title: Low birth weight, nephron number, and kidney disease.
abstract: More and more evidence is emerging that highlights the far-reaching consequences of prenatal (intrauterine) programming on organ function and adult disease. In humans, low birth weight (LBW) occurs more frequently in disadvantaged communities among whom there is often a disproportionately high incidence of adult cardiovascular disease, hypertension, diabetes mellitus, and kidney disease. Indeed, many epidemiologic studies have found an inverse association between LBW and higher blood pressures in infancy and childhood, and overt hypertension in adulthood. Multiple animal models have demonstrated the association of LBW with later hypertension, mediated, at least in part, by an associated congenital nephron deficit. Although no direct correlation has been shown between nephron number and birth weight in humans with hypertension, nephron numbers were found to be lower in adults with essential hypertension, and glomeruli tend to be larger in humans of lower birth weight. An increase in glomerular size is consistent with hyperfiltration necessitated by a reduction in total filtration surface area, which suggests a congenital nephron deficit. Hyperfiltration manifests clinically as microalbuminuria and accelerated loss of renal function, the prevalence of which are higher among adults who had been of LBW. A kidney with a reduced nephron number has less renal reserve to adapt to dietary excesses or to compensate for renal injury, as is highlighted in the setting of renal transplantation, where smaller kidney to recipient body-weight ratios are associated with poorer outcomes, independent of immunologic factors. Both hypertension and diabetes are leading causes of end-stage renal disease worldwide, and their incidences are increasing, especially in underdeveloped communities. Perinatal programming of these 2 diseases, as well as of nephron number, may therefore have a synergistic impact on the development of hypertension and kidney disease in later life. Existing evidence suggests that birth weight should be used as a surrogate marker for future risk of adult disease. Although the ideal solution to minimize morbidity would be to eradicate LBW, until this panacea is realized, it is imperative to raise awareness of its prognostic implications and to focus special attention toward early modification of risk factors for cardiovascular and renal disease in individuals of LBW.
authors: Renal Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. vluyckx@partners.org
authors: Valerie A
authors: VA
authors: Luyckx
authors: Barry M
authors: BM
authors: Brenner
mesh_terms: D000328:Adult; D003920:Diabetes Mellitus / Q000453:epidemiology; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology*; D024821:Metabolic Syndrome / Q000453:epidemiology; D009399:Nephrons / Q000473:pathology*; D012307:Risk Factors