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      Low Nephron Number and Its Clinical Consequences

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          Abstract

          Epidemiologic studies now strongly support the hypothesis, proposed over two decades ago, that developmental programming of the kidney impacts an individual’s risk for hypertension and renal disease in later life. Low birth weight is the strongest current clinical surrogate marker for an adverse intrauterine environment and, based on animal and human studies, is associated with a low nephron number. Other clinical correlates of low nephron number include female gender, short adult stature, small kidney size, and prematurity. Low nephron number in Caucasian and Australian Aboriginal subjects has been shown to be associated with higher blood pressures, and, conversely, hypertension is less prevalent in individuals with higher nephron numbers. In addition to nephron number, other programmed factors associated with the increased risk of hypertension include salt sensitivity, altered expression of renal sodium transporters, altered vascular reactivity, and sympathetic nervous system overactivity. Glomerular volume is universally found to vary inversely with nephron number, suggesting a degree of compensatory hypertrophy and hyperfunction in the setting of a low nephron number. This adaptation may become overwhelmed in the setting of superimposed renal insults, e.g. diabetes mellitus or rapid catch-up growth, leading to the vicious cycle of on-going hyperfiltration, proteinuria, nephron loss and progressive renal functional decline. Many millions of babies are born with low birth weight every year, and hypertension and renal disease prevalences are increasing around the globe. At present, little can be done clinically to augment nephron number; therefore adequate prenatal care and careful postnatal nutrition are crucial to optimize an individual’s nephron number during development and potentially to stem the tide of the growing cardiovascular and renal disease epidemics worldwide.

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          Most cited references152

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          The thrifty phenotype hypothesis.

          The thrifty phenotype hypothesis proposes that the epidemiological associations between poor fetal and infant growth and the subsequent development of type 2 diabetes and the metabolic syndrome result from the effects of poor nutrition in early life, which produces permanent changes in glucose-insulin metabolism. These changes include reduced capacity for insulin secretion and insulin resistance which, combined with effects of obesity, ageing and physical inactivity, are the most important factors in determining type 2 diabetes. Since the hypothesis was proposed, many studies world-wide have confirmed the initial epidemiological evidence, although the strength of the relationships has varied from one study to another. The relationship with insulin resistance is clear at all ages studied. Less clear is the relationship with insulin secretion. The relative contribution of genes and environment to these relationships remains a matter of debate. The contributions of maternal hyperglycaemia and the trajectory of postnatal growth need to be clarified.
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            Socioeconomic disparities in adverse birth outcomes: a systematic review.

            Adverse birth outcomes, such as preterm birth and low birth weight, have serious health consequences across the life course. Socioeconomic disparities in birth outcomes have not been the subject of a recent systematic review. The aim of this study was to systematically review the literature on the association of socioeconomic disadvantage with adverse birth outcomes, with specific attention to the strength and consistency of effects across socioeconomic measures, birth outcomes, and populations. Relevant articles published from 1999 to 2007 were obtained through electronic database searches and manual searches of reference lists. English-language studies from industrialized countries were included if (1) study objectives included examination of a socioeconomic disparity in a birth outcome and (2) results were presented on the association between a socioeconomic predictor and a birth outcome related to birth weight, gestational age, or intrauterine growth. Two reviewers extracted data and independently rated study quality; data were analyzed in 2008-2009. Ninety-three of 106 studies reported a significant association, overall or within a population subgroup, between a socioeconomic measure and a birth outcome. Socioeconomic disadvantage was consistently associated with increased risk across socioeconomic measures, birth outcomes, and countries; many studies observed racial/ethnic differences in the effect of socioeconomic measures. Socioeconomic differences in birth outcomes remain pervasive, with substantial variation by racial or ethnic subgroup, and are associated with disadvantage measured at multiple levels (individual/family, neighborhood) and time points (childhood, adulthood), and with adverse health behaviors that are themselves socially patterned. Future reviews should focus on identifying interventions to successfully reduce socioeconomic disparities in birth outcomes. 2010 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
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              Nephron number in patients with primary hypertension.

              A diminished number of nephrons has been proposed as one of the factors contributing to the development of primary hypertension. To test this hypothesis, we used a three-dimensional stereologic method to compare the number and volume of glomeruli in 10 middle-aged white patients (age range, 35 to 59 years) with a history of primary hypertension or left ventricular hypertrophy (or both) and renal arteriolar lesions with the number and volume in 10 normotensive subjects matched for sex, age, height, and weight. All 20 subjects had died in accidents. Patients with hypertension had significantly fewer glomeruli per kidney than matched normotensive controls (median, 702,379 vs. 1,429,200). Patients with hypertension also had a significantly greater glomerular volume than did the controls (median, 6.50x10(-3) mm3 vs. 2.79x10(-3) mm3; P<0.001) but very few obsolescent glomeruli. The data support the hypothesis that the number of nephrons is reduced in white patients with primary hypertension. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Journal
                Rambam Maimonides Med J
                Rambam Maimonides Med J
                RMMJ
                Rambam Maimonides Medical Journal
                Rambam Health Care Campus
                2076-9172
                October 2011
                31 October 2011
                : 2
                : 4
                : e0061
                Affiliations
                [1* ]Associate Professor, Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada;
                [2 ]Internal Medicine Resident, Mount Auburn Hospital, Cambridge, MA, USA; and
                [3 ]Samuel A. Levine Distinguished Professor of Medicine Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
                Author notes
                [* ]To whom correspondence should be addressed. E-mail: vluyckx@ 123456ualberta.ca
                Article
                rmmj-2-4-e0061
                10.5041/RMMJ.10061
                3678805
                23908819
                8fb81727-bef6-4066-8b67-b6cdd7141503
                Copyright: © 2011 Luyckx et al.

                This is an open-access article. All its content, except where otherwise noted, is distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Clinical Implications of Basic Research

                low birth weight,nephron number,developmental programming,hypertension,renal disease,kidney size

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