Volume 87, Issue 2, Pages 434-441 (February 2015) Magnetic resonance–determined sodium removal from tissue stores in hemodialysis patients  Anke Dahlmann, Kathrin Dörfelt, Florian Eicher, Peter Linz, Christoph Kopp, Irina Mössinger, Stephan Horn, Beatrix Büschges-Seraphin, Peter Wabel, Matthias Hammon, Alexander Cavallaro, Kai-Uwe Eckardt, Peter Kotanko, Nathan W. Levin, Bernd Johannes, Michael Uder, Friedrich C. Luft, Dominik N. Müller, Jens M. Titze  Kidney International  Volume 87, Issue 2, Pages 434-441 (February 2015) DOI: 10.1038/ki.2014.269 Copyright © 2015 International Society of Nephrology Terms and Conditions

Figure 1 Age-dependent tissue Na+ content and serum vascular endothelial growth factor-C (VEGF-C) levels in patients with end-stage renal disease and in age-matched healthy controls. (Study 1) (a) Muscle and skin Na+ content in younger (<60 years) and older (≥60years) ESRD patients before (green box plot) and after HD treatment (striped green box plot) and in aged-matched normal controls (white box plot). (b) Plasma Na+ and serum VEGF-C levels in the patients (before HD treatment) and the same controls. (c) Relationship between age and skin Na+ content. (d) Relationship between age and circulating VEGF-C levels in controls with normal creatinine levels. (e) Inverse correlation between circulating VEGF-C levels and skin Na+ content in the same controls. Older age was associated with lower VEGF-C levels and with increased tissue Na+ content, suggesting that a reduction in VEGF-C levels may predispose to tissue Na+ accumulation with advancing age. *P(age)<0.05; †P(HD treatment)<0.05; ‡P(controls vs. ESRD patients)<0.05. ESRD, end-stage renal disease; HD, hemodialysis. TE 2.07 ms refers to echo time. Kidney International 2015 87, 434-441DOI: (10.1038/ki.2014.269) Copyright © 2015 International Society of Nephrology Terms and Conditions

Figure 2 Study 2: effects of dialysis on muscle and skin Na+. (a) Na+ content in muscle and in skin in 20 hemodialysis (HD) patients before and after HD with the batch dialysis (Genius) system. (b) MRI-determined muscle and skin water (arbitrary units) in the same 20 patients. (c) Relationship between calculated Na+ removal and measured Na+ removal from plasma in the same 20 patients. (d) Relationship between measured Na+ removal from plasma and measured muscle Na+ removal in the same patients. (e) Relationship between measured Na+ removal from plasma and measured skin Na+ removal in the same patients. Kidney International 2015 87, 434-441DOI: (10.1038/ki.2014.269) Copyright © 2015 International Society of Nephrology Terms and Conditions

Figure 3 Study 2: represen tative lower limb 23Na magnetic resonance imaging (Na-MRI) images from two end-stage renal disease patients before and after hemodialysis (HD). (a) Patient with high Na+ removal after HD, ultrafiltration rate 2.7l. (b) Patient with low Na+ removal, ultrafiltration rate 3.5l. Standards contain 10, 20, 30, and 40mmol/l Na+. Kidney International 2015 87, 434-441DOI: (10.1038/ki.2014.269) Copyright © 2015 International Society of Nephrology Terms and Conditions

Figure 4 Effect of age and circulating serum vascular endothelial growth factor-C (VEGF-C) levels on tissue Na+ content before and after hemodialysis (HD) and on tissue Na+ removal with HD in 33 male end-stage renal disease patients from studies 1 and 2. (a, b) Effect of younger (red) or older (black) age on Na+ content in muscle and in skin and effect of age on Na+ removal (ΔNa+). Younger age leads to lower muscle Na+ content before and after HD therapy and to lower skin Na+ content post HD. (c, d) Effect of lower (green) or higher (black) VEGF-C levels on Na+ content in muscle and in skin and effect of VEGF-C on Na+ removal (ΔNa+). Higher VEGF-C levels are associated with lower tissue Na+ content after dialysis and tend to improve skin Na+ removal with HD. TE 2.07ms refers to echo time. Kidney International 2015 87, 434-441DOI: (10.1038/ki.2014.269) Copyright © 2015 International Society of Nephrology Terms and Conditions