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      Gender-dependent effects of aging on the kidney

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          Abstract

          It is well known that the kidney plays an important role in the development of cardiovascular diseases such as hypertension. The normal aging process leads to changes in kidney morphology, hemodynamics and function, which increase the incidence of cardiovascular events in the elderly population. These disturbances are influenced by several factors, including gender. In general, females are protected by the effects of estrogens on the cardiorenal system. Several studies have demonstrated the beneficial effects of estrogens on renal function in the elderly; however, the relationships between androgens and kidney health during one’s lifetime are not well understood. Sex steroids have many complex actions, and the decline in their levels during aging clearly influences kidney function, decreases the renal reserve and facilitates the development of cardiovascular disorders. Therefore, in this review, we discuss the cellular, biochemical, and molecular mechanisms by which sex hormones may influence renal function during the aging process.

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          Most cited references63

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          Differences in decline in GFR with age between males and females. Reference data on clearances of inulin and PAH in potential kidney donors.

          U Berg (2006)
          To ensure that potential kidney donors have no renal impairment, it is extremely important to have accurate methods for evaluating the glomerular filtration rate (GFR). The golden standard, clearance of inulin, has been used in the present study. The aim was to evaluate the effects of age and sex on renal function and present reference data. A total of 122 potential kidney donors, 62 females, aged 21-67 years, were investigated with the GFR and effective renal plasma flow (ERPF) determined by clearances of inulin and para-amino hippurate. The mean +/- SD GFR and ERPF were 105 +/- 13 and 545 +/- 108 ml/min/1.73 m(2), respectively, and we found no difference between the males and females. When relating GFR and ERPF to age, however, a significant decline was found in GFR and ERPF in males, but not in females in the age range of 20-50 years. GFR fell by a mean of 8.7 ml/min/1.73 m(2) and ERPF by 90 ml/min/1.73 m(2) per decade in male donors. With adequate methods for determining GFR and ERPF, a clear difference in the effect of age was seen between the sexes. Males showed a significant decrease between 20 and 50 years of age, which was not seen in females. Females seem to be protected in the pre-menopausal period probably by oestrogens. These results confirm clinically those found in rats.
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            Testosterone Exacerbates Hypertension and Reduces Pressure-Natriuresis in Male Spontaneously Hypertensive Rats

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              Sexual dimorphism in the aging kidney: differences in the nitric oxide system.

              Females-both rats and women-are substantially protected against the age-dependent decrease in renal function that occurs in males of the species. In part, this finding reflects the cardioprotective and renoprotective effects of estrogens, but estrogen has multiple actions, not all of which are beneficial. In addition, the low androgen level in women might be protective against a decline in renal function, but animal and clinical data on possible adverse effects of androgens are controversial. Androgens also have multiple actions, one of which-aromatization to estrogen-is likely to be protective. Sex steroids clearly have many complex actions, which explains the conflicting information on their relative benefits and dangers. Endothelial nitric oxide (NO) deficiency contributes importantly to cardiovascular risk and intrarenal NO deficiency is clearly linked to chronic kidney disease progression in animal models. Endothelial dysfunction develops with increasing age but is delayed in females, correlating with a delayed rise in asymmetric dimethylarginine level. There is no clear link between aging and arginine (the NO synthase substrate) deficiency. Animal data suggest that the aging kidney develops NO deficiency as a result of changes in neuronal NO synthase. The increased oxidative stress that occurs with aging affects multiple stages of the NO biosynthetic pathway and results in decreased production and/or action of NO. NO production is better preserved in females than in males, partly as a result of the actions of estrogens.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                bjmbr
                Brazilian Journal of Medical and Biological Research
                Braz J Med Biol Res
                Associação Brasileira de Divulgação Científica (Ribeirão Preto )
                1414-431X
                September 2011
                : 44
                : 9
                : 905-913
                Affiliations
                [1 ] Universidade Federal do Espírito Santo Brazil
                [2 ] Universidade Federal do Espírito Santo Brazil
                Article
                S0100-879X2011000900012
                10.1590/S0100-879X2011000900012
                507d21d4-8f81-4d23-b359-7c4047223d29

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0100-879X&lng=en
                Categories
                BIOLOGY
                MEDICINE, RESEARCH & EXPERIMENTAL

                Medicine,General life sciences
                Sexual dimorphism,Renal function,Aging,Cardiovascular disorders,Sex hormones

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