Indomethacin and renal impairment in neonates

Akima, Satoshi; Kent, Alison; Reynolds, Graham; Gallagher, Martin; Falk, Michael C.

doi:10.1007/s00467-003-1402-z

Cited by 65 publications

(62 citation statements)

References 20 publications

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“…In a study on infants of <30 weeks gestation, a significant decrease in glomerular filtration rate was noted on days 2 and 7 after administration of indomethacin. 45 Some previous studies have shown a decline in peak systolic and mean velocities in SMA after its administration. 45,46 On the other hand, the theoretical benefit of therapeutic intervention relates to enhanced intestinal perfusion by minimizing transductal flow, therein reducing ductal steal.…”

Section: Ductal Steal and Nonsteroidal Anti-inflammatory Agentsmentioning

confidence: 95%

Spectral Doppler waveforms in systemic arteries and physiological significance of a patent ductus arteriosus

et al. 2010

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Patent ductus arteriosus in extremely premature babies is associated with major neonatal morbidities, such as necrotizing enterocolitis and intraventricular hemorrhage. This may be attributable, at least in part, to systemic hypoperfusion secondary to ductal steal. A hemodynamically significant ductus arteriosus (HSDA) is known to be associated with altered systemic blood flow and end-organ hypoperfusion. Although descending aorta blood flow profiles may show abnormal diastolic retrograde flow, Doppler studies of blood flow in the systemic arteries may help improve our understanding of the relationship of a HSDA with these morbidities. In this article, we discuss aspects of diastolic blood flow reversal in the systemic arteries in premature infants with a hemodynamically significant duct. Whether these hemodynamic effects are significant enough to form the basis for initiating treatment is still unclear; these should form the basis for prospective studies.

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Section: Ductal Steal and Nonsteroidal Anti-inflammatory Agentsmentioning

confidence: 95%

Spectral Doppler waveforms in systemic arteries and physiological significance of a patent ductus arteriosus

et al. 2010

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“…Adverse physiological consequences of indomethacin on the cerebral, renal and/or intestinal circulation have been demonstrated in animal and human studies [5][6][7][8] .…”

Section: Indomethacin and Coronary Blood Flowmentioning

confidence: 99%

Indomethacin Impairs Coronary Perfusion in Infants with Hemodynamically Significant Ductus Arteriosus

2011

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Background: A haemodynamically significant ductus arteriosus (HSDA) is commonly associated with morbidity in preterm infants. Aim: To study the effect of the first dose of indomethacin on coronary blood flow in preterm neonates diagnosed with an HSDA. Method: A prospective observational echocardiographic study was performed on preterm infants. A single study dose of intravenous indomethacin (0.1 mg/kg) was administered over 1 h. Serial echocardiography was performed before and after indomethacin treatment to study the effect on coronary artery perfusion and cardiovascular performance. Results: Eighteen infants born at a median gestation of 25.8 (24.2, 28.1) weeks and a birth weight of 773 g (704, 1,002) were evaluated. The median age at indomethacin administration was 7.5 days (4, 17). There was no significant change in arterial pressure or ventilatory indices. Left anterior descending artery diastolic velocity and time integral declined from 0.3 ± 0.1 and 3.19 ± 1.2 m/s to 0.22 ± 0.08 and 2.01 ± 0.9 m/s, respectively, within 10 min of completion of infusion. These indices showed partial recovery when reassessed after 60 min. There were no changes in left ventricular output or transductal flow. Conclusions: Intravenous indomethacin was followed by a decline in coronary arterial diastolic blood flow.

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“…Both of these drugs are successful in closing the ductus (3,4), but the morphologic effects these drugs may have on the developing kidney are unknown. Both drugs are known to be nephrotoxic, with indomethacin causing acute renal failure in 25% of premature neonates treated (5). Ibuprofen is considered to have less renal toxicity than indomethacin, but is as efficacious as indomethacin at closing the patent ductus (6).…”

mentioning

confidence: 99%

Renal Glomeruli and Tubular Injury Following Indomethacin, Ibuprofen, and Gentamicin Exposure in a Neonatal Rat Model

et al. 2007

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Indomethacin, ibuprofen, and gentamicin are commonly administered to neonates between 24 and 28 wk gestation when glomerulogenesis is still occurring. Indomethacin is known to cause renal failure in up to 25% of infants treated. Possible morphologic effects of these drugs are largely unknown. The purpose of this study was to determine the type of renal changes found on light (LM) and electron microscopy (EM) following administration of indomethacin, ibuprofen, and gentamicin in a neonatal rat model. Rat pups were exposed to indomethacin or ibuprofen and/or gentamicin antenatally for 5 d before birth or postnatally for 5 d from d 1 of life. Pups were killed at 14 d of age. LM examination in all indomethacin-and ibuprofen-treated pups both antenatally and postnatally showed vacuolization of the epithelial proximal tubules, interstitial edema, intratubular protein deposition but no significant glomerular changes. EM examination showed pleomorphic mitochondria and loss of microvilli in the tubules. The glomeruli showed extensive foot process effacement and irregularities of the glomerular basement membrane. EM changes were most marked in pups treated antenatally with ibuprofen, and indomethacin with gentamicin postnatally. Indomethacin, ibuprofen, and gentamicin cause significant change in glomerular and tubular structure in the neonatal rat model. U p to 5% of infants are delivered between 24 and 28 wk gestation, at a time when glomerulogenesis is occurring. Indomethacin and ibuprofen are commonly used in extremely premature neonates to close a patent ductus arteriosus at this time (1,2). Both of these drugs are successful in closing the ductus (3,4), but the morphologic effects these drugs may have on the developing kidney are unknown. Both drugs are known to be nephrotoxic, with indomethacin causing acute renal failure in 25% of premature neonates treated (5). Ibuprofen is considered to have less renal toxicity than indomethacin, but is as efficacious as indomethacin at closing the patent ductus (6). Two animal studies have shown an effect on glomerulogenesis by ibuprofen and a COX-2 selective inhibitor. In both studies, the number and size of glomeruli was decreased (7,8).Gentamicin is frequently administered at the same time as indomethacin or ibuprofen. Gentamicin has been shown in in vitro studies to affect nephron development (9). The combination of nonsteroidal anti-inflammatory drugs (NSAID) and gentamicin on glomerular development is unknown. The renal effect of indomethacin has not been examined in a neonatal animal model, nor has the combination of both indomethacin or ibuprofen and gentamicin.In the human, glomerulogenesis is complete at 36 wk gestation. The metanephron develops at 5 wk gestation, with vesicular glomeruli development occurring at 18 wk gestation. Glomerular tubular development occurs from 24 wk gestation and is complete at 36 wk (10 -12). In the rat model, glomerulogenesis continues after birth until 14 d of life (13). At birth the neonatal rat kidney is similar to that of a ...

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Indomethacin and renal impairment in neonates

Cited by 65 publications

References 20 publications

Spectral Doppler waveforms in systemic arteries and physiological significance of a patent ductus arteriosus

Spectral Doppler waveforms in systemic arteries and physiological significance of a patent ductus arteriosus

Indomethacin Impairs Coronary Perfusion in Infants with Hemodynamically Significant Ductus Arteriosus

Renal Glomeruli and Tubular Injury Following Indomethacin, Ibuprofen, and Gentamicin Exposure in a Neonatal Rat Model

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