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      Age-Dependent Telomere Attrition as a Potential Indicator of Racial Differences in Renal Growth Patterns

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          Abstract

          Background: Racial differences in the predilection to salt sensitivity may arise from different renal growth patterns. To test this idea, we monitored age-dependent telomere attrition rate, reflecting largely the replicative history of somatic cells, in the outer renal cortex and the inner renal medulla of African Americans and Caucasians. Methods: Telomere length, determined by the mean length of the terminal restriction fragments (TRF), was measured in specimens from 58 African-American and 63 Caucasian males, ages 1 day to 71 years. Results: In the outer renal cortex, TRF length attrition rate was significantly slower in African Americans (–0.021 ± 0.0064 kb/year) than in Caucasians (–0.060 ± 0.0094 kb/year) (p = 0.0007). In both ethnic groups the TRF length attrition rate was slower in the inner medulla than in the outer renal cortex, but without significant racial differences. Conclusions: The proximal tubule is the most abundant nephron structure in the outer renal cortex. Less proliferative growth of proximal tubular cells in kidneys from African Americans may be one factor explaining the slower age-dependent telomere attrition rate in the outer renal cortex of African Americans than in Caucasians.

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          Oxidative stress shortens telomeres.

          Telomeres in most human cells shorten with each round of DNA replication, because they lack the enzyme telomerase. This is not, however, the only determinant of the rate of loss of telomeric DNA. Oxidative damage is repaired less well in telomeric DNA than elsewhere in the chromosome, and oxidative stress accelerates telomere loss, whereas antioxidants decelerate it. I suggest here that oxidative stress is an important modulator of telomere loss and that telomere-driven replicative senescence is primarily a stress response. This might have evolved to block the growth of cells that have been exposed to a high risk of mutation.
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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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              Glomerular number and size in autopsy kidneys: the relationship to birth weight.

              In the Southeast United States, African Americans have an estimated incidence of hypertension and end-stage renal disease (ESRD) that is five times greater than Caucasians. Higher rates of low birth weight (LBW) among African Americans is suggested to predispose African Americans to the higher risk, possibly by reducing the number of glomeruli that develop in the kidney. This study investigates the relationships between age, race, gender, total glomerular number (Nglom), mean glomerular volume (Vglom), body surface area (BSA), and birth weight. Stereologic estimates of Nglom and Vglom were obtained using the physical disector/fractionator combination for autopsy kidneys from 37 African Americans and 19 Caucasians. Nglom was normally distributed and ranged from 227,327 to 1,825,380, an 8.0-fold difference. A direct linear relationship was observed between Nglom and birth weight (r = 0.423, P = 0.0012) with a regression coefficient that predicted an increase of 257,426 glomeruli per kilogram increase in birth weight (alpha = 0.050:0.908). Among adults there was a 4.9-fold range in Vglom, and in adults, Vglom was strongly and inversely correlated with Nglom (r =-0.640, P = 0.000002). Adult Vglom showed no significant correlation with BSA for males (r = -0.0150, P = 0.936), although it did for females (r = 0.606, P = 0.022). No racial differences in average Nglom or Vglom were observed. Birth weight is a strong determinant of Nglom and thereby of glomerular size in the postnatal kidney. The findings support the hypothesis that LBW by impairing nephron development is a risk factor for hypertension and ESRD in adulthood.
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                Author and article information

                Journal
                NEE
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                2004
                November 2004
                17 November 2004
                : 98
                : 3
                : e82-e88
                Affiliations
                aHypertension Research Center, bDepartment of Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, N.J., cDivision of Nephrology, The Mount Sinai School of Medicine, New York, N.Y., and dThe Brain and Tissue Bank for Developmental Disorders, University of Maryland, Baltimore, Md., USA
                Article
                80683 Nephron Exp Nephrol 2004;98:e82–e88
                10.1159/000080683
                15528948
                2079a4d9-8407-4a80-9775-acc648c74ac0
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 28 January 2004
                : 20 May 2004
                Page count
                Figures: 4, Tables: 1, References: 34, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Hypertension,African Americans,Renal growth,Telomeres,Caucasians,Sodium chloride

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