Foetal kidney maldevelopment in maternal use of angiotensin II type I receptor antagonists
We report renal lesions observed in a foetus exposed throughout pregnancy to angiotensin II type I (AT 1) receptor antagonists. The mother suffered from essential hypertension and was treated with Cozaar (losartan 50 mg). Autopsy examination of the foetus revealed severe renal lesions, including tubular dysgenesis, hypertrophy of the endothelial and medial cells lining the arterial and arteriolar walls, hyperplasia of the juxtaglomerular apparatus and poorly developed vasa recta. Similar lesions have already been observed in foetuses of women treated with angiotensin-converting enzyme antagonists and also in foetuses and neonates of animals undergoing experimental blockade of the renin–angiotensin system. The purpose of this report is to describe structural lesions observed in the kidneys, and, particularly, vascular lesions. Our results suggest that the use of AT 1 receptor antagonists during pregnancy may have a severe deleterious effect on kidney development in the foetus.
KeywordsFetal kidney AT 1 receptor antagonists Pregnancy
- 17.Friberg P, Guron G, Sundelin B, Wickman A, Adams MA (1996) Neonatal ACE inhibition in the pig causes irreversible abnormalities in the kidney. J Hypertens 14 [Suppl 1]:S54Google Scholar
- 18.Nilsson A, Adams M, Guron G, Sundelin B, Friberg P (1996) Reduced ability to excrete an acute volume load after neonatal ACE inhibition in the rat. J Am Soc Nephrol 7:1586Google Scholar
- 22.Tsuchida S, Matsusaka T, Chen X, Okubo S, Niimura F, Nishimura H, Fogo A, Utsunomiya H, Inagami T, Ichikawa I (1998) Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes. J Clin Invest 101:755–760PubMedCrossRefGoogle Scholar
- 23.Niimura F, Labosky PA, Kakuchi J, Okubo S, Yoshida H, Oikawa T, Ichiki T, Naftilan A, Fogo A, Inagami T, Hogan B, Ichikawa I (1995) Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest 96:2947–2954PubMedCrossRefGoogle Scholar