RAS and sex differences in diabetic nephropathy

Clotet, Sergi; Riera, Marta; Pascual, Julio; Soler, María José

doi:10.1152/ajprenal.00292.2015

Cited by 49 publications

(52 citation statements)

References 143 publications

(160 reference statements)

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“…Despite the relatively small number of volunteers, the homogeneity of our sample resulted in variables with Gaussian distribution, thus allowing the use of parametric methods for statistical analysis. The inclusion of only males also avoided the wellknow interferences of menstrual cycles and hormone release of female gender on physical activities and RAS profile (Clotet et al, 2016). On the contrary, the inclusion of only young healthy men did not allow us to infer our findings for women, children, elderly individuals and patients with chronic diseases.…”

Section: Discussionmentioning

confidence: 91%

Two protocols of aerobic exercise modulate the counter-regulatory axis of the renin-angiotensin system

Magalhães

Nunes-Silva

Rocha

et al. 2020

Heliyon

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Aims: The renin-angiotensin system (RAS) is a dual system with two opposite arms: i) the classical one formed by the angiotensin converting enzyme (ACE), angiotensin (Ang) II and angiotensin type 1 (AT1) receptors; ii) the counter-regulatory arm consisting of ACE2, Ang-(1-7) and Mas receptor. Physical exercise can modulate this system, however, only animal studies have compared the effects of different intensity protocols on the RAS. No data with humans were provided. Therefore, we investigated the acute effect of two protocols of isowork aerobic exercise [High-Intensity Interval Exercise (HIIE) and Moderate-Intensity Continuous Exercise (MICE)] in plasma and urinary levels of RAS components in physically active men. Main methods: The HIIE protocol included a 5-minute warm-up cycling at 60-70% of heart rate peak (HRp) intensity followed by 10 sets of 30 s above 90% with 1 min of recovery and 3 min of cool down. The MICE protocol was performed at a constant power corresponding to 60-70% of HRp and finalized at the same total work of HIIE. Blood and urine samples were collected before and after the protocols. Plasma and urinary levels of ACE, ACE2, Ang-(1-7) and Ang II were analyzed by enzyme-linked immunoassay. Key findings: While the HIIE protocol significantly increased urinary levels of ACE and plasma levels of ACE2, the MICE protocol elevated urinary concentrations of ACE2 and of Ang-(1-7). A greater increase of urine concentrations of Ang-(1-7) occurred in the MICE if compared with the HIIE protocol. Significance: Aerobic physical exercise acutely increases the activity of the counter-regulatory RAS axis, mostly the MICE protocol.

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Section: Discussionmentioning

confidence: 91%

Two protocols of aerobic exercise modulate the counter-regulatory axis of the renin-angiotensin system

Magalhães

Nunes-Silva

Rocha

et al. 2020

Heliyon

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“…As will be discussed below, sex hormones are thought to regulate renal hemodynamics, oxidative stress, inflammation, and key biological pathways involved in the pathophysiology of DKD. 42,[63][64][65][66] Other general factors that lead to DKD in a sex-specific manner include: type and duration of diabetes, biological age, age at onset of diabetes, and genetic and epigenetic factors, et cetera. 67,68 Classical risk factors for DKD, including glycemic control, hypertension, obesity, and dyslipidemia have also been reported to differentially contribute to disease pathophysiology according to sex.…”

Section: Mechanisms Underlying Sex Differ-ences In Dkdmentioning

confidence: 99%

Sex Differences in Diabetic Kidney Disease

Maric‐Bilkan

2020

Mayo Clinic Proceedings

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While the global prevalence of both type 1 and type 2 diabetes mellitus is similar in men and women, the consequences of diabetes on associated end-organ complications, including diabetic kidney disease appear to be more sex-specific. Particularly, women with diabetes have higher mortality rates for diabetes-related deaths, and higher prevalence of diabetic kidney disease risk factors such as hypertension, hyperglycemia, obesity, and dyslipidemia. However, the evidence for the impact of sex on diabetic kidney disease prevalence and disease progression is limited and inconsistent. Although most studies agree that the protective effect of the female sex against the development of kidney disease is diminished in the setting of diabetes, the reasons for this observation are unclear. Whether or not sex differences exist in the risk of diabetic kidney disease is also unclear, with studies reporting either higher risk in men, women, or no sex differences. Despite the remaining controversies, some of the factors that associate with sex differences in the risk of diabetic kidney disease are age at onset, and type and duration of diabetes. There is growing appreciation of the importance of sex hormones in the regulation of renal function, with estrogens generally considered to be renoprotective. Although some progress has been made towards better understanding of the mechanisms by which sex hormones play a role in the pathophysiology of diabetic kidney disease, the translational potential

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“…Diabetic kidney disease (DKD) is the most prevalent cause of end-stage kidney disease (ESKD) affecting both men and women (Harjutsalo and Groop, 2014). Several studies have indicated that diabetic males have an increased risk of developing albuminuria and renal function impairment, although this does vary with age and is confounded by hypertension and obesity (Harjutsalo et al 2011;Neugarten and Golestaneh, 2013;Clotet et al 2016). Gender differences in DKD are thought to be related to levels of the sex hormones 17b-estradiol and testosterone (Dixon and Maric, 2007;Xu et al 2008;Catanuto et al 2009), but are not clearly defined (Diamond-Stanic et al 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Gender differences in DKD are thought to be related to levels of the sex hormones 17b-estradiol and testosterone (Dixon and Maric, 2007;Xu et al 2008;Catanuto et al 2009), but are not clearly defined (Diamond-Stanic et al 2012). Some experimental studies suggest that these sex hormones can influence the progression of diabetic nephropathy by regulating TGF-b signaling, macrophage infiltration, or components of the renin angiotensin system (Diamond-Stanic et al 2012;Clotet et al 2016). These findings indicate that optimal clinical treatment of patients with DKD may require a better understanding of potential sex differences in disease progression associated with age and other comorbidities.…”

Section: Introductionmentioning

confidence: 99%

Establishing equivalent diabetes in male and female Nos3‐deficient mice results in a comparable onset of diabetic kidney injury

Tian

Tesch

2019

Physiol Rep

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Clinical studies indicate that sex differences exist in susceptibility for developing diabetic kidney disease (DKD), supporting the need to examine both sexes in animal studies of DKD. Streptozotocin (STZ) is commonly used in male mice to induce diabetes and DKD. However, females are not normally included because their sex hormones partially protect them from STZ‐induced islet injury and consequent diabetes. To address this issue, we identified a strategy to induce comparable diabetes in male and female mice using STZ and determined whether both sexes develop equivalent renal injury. Male and female mice lacking the gene for endothelial nitric oxide synthase (Nos3‐/‐) were made diabetic with five or six low‐dose STZ injections, respectively. Groups of male and female mice with equivalent hyperglycemia at week 3 after STZ were assessed for DKD at week 8. STZ‐treated male and female Nos3‐/‐ mice maintained comparable hyperglycemia between weeks 3 and 8 had an equivalent increase in HbA1c levels and comparable hypertension. Urine albumin/creatinine levels were elevated eightfold in mice of both sexes at week 8, accompanied by an equivalent loss of podocytes. In diabetic males and females, plasma cystatin C levels and glomerular collagen deposition were similarly increased. Kidney mRNA levels of proinflammatory and profibrotic markers and kidney injury molecule‐1 (KIM‐1) were equally elevated in males and females, indicating comparable kidney injury. This study shows that equivalent diabetes induces a comparable onset of DKD in male and female Nos3‐/‐ mice, demonstrating that it is possible to include males and females together in studies of DKD.

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RAS and sex differences in diabetic nephropathy

Cited by 49 publications

References 143 publications

Two protocols of aerobic exercise modulate the counter-regulatory axis of the renin-angiotensin system

Two protocols of aerobic exercise modulate the counter-regulatory axis of the renin-angiotensin system

Sex Differences in Diabetic Kidney Disease

Establishing equivalent diabetes in male and female Nos3‐deficient mice results in a comparable onset of diabetic kidney injury

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