High tissue-sodium associates with systemic inflammation and insulin resistance in obese individuals.

BACKGROUND AND AIMS: High sodium intake is associated with obesity and insulin resistance, and high extracellular sodium content may induce systemic inflammation, leading to cardiovascular disease. In this study, we aim to investigate whether high tissue sodium accumulation relates with obesity-related insulin resistance and whether the pro-inflammatory effects of excess tissue sodium accumulation may contribute to such association. METHODS AND RESULTS: In a cross-sectional study of 30 obese and 53 non-obese subjects, we measured insulin sensitivity determined as glucose disposal rate (GDR) using hyperinsulinemic euglycemic clamp, and tissue sodium content using 23Na magnetic resonance imaging. Median age was 48 years, 68% were female and 41% were African American. Median (interquartile range) BMI was 33 (31.5, 36.3) and 25 (23.5, 27.2) kg/m2 in the obese and non-obese individuals, respectively. In obese individuals, insulin sensitivity negatively correlated with muscle (r = -0.45, p = 0.01) and skin sodium (r = -0.46, p = 0.01). In interaction analysis among obese individuals, tissue sodium had a greater effect on insulin sensitivity at higher levels of high-sensitivity C-reactive protein (p-interaction = 0.03 and 0.01 for muscle and skin Na+, respectively) and interleukin-6 (p-interaction = 0.024 and 0.003 for muscle and skin Na+, respectively). In interaction analysis of the entire cohort, the association between muscle sodium and insulin sensitivity was stronger with increasing levels of serum leptin (p-interaction = 0.01). CONCLUSIONS: Higher muscle and skin sodium are associated with insulin resistance in obese patients. Whether high tissue sodium accumulation has a mechanistic role in the development of obesity-related insulin resistance through systemic inflammation and leptin dysregulation remains to be examined in future studies. CLINICALTRIALS: gov registration: NCT02236520.

Association of longitudinal high-sensitive C-reactive protein levels with changing membrane characteristics in peritoneal dialysis.

BACKGROUND: Increasing peritoneal permeability with ultrafiltration and solute removal inadequacy is a challenging issue in peritoneal dialysis (PD). Decreasing permeability is less frequent but also results in diminished solute clearance. We evaluated the association between longitudinal high-sensitive C-reactive protein (hs-CRP) values and the change in transport characteristics of the peritoneal membrane in PD patients. METHODS: This is a retrospective, single-center study of incident PD patients. An increase or decrease in peritoneal transport status is defined as two or more categories of a rise or decline in the peritoneal equilibration test (PET) from their baseline during follow-up. The 4-h dialysate/plasma creatinine ratio was used to classify transport characteristics. Hs-CRP values were obtained from the routine annual examinations of the patients. RESULTS: Baseline demographics, residual kidney function, frequency of high glucose-containing dialysate, and icodextrin use were similar between the groups. Total episodes of peritonitis within the first 5 years of follow-up were higher in stable transporters than in increased and decreased transporters (p = 0.009). Stable transporters' mean hs-CRP values did not change within 5 years (Wilks' λ = 0.873, F (2.317, 180.740) = 2.210, p = 0.10). Increased and decreased transporters' hs-CRP values significantly raised over the years (Wilks' λ = 0.422, F (1.979, 77.163) = 3.405, p = 0.04 and Wilks' λ = 0.558, F (3.673, 66.107) = 4.396, p = 0.001, respectively). CONCLUSIONS: Our study shows that the peritoneal membrane may change into different characteristics in many patients over time, despite very low peritonitis frequencies and similar baseline characteristics that may be significantly affected by systemic inflammation.

Comparison of geriatric nutritional risk index and creatinine index in short-term mortality prediction in maintenance hemodialysis patients.

BACKGROUND: The aim of this study is to analyze and compare the predictive values of the Geriatric Nutritional Risk Index (GNRI) and Creatinine Index (CI) in the short-term mortality of maintenance hemodialysis patients and to determine their best cut-offs. METHODS: A total of 169 adult hemodialysis patients were included in this retrospective, cross-sectional, and single-center study. The demographic, clinical, and laboratory data of the month in which the patients were included in the study were obtained from their medical files and computer records. All-cause death was the primary outcome of the study during a 12-month follow-up after baseline GNRI and CI calculations. RESULTS: The mean age of the study population was 57 ± 16 years (49.7% were women, 15% were diabetic). During the one-year observation period, 19 (11.24%) of the cases died (8 CV deaths). The optimal cut-off value for GNRI was determined as 104.2 by ROC analysis [AUC = 0.682 ± 0.06, (95% CI, 0.549-0.815), p = 0.01]. The low GNRI group had a higher risk for all-cause and CV mortality compared to the higher GNRI group (p = 0.02 for both in log-rank test). The optimal sex-specific cut-off was 12.18 mg/kg/day for men [AUC = 0.723 ± 0.07, (95% CI, 0.574-0.875), p = 0.03] and was 12.08 mg/kg/day for females [AUC = 0.649 ± 0.13, (95% CI, 0.384- 0.914), p = 0.01]. Patients with lower sex-specific CI values had higher all-cause and CV mortality (p = 0.001 and p = 0.009 in log-rank test, respectively). In multivariate cox models, both GNRI [HR = 4.904 (% 95 CI, 1.77-13.56), p = 0.002] and sex-specific CI [HR = 5.1 (95% CI, 1.38-18.9), p = 0.01] predicted all-cause mortality. The association of GNRI with CV was lost [HR = 2.6 (CI 95%, 0.54-13.455), p = 0.22], but low CI had a very strong association with CV mortality [HR = 11.48 (CI 95%, 1.25 -104), p = 0.03]. DISCUSSION: In hemodialysis patients, GNRI and CI have similar powers in predicting all-cause short-term mortality. The association of CI with all-cause death depends on gender. On the other hand, sex-specific CI predicts CV mortality better than GNRI.

Effects of long-term intradialytic oral nutrition and exercise on muscle protein homeostasis and markers of mitochondrial content in patients on hemodialysis.

Patients with end-stage kidney disease on maintenance hemodialysis commonly develop protein-energy wasting, a syndrome characterized by nutritional and metabolic abnormalities. Nutritional supplementation and exercise are recommended to prevent protein-energy wasting. In a 6-mo prospective randomized, open-label, clinical trial, we reported that the combination of resistance exercise and nutritional supplementation does not have an additive effect on lean body mass measured by dual-energy X-ray absorptiometry. To provide more mechanistic data, we performed a secondary analysis where we hypothesized that the combination of nutritional supplementation and resistance exercise would have additive effects on muscle protein accretion by stable isotope protein kinetic experiments, muscle mass by MRI, and mitochondrial content markers in muscle. We found that 6 mo of nutritional supplementation during hemodialysis increased muscle protein net balance [baseline: 2.5 (-17.8, 13.0) µg·100 mL-1·min-1 vs. 6 mo: 43.7 (13.0, 98.5) µg·100 mL-1·min-1, median (interquartile range), P = 0.04] and mid-thigh fat area [baseline: 162.3 (104.7, 226.6) cm2 vs. 6 mo: 181.9 (126.3, 279.2) cm2, median (interquartile range), P = 0.04]. Three months of nutritional supplementation also increased markers of mitochondrial content in muscle. Although the study is underpowered to detected differences, the combination of nutritional supplementation and exercise failed to show further benefit in protein accretion or muscle cross-sectional area. We conclude that long-term nutritional supplementation increases the skeletal muscle anabolic effect, the fat cross-sectional area of the thigh, and markers of mitochondrial content in skeletal muscle.

Tissue sodium stores in peritoneal dialysis and hemodialysis patients determined by 23-sodium magnetic resonance imaging.

BACKGROUND: Tissue sodium content in patients on maintenance hemodialysis (MHD) and peritoneal dialysis (PD) were previously explored using 23Sodium magnetic resonance imaging (23NaMRI). Larger studies would provide a better understanding of sodium stores in patients on dialysis as well as the factors influencing this sodium accumulation. METHODS: In this cross-sectional study, we quantified the calf muscle and skin sodium content in 162 subjects (10 PD, 33 MHD patients, and 119 controls) using 23NaMRI. Plasma levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were measured to assess systemic inflammation. Sixty-four subjects had repeat 23NaMRI scans that were analyzed to assess the repeatability of the 23NaMRI measurements. RESULTS: Patients on MHD and PD exhibited significantly higher muscle and skin sodium accumulation compared to controls. African American patients on dialysis exhibited greater muscle and skin sodium content compared to non-African Americans. Multivariable analysis showed that older age was associated with both higher muscle and skin sodium. Male sex was also associated with increased skin sodium deposition. Greater ultrafiltration was associated with lower skin sodium in patients on PD (Spearman's rho=-0.68, P = 0.035). Higher plasma IL-6 and hsCRP levels correlated with increased muscle and skin sodium content in the overall study population. Patients with higher baseline tissue sodium content exhibited greater variability in tissue sodium stores on repeat measurements. CONCLUSIONS: Our findings highlight greater muscle and skin sodium content in dialysis patients compared to controls without kidney disease. Tissue sodium deposition and systemic inflammation seen in dialysis patients might influence one another bidirectionally.

Prevalence of Chronic Kidney Disease in Turkish Adults With Obesity and Metabolic Syndrome: A Post Hoc Analysis from Chronic Renal Disease in Turkey Study.

BACKGROUND: Obesity confers an increased risk of chronic kidney disease (CKD), which is increased further by accompanying metabolic abnormalities. OBJECTIVE: To investigate the relationship of the risk of CKD with obesity and metabolic syndrome (MS) in adults by means of post hoc analysis of data from the Chronic Renal Disease in Turkey (CREDIT) study. METHODS: The anthropometric measurements of a total of 9,100 adult participants in the CREDIT study were included in the analyses. Subjects were classified according to the presence or absence of obesity (body mass index [BMI] > 30) and MS. Logistic regression analyses were used to estimate odds ratio for CKD. Effect modification analyses were also performed. RESULTS: The prevalence of obesity was 20.6% and that of MS was 31.3%. The prevalence of CKD was higher among obese subjects compared to those with a normal BMI (20.5% vs. 14%; P < .001). The odds ratio (OR) for CKD was 1.296 (95% confidence interval [CI], 1.121-1.498) for subjects who were overweight, 1.718 (95% CI, 1.444-2.044) for those with class I obesity, 1.983 (95% CI, 1.489-2.641) for those with class II obesity and 2.799 (95% CI, 1.719-4.557) for subjects with extreme obesity (P < .001 for each subgroup) compared to subjects with a normal BMI. CKD was significantly more prevalent in subjects with MS (21.9% vs. 12.3%, P < .001). The OR for CKD was higher in obese subjects with MS (adjusted OR, 1.321; 95% CI, 1.109-1.573; P = .002). CONCLUSION: The stratification of obese individuals based on their metabolic phenotype is important for prevention and treatment of CKD.

The relationship between changes in peritoneal membrane solute transfer characteristics and cardiac remodeling in patients with peritoneal dialysis.

INTRODUCTION: We aimed to determine the relationship between the dilatation of the heart chambers and the change in peritoneal membrane solute transfer characteristics (PMTC) in long-term peritoneal dialysis (PD) patients. METHODS: This is a retrospective, single-center study including the follow-up of maintenance PD patients. According to the changes in PMTC from baseline to the last visit, patients were divided into three groups; stable (n = 11), increased (n = 41), and decreased transporters (n = 35). RESULTS: Left atrium (LA) and Right ventricle (RV) dilatation were more prominent in the PMTC-decreased group compared to PMTC-increased and stable groups (p < 0.001 and p = 0.07, respectively). The Cox regression analysis showed that only decreased PMTC was associated with LA dilatation (HR 2.89 [CI 95%1.54, 5.45] p < 0.01) and RV dilatation (HR 3.01 [CI 95%1.40, 6.21] p < 0.01). CONCLUSION: PD can be associated with unfavorable dynamic changes in cardiac structure and functions even at the subclinical level.

How many blood pressure measurements should we take in the office?

No consensus has emerged among different guidelines concerning how many blood pressure (BP) measurements should be performed at office visits in the diagnosis of hypertension. The purpose of this study was to examine the compatibility of various multiple average office BP measurements and 24-h BP monitoring (ABPM) in patients followed up in the posthoc analysis of the Cappadocia hypertension cohort. A total 1158 office BP measurements by 207 patients were examined. The results were then classified as G1 (average of the 1st and 2nd BP), G2 (average of the 2nd and 3rd), G3 (average of the 2nd, 3rd, and 4th), G4 (average of the 2nd, 3rd, 4th, and 5th), and G5 (average of all five measurements). Compatibility between the average values in the groups and concomitant 24-h ABPM data was examined. While a significant difference was observed between daytime 24-h ABPM SBP and G1 (p = .002), no difference was found in the other groups. Office DBP approached the daytime 24-h ABPM values as the number of measurements in the five groups increased, although average office DBP data in all groups were higher than daytime 24-h ABPM DBP (p = .000 for all). In light of our study results, we recommend that three office BP measurements be performed and that the average of the 2nd and 3rd measurements be used for SBP, while in terms of DBP, we recommend that as many measurements as possible be taken without the 1st value being included in the average.

A randomized controlled pilot trial of anakinra and pioglitazone for protein metabolism in patients on maintenance haemodialysis.

BACKGROUND: Chronic inflammation and insulin resistance are highly prevalent in patients on maintenance haemodialysis (MHD) and are strongly associated with protein energy wasting. We conducted a pilot, randomized, placebo-controlled trial of recombinant human interleukin-1 receptor antagonist (IL-1ra) and pioglitazone to explore the safety, feasibility and efficacy for insulin-mediated protein metabolism in patients undergoing MHD. METHODS: Twenty-four patients were randomized to receive IL-1ra, pioglitazone or placebo for 12 weeks. Changes in serum inflammatory markers and insulin-mediated protein synthesis, breakdown and net balance in the whole-body and skeletal muscle compartments were assessed using hyperinsulinaemic-hyperaminoacidemic clamp technique at baseline and Week 12. RESULTS: Among 24 patients, median (interquartile range) age was 51 (40, 61), 79% were African American and 21% had diabetes mellitus. All patients initiated on intervention completed the study, and no serious adverse events were observed. There was a statistically significant decrease in serum high-sensitivity C-reactive protein in the pioglitazone group compared with placebo, but not in the IL-1ra group. No significant differences in the changes of whole-body or skeletal muscle protein synthesis, breakdown and net balance were found between the groups. CONCLUSIONS: In this pilot study, there were no statistically significant effects of 12 weeks of IL-1ra or pioglitazone on protein metabolism in patients on MHD. CLINICALTRIALS: gov registration: NCT02278562.

Intermuscular adipose tissue accumulation is associated with higher tissue sodium in healthy individuals.

BACKGROUND AND AIMS: High tissue sodium accumulation and intermuscular adipose tissue (IMAT) are associated with aging, type 2 diabetes, and chronic kidney disease. In this study, we aim to investigate whether high lower-extremity tissue sodium accumulation relates to IMAT quantity and whether systemic inflammatory mediators and adipocytokines contribute to such association. METHODS: Tissue sodium content and IMAT accumulation (percentage of IMAT area to muscle area) were measured in 83 healthy individuals using sodium imaging (23Na-MRI) and proton (1H-MRI) imaging of the calf. Insulin sensitivity was assessed by glucose disposal rate (GDR) measured with the hyperinsulinemic-euglycemic clamp. RESULTS: Median (interquartile range) muscle and skin sodium contents were 16.6 (14.9, 19.0) and 12.6 (10.9, 16.7) mmol/L, respectively. Median IMAT was 3.69 (2.80, 5.37) %. In models adjusted for age, sex, BMI, GDR, adiponectin, and high-sensitivity C-reactive protein, increasing tissue sodium content was significantly associated with higher IMAT quantity (p = 0.018 and 0.032 for muscle and skin tissue sodium, respectively). In subgroup analysis stratified by sex, skin sodium was significantly associated with IMAT only among men. In interaction analysis, the association between skin sodium and IMAT was greater with increasing levels of high-sensitivity C-reactive protein and interleukin-6 (p for interaction = 0.022 and 0.006, respectively). CONCLUSIONS: Leg muscle and skin sodium are associated with IMAT quantity among healthy individuals. The relationship between skin sodium and IMAT may be mediated by systemic inflammation.