Comparative renal histomorphometry: a case study of oligonephropathy of prematurity

Rodríguez, Maria M.; Gómez, Alexander H.; Abitbol, Carolyn; Chandar, Jayanthi; Montané, Brenda; Zilleruelo, Gastón

doi:10.1007/s00467-004-1800-x

Cited by 84 publications

(61 citation statements)

References 10 publications

(37 reference statements)

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“…However, it has been consistently shown that intrauterine growth restriction leads to a reduced number of nephrons (5). There are data suggesting that premature birth (i.e., before completion of nephrogenesis) is also associated with a reduced nephron endowment (6,7). This may be due to extrauterine growth restriction, which is very common in premature infants (8) and which we have shown to lead to a reduced nephron number in an animal model (9).…”

Section: Renal Developmentmentioning

confidence: 70%

Effect of Drugs on Renal Development

Schreuder¹,

Bueters²,

Huigen³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryMany nephrotoxic effects of drugs have been described, whereas the effect on renal development has received less attention. Nephrogenesis ceases at approximately 36 weeks of gestation, indicating that drugs administered to pregnant women and to preterm-born neonates may influence kidney development. Such an effect on renal development may lead to a wide spectrum of renal malformations (congenital anomalies of the kidney and urinary tract [CAKUT]), ranging from renal agenesis to a reduced nephron number. Any of these anomalies may have long-term sequelae, and CAKUT is the primary cause for renal replacement therapy in childhood. This review focuses on research into the effect of drug treatment during active nephrogenesis during pregnancy and in preterm-born infants. Because the effects of many widely used drugs have not been unraveled thus far, more research is needed to study the effect on renal development and long-term renal sequelae after drug treatment during nephrogenesis.

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Section: Renal Developmentmentioning

confidence: 70%

Effect of Drugs on Renal Development

Schreuder¹,

Bueters²,

Huigen³

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…Evidence of long-term renal impairment has been found by Rodriguez-Soriano et al (46) with abnormal tubular phosphate transport along with urinary calcium excretion, however, they found no difference in blood pressure. Changes in renal histomorphometry have been noted in extremely premature infants (47,48), indicating that oligonephropathy can occur and may subsequently predispose these infants to renal disease and hypertension later in life. Our study, although not showing glomerulosclerosis, has indicated far more extensive glomerular injury than expected following exposure to these drugs.…”

Section: Discussionmentioning

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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“…Radial glomerular counts (RGCs) were determined on mid-longitudinal sections as mean glomerular generations from eight different 10ϫ photomicrograph fields of kidney cortex, with care to include the corticomedullary junction (20,21). Generations were identified by drawing parallel lines perpendicular to a mid-kidney medullary ray starting at the first glomerulus seen at the corticomedullary junction, continuing the process to the capsule, and ensuring every glomerulus traverses a line (20).…”

Section: Animalsmentioning

confidence: 99%