•Cautious dosing and close monitoring are crucial to minimizing renal complications.•Further research is needed to establish optimal dosing and long-term safety.

Cautious dosing and close monitoring are crucial to minimizing renal complications.

Further research is needed to establish optimal dosing and long-term safety.

Background/Objectives: Furosemide is frequently used in preterm neonates for respiratory and fluid management but has been linked to nephrocalcinosis (NC), a renal complication with unclear long-term impact. Clarifying this association is crucial for safe diuretic use. Methods: A focused literature review included observational studies published between 1982 and 2025 reporting NC incidence by renal ultrasound in preterm infants receiving furosemide. Data on sample size, gestational age, birth weight, NC prevalence, and furosemide dosing/duration were extracted. Results were synthesized descriptively. Results: Twenty-two studies with 1489 infants were included. NC prevalence ranged 6–83%, higher in infants <32 weeks’ gestation or <1500 g. Across studies, incidence clustered at 17–41% between 4 weeks and term-equivalent age. Cumulative furosemide doses were generally three- to fourfold higher in NC groups (10–19 mg/kg cumulative vs. ≤5 mg/kg cumulative, p < 0.001). A dose-dependent risk was noted, with odds ratios increasing above a cumulative dose of 10 mg/kg. Some studies found no significant dose–response, indicating variability and confounding factors. NC was detected during NICU stay or around term-equivalent age; ~60% resolved after discontinuation, while persistent cases were associated with prolonged exposure and renal dysfunction. A recent multicenter, dose-escalation randomized trial showed that carefully dosed furosemide (≤2 mg/kg/day for 28 days) did not increase NC risk, though electrolyte disturbances were more frequent. Conclusions: Evidence supports a dose-related association between furosemide and NC in preterm infants. When administered cautiously within defined limits, risk may be mitigated. Careful dosing, monitoring, and further studies are essential for safe use.

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