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PEDIATRICS Vol. 113 No. 4 April 2004, pp. 1084-1091

SUPPLEMENT ARTICLE

The Developing Kidney and Environmental Toxins

Michael J. Solhaug, MD*, Philip M. Bolger, PhD{ddagger} and Pedro A. Jose, MD, PhD§

* Department of Physiology, Eastern Virginia School of Medicine, Norfolk, Virginia
{ddagger} Food and Drug Administration, Washington, DC
§ Department of Pediatrics and Physiology and Biophysics, Georgetown University Medical Center, Washington, DC

The effects of environmental chemicals, drugs, and physical agents on the developing kidney are influenced by the state of renal development and maturation. The development of the kidney, the major excretory organ after birth, consists of 3 stages: the pronephros, or cervical kidney; mesonephros, or thoracic kidney; and metanephros, or abdominal kidney, the definitive kidney. In humans, nephrogenesis and organogenesis occur from the 6th to the 36th weeks of gestational age. After 36 weeks, nephrogenesis is complete and each kidney has a full complement of nephrons. The extent of chemical-induced renal toxicity is related, in part, to the efficiency in which the particular compound is transported by renal tubules. Because renal tubular transport capacities vary with maturation, the degree of nephrotoxicity may also vary with maturation. The signs and symptoms of nephrotoxicity can appear acutely or insidiously. Unexplained acute renal failure, chronic mild proteinuria, or even hypertension can be a manifestation of nephrotoxic agents. Species differences occur, thus the need for studies in humans.

Key Words: kidney • toxins • development • angiotensin • prostanoids

Abbreviations: RBF, renal blood flow • GFR, glomerular filtration rate • ACE, angiotensin-converting enzyme • OAT, organic anion transporter • OCT, organic cation transporter • OCTN, organic cation/carnitine transporters • PAH, p-aminohippuric acid

Received for publication Oct 7, 2003; Accepted Oct 20, 2003.


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