Impact of Early Postnatal NSAID Treatment on Nephrogenesis in Wistar Rats

Bueters, Ruud; Klaasen, Annelies; Maicas, Nuria; Florquin, Sandrine; Heuvel, Lambertus P. van den; Schreuder, Michiel F.

doi:10.1002/bdrb.21161

Cited by 9 publications

(7 citation statements)

References 27 publications

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“…Consistent with previous experimental data in human embryonic kidney (HEK) 293 cells, 69 ibuprofen‐triggered apoptosis in human fetal kidney explants, a phenomenon also reported in human fetal ovarian explants 60 . In newborn rats exposed to ibuprofen, an altered proliferation/apoptosis ratio associated with decreased nephrons counts was also described 15 . In addition, ibuprofen‐induced apoptosis clearly targets developing glomeruli as it does in the adult human kidney 70 .…”

Section: Discussionsupporting

confidence: 86%

Exposure of human fetal kidneys to mild analgesics interferes with early nephrogenesis

et al. 2021

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Acetaminophen, aspirin, and ibuprofen are mild analgesics commonly used by pregnant women, the sole current recommendation being to avoid ibuprofen from the fifth month of gestation. The nephrotoxicity of these three analgesics is well documented in adults, as is their interference with prostaglandins biosynthesis. Here we investigated the effect of these analgesics on human first trimester kidneys ex vivo. We first evaluated prostaglandins biosynthesis functionality by performing a wide screening of prostaglandin expression patterns in first trimester human kidneys. We demonstrated that prostaglandins biosynthesis machinery is functional during early nephrogenesis. Human fetal kidney explants aged 7‐12 developmental weeks were exposed ex vivo to ibuprofen, aspirin or acetaminophen for 7 days, and analyzed by histology, immunohistochemistry, and flow cytometry. This study has revealed that these analgesics induced a spectrum of abnormalities within early developing structures, ranging from cell death to a decline in differentiating glomeruli density. These results warrant caution for the use of these medicines during the first trimester of pregnancy.

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Section: Discussionsupporting

confidence: 86%

Exposure of human fetal kidneys to mild analgesics interferes with early nephrogenesis

et al. 2021

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“…16 According to several reports, IBU (on label intravenous dose of 10-5-5 mg/kg/day and PDA closure) exposure in preterm neonates results in transient reduction of urine output, a significant increase in sCr of up to 6 weeks after exposure and decreased drug clearance (À20%) for drugs cleared by glomerular filtration. [17][18][19] In addition to these short-term outcome observations in human neonates, animal experimental observations have been conducted on the reduction (from À7% to À12%) of glomerular number count in adult rodents 19 and on the reduction (À27%) of the renal cortex in adult primates after being exposed to IBU at a maturational age equivalent to extremely preterm human neonates. Although nephrotoxicity is lower than that of IND, short-term follow-up of renal function should also be performed when administering IBU for premature infants.…”

Section: Discussionmentioning

confidence: 99%

“…According to experimental evidence, another mechanism partially explains the differences in the effects of both drugs on regional circulations . According to several reports, IBU (on label intravenous dose of 10–5–5 mg/kg/day and PDA closure) exposure in preterm neonates results in transient reduction of urine output, a significant increase in sCr of up to 6 weeks after exposure and decreased drug clearance (−20%) for drugs cleared by glomerular filtration . In addition to these short‐term outcome observations in human neonates, animal experimental observations have been conducted on the reduction (from −7% to −12%) of glomerular number count in adult rodents and on the reduction (−27%) of the renal cortex in adult primates after being exposed to IBU at a maturational age equivalent to extremely preterm human neonates.…”

Section: Discussionmentioning

confidence: 99%

The influence on renal function of ibuprofen treatment for patent ductus arteriosus in extremely low birthweight infants

Nishizaki

Matsuda

Yoneyama

et al. 2020

Pediatrics International

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Background Ibuprofen (IBU) has been used recently for the treatment of patent ductus arteriosus (PDA) in Japan. We aimed to investigate the efficacy and adverse events of IBU and compare them with those of indomethacin (IND) as PDA treatment for extremely low‐birthweight infants (ELBWIs), focusing on short‐term renal function. Methods A case‐control study was conducted on 16 ELBWIs. The data from eligible patients were divided into two groups. Ten patients had undergone IND treatment (IND group) between January 2017 and June 2018, whereas six had undergone IBU treatment (IBU group) for PDA between July 2018 and December 2018. The IND group received 0.1 mg/kg/12h IND IV infusion for three doses, whereas the IBU group received 10 mg/kg IV IBU infusion followed by 5 mg/kg/day for 2 days. We compared the efficacy for PDA closure and renal impairment between the two groups. Results No significant differences in primary closure rates and the PDA ligation required were observed between the two groups. No significant differences were observed between the incidence of intraventricular hemorrhage and gastrointestinal complications in both groups. Changes in urine volume (%) in the IBU group were significantly higher than in the IND group at 24–36 h post‐administration. The urinary L‐type fatty acid binding protein concentration level at 7 days of life was significantly lower in the IBU group than in the IND group. Conclusion Although IBU was comparable to IND in PDA closure rate, IBU was superior to short‐term renal injury in ELBWIs.

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“…Our second aim was to evaluate whether extrauterine growth restriction could modulate the potential toxicity of drug treatment. Using the rat model of litter enlargement, we have previously shown that extrauterine growth restriction results in a reduction in nephron numbers (Bueters et al, , ). From the changes noted in body weight, it is clear that a state of extrauterine growth restriction was induced, even though body weights were slightly different from the start of the study.…”

Section: Discussionmentioning

confidence: 99%

Early postnatal gentamicin and ceftazidime treatment in normal and food restricted neonatal wistar rats: Implications for kidney development

Bueters

Jeronimus-Klaasen

Brüggemann

et al. 2017

Birth Defects Research

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Impact of Early Postnatal NSAID Treatment on Nephrogenesis in Wistar Rats

Abstract: A clinical Ibuprofen dose showed potential to inhibit kidney development in neonatal rats. FR did not modulate these effects.

Cited by 9 publications

References 27 publications

Exposure of human fetal kidneys to mild analgesics interferes with early nephrogenesis

Exposure of human fetal kidneys to mild analgesics interferes with early nephrogenesis

The influence on renal function of ibuprofen treatment for patent ductus arteriosus in extremely low birthweight infants

Early postnatal gentamicin and ceftazidime treatment in normal and food restricted neonatal wistar rats: Implications for kidney development

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