Magnetic resonance-determined sodium removal from tissue stores in hemodialysis patients

Abstract

We have previously reported that sodium is stored in skin and muscle. The amounts stored in hemodialysis (HD) patients are unknown. We determined whether (23)Na magnetic resonance imaging (sodium-MRI) allows assessment of tissue sodium and its removal in 24 HD patients and 27 age-matched healthy controls. We also studied 20 HD patients before and shortly after HD with a batch dialysis system with direct measurement of sodium in dialysate and ultrafiltrate. Age was associated with higher tissue sodium content in controls. This increase was paralleled by an age-dependent decrease of circulating levels of vascular endothelial growth factor-C (VEGF-C). Older (>60 years) HD patients showed increased sodium and water in skin and muscle and lower VEGF-C levels compared with age-matched controls. After HD, patients with low VEGF-C levels had significantly higher skin sodium content compared with patients with high VEGF-C levels (low VEGF-C: 2.3 ng/ml and skin sodium: 24.3 mmol/l; high VEGF-C: 4.1 ng/ml and skin sodium: 18.2 mmol/l). Thus, sodium-MRI quantitatively detects sodium stored in skin and muscle in humans and allows studying sodium storage reduction in ESRD patients. Age and VEGF-C-related local tissue-specific clearance mechanisms may determine the efficacy of tissue sodium removal with HD. Prospective trials on the relationship between tissue sodium content and hard end points could provide new insights into sodium homeostasis, and clarify whether increased sodium storage is a cardiovascular risk factor.

Conflict of interest statement

Disclosure statement

The authors have no interest conflicts and nothing to disclose.

Figures

Figure 1

A. (Study 1) 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 circulating VEGF-C levels and skin Na+ content in the controls with normal creatinine levels. 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 versus ESRD patients) <0.05.

Figure 2

A. (Study 2) Na+ content in muscle and in skin in 20 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.

Fig. 3

(Study 2) Representative lower limb Na-MRI images from two ESRD patients before and after HD. A. Patient with high Na+ removal after HD, ultrafiltration rate 2.7 liter. B. Patient with low Na+ removal, ultrafiltration rate 3.5 liter. Standards contain 10, 20, 30, 40 mmol/L Na+.

Fig. 4

Effect of age and circulating serum VEGF-C levels on tissue Na+ content before and after HD and on tissue Na+ removal with HD in 33 male ESRD patients from studies 1 and 2. A. and 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. and 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 = 2.07 ms refers to echo time.