Developmental Programming of the Kidney

As noted in the introduction, renewed interest in renal development, and in particular in the formation of an adequate nephron endowment, has occurred over the last decade, with worldwide interest in the concept that many diseases with onset in adult life in fact have their origins during development. During the 1990s, this concept was known as the Barker hypothesis or the fetal origins of adult disease, but subsequent studies demonstrating the crucial role played by the early postnatal environment have led to the developmental origins of health and disease (DOHaD) hypothesis. Simplistically, it is proposed that upon exposure to an insult or sub-optimal exposure in utero, the fetus makes adaptations to ensure short-term survival; however, many of these adaptations may increase the subsequent risk of developing particular diseases in adulthood. Low birthweight has been taken as a marker of a poor intrauterine environment. Of course, in reality, the situation is much more complex, with the eventual disease outcome being highly dependent upon interactions with the environment including lifestyle choices. It is not within the scope of this review to discuss in detail the extensive epidemiological and experimental studies undertaken to test this hypothesis; however, an understanding of the adult disease outcomes is crucial to fully appreciate the fundamental role that altered kidney development may play. In the remaining subsections of Sect. 8, we shall consider the evidence that altered renal development is a common underlying mechanism through which many prenatal perturbations may result in adult disease and explore the potential ways in which renal development may be affected. Finally, although the impact of developmental programming in the aetiology of many diseases is unknown, it is likely to be very significant. For example, it has been estimated that if all individuals were in the most favourable tertile of body size at birth and remained so throughout childhood, the incidence of coronary artery disease would be reduced by 40% in men and 63% in women (Barker et al. 2002).