Perinatal drug exposure and renal function in very preterm infants

Vieux, Rachel; Fresson, Jeanne; Guillemin, Françis; Hascoët, Jean‐Michel

doi:10.1136/adc.2009.197699

Cited by 35 publications

(19 citation statements)

References 35 publications

(43 reference statements)

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“…The lower GFR in infants administered ibuprofen persisted for the month of follow-up. Importantly, aminoglycoside serum concentrations were higher in infants receiving ibuprofen, suggesting potentially enhanced toxicity [151]. Exposure to aminoglycosides was not associated with a lower GFR in this study although 7 days could be too soon to detect an effect.…”

Section: Introduction To a Health Problemmentioning

confidence: 72%

“…Tocolytic therapy administered to the mother until the day of delivery was significantly associated with a lower GFR in the infant on day 7, and administration of the COX-2 inhibitor nimusulide as a tocolytic has been reported to induce renal failure and ESKD in neonates in multiple case reports [151,155,156]. In animals, multiple medications that could be prescribed during pregnancy have been found to impact offspring kidney development, including β-lactam antibiotics, cyclosporine, and long-term steroids, although their renal impact in humans is largely not known and long-term follow-up is needed [48,65,157].…”

Section: Introduction To a Health Problemmentioning

confidence: 99%

“…The true risk of AKI in neonates exposed to nephrotoxic medications is not well described, however, as the toxicity cannot merely be extrapolated from knowledge in older children and adults. A prospective study of 269 infants exposed to medication perinatally (i.e., medication prescribed to mothers during late pregnancy or administered to the infant within the first 7 days of life) and stratified according to whether they had a GFR below or above the group median on day 7 found that ibuprofen administration before day 7 was associated with an OR of 2.6 (95% CI, 1.2-5.3) for having a lower GFR [151]. The lower GFR in infants administered ibuprofen persisted for the month of follow-up.…”

Section: Introduction To a Health Problemmentioning

confidence: 99%

See 2 more Smart Citations

The Impact of Kidney Development on the Life Course: A Consensus Document for Action

Brenner

Charlton

Luyckx

et al. 2017

Nephron

124

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Hypertension and chronic kidney disease (CKD) have a significant impact on global morbidity and mortality. The Low Birth Weight and Nephron Number Working Group has prepared a consensus document aimed to address the relatively neglected issue for the developmental programming of hypertension and CKD. It emerged from a workshop held on April 2, 2016, including eminent internationally recognized experts in the field of obstetrics, neonatology, and nephrology. Through multidisciplinary engagement, the goal of the workshop was to highlight the association between fetal and childhood development and an increased risk of adult diseases, focusing on hypertension and CKD, and to suggest possible practical solutions for the future. The recommendations for action of the consensus workshop are the results of combined clinical experience, shared research expertise, and a review of the literature. They highlight the need to act early to prevent CKD and other related noncommunicable diseases later in life by reducing low birth weight, small for gestational age, prematurity, and low nephron numbers at birth through coordinated interventions. Meeting the current unmet needs would help to define the most cost-effective strategies and to optimize interventions to limit or interrupt the developmental programming cycle of CKD later in life, especially in the poorest part of the world.

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Section: Introduction To a Health Problemmentioning

confidence: 72%

Section: Introduction To a Health Problemmentioning

confidence: 99%

Section: Introduction To a Health Problemmentioning

confidence: 99%

See 1 more Smart Citation

The Impact of Kidney Development on the Life Course: A Consensus Document for Action

Brenner

Charlton

Luyckx

et al. 2017

Nephron

124

View full text Add to dashboard Cite

show abstract

“…Given these potential nephrotoxic insults, other possible treatment options might be considered for treatment of a PDA. However, the only other medical option for closure of the PDA is ibuprofen, which is also shown to injure glomeruli in a neonatal animal model and has been shown to affect glomerular filtration rate (GFR) during the first month of life in human studies [12,29,30]. Judicious use of these medications during the neonatal period is warranted and should be balanced with the clinical condition of the neonate and the severity of the PDA.…”

Section: Discussionmentioning

confidence: 97%

Increased urinary podocytes following indomethacin suggests drug-induced glomerular injury

et al. 2012

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“…Indomethacin was shown to have more significant suppressive effects than ibuprofen on renal COX-2 and vasodilator prostanoids in a neonatal rat model (26). Ibuprofen has been shown in premature neonates to result in a low glomerular filtration rate for a month following administration (60). A recent study has shown increased numbers of podocytes in the urine of preterm neonates receiving indomethacin, suggesting drug-induced glomerular injury at the time of ongoing glomerulogenesis (31).…”

mentioning

confidence: 99%

Indomethacin administered early in the postnatal period results in reduced glomerular number in the adult rat

Kent

Koina

Gubhaju

et al. 2014

American Journal of Physiology-Renal Physiology

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Indomethacin and ibuprofen are administered to close a patent ductus arteriosus (PDA) during active glomerulogenesis. Light and electron microscopic glomerular changes with no change in glomerular number were seen following indomethacin and ibuprofen treatment during glomerulogenesis at 14 days after birth in a neonatal rat model. This present study aimed to determine whether longstanding renal structural changes are present at 30 days and 6 mo (equivalent to human adulthood). Rat pups were administered indomethacin or ibuprofen antenatally on days 18 -20 (0.5 mg·kg Ϫ1 ·dose Ϫ1 indomethacin; 10 mg·kg Ϫ1 ·dose Ϫ1 ibuprofen) or postnatally intraperitoneally from day 1 to 3 or day 1 to 5 (0.2 mg·kg Ϫ1 ·dose Ϫ1 indomethacin; 10 mg·kg Ϫ1 ·dose Ϫ1 ibuprofen). Control groups received no treatment or normal saline intraperitoneally. Pups were killed at 30 days of age and 6 mo of age. Tissue blocks from right kidneys were prepared for light and electron microscopic examination, while total glomerular number was determined in left kidneys using unbiased stereology. Eight pups were included in each group from 14 maternal rats. At 30 days and 6 mo, there were persistent electron microscopy abnormalities of the glomerular basement membrane in those receiving postnatal indomethacin and ibuprofen. There were no significant light microscopy findings at 30 days or 6 mo. At 6 mo, there were significantly fewer glomeruli in those receiving postnatal indomethacin but not ibuprofen (P ϭ 0.003). In conclusion, indomethacin administered during glomerulogenesis appears to reduce the number of glomeruli in adulthood. Alternative options for closing a PDA should be considered including ibuprofen as well as emerging therapies such as paracetamol. kidney; glomerular number; indomethacin; ibuprofen; premature neonate; fetus INDOMETHACIN MAY BE ADMINISTERED to a pregnant woman as a tocolytic to prevent preterm delivery. Adverse effects of indomethacin on the fetus and neonate have been described including oligohydramnios, persistent renal insufficiency, gastrointestinal bleeding and perforation, and persistent pulmonary hypertension (8,11,21,54,58). It has not been determined whether there is any long-term effect on fetal glomerular development or glomerular endowment following exposure to intrauterine indomethacin.Indomethacin and ibuprofen have been shown to close a patent ductus arteriosus (PDA). The timing of administration of these medications is during a time of active glomerulogenesis (15,16,41,59). Indomethacin is known to be nephrotoxic causing acute renal failure in 25% of premature neonates treated for a PDA (2). Ibuprofen is felt to be less renal toxic than indomethacin, but it is as efficacious as indomethacin at closing the patent ductus (45). Two animal studies have shown an effect on glomerulogenesis (induction of new nephrons and glomeruli) in the rat and mouse with ibuprofen and a cyclooxygenase-2 (COX-2)-selective inhibitor. In both studies, the number and size of glomeruli were decreased (3, 34). Administration of indomet...

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Perinatal drug exposure and renal function in very preterm infants

Cited by 35 publications

References 35 publications

The Impact of Kidney Development on the Life Course: A Consensus Document for Action

The Impact of Kidney Development on the Life Course: A Consensus Document for Action

Increased urinary podocytes following indomethacin suggests drug-induced glomerular injury

Indomethacin administered early in the postnatal period results in reduced glomerular number in the adult rat

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