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The impact of intrauterine growth restriction and prematurity on nephron endowment

Nature Reviews Nephrology volume 19, pages 218–228 (2023)Cite this article

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Abstract

In humans born at term, maximal nephron number is reached by the time nephrogenesis is completed — at approximately 36 weeks’ gestation. The number of nephrons does not increase further and subsequently remains stable until loss occurs through ageing or disease. Nephron endowment is key to the functional capacity of the kidney and its resilience to disease; hence, any processes that impair kidney development in the developing fetus can have lifelong adverse consequences for renal health and, consequently, for quality and length of life. The timing of nephrogenesis underlies the vulnerability of developing human kidneys to adverse early life exposures. Indeed, exposure of the developing fetus to a suboptimal intrauterine environment during gestation — resulting in intrauterine growth restriction (IUGR) — and/or preterm birth can impede kidney development and lead to reduced nephron endowment. Furthermore, emerging research suggests that IUGR and/or preterm birth is associated with an elevated risk of chronic kidney disease in later life. The available data highlight the important role of early life development in the aetiology of kidney disease and emphasize the need to develop strategies to optimize nephron endowment in IUGR and preterm infants.

Key points

  • Low birthweight, small for gestational age, intrauterine growth restriction (IUGR) and preterm birth are often overlapping terms used to describe infants that have not met their growth potential; however, it is important to recognize them as distinct conditions.

  • The majority of nephrons are formed in the third trimester; both preterm birth and IUGR — although temporally and mechanistically distinct processes — can adversely affect a considerable proportion of the nephrogenic period.

  • Strong clinical and experimental evidence indicates that a nephron deficit occurs in the kidneys of infants exposed to IUGR during development; the effect of preterm birth on nephron number is less clear.

  • Reduced nephron endowment at birth is associated with a reduction in total renal filtration surface area, and therefore diminished renal functional capacity and disease resilience across the life course.

  • A surge in epidemiological research has persuasively demonstrated a link between all-cause low birthweight, small for gestational age and preterm birth, on the one hand, and the later development of chronic kidney disease on the other.

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Fig. 1: Terminology used to describe infants born too small and/or too soon.
Fig. 2: Timeline of nephrogenesis.
Fig. 3: Impact of intrauterine growth restriction and preterm birth on kidney development.

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  1. Department of Anatomy and Developmental Biology and Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia

    Megan R. Sutherland & Mary Jane Black

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Sutherland, M.R., Black, M.J. The impact of intrauterine growth restriction and prematurity on nephron endowment. Nat Rev Nephrol 19, 218–228 (2023). https://doi.org/10.1038/s41581-022-00668-8

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