Salt and Water Retention Is Associated with Microinflammation and Endothelial Injury in Chronic Kidney Disease.

BACKGROUND: Progressive chronic kidney disease (CKD) inevitably leads to salt and water retention and disturbances in the macro-and microcirculation. OBJECTIVES: We hypothesize that salt and water dysregulation in advanced CKD may be linked to inflammation and microvascular injury pathways. METHODS: We studied 23 CKD stage 5 patients and 11 healthy controls (HC). Tissue sodium concentration was assessed using 23Sodium magnetic resonance (MR) imaging. Hydration status was evaluated using bioimpedance spectroscopy. A panel of inflammatory and endothelial biomarkers was also measured. RESULTS: CKD patients had fluid overload (FO) when compared to HC (overhydration index: CKD = 0.5 ± 1.9 L vs. HC = -0.5 ± 1.0 L; p = 0.03). MR-derived tissue sodium concentrations were predominantly higher in the subcutaneous (SC) compartment (median [interquartile range] CKD = 22.4 mmol/L [19.4-31.3] vs. HC = 18.4 mmol/L [16.6-21.3]; p = 0.03), but not the muscle (CKD = 24.9 ± 5.5 mmol/L vs. HC = 22.8 ± 2.5 mmol/L; p = 0.26). Tissue sodium in both compartments correlated to FO (muscle: r = 0.63, p < 0.01; SC: rs = 0.63, p < 0.01). CKD subjects had elevated levels of vascular cell adhesion molecule (p < 0.05), tumor necrosis factor-alpha (p < 0.01), and interleukin (IL)-6 (p = 0.01) and lower levels of vascular endothelial growth factor-C (p = 0.04). FO in CKD was linked to higher IL-8 (r = 0.51, p < 0.05) and inversely associated to E-selectin (r = -0.52, p = 0.01). Higher SC sodium was linked to higher intracellular adhesion molecule (ICAM; rs = 0.54, p = 0.02). CONCLUSION: Salt and water accumulation in CKD appears to be linked with inflammation and endothelial activation pathways. Specifically IL-8, E-Selectin (in FO), and ICAM (in salt accumulation) may be implicated in the pathophysiology of FO and merit further investigation.

Elevated tissue sodium deposition in patients with type 2 diabetes on hemodialysis detected by 23Na magnetic resonance imaging.

Long-term elevated blood sugar levels result in tissue matrix compositional changes in patients with diabetes mellitus type 2 (T2DM). We hypothesized that hemodialysis patients with T2DM might accumulate more tissue sodium than control hemodialysis patients. To test this, 23Na magnetic resonance imaging (23Na MRI) was used to estimate sodium in skin and muscle tissue in hemodialysis patients with or without T2DM. Muscle fat content was estimated by 1H MRI and tissue sodium content by 23Na MRI pre- and post-hemodialysis in ten hemodialysis patients with T2DM and in 30 matched control hemodialysis patients. We also assessed body fluid distribution with the Body Composition Monitor. 1H MRI indicated a tendency to higher muscle fat content in hemodialysis patients with T2DM compared to non-diabetic hemodialysis patients. 23Na MRI indicated increased sodium content in muscle and skin tissue of hemodialysis patients with T2DM compared to control hemodialysis patients. Multi-frequency bioimpedance was used to estimate extracellular water (ECW), and excess ECW in T2DM hemodialysis patients correlated with HbA1c levels. Sodium mobilization during hemodialysis lowered muscle sodium content post-dialysis to a greater degree in T2DM hemodialysis patients than in control hemodialysis patients. Thus, our findings provide evidence that increased sodium accumulation occurs in hemodialysis patients with T2DM and that impaired serum glucose metabolism is associated with disturbances in tissue sodium and water content.

Estimating dual-energy X-ray absorptiometry-derived total body skeletal muscle mass using single-slice abdominal magnetic resonance imaging in obese subjects with and without diabetes: a pilot study.

BACKGROUND/OBJECTIVES: Single-slice abdominal computed tomography or magnetic resonance imaging (MRI) performed to measure visceral adipose tissue in individuals with obesity and diabetes mellitus can also image skeletal muscle. The aim of this study was to validate a method developed in cancer patients using a single abdominal cross-sectional image to estimate fat-free mass (FFM) and appendicular lean tissue mass index (LTMI), a total body skeletal muscle mass surrogate, in an obese cohort of subjects with and without type 2 diabetes. SUBJECTS/METHODS: In total, 49 obese subjects (22 with diabetes) recruited into a weight loss study underwent dual-energy X-ray absorptiometry (DXA) and abdominal MRI at baseline. DXA-derived FFM and LTMI were compared with skeletal muscle area at the level of the third lumbar vertebra (L3) on MRI. RESULTS: L3 skeletal muscle area correlated with FFM (R (adj) (2)=0.825; P<0.001) and LTMI (R (adj) (2)=0.6; P<0.001). A simple formula, previously shown to predict LTMI in cancer patients, produced a good estimation of LTMI from L3 skeletal muscle area (95% confidence interval -3.70, 2.56%) in our obese cohort. Equations incorporating age, sex, height, weight and diabetic status improved the relationship between L3 skeletal muscle area and estimated FFM (r=0.976, P<0.001) and LTMI (r=0.879, P<0.001). CONCLUSION: A single-axial slice at the L3 level can be used to estimate FFM and LTMI in obese diabetic and non-diabetic subjects, allowing precise analysis of body composition using a single imaging modality in clinical research and practice.

The association between abdominal body composition and vascular calcification.

Subclinical cardiovascular disease (CVD) may be associated with both adipose and skeletal muscle tissues in the abdomen. Accordingly, we examined whether subcutaneous, intermuscular, and visceral adipose tissue, as well as abdominal lean muscle, were associated with the presence and extent of vascular calcification in multiple vascular beds. Three hundred and ninety four patients (58.1% men) underwent electron beam computed tomography (EBCT) scans as part of routine health maintenance screening. The coronary and carotid calcium scores were analyzed at the time of the scan, whereas the other calcium scores, as well as the body composition analyses, were analyzed retrospectively. Mean age was 55.2 ± 11.1 years and BMI was 26.9 ± 4.2. The prevalence of any calcification in the carotids, coronaries, thoracic aorta, abdominal aorta, and iliacs was 30.1, 60.1, 39.8, 55.7, and 56.8%, respectively. Compared to those with calcification in different vascular beds, those without vascular calcification generally had significantly more lean muscle and less adipose tissue. In separate multivariable logistic models, a 1 s.d. increment in the ratio of abdominal and visceral fat to total area of each corresponding compartments was significantly associated with an increased odds for the presence of thoracic aortic calcium (odds ratio (OR) = 1.6, 1.5, respectively; P = 0.01 for both). Conversely, increases in abdominal lean muscle were associated with significantly decreased odds of thoracic aortic calcification (OR = 0.34; P ≤ 0.01). A similar pattern of associations existed among the other vascular beds. Also, the association between lean muscle and vascular calcification was independent of visceral adipose tissue. In conclusion, adipose tissue was positively and lean body mass inversely associated with prevalent aortic calcification.

Regional body composition: cross-calibration of DXA scanners--QDR4500W and Discovery Wi.

Differences exist in body composition assessed by dual-energy X-ray absorptiometers (DXAs) between devices produced by different manufacturers and different models from the same manufacturer. Cross-calibration is needed to allow body composition results to be compared in multicenter trials or when scanners are replaced. The aim was to determine reproducibility and extent of agreement between two fan-beam DXA scanners (QDR4500W, Discovery Wi) for body composition of regional sites. The sample was: 39 women 50.6 +/- 9.6 years old with BMI 26.8 +/- 5.5 kg/m(2), body fat 33 +/- 7%. Four whole body scans (two on each device) were performed over 3 weeks. Major variables were fat mass, nonosseous lean mass, and bone mineral content (BMC) for the truncal and appendicular regions. Extent of agreement was assessed using Bland and Altman plots. Both devices demonstrated good precision with mean test-retest differences close to zero for fat mass, nonosseous lean mass, and BMC of the truncal and appendicular regions. Evaluation of interdevice agreement revealed significant differences for truncal and appendicular BMC, nonosseous lean mass, and fat mass. The greatest interdevice difference was for truncal fat mass (0.69 +/- 0.60 kg). Differences in truncal and appendicular fat mass increased in magnitude at higher mean values. Furthermore, differences in truncal and appendicular fat mass were strongly related to BMI (R = -0.61, R = -0.55, respectively). In conclusion, in vivo cross-calibration is important to ensure comparability of regional body composition data between scanners, especially for truncal fat mass and for subjects with higher BMI.