A 14-year-old girl with renal abnormalities after brief intrauterine exposure to enalapril during late gestation

Abstract

In addition to its important role in the regulation of extracellular fluid homeostasis, an intact renin– angiotensin system (RAS) is essential for normal kidney development [1]. Several case reports have described fatal acute renal failure and renal tubular dysplasia in fetuses and newborns exposed to angiotensin-converting enzyme (ACE) inhibitors [2] or angiotensin II type-1 (AT1) receptor antagonists [3] during the second or third trimester. Notably, nephrogenesis is completed at about gestational week 36 in humans. Experimental studies have shown that interruption of the RAS during ongoing nephrogenesis, either pharmacologically or by gene knockout techniques, produces abnormalities in renal morphology and function that bear similarities to those described in case reports, and that normal kidney development is mainly mediated through the AT1 receptor [1,4,5]. Renal morphological abnormalities in these animals are characterized by papillary atrophy, wall thickening of pre-glomerular arterioles, and tubular atrophy and dilatation [1,4,5]. Functional defects are mainly characterized by a marked impairment in urinary concentrating ability [1]. Recent studies have demonstrated important roles for the AT1 receptor in tubular growth [6], branching morphogenesis [5] and the establishment of normal tubular cell–cell and cell–matrix interactions [7] in the developing kidney. In addition, angiotensin II is important for normal development of the renal pelvis and ureter [4]. Although maternal use of drugs that block the RAS during the second and third trimester sometimes induces fatal acute renal failure and renal tubular dysplasia in newborns, it is not known what the longterm consequences are on the kidney in survivors. We here describe a patient who was exposed to the ACE inhibitor enalapril during gestational weeks 28–36 and who at 14 years of age presented with a marked impairment in urinary concentrating ability, proteinuria and a reduction in glomerular filtration rate (GFR). This renal phenotype resembles that described in laboratory animals exposed to ACE inhibitors during a corresponding interval of kidney development.