Malnutrition-inflammation-atherosclerosis Research Articles

Malnutrition- inflammation- atherosclerosis (MIA) syndrome associates with periodontitis in end-stage renal disease patients undergoing hemodialysis: a cross-sectional study

Malnutrition-inflammation-atherosclerosis (MIA) syndrome is a significant risk factor for mortality in patients undergoing hemodialysis. This study aimed to investigate the association between MIA syndrome and oral health status in hemodialysis patients. A cross-sectional study was conducted on 254 hemodialysis patients. Comprehensive medical and dental examinations were performed. Three components were included to define MIA syndrome: Geriatric Nutritional Risk Index, serum high-sensitivity C-reactive protein, and history of cardiovascular events as indicators of malnutrition, inflammation, and atherosclerosis, respectively. The association of MIA syndrome components with periodontitis and occlusal support was examined by multiple-ordered logistic regression analysis. Of 254 participants, 188 (74.0%) had at least one component of MIA syndrome. After adjusting for possible confounding factors, severe periodontitis was significantly associated with presence of more components of MIA syndrome (odds ratio [OR]: 2.64, 95% confidence interval [CI], 1.44–4.84, p = 0.002) and inflammation and malnutrition components (OR: 2.47 and 3.46, 95% CI 1.16–5.28 and 1.70–7.05, p = 0.020 and 0.001). On the other hand, occlusal support, evaluated by Eichner index, was not significantly associated with MIA syndrome or any of its components. In conclusion, periodontitis is associated with MIA syndrome, particularly with inflammation and malnutrition in hemodialysis patients, independent of occlusal support.

Association of serum thymosin β4 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 β4 (sTβ4) protects against inflammation, fibrosis and cardiac dysfunction. Objectives The present study aimed to characterize the association between sTβ4 and MIA syndrome as well as to investigate the potential of regulating sTβ4 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 sTβ4 levels were collected and subjected to association analysis for sTβ4 and MIA syndrome. Results sTβ4 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 sTβ4. PD patients with higher levels of sTβ4 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 sTβ4 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 sTβ4 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 sTβ4 level decreases in PD patients with MIA syndrome. The prevalence of MIA syndrome decreases significantly as the level of sTβ4 increases in PD patients.

WCN23-0590 Effect of malnutrition-inflammation-atherosclerosis (MIA) syndrome on clinical adverse prognosis among patients with peritoneal dialysis associated peritonitis after recovery

WCN23-0590 Effect of malnutrition-inflammation-atherosclerosis (MIA) syndrome on clinical adverse prognosis among patients with peritoneal dialysis associated peritonitis after recovery

From MIA to FIFA: The vicious matrix of frailty, inflammation, fluid overload and atherosclerosis in peritoneal dialysis.

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Two decades ago, the common co-existence of malnutrition and systemic inflammation PD patients with atherosclerosis and CVD led to the proposed terminology of 'malnutrition-inflammation-atherosclerosis (MIA) syndrome'. Although the importance of malnutrition is well accepted, frailty represents a more comprehensive assessment of the physical and functional capability of the patient and encompasses the contributions of sarcopenia (a key component of malnutrition), obesity, cardiopulmonary as well as neuropsychiatric impairment. In recent years, it is also increasingly recognized that fluid overload is not only the consequence but also play an important role in the pathogenesis of CVD. Moreover, fluid overload is closely linked with the systemic inflammatory status, presumably by gut oedema, gastrointestinal epithelial barrier dysfunction and leakage of bacterial fragments to the systemic circulation. There are now a wealth of published evidence to show intricate relations between frailty, inflammation, fluid overload and atherosclerotic disease in patients with chronic kidney disease (CKD) and those on PD, a phenomenon that we propose the term 'FIFA complex'. In this system, frailty and atherosclerotic disease may be regarded as two patient-oriented outcomes, while inflammation and fluid overload are two inter-connected pathogenic processes. However, there remain limited data on how the treatment of one component affect the others. It is also important to define how treatment of fluid overload affect the systemic inflammatory status and to develop effective anti-inflammatory strategies that could alleviate atherosclerotic disease and frailty.

α1-Acid Glycoprotein and Dietary Intake in End-Stage Renal Disease Patients

Management of end-stage renal disease (ESRD) patients requires monitoring each of the components of malnutrition–inflammation–atherosclerosis (MIA) syndrome. Restrictive diet can negatively affect nutritional status and inflammation. An acute-phase protein—α1-acid glycoprotein (AGP), has been associated with energy metabolism in animal and human studies. The aim of our study was to look for a relationship between serum AGP concentrations, laboratory parameters, and nutrient intake in ESRD patients. The study included 59 patients treated with maintenance hemodialysis. A 24 h recall assessed dietary intake during four non-consecutive days—two days in the post-summer period, and two post-winter. Selected laboratory tests were performed: complete blood count, serum iron, total iron biding capacity (TIBC) and unsaturated iron biding capacity (UIBC), vitamin D, AGP, C-reactive protein (CRP), albumin, prealbumin, and phosphate–calcium metabolism markers (intact parathyroid hormone, calcium, phosphate). Recorded dietary intake was highly deficient. A majority of patients did not meet recommended daily requirements for energy, protein, fiber, iron, magnesium, folate, and vitamin D. AGP correlated positively with CRP (R = 0.66), platelets (R = 0.29), and negatively with iron (R = −0.27) and TIBC (R = −0.30). AGP correlated negatively with the dietary intake of plant protein (R = −0.40), potassium (R = −0.27), copper (R = −0.30), vitamin B6 (R = −0.27), and folates (R = −0.27), p < 0.05. However, in multiple regression adjusted for confounders, only CRP was significantly associated with AGP. Our results indicate that in hemodialyzed patients, serum AGP is weakly associated with dietary intake of several nutrients, including plant protein.

The impact of malnutrition-inflammation-atherosclerosis (MIA) syndrome on the prognosis of elderly patients with chronic limb-threatening ischemia after endovascular therapy

Abstract Background Chronic limb-threatening ischemia (CLTI) is known to the most advanced form of severe arteriosclerosis in peripheral artery disease and cause poor prognosis. Whereas malnutrition (M), inflammation (I) and atherosclerosis (A) are reported to be involved in the pathophysiology of end-stage renal disease with close relevancy and affect its clinical outcomes, the effect of such MIA syndrome on the mortality in elderly patients with CLTI has not been well evaluated. Purpose The aim of the present study was to investigate the influence of patient characteristics including MIA syndrome on the mortality in elderly CLTI patients &amp;lt;3 years after endovascular therapy (EVT). Methods The subject was 222 consecutive elderly (≥65 year) CLTI patients who were admitted to undergo endovascular therapy (EVT). We assessed nutritional status using Geriatric Nutritional Risk Index (GNRI) in this study, and defined patients with GNRI &amp;lt;92 at admission as malnutrition. We also assessed inflammatory status using hs-CRP. The patients were divided into four groups based on their nutrition and inflammatory status as follows; Group A; GNRI &amp;lt;92+hs-CRP ≥1 mg/dL, Group B; GNRI &amp;lt;92+hs-CRP &amp;lt;1 mg/dL, Group C; GNRI &amp;gt;92+hs-CRP ≥1 mg/dL, Group D; GNRI &amp;gt;92+hs-CRP &amp;lt;1 mg/dL. Patients in the group A were considered to be under MIA syndrome. We evaluated which Group affected prognosis of elderly CLTI patients after endovascular therapy (EVT). Results All-cause death after EVT were 37 cases (17%). In this study, all patients underwent successful EVT for target lesions. As a result of cox proportional hazards analysis, all-cause death was associated with MIA syndrome [hazard ratio (HR): 2.41, 95% confidence interval (CI): 1.13–5.17, p&amp;lt;0.001)], Clinical Fraility Scale (HR: 1.46, 95% CI: 1.127–1.93, p=0.005), and history of stroke (HR: 2.32, 95% CI: 1.11–4.86, p=0.026) in the univariate analysis. Multivariate cox proportional hazards analysis models after adjusted for the demographic characteristics of patients and clinically relevant factors for all-cause death after EVT revealed that MIA syndrome and history of stroke were independent risk factors (HR: 3.94, 95% CI: 1.34–11.63, p=0.013, HR: 3.06, 95% CI: 1.14–8.18, p=0.026,). Kaplan Meier analysis also elucidated that survival rate was significantly lower in Group A compared to those in other Groups (p=0.0131). Furthermore, cox proportional hazards models using each Group A to D revealed that only Group A was associated with all-cause death (Group A: HR 2.41, 95% CI: 1.13–5.17, p=0.024, Group B: HR 1.01, 95% CI: 0.41–2.46, p=0.976, Group C: HR 1.01, 95% CI: 0.35–2.88, p=0.987, Group D: HR 0.57, 95% CI: 0.30–1.13, p=0.109). Conclusions MIA syndrome was a strong predictor for incidence of all-cause death in elderly CLTI patients after EVT. Funding Acknowledgement Type of funding sources: None.

Individual and Combined Prevalence of Malnutrition, Inflammation and Atherosclerosis with Cardiovascular Calcification in Hemodialysis Patients

The triad of Malnutrition, Inflammation, Atherosclerosis (MIA) is associated with a high mortality rate in hemodialysis patients. The concomitant existence of cardiovascular calcification worsens the condition. Hence, it is of interest to study whether patients with calcification present with higher prevalence of MIA. The main objective of the study was to assess individual and combined prevalence of MIA with cardiovascular calcification in hemodialysis patients. This was a cross sectional study. Subjects above 18 years of age, undergoing chronic hemodialysis not less than twice a week were screened. Out of 126 screened subjects, 109 were eligible and 100 completed the study. Blood samples were drawn for renal profile, calcium, phosphorus, vitamin D3, parathyroid hormone (PTH), lipid profile and high sensitivity (hs) CRP. Computed Tomography (CT) scans of coronary arteries and Subjective Global Assessment (SGA) score were performed. A comparison of individual and combined prevalence of MIA was reported using Z-test for proportions. When individual conditions were compared, the prevalence of atherosclerosis was found to be highly significant (P: 42%, N: 10%, p-value: 0.00001). When a combined prevalence of all three conditions was compared, it was found to be highly significant in calcified subjects (P: 17%, N: 0%, p-value: 0.000001). It was concluded that the prevalence of MIA syndrome individually or in a combined form was greater in subjects with cardiovascular calcification. This may further predispose this group to increased risk of morbidity and mortality. Early screening of these conditions and planning of treatment strategies to lower them are recommended.

P1569ADIPONECTIN IS ASSOCIATED WITH DECLINE IS SKELETAL MUSCLE MASS AND BONE MINERAL CONTENT IN PATIENTS ON HEMODIALYSIS

Abstract Background and Aims Patients on hemodialysis are prone to undernutrition, malnutrition-inflammation-atherosclerosis (MIA) syndrome, and protein-energy wasting (PEW). One of the major adipocytokines adiponectin (ADPN) is involved in anti-arteriosclerotic and anti-inflammatory processes. However, ADPN is implicated in muscle weakness and loss of muscle mass in the elderly in addition to sarcopenia. At the 2019 ERA-EDTA Congress, we announced that total plasma ADPN levels in patients on hemodialysis (HD) showed a significant inverse correlation with BMI, body fat in percentage, mass and estimated skeletal muscle mass, and ADPN may be involved in sarcopenia in patients on HD. Herein, we investigated the association of ADPN level with sarcopenia in patients on HD using a method different from the one used in our previous study. We examined the relationship between total plasma ADPN level and the rate of change in estimated skeletal muscle mass, bone mineral content, and body fat mass over 5 years after the plasma ADPN measurement. Furthermore, we analyzed whether an elevated ADPN level was predictive of a subsequent decline in these parameters. Method Total plasma ADPN levels were measured using ELISA (Bio Vendor-Laboratorni Medicina a.s., Czech Republic) in 42 male patients on HD (age: 51.1 ± 9.0 years, dialysis vintage: 144.8 ± 99.2 months, BMI: 21.8 ± 3.2, dry BW: 62.0 ± 10.9 kg, dialysis time: 15.6 ± 3.1 hours/week). The estimates of skeletal muscle mass, bone mineral content, and body fat mass were made using multi-frequency bioelectrical impedance analysis (MFBIA) within the same year when total plasma ADPN level were first measured in 2011 as well as in 2016. We then calculated the rates of change in the estimated skeletal muscle mass, bone mineral content, and body fat mass over the 5 years and correlated these parameters with the total plasma ADPN measurements. Results Conclusion Total plasma ADPN levels inversely correlate with larger rates of decrease in estimated skeletal muscle mass and bone mineral content in patients on HD. This suggests that ADPN may play a role in the decline in skeletal muscle mass and bone mineral content over time in patients on HD.

The value of malnutrition-inflammation-atherosclerosis (MIA) syndrome for predicting mortality in patients with end-stage renal disease at Hue Central Hospital

Background: the role of malnutrition, inflammation, atherosclerosis, and particularly the combination of these three factors were closely related to cardiovascular events, hospitalisation frequency, and death in end-stage renal disease (ESRD) patients. This study examines the relationship between malnutrition-inflammation-atherosclerosis (MIA) syndrome and mortality among these patients during an 18-month period.Subjects and methods: in this prospective observational cohort study, all cause-mortalitywas evaluated during an 18-month follow-up period. A total of 174 patients with ESRD (including 57 non-dialysis patients, 56 peritoneal dialysis patients, and 61 hemodialysis patients) were enrolled. M (malnutrition) was assessed by the seven-point subjective global assessment (SGA), serum albumin. I (inflammation) was assessed by serum hs-CRP, serum IL-6. A (atherosclerosis) was defined asIMT ≥0.9 mm or the presence of plaque in the carotid artery. The patients are classified into four groups by number of components (MIA0, MIA1, MIA2, MIA3). Results: 73.6% of patients had at least one component of MIA syndrome. The proportion of patients with malnutrition, inflammation, and atherosclerosis accounted for 36.8%, 21.3%, and 50.6%, respectively. The proportion of patients with 3, 2, 1 component accounted for 4.0, 27.0, and 42.5%. There was no difference between MIA groups based on age, sex, percentage suffering from dyslipidemia, anemia, or Hb levels. Relative to patients experiencing no elements of MIA syndrome, patients with three components experienced a 13.16 times higher risk of mortality. Only malnutrition was a strong predictor of mortality with HR (95% CI): 5.90 (2.46-14.14).Conclusion: clinical physicians should attend more closely to and provideearly assessments ofMIA syndrome in patients with ESRD. They should care for nutrition conditions and thereby provide early and effective treatments. This can contribute to enhancements in quality of life, and decrease mortalityrates inpatients.

Association of malnutrition-inflammation-cardiovascular disease with cognitive deterioration in peritoneal dialysis patients

To investigate the relationship between malnutrition-inflammation-atherosclerosis (MIA) syndrome and deterioration of global and specific domains of cognitive function in peritoneal dialysis (PD) patients. This was a multi-center prospective cohort study. The PD patients who met the inclusion criteria were examined with general and specific cognitive function between March 2013 and November 2013. The patients were divided into MIA0, MIA1 and MIA2 groups, according to items of "Yes" for whether or not having cardiovascular disease, serum albumin≤35 g/L or high-sensitive C-reactive protein (hs-CRP) ≥3 mg/L. After 2 years, the patients maintained on PD would be repeatedly measured with cognitive function. The Chi-square test, One-way ANOVA, Kruskal-wallis H rank sum test were used to compare the differences of clinical characteristics, biochemical data, and global and specific cognitive function parameters among the three groups at baseline, and two years later, respectively. The Bonferroni method was applied to adjust the significance level for further comparison between each two different groups. The change of score in each cognitive parameter of global and specific domains was used as dependent variable. Age, gender, education level, depression index, body-mass index, diabetes mellitus, serum sodium levels and MIA (MIA0 was control, MIA1 and MIA2 as dummy variables) were all included in the multivariable linear regression models to analyze the risk factors of the deterioration of cognitive function. The analysis for each cognitive domain was adjusted for the baseline score of the corresponding cognitive parameter. All the analyses were performed using SPSS for Windows, software version 25.0 (SPSS Inc., Chicago, IL). Over two-year follow up, the prevalence of cognitive impairment increased from 20.0% to 24.7%, absolute decrease of 3MS scores were more significantly decreased in MIA2 (-3.9±12.0 vs. 1.1±6.7, P<0.01) and MIA1 group (-2.3±11.8 vs. 1.1±6.7, P<0.05) than those in MIA0 group respectively. Specific cognitive functions, included executive function (trail-making tests A and B, P=0.401, P=0.176), immediate memory (P=0.437), delayed memory (P=0.104), visuospatial skill (P=0.496), and language ability (P=0.171) remained unchanged. Advanced age, lower education, diabetes mellitus and depression were all correlated with the deterioration of one or more cognitive domains, and the patients having one item of MIA syndrome were prone to develop the deterioration of 3MS (P=0.022). Furthermore, the patients having two or more items of MIA syndrome were more likely to develop the deterioration of not only 3MS (P <0.001), but also delayed memory, visuospatial skill, and language ability (P=0.002, P=0.007, P=0.004, respectively). Patients with one item or above of MIA syndrome were at high-risk for the deterioration of global cognitive function. The more MIA syndrome items there were, the more specific cognitive domains deteriorated.

MALNUTRITION-INFLAMMATION-ATHEROSCLEROSIS (MIA) SYNDROME IN HEMODIALYSIS PATIENTS

Background: Mortality resulting from cardiovascular disease in patients with end-stage renal disease (ESRD) is high. In this study we study characteristics of the malnutrition, inflammation, atherosclerosis (MIA) syndrome; relationship between MIA syndrome and the cardiovascular events in hemodialysis patients. Subjects and methods: A total of 61 hemodialysis patients were enrolled. Inflammatory marker (hs CRP) and nutritional parameters (albumin, prealbumin, BMI) were determined. Carotid atherosclerosis was investigated by ultrasonographically evaluated carotid intima-media thickness (cIMT). Results: -The characteristics of the malnutrition, inflammation, atherosclerosis(MIA) syndrome in in peritoneal dialysis patients: + MIA2-3 group had an average age lower than MIA0 group + MIA2-3 group had lower albumin levels and BMI than MIA0 group. + The prevalence of malnutrition (50.8%), inflammation (27.9%), and atherosclerosis (52.5%); 24 (39.3%) of the patients had one risk factor; 22 (36.1%) of the patients had two risk factors; 4 (6.6%) of the patients had all three risk factors. No signs of either malnutrition, inflammation or atherosclerosis were seen in 11 (18.0%) of patients. Note that a considerable number of patients with malnutrition (23/31 patients) had signs of inflammation or atherosclerosis or both; 12/32 patients with atherosclerosis had signs of inflammation or malnutrition or both. - The relationship between MIA syndrome and the cardiovascular events in peritoneal dialysis patients: We have found the relationship between component M (malnutrition) and the cardiovascular events in syndrome MIA (HR: 4.23 95% CI: 1.89-9.50). Our study suggests that high risk cardiovascular events in patients with 2 or more elements in MIA syndrome (HR: 2.40 95% CI: 1.16-5.00). Conclusion: We had demonstrated an association between malnutrition, inflammation and atherosclerosis; component M (malnutrition) and the cardiovascular events in hemodialysis patients; high risk cardiovascular events in patients with 2 or more elements in MIA syndrome. Key words: Malnutrition-inflammation-atherosclerosis syndrome, hemodialysis

Malnutrition and its association with inflammation and vascular disease in children on maintenance dialysis

Malnutrition is associated with both inflammation and atherosclerotic cardiovascular disease in adults with chronic kidney disease. We studied the prevalence of malnutrition and its possible associations with inflammation and vascular disease in children on chronic dialysis. Thirty-three patients on maintenance dialysis (18 peritoneal dialysis, 15 hemodialysis) and 19 age- and gender- matched healthy controls were studied. Nutritional status was assessed by anthropometric measurements including body mass index (BMI), upper arm measurements, multifrequency bioimpedance analysis (BIA) and serum levels of albumin, prealbumin, and cholesterol. Inflammation was assessed by serum levels of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha. The carotid artery intima thickness (cIMT) was measured to assess vascular disease. Compared with healthy children, patients had lower anthropometric measurements (P < 0.05) and serum albumin level (P < 0.001), and higher CRP and TNF-alpha (P = 0.030 and P = 0.007, respectively), and higher cIMT-SDS (P < 0.001). Malnutrition was present in 8 (24%) and lower BIA-based fat mass was independently associated with higher IL-6 levels (P = 0.035). An increased cIMT was present in 16 (48.5%); however, there was no difference in cIMT-SDS between patients with and without malnutrition. Carotid IMT did not show any association with nutritional indices; but positively correlated with serum IL-6 (P = 0.037), CRP (P = 0.012), and iPTH (P = 0.009), and independently associated with only iPTH (P = 0.018). Children on dialysis are at an increased risk of malnutrition, inflammation, and vascular disease. Although each of these three conditions exists, there is no interaction among them all. We postulate that the malnutrition-inflammation-atherosclerosis (MIA) complex might not exist in pediatric dialysis patients.

The malnutrition inflammation complex syndrome-the micsing factor in the perio-chronic kidney disease interlink.

The patients who undergo Maintenance Haemodialysis (MHD) have a high prevalence of Protein-Energy Malnutrition (PEM) and inflammation. Because these two conditions often occur concomitantly in the MHD patients, they have been referred to together as the Malnutrition-Inflammation Complex Syndrome (MICS) or Malnutrition-inflammation atherosclerosis, to underscore the atherosclerotic complications of this entity. MICS is also reported to correlate with a poor outcome, including a decreased quality of life, refractory anaemia and significantly greater rates of hospitalization and mortality in the MHD patients .Indeed, MICS may be the major cause of the paradoxical exposure-outcome association, which is also known as reverse epidemiology of the cardiovascular disease risk factors in the maintenance dialysis patients. Periodontitis is a chronic inflammatory disease of the supporting tissues from the dentition, which results from the infection of and the interaction of selected bacterial species with the components of the host response in disease-susceptible individuals as the haemodialysis (HD) patients. Only in recent years, did an emerging evidence link the dental infection, especially periodontitis, to an increased risk of atherosclerosis and thrombosis. In the HD patients, studies have been showing a positive link between periodontal disease and systemic inflammation on correlation between the levels of CRP and immunoglobulin G of Porphyromonas gingivalis. Recent researches have confirmed that the periodontal health is poor in haemodialysis patients and that it correlates with the markers of malnutrition and inflammation.

Elevated osteoprotegerin is associated with inflammation, malnutrition and new onset cardiovascular events in peritoneal dialysis patients

BackgroundsOsteoprotegerin (OPG) is known to regulate bone mineral metabolism and to be also associated with inflammation, cardiovascular disease (CVD) and mortality. Malnutrition-inflammation-atherosclerosis (MIA) syndrome is commonly found and closely linked to mortality in dialysis patients. The aim of this study was to investigate the associations between OPG and MIA syndrome in prevalent peritoneal dialysis (PD) patients. MethodsPrevalent PD patients for more than 6 months were prospectively followed up from March 2005 to May 2010. At baseline, OPG, hs-CRP, albumin, and %lean body mass (LBM) by creatinine kinetics were checked, and subjective global assessment (SGA) was performed. New-onset cardiovascular events were evaluated during the study period. Based on the median level of OPG, patients were classified as lower OPG (LO) group (n=88) and higher OPG (HO) group (n=88). ResultsA total of 176 patients (age 52.0±11.8 years, male 50.6%, duration of PD 105.3±67.2 months) were recruited and followed. In HO group, age, hs-CRP level and Charlson's comorbidity indices were higher, whereas serum albumin level, %LBM and SGA score were significantly lower than LO group. OPG levels were positively correlated with inflammatory markers, whereas negatively correlated with nutritional status. Cardiovascular events occurred in 51 patients during the study period. Newly developed cardiovascular events were significantly common in HO group (n=36, 40.9%) than LO group (n=15, 17%, p=0.002). Cox regression analysis revealed that higher OPG level (per 1-SD increase in OPG, HR: 1.44; 95% CI: 1.03–2.00; p=0.034) was a significant risk factor for cardiovascular events even after adjustments for demographic and biochemical parameters. ConclusionOPG was significantly correlated with markers of systemic inflammation and malnutrition and was a significant predictor of CVD in PD patients. These findings suggest OPG might be a prognostic indicator of MIA syndrome in prevalent PD patients.

MALNUTRITION‐INFLAMMATION‐ATHEROSCLEROSIS SYNDROME IN PATIENTS WITH END‐STAGE RENAL DISEASE

Malnutrition-inflammation-atherosclerosis (MIA) syndrome is where three dominant clinical entities which occur in patients with end-stage renal disease--malnutrition, inflammation and atherosclerosis--coexist and interact with each other. This literature review aims to present the factors which are responsible for the existence of MIA syndrome in patients with end-stage chronic kidney disease (CKD) on renal replacement therapy. Studies have shown that the main role in the pathogenesis of the MIA syndrome is played by inflammatory cytokines. The main inflammatory cytokines are tumour necrosis factor-a, interleukin-1 and interleukin-6. The following work examines these cytokines, indicating their main characteristics and the basic mode of action in patients with end-stage CKD as well as the further development of the syndrome. The existence of this syndrome is responsible for the high rates of morbidity and mortality in this group of patients who reach a level comparable with persons suffering from metastatic cancer.

Relationship Between Erythropoietin Responsiveness, Insulin Resistance, and Malnutrition-Inflammation-Atherosclerosis (Mia) Syndrome in Hemodialysis Patients with Diabetes

This study aimed to explore the relationship between recombinant human erythropoietin (EPO) responsiveness, insulin resistance, and malnutrition-inflammation-atherosclerosis (MIA) syndrome in hemodialysis patients. This was an observational cohort study in hemodialysis patients. Adipokines, inflammatory cytokines, and required EPO dosage were measured in diabetes (DM; n=58) and non-diabetes (non-DM; n=58) groups over 48 weeks. Furthermore, the EPO responsiveness index (required EPO dosage divided by hemoglobin) was evaluated with or without MIA syndrome in both groups. The DM group had significantly higher plasma leptin, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hs-CRP) levels but lower plasma high molecular weight (HMW) adiponectin levels compared to the non-DM group. Although hemoglobin levels were not significantly different, required EPO dosage was significantly higher in the DM group than in the non-DM group, particularly in the presence of MIA syndrome. The DM group with MIA syndrome had significantly higher plasma leptin, IL-6, and hs-CRP levels but lower plasma HMW adiponectin levels compared to the non-DM group with MIA syndrome. There was also a significant association between EPO dosage and homeostasis model assessment for insulin resistance (HOMA-IR), hs-CRP, IL-6, tumor necrosis factor a, leptin, and HMW adiponectin levels in DM patients with MIA syndrome. Diabetic hemodialysis patients with MIA syndrome have a lower response to EPO and a higher resistance to insulin. This fact may explain the poor outcome of these patients and demonstrate the importance of diagnosis and therapeutic management.

Could depression be a new branch of MIA syndrome?

The aims of the present study were to determine the prevalence of depression in our dialysis patients, to detect the most powerful variables associated with depression, and to determine the role of depression in prediction of mortality. The prospective follow-up study of 128 patients (77 HD and 51 CAPD, 65 male, aged 53.8 +/- 13.5 years, dialysis duration 64.7 +/- 64.8 months) was carried out over 36 months. Depression by the Beck Depression Inventory-BDI-II score, laboratory parameters (hemoglobin, serum albumin and creatinine concentration), immunological status (cytokines and hsCRP), comorbidity by Index of Physical Impairment (IPI) and adequacy of dialysis by Kt/V were monitored. The overall prevalence of depression in the dialysis patients (BDI score > or = 14) was 45.3%, and 28.2%, respectively, for moderate and severe depression (BDI > or = 20). The most powerful variable associated with depression was IL-6, but associations with albumin, hemoglobin, creatinine and IPI score were also found. During the follow-up period 36 patients died, 7 patients left the cohort and 2 patients were transplanted. If IPI score was not included in the multivariate Cox analysis, the BDI score remained one of the best predictors of mortality along with albumin. In conclusion, because of the close association of depression with inflammation, malnutrition, and cardiovascular mortality, it could be speculated that depression is one branch of the MIA (malnutrition, inflammation, atherosclerosis) syndrome.

Clinical Value of the Malnutrition-Inflammation-Atherosclerosis Syndrome for Long-Term Prediction of Cardiovascular Mortality in Patients with End-Stage Renal Disease: A 5-Year Prospective Study

Background/Aim: Mortality resulting from cardiovascular disease in patients with end-stage renal disease (ESRD) is high. In this study we sought to investigate the clinical value of the malnutrition-inflammation-atherosclerosis (MIA) syndrome for long-term prediction of cardiovascular mortality in patients treated with ESRD. Methods: A total of 42 ESRD patients on hemodialysis were enrolled. Inflammatory markers and nutritional parameters were determined. Carotid atherosclerosis was investigated by ultrasonographically evaluated carotid intima-media thickness (cIMT). Mortality was evaluated at a 5-year follow-up. Results: No correlation was evident between nutritional markers and inflammatory indexes. cIMT was inversely correlated with predialysis serum albumin. In the overall population of 42 patients, 11 (26.2%) died of cardiovascular causes during follow-up. Kaplan-Meier survival curves indicate that cIMT (≧0.9 mm), C-reactive protein (CRP) (>1 mg/dl), and serum albumin (<3.5 g/dl) predict cardiovascular death in patients with ESRD. Conclusions: We have demonstrated that cIMT, CRP and serum albumin predict long-term mortality in ERSD patients. Our study suggests that further investigation of the MIA syndrome will provide insights into the susceptibility to CVD in this patient group.

Review: Clinical Usefulness of Ultrapure Dialysate— Recent Evidence and Perspectives

It has generally been accepted that biological contamination of dialysate deteriorates the biocompatibility of dialysis therapy and accelerates dialysis-related complications such as dialysis-related amyloidosis (DRA) and malnutrition-inflammation-atherosclerosis (MIA) syndrome. During the past decade several studies have clarified that very slight amounts of contamination can lead to inflammatory response, and we could not confirm biological dialysate quality only by measuring endotoxin levels despite of measuring viable cell counts or biofilms. To achieve this, the European Renal Association/European Dialysis Transplantation Association and the American National Standardization Institute/Association for the Advancement of Medical Instrumentation published new standards for dialysate, in which very strict control levels were recommended with regard to viable bacterial cell counts. In 2004 JSDT raised the required standard of the levels of endotoxin, and began to develop a standard for bacterial cell counts. In Japan, many chronic kidney disease patients are treated with centralized dialysate supply systems which have weak spots in disinfecting the system. This causes some difficulties in making a standard for viable bacterial cell counts. In the present paper, we summarize evidences of clinical usefulness of ultrapure dialysate and perspectives of the standard for dialysate in Japan.

Impairment of small intestinal protein assimilation in patients with end-stage renal disease: extending the malnutrition-inflammation-atherosclerosis concept

Protein malnutrition is a common finding in renal disease. Recently, we showed that impaired protein assimilation (digestion and absorption) may contribute to protein malnutrition in nondiabetic patients with chronic renal failure. The aim of the present study was to evaluate whether these findings can be extended to the dialysis population. Moreover, relations with indexes of the malnutrition-inflammation-atherosclerosis (MIA) syndrome were investigated. Protein assimilation was evaluated in 24 healthy control subjects and in 40 patients with end-stage renal disease (ESRD; 14 treated with peritoneal dialysis and 26 with hemodialysis) by means of a [13C]protein breath test, quantification of the generation rate of p-cresol, or both methods. Both approaches provide reliable information on the efficiency of protein assimilation. Breath test results were expressed as the maximum percentage recovery per hour of the administered dose of 13C (%max) and as the cumulative percentage recovery at the end of the test (%cum end). Several indexes of nutritional status, inflammation, and atherosclerosis were assessed. Compared with the control subjects, ESRD patients had significantly lower breath-test derived indexes of protein assimilation [%max=3.75 +/- 0.30 compared with 4.90 +/- 0.25, P=0.006; %cum end=12.41 (5.74-23.22) compared with 16.87 (9.42-22.99), P=0.020] and a higher 24-h p-cresol generation rate corrected for dietary protein intake [3.89 (0.48-11.60) compared with 2.81 (0.21-11.20) mg p-cresol/g urea nitrogen; P=0.028]. The presence of impaired protein assimilation was associated with indexes of the MIA syndrome. Our study provides evidence that protein assimilation is impaired in ESRD patients. Moreover, this disorder is associated with the severity of the MIA syndrome.