Developmental Origins of Chronic Renal Disease: An Integrative Hypothesis

Abstract

Cardiovascular diseases are one of the leading causes of mortality. Hypertension (HT) is one of the principal risk factors associated with death. Chronic kidney disease (CKD), which is probably underestimated, increases the risk and the severity of adverse cardiovascular events. It is now recognized that low birth weight is a risk factor for these diseases, and this relationship is amplified by a rapid catch-up growth or overfeeding during infancy or childhood. The pathophysiological and molecular mechanisms involved in the “early programming” of CKD are multiple and partially understood. It has been proposed that the developmental programming of arterial hypertension and chronic kidney disease is related to a reduced nephron endowment. However, this mechanism is still discussed. This review discusses the complex relationship between birth weight and nephron endowment and how early growth and nutrition influence long term HT and CKD. We hypothesize that fetal environment reduces moderately the nephron number which appears insufficient by itself to induce long term diseases. Reduced nephron number constitutes a “factor of vulnerability” when additional factors, in particular a rapid postnatal growth or overfeeding, promote the early onset of diseases through a complex combination of various pathophysiological pathways.

High protein intake in neonatal period induces glomerular hypertrophy and sclerosis in adulthood in rats born with IUGR

“…These changes are known to increase SNGFR, to affect the glomerular endothelium barrier, to impair endothelium-dependent vasodilatation, and to stimulate the sympathetic nervous activity responsible for HT, one of the leading causes of CKD (28)(29)(30)(31)(32). Even though blood pressure was not monitored in the current study, we hypothesize that such metabolic, hormonal, and vascular changes enhanced the adaptive glomerular hemodynamic changes and renal injury already acquired during the neonatal period and accelerated the occurrence of proteinuria and glomerular sclerosis (33). Further investigation would be needed to confirm this hypothesis.…”

Increased Urinary Cystatin-C Levels Correlate with Reduced Renal Volumes in Neonates with Intrauterine Growth Restriction

“…This mechanism is still being discussed and recent experimental studies have failed to show such a link. Boubred et al [23] reported that the reduced nephron number is not sufficient by itself to induce long-term renal diseases, but that it constitutes a factor of vulnerability when additional factors, in particular a rapid postnatal growth or overfeeding, promote the early onset of diseases through a complex combination of various pathophysiological pathways. The authors suggest that future research may aim to clarify early biomarkers of nephron endowment and early renal injury in order to determine optimal perinatal nutrition and eventual prophylactic measures to be applied to infants at increased risk of developmentally programmed adult diseases [23].…”

Di(2‐ethylhexyl) phthalate (DEHP) [MAK Value Documentation, 2016]

“…Humans have an average of 1 million nephrons per kidney, but the number varies in individuals from 200 000 to more than 2 million (Bertram et al 2011). A small number of nephrons is associated with increased sensitivity to the development of high blood pressure and chronic kidney disorders in adulthood together with further factors such as rapid postnatal growth or overfeeding during infancy or childhood (Abitbol and Rodriguez 2009;Bertram et al 2011;Boubred et al 2013). In rats, intrauterine growth retardation may induce a reduced number of nephrons at birth, which may not be fully compensated for during the first weeks after birth (Merlet-Bénichou et al 1994).…”