Sex and the Kidney

Iliescu, Radu; Reckelhoff, Jane F.

doi:10.1161/hypertensionaha.107.101345

Cited by 17 publications

(14 citation statements)

References 14 publications

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“…In addition, male mice were more susceptible to C2RD than female mice (Fig.2B), which is reminiscent of the sex differences in human chronic kidney diseases (23). Histological analysis revealed inflammation and varied loss of the renal medulla and the cortex (Supplemental Fig.1A).…”

Section: Resultsmentioning

confidence: 88%

Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell–Mediated Ureteritis and Hydronephrosis

Park

Goergen

HogenEsch

et al. 2016

The Journal of Immunology

146

104

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Short-chain fatty acids (SCFAs) are major products of gut microbial fermentation and profoundly affect host health and disease. SCFAs generate IL-10+ regulatory T cells, which may promote immune tolerance. However, SCFAs can also induce Th1 and Th17 cells upon immunological challenges and, therefore, also have the potential to induce inflammatory responses. Because of the seemingly paradoxical SCFA activities in regulating T cells, we investigated, in depth, the impact of elevated SCFA levels on T cells and tissue inflammation in mice. Orally administered SCFAs induced effector (Th1 and Th17) and regulatory T cells in ureter and kidney tissues, and they induced T cell–mediated ureteritis, leading to kidney hydronephrosis (hereafter called acetate-induced renal disease, or C2RD). Kidney hydronephrosis in C2RD was caused by ureteral obstruction, which was, in turn, induced by SCFA-induced inflammation in the ureteropelvic junction and proximal ureter. Oral administration of all major SCFAs, such as acetate, propionate, and butyrate, induced the disease. We found that C2RD development is dependent on mammalian target of rapamycin activation, T cell–derived inflammatory cytokines such as IFN-γ and IL-17, and gut microbiota. Young or male animals were more susceptible than old or female animals, respectively. However, SCFA receptor (GPR41 or GPR43) deficiency did not affect C2RD development. Thus, SCFAs, when systemically administered at levels higher than physiological levels, cause dysregulated T cell responses and tissue inflammation in the renal system. The results provide insights into the immunological and pathological effects of chronically elevated SCFAs.

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Section: Resultsmentioning

confidence: 88%

Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell–Mediated Ureteritis and Hydronephrosis

Park

Goergen

HogenEsch

et al. 2016

The Journal of Immunology

146

104

View full text Add to dashboard Cite

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“…The relation of sex dimorphism to CKD is still not well known. Even though male gender is thought to be associated with severe progression of CKD, it is still not known whether it is male or female gender that is at higher risk of CKD occurrence and progression and what is the potential mechanism of the phenomenon [30–32]. …”

Section: Discussionmentioning

confidence: 99%

Association of rs1800471 polymorphism of TGFB1 gene with chronic kidney disease occurrence and progression and hypertension appearance

Nabrdalik¹,

Gumprecht²,

Adamczyk³

et al. 2013

aoms

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IntroductionTransforming growth factor β1 (TGF-β1) is a cytokine involved in the process of pathological tissue sclerosis, which is part of the pathophysiological mechanism of end stage renal disease development. The aim of the study was to evaluate the association of the single nucleotide polymorphism rs1800471 of the TGFB1 gene with chronic kidney disease (CKD) occurrence and progression as well as hypertension appearance.Material and methodsIt was a case-control study where 109 patients with CKD and 111 very old people were enrolled. The association of the studied polymorphism with mentioned diseases was assessed in the whole study group as well as in the subgroups stratified according to the underlying etiology of CKD: nephropathy in type 1 diabetes (n = 13), chronic glomerulonephritis (n = 50) and chronic interstitial nephritis (n = 46).ResultsNo association of CKD progression with rs1800471 polymorphism was observed. The C allele was identified as the one associated with higher risk of the disease occurrence in the dominant model of inheritance (p = 0.035). The C allele in women, opposite to male gender, was associated with higher risk of CKD development (p = 0.038). GG genotype was associated with elevated risk of hypertension appearance (p = 0,0021).ConclusionsDue to the lack of accordance with previously performed studies it is still impossible to state an unequivocal conclusion regarding the association between rs1800471 polymorphism of the TGFB1 gene and risk of CKD occurrence and progression as well as hypertension appearance. That is why it is necessary to perform further studies in this field.

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“…Notably, sex-related differences in the incidence and severity of renal disease are not uncommon. 38 Multiple studies have found higher levels of UAE in men than in women, 13,39,40 which may be due to sex-related differences in endothelial function 41 or glomerular hemodynamics. 42 …”

Section: Discussionmentioning

confidence: 99%

Is Longitudinal Pulse Pressure a Better Predictor of 24-Hour Urinary Albumin Excretion Than Other Indices of Blood Pressure?

et al. 2010

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Background The strong relationship between urinary albumin excretion (UAE) and pulse pressure (PP) in cross-sectional studies suggests that pressure pulsatility may contribute to renal microvascular injury. The longitudinal relationships between UAE and the various indices of blood pressure (BP) are not well studied. We compared the associations of UAE with the longitudinal burden of PP, systolic, diastolic, and mean BP. Methods and Results UAE was measured from 24-hour urine collections in 450 community-dwelling subjects (age=57±15 years, 53% women, all with UAE<200 µg/min). For each subject, longitudinal indices of BP were estimated by dividing the area under the curve of serial measurements of BP (median=5) during 1–22 years preceding UAE measurement by the number of follow-up years. Median [interquartile range] UAE was 4.7 [3.3–7.8] µg/min in women and 5.2 [3.7–9.8] µg/min in men. In women, UAE was not related to longitudinal indices of BP. In men, in multivariable-adjusted models that included either longitudinal systolic and diastolic BP, or longitudinal PP and mean BP, UAE was independently associated with systolic (β=0.227, P=0.03), but not with diastolic (β=−0.049, P=0.59) BP, and with PP (β=0.216, P=0.01), but not with mean BP (β=0.032, P=0.72). Comparisons of these two models and stepwise regression analyses both indicated that, of the four longitudinal indices of BP, PP was the strongest predictor of UAE in men. Conclusion Chronic exposure to high pressure pulsatility is a strong risk factor for hypertensive nephropathy. Future studies should examine whether PP reduction provides additional renoprotection beyond that conferred by conventional BP goals alone.

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Sex and the Kidney

Cited by 17 publications

References 14 publications

Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell–Mediated Ureteritis and Hydronephrosis

Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell–Mediated Ureteritis and Hydronephrosis

Association of rs1800471 polymorphism of TGFB1 gene with chronic kidney disease occurrence and progression and hypertension appearance

Is Longitudinal Pulse Pressure a Better Predictor of 24-Hour Urinary Albumin Excretion Than Other Indices of Blood Pressure?

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