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Impact of nephrotoxic drugs on urinary biomarkers of renal function in very preterm infants

Abstract

Background

Following preterm birth, the immature kidney is exposed to several harmful conditions, with an increased risk of renal impairment. We aimed to assess urinary biomarkers of renal function in very preterm infants during early nephrotoxic treatments.

Methods

Infants ≤32 weeks’ gestation and ≤1500 g were enrolled in this observational prospective study. Urine samples were collected on day 1(T1), 2–4(T2), 5–7(T3), 8–10(T4), 11–13(T5). The following urinary biomarkers were determined: osteopontin (uOPN), epidermal growth factor (uEGF), neutrophil gelatinase-associated lipocalin (uNGAL), cystatin C (uCysC). The infants were grouped according to their exposure to amikacin or ibuprofen during the study period and a between-group comparison of urinary biomarkers at each time point was performed.

Results

Thirty-six infants were included. Urinary CysC, uOPN, and uNGAL rose significantly during ibuprofen or amikacin treatment, while no difference was observed for uEGF. After adjustment for possible influencing factors, amikacin administration was associated with higher uCysC at T1 (p = 0.007) and T2 (p = 0.016), whereas ibuprofen increased uOPN (p = 0.001) and uNGAL concentration (p = 0.009) at T3.

Conclusion

Nephrotoxic therapies induce molecule-specific change patterns of renal function biomarkers in treated preterm infants. Serial assessments of these biomarkers may aid to identify neonates at risk of renal impairment and to develop tailored therapeutic approaches.

Impact

  • Despite the wide use of nephrotoxic therapies in neonatal settings, little is known on their effect on renal function biomarkers in preterm infants.

  • This study describes molecule-specific change patterns of urinary biomarkers during ibuprofen and amikacin administration, suggesting underlying pathophysiological effects on renal function.

  • Given their low analytical costs and non-invasive collection, the urinary biomarkers investigated in this study represent a promising strategy for serial monitoring of renal function in at-risk neonates and may aid the early detection of renal function impairment at different kidney levels during nephrotoxic treatments.

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Fig. 1: Time patterns of urinary cystatin C (uCysC), osteopontin (uOPN) and neutrophil gelatinase-associated lipocalin (uNGAL) in infants who received amikacin (full line) vs. those who did not (dotted line) at T1 (day 1), T2 (days 2–4), T3 (days 5–7), T4 (days 8–10), T5 (days 11–13).
Fig. 2: Time patterns of urinary cystatin C (uCysC), osteopontin (uOPN) and neutrophil gelatinase-associated lipocalin (uNGAL) in infants who received ibuprofen (full line) vs. those who did not (dotted line) at T1 (day 1), T2 (days 2–4), T3 (days 5–7), T4 (days 8–10), T5 (days 11–13).

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Acknowledgements

We thank Anna Girardi and Luca Leonardi for their contribution in data collection, and Maria Cappuccilli for supervising sample analysis.

Funding

This study received financial support by the “Fondazione del Monte” institution (grant no. FdM/3884).

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Authors and Affiliations

Authors

Contributions

E.P., I.C., and S.G. designed the study. F.V. enrolled the patients and acquired the data. C.D. analyzed the study samples. S.M. and E.P. performed the statistical analysis. E.R., V.A., F.D.P., and L.C. contributed to data interpretation. S.M. wrote the first draft of the manuscript; E.P., F.V., and I.C. contributed to the draft writing. All the authors critically revised the manuscript for important intellectual content, approved the final version of the manuscript submitted for publication and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed.

Corresponding author

Correspondence to Silvia Martini.

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The authors declare no competing interests.

Consent to participate

The study protocol was approved by the S. Orsola University Hospital Ethics Committee, Bologna, Italy (protocol no. 154/2015/U/Oss) and written informed consent for study participation was obtained from the parents/legal guardians of each patient.

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Martini, S., Vitali, F., Capelli, I. et al. Impact of nephrotoxic drugs on urinary biomarkers of renal function in very preterm infants. Pediatr Res 91, 1715–1722 (2022). https://doi.org/10.1038/s41390-021-01905-9

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  • DOI: https://doi.org/10.1038/s41390-021-01905-9

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