Association of serum thymosin ß4 with malnutrition-inflammation-atherosclerosis syndrome in peritoneal dialysis patients: a cross-sectional study.

BACKGROUND: Malnutrition-inflammation-atherosclerosis (MIA) syndrome may worsen the prognosis of peritoneal dialysis (PD) patients. Serum thymosin ß4 (sTß4) protects against inflammation, fibrosis and cardiac dysfunction. OBJECTIVES: The present study aimed to characterize the association between sTß4 and MIA syndrome as well as to investigate the potential of regulating sTß4 to improve the prognosis of PD patients. METHODS: We performed a cross-sectional, single-center pilot study involving 76 PD patients. Demographic characteristics, clinical characteristics, nutritional profiles, inflammatory mediators, atherosclerosis-related factors and sTß4 levels were collected and subjected to association analysis for sTß4 and MIA syndrome. RESULTS: sTß4 levels did not significantly vary with sex or primary disease in PD patients. Ages and PD features did not vary between patients with different levels of sTß4. PD patients with higher levels of sTß4 had significantly higher levels of nutritional indicators, including subjective global nutritional assessment (SGA) (p < 0.001) and serum albumin (ALB) (p < 0.001) but lower levels of inflammatory and atherosclerotic indicators, including serum C reaction protein (CRP) (p = 0.009), the right common carotid artery (RCCA) intimal thickness (p < 0.001) and the left common carotid artery (LCCA) intimal thickness (p = 0.02). Correlation analysis showed that sTß4 was positively associated with SGA (p < 0.001) and serum ALB (p < 0.001) but negatively associated with CRP (p = 0.020), RCCA intimal thickness (p < 0.001) and LCCA intimal thickness (p = 0.033). In multiple adjusted models, the prevalence of MIA syndrome was significantly decreased in PD patients with increased levels of sTß4 when patients without MIA syndrome were compared to those with all indicators of MIA syndrome (OR = 0.996, 95% CI 0.993-0.999, p = 0.003) or those with at least one indicator of MIA syndrome (OR = 0.997, 95% CI 0.995-0.998, p < 0.001). CONCLUSIONS: The sTß4 level decreases in PD patients with MIA syndrome. The prevalence of MIA syndrome decreases significantly as the level of sTß4 increases in PD patients.

Phosphate overload directly induces systemic inflammation and malnutrition as well as vascular calcification in uremia.

Hyperphosphatemia contributes to increased cardiovascular mortality through vascular calcification (VC) in patients with chronic kidney disease (CKD). Malnutrition and inflammation are also closely linked to an increased risk of cardiovascular death in CKD. However, the effects of Pi overload on inflammation and malnutrition remain to be elucidated. The aim of the present study was to investigate the effects of dietary Pi loading on the interactions among inflammation, malnutrition, and VC in CKD. We used control rats fed normal diets and adenine-induced CKD rats fed diets with different Pi concentrations ranging from 0.3% to 1.2% for 8 wk. CKD rats showed dietary Pi concentration-dependent increases in serum and tissue levels of TNF-α and urinary and tissue levels of oxidative stress markers and developed malnutrition (decrease in body weight, serum albumin, and urinary creatinine excretion), VC, and premature death without affecting kidney function. Treatment with 6% lanthanum carbonate blunted almost all changes induced by Pi overload. Regression analysis showed that serum Pi levels closely correlated with the extent of inflammation, malnutrition, and VC. Also, in cultured human vascular smooth muscle cells, high-Pi medium directly increased the expression of TNF-α in advance of the increase in osteochondrogenic markers. Our data suggest that dietary Pi overload induces systemic inflammation and malnutrition, accompanied by VC and premature death in CKD, and that inhibition of Pi loading through dietary or pharmacological interventions or anti-inflammatory therapy may be a promising treatment for the prevention of malnutrition-inflammation-atherosclerosis syndrome.

Endocrine manifestations of chronic kidney disease and their evolving management: A systematic review.

BACKGROUND: Chronic Kidney Disease (CKD) shows a wide range of renal abnormalities including the excretory, metabolic, endocrine, and homeostatic function of the kidney. The prognostic impact of the 'endocrine manifestations' which are often overlooked by clinicians cannot be overstated. METHODS AND OBJECTIVES: A systematic review was attempted to provide a comprehensive overview of all endocrine abnormalities of CKD and their evolving principles of management, searching databases of PubMed, Embase, and Scopus and covering the literature between 2002 and 2022. RESULTS: The endocrine derangements in CKD can be attributed to a myriad of pathologic processes, in particular decreased clearance, impaired endogenous hormone production, uremia-induced cellular dysfunction, and activation of systemic inflammatory pathways. The major disorders include anemia, hyperprolactinemia, insulin resistance, reproductive hormone deficiency, thyroid hormone deficiency, and serum FGF (Fibroblast Growth Factor) alteration. Long-term effects of CKD also include malnutrition and increased cardiovascular risk. The recent times have unveiled their detailed pathogenesis and have seen an evolution in the principles of management which necessitates a revision of current guidelines. CONCLUSION: Increased advertence regarding the pathology, impact, and management of these endocrine derangements can help in reducing morbidity as well as mortality in the CKD patients by allowing prompt individualized treatment. Moreover, with timely and appropriate intervention, a long-term reduction in complications, as well as an enhanced quality of life, can be achieved in patients with CKD.

Correlation between serum magnesium and malnutrition-inflammation-atherosclerosis syndrome in maintenance hemodialysis patients / 中华临床营养杂志

Objective To investigate the potential correlation between serum magnesium and malnutrition-inflammation-atherosclerosis (MIA) syndrome in maintenance hemodialysis (MHD) patients.Methods A total of 120 patients who received MHD in Department of Blood Purification of Beijing Chaoyang Hospital from March to August 2013 were enrolled.Anthropometric and laboratory data were collected for the analysis of correlation between serum magnesium and indicators relating to malnutrition,chronic inflammation,and atherosclerosis,and the analysis of relevant factors of MIA syndrome.Results In the 120 MHD patients,the mean serum magnesium level was (1.11 ±0.14) mmol/L.44 patients had malnutrition (36.7％),whose serum magnesium level was significantly lower than that of patients in normal nutritious status [(1.04 ±0.12) mmol/L vs.(1.14 ±0.15) mmol/L,t =3.576,P =0.001] ; 43 patients had chronic inflammation (35.8％),with serum magnesium level significantly lower than that of patients without inflammation [(1.07 ±0.13) mmol/L vs.(1.13 ±0.15) mmol/L,t =2.138,P =0.035]; 79 patients had atherosclerosis (65.8％),whose serum magnesium level was significantly lower than that of patients without atherosclerosis [(1.08 ±0.12) mmol/L vs.(1.15 ±0.08) mmol/L,t =0.385,P =0.019] ; and 26 patients had MIA syndrome (21.7％),whose serum magnesium level was significantly lower than that of non-MIA patients [(1.02 ± 0.10) mmol/L vs.(1.13 ± 0.14) mmol/L,t =3.534,P =0.001].Serum magnesium level was found negatively correlated with high-sensitivity C-reactive protein (hs-CRP,r =-0.237,P =0.010) and carotid intima-media thickness (IMT,r =-0.331,P =0.000),and positively correlated with serum albumin,blood urea nitrogen,serum creatinine,uric acid,serum potassium,triceps skin-fold thickness,mid-arm circumference,mid-arm muscle circumference and hemoglobin (r =0.191,P =0.037; r =0.345,P =0.000; r =0.242,P=0.008; r =0.282,P=0.002; r=0.254,P=0.005; r=0.265,P=0.011; r=0.233,P=0.018; r=0.282,P=0.007; r=0.374,P =0.000).Multivariate logistic regression analysis showed that age (OR =1.142,95％ CI =1.026-1.271,P=0.049),hs-CRP (OR=1.415,95％ CI=1.152-1.740,P=0.001),IMT (OR =1.386,95％ CI=1.009-1.904,P=0.044),serum albumin (OR =0.944,95％ CI=0.910-0.978,P=0.002) and serum magnesium (OR =0.886,95％ CI =0.788-0.996,P =0.042) were related factors of MIA syndrome.Conclusions Serum magnesium level is correlated to malnutrition,inflammation,atherosclerosis,and MIA syndrome in MHD patients.

Correlation of peritoneal albumin leakage with malnutrition-inflammation-atherosclerosis syndrome in continuous ambulatory peritoneal dialysis patients / 中华肾脏病杂志

Objective To investigate the impact of peritoneal albumin leakage on malnutrition-inflammation-atherosclerosis (MIA) syndrome in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods A cross-sectional study of a cohort of 130 CAPD patients without edema or active infection was performed. In order to identify peritoneal transport characteristics in CAPD patients, a standard peritoneal equilibration test (PET) was carried out. For malnutrition and inflammation, serum albumin and high-sensitivity C-reactive protein (hs-CRP) levels were measured. Mean-carotid artery intima media thickness (IMT) was used to determine atherosclerosis. Residual glomerular filtration rate (rGFR) was defined as the average of 24-hour urinary urea and creatinine clearances. Results Pearson and Spearman correlation analysis showed that peritoneal albumin leakage amount was positively correlated with age, body mass index, night dwell time, blood glucose, 4 h D/P creatinine levels and hs-CRP levels (r=0.204, P<0.05 ;r=0.314, P<0.01; r=0.265, P<0.01; r=0.212, P<0.05; r=0.401, P<0.01; r=0.216, P<0.05); whereas it was negatively correlated with diastolic perssure, serum albumin levels, glucose level of dialyzate and peritoneal Kt/V (r=-0.209, P<0.05; r=-0.123, P<0.05; r=-0.271, P<0.01; r=-0.212, P<0.01). Overall, there was no correlation between peritoneal albumin leakage and IMT. Patients was significantly greater (P<0.01), and there was a positive correlation between peritoneal albumin leakage amount and IMT (r=0.650, P<0.01). Conclusions Peritoneal albumin leakage is significantly associated with peritoneal transport characteristics, malnutrition and inflammatory state in CAPD patients. High peritoneal albumin leakage amount is a risk factor for atherosclerosis in patients with rGFR less than 1 ml·min-1(1.73 m2)-1.