Loss of the Endothelial Glycocalyx Links Albuminuria and Vascular Dysfunction

Salmon, Andrew; Ferguson, Joanne; Burford, James; Gevorgyan, Haykanush; Nakano, Daisuke; Harper, Steven J.; Bates, David O.; Peti‐Peterdi, Janos

doi:10.1681/asn.2012010017

Cited by 225 publications

(232 citation statements)

References 82 publications

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“…Apart from proangiogenic growth factors (150), several proteins have been suggested to play a role in endothelial cell remodeling leading to fibrosis including ephrin-B (208), Crim-1 (209), Id proteins (210), miR-126 (211), and the glycocalyx of glomerular endothelial cells (212). In renal transplantation, peritubular endothelial damage, in particular endothelial C4d staining, reflects rejection (213).…”

Section: The Role Of Interstitial Mesenchymal Cellsmentioning

confidence: 99%

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Floege

2015

American Journal of Transplantation

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Section: The Role Of Interstitial Mesenchymal Cellsmentioning

confidence: 99%

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Floege

2015

American Journal of Transplantation

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“…7 The two photon microscopy method has been associated with technical issues, with some reports of albumin GSC values <0.0006. 8,9 These have been resolved by testing various background settings on the microscope. 10 Another technical issue raised has been 'out of focus' fluor escence, 11 but this has no physical basis in two photon microscopy.…”

Section: Wayne D Compermentioning

confidence: 99%

Albuminuria is controlled primarily by proximal tubules

Comper¹

2014

Nat Rev Nephrol

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“…Loss of the glomerular ESL has been associated with albuminuria in patients with diabetic nephropathy and in an experimental animal model (31,32). In the present study, the loss of anionic charges in the GBM and ESL was not assessed in UNx-THM.…”

Section: Discussionmentioning

confidence: 70%

Effects of aging and uninephrectomy on renal changes in Tsukuba hypertensive mice

Inui¹,

Mochida²,

Yamairi

et al. 2013

Biomedical Reports

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Abstract. Renal dysfunction is accelerated by various factors such as hypertension, aging and diabetes. Glomerular hyperfiltration, considered one of the major risk factors leading to diabetic nephropathy, is often encountered in diabetic patients. However, the interrelationship of these risk factors during the course and development of renal dysfunction has not been fully elucidated. In this study, the effects of aging and uninephrectomy (UNx)-induced hyperfiltration on renal changes were investigated in Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes. In THM, the urinary albumin/creatinine (Alb/Cr) ratio was elevated with age without a concomitant increase in the plasma Cr concentration. Moreover, the urinary neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr) ratio, the renal monocyte chemoattractant protein-1 (MCP-1) mRNA expression and the renal collagen type I α 2 (COL1A2) mRNA expression were also increased with age. Age-related albuminuria in THM is likely caused by renal tubular damage, enhanced inflammatory response and tubulointerstitial fibrosis. Furthermore, following UNx, the urinary Alb̸Cr ratio and the plasma Cr concentration were increased in THM. The urinary NGAL/Cr ratio and the renal MCP-1 and COL1A2 mRNA expression were not affected by UNx. These results suggested that UNx-induced albuminuria in THM was caused by glomerular dysfunction, rather than renal tubular injury. In conclusion, this study demonstrated for the first time the effects of aging and UNx on renal changes in THM. These findings strongly reinforce the significance of applying a diversity of therapeutic approaches to the management of renal dysfunction. IntroductionChronic kidney disease (CKD) is a major public health concern worldwide because of the increasing prevalence of end-stage renal failure requiring dialysis or kidney transplantation and the increased risk of morbidity and mortality due to cardiovascular diseases (1-6). Aging leads to renal structural changes and functional decline. Imai et al (7) and Coresh et al (8) suggested that the prevalence of CKD increases with age. Moreover, a significantly higher prevalence of CKD was reported in hypertensive patients compared to normotensive subjects (8,9). High systemic blood pressure leads to pressure elevation in the glomerular capillaries, which is associated with renal vascular dysfunction. Elevated pressure in the glomerular capillaries results in glomerular sclerosis, increased albuminuria and decreased glomerular filtration rate (10). Furthermore, glomerular hyperfiltration is often observed during the early stages of diabetes and may contribute to the development of diabetic nephropathy (11,12). Thus, the progression of CKD is affected by various risk factors such as aging, hypertension and hyperfiltration. However, the interrelationship of individual risk factors during the course of renal dysfunction has not been fully elucidated.Tsukuba hypertensive mice (THM) are transgenic mice carrying both human renin and angiotensino...

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Loss of the Endothelial Glycocalyx Links Albuminuria and Vascular Dysfunction

Cited by 225 publications

References 82 publications

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Albuminuria is controlled primarily by proximal tubules

Effects of aging and uninephrectomy on renal changes in Tsukuba hypertensive mice

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