Children's toxicology from bench to bed - Drug-induced Renal Injury (1): The toxic effects of ARB/ACEI on fetal kidney development

Abstract

Development of fetal kidney is a finely programmed sequence, and is regulated by many important molecules. The perturbation of normal kidney development leads to congenital anomalies of kidney and urinary tract (CAKUT). CAKUT includes hypoplastic/dysplastic kidney, obstructive nephropathy and several other anomalies. CAKUT is of clinically importance, since it could lead to end stage renal failure when its anomaly grade is severe. So far, several causative genes responsible for development of CAKUT have been identified, including genes encoding molecules related to the renin-angiotensin-aldosterone system, RAS system. In humans, maternal administration of agents with inhibitory effects on the RAS system, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin type 1 receptor blockers (ARBs), have been reported to cause severe renal malformation, designated as ACEI/ ARB fetopathy. In this paper, we overview the development of fetal kidney and address the effects of ACEIs/ARBs on fetal kidney.