The short life span of dialysis patients is induced by traditional cardiovascular and non-traditional dialysis related factors such as inflammation, oxidative stress, protein energy malnutrition. Malnutrition-Inflammation Score (MIS) has been proposed as a new quantitative system for assessment of malnutrition and inflammation. In this study we sought to investigate the association of MIS and five-year-mortality in dialysis patients. In a prospective study were included 131 prevalent dialysis patients. Kalantar-Zadeh method (7) was used to calculate the malnutrition score. Patients were followed for five years. Kaplan-Meier survival and Cox-proportional mortality analysis were performed according to higher and lower malnutrition inflammation score, by cut-off value of 7. The mean age of study participants was 55.45 years and mean dialysis vintage was 111.04 months. After follow-up of 60 months 55 (42%) patients died from all-cause mortality and out of those 65% (36) were cardiovascular deaths. In comparative analysis among the survived and died patients, none of the inflammatory or nutritional variables such as CRP, albumin, creatinine, BMI or SGA significantly differed. There was a significantly longer survival among patients with lower MIS in respect of all-cause and cardiovascular mortality [49.28 ±1.88 vs. 39.29±3.53 months, p=0.011], [52.20 ±1.7 vs. 45.07 ±3.41, p=0.045], respectively. MIS emerged as a powerful predictor of all-cause and cardiovascular mortality through Cox regression analysis: HR 1.97 95%CI:(1.15 – 3.38), p=0.013; HR 1.063 95%CI-0.952-1.186, p=0.055), respectively. The malnutrition-inflammation score is a useful tool to predict outcomes. The key to improving survival and quality of life in dialysis patients could be gained by understanding of the malnutrition-inflammation complex syndrome and its interactions with cardiovascular disease and outcome.
Tissue advanced glycation end products (AGEs) are a measure of cumulative metabolic and oxidative stress and cytokine-driven inflammatory reactions. AGEs are thought to contribute to the cardiovascular complications of hemodialysis (HD) patients. Skin autofluorescence (SAF) is related to the tissue accumulation of AGEs and rises with age. SAF is one of the strongest prognostic markers of mortality in these patients. The content of AGEs is high in barbecue food. Due to the location in northern Sweden, there is a short intense barbecue season between June and August. The aim of this study was to investigate if seasonal variations in SAF exist in HD patients, especially during the barbecue season. SAF was measured noninvasively with an AGE Reader in 34 HD-patients (15 of those with diabetes mellitus, DM). Each time the median of three measures were used. Skin-AF was measured before and after each one HD at the end of February and May in 31 patients (22 men/9 women); the end of May and August in 28 (20 m/8 w); the end of August and March in 25 (19 m/6 w). Paired statistical analyses were performed during all four periods (n = 23, 17 m/6 w); as was HbA1c of those with DM. There was at a median 5.6% increase in skin-AF during the winter period (February-May, P = 0.004) and a 10.6% decrease in the skin-AF during the summer (May-August, P < 0.001). HbA1c in the DM rose during the summer (P = 0.013). In conclusion, skin-AF decreased significantly during the summer. Future studies should look for favorable factors that prevent skin-AF and subsequently cardiovascular diseases.
Introduction:Advanced glycation end products (AGEs) are considered as uremic toxins and contribute to cardiovascular complications in HD patients.Consumption of specific foods is associated with increased AGEs.In this study we investigated the AGE food consumption as a potential risk of mortality in dialysis patients.Methods:A study group of 150 dialysis patients were asked to fill in a 7-day diet questionnaire where from the data on protein, calorie and AGEs daily food intakes were extrapolated.Patients were followed for 36 months. Kaplan-Meier survival curves were applied to estimate difference in survival in patients with low(below median intake), or high (above median intake) of AGEs. The median CRP level was obtained for survival correction by inflammation. Results:The mean age of study participants was 55 years and 62% of them were men. The average amount of daily intake of AGEs was 9.4 ±4.0 MU/24 hours. The average daily protein and calories intake were within current recommendations. The median level of daily AGEs intake was 8.9 MU/day.When patients were stratified by AGEs rich or poor diet and inflammatory state, no difference for survival was found in all groups. Patients with high inflammation did not differ in survival in relation to rich or poor AGEs diet (p=0.614). In patients with low CRP better survival had patients consuming more AGEs, but the difference was not statistically significant (p= 0.167).Conclusion:Inflammation strongly impacts survival of dialysis patients. Rich AGEs food diet was not found to be at risk of mortality. Traditional diet explains better outcomes in dialysis patients.
Haemodialysis (HD) patients suffer from an increased risk of cardiovascular disease (CVD). Skin autofluorescence (SAF) is a strong marker for CVD. SAF indirectly measures tissue advanced glycation end products (AGE) being cumulative metabolites of oxidative stress and cytokine-driven inflammatory reactions. The dialysates often contain glucose.
Tissue advanced glycation end products (AGE) are a measure of cumulative metabolic and oxidative stress and cytokine driven inflammatory reactions. AGEs are thought to contribute to the car ...
Correction to: European Journal of Clinical Nutrition (2015) 69, 309–313; doi: 10.1038/ejcn.2014.261; published online 14 January 2015 Since the publication of this article, the authors have noticed that several of the author names were published incorrectly. The correct author names are listed above.
Background Tissue advanced glycation end products (AGE) are increased in hemodialysis (HD) patients, especially those with cardiovascular complications. Skin autofluorescence (skin-AF) can noninvasively estimate the accumulation of AGE in tissue. The aim was to clarify whether HD using a high-flux (HF) dialyzer favors plasma- or skin-AF removal compared to low-flux (LF) dialysis. Material and methods 28 patients were treated with either an HF-HD or LF-HD but otherwise unchanged conditions in a cross-over design. A glucose containing dialysate was used. Skin-AF was measured noninvasively with an AGE reader before and after HD. Fluorescence (370 nm/465 nm) of plasma (p-AF) was determined as total and nonprotein-bound fractions. Correction for hemoconcentrations were made using the change in serum albumin. Paired and nonpaired statistical analyses were used. Results Skin-AF was unchanged after LF- and HF-dialysis. Total, free, and protein- bound p-AF was reduced after a single LF-HD by 21%, 28%, and 17%, respectively (P<.001). After HF HD total and free p-AF was reduced by 5% and 15%, respectively (P<.001), while protein bound values were unchanged. The LF-HD resulted in a more pronounced reduction of p-AF than did HF HD (P<.001). Serum albumin correlated inversely with p-AF in HF-HD. Conclusions In the dialysis settings used there was no significant change in skin AF after dialysis, with LF or with HF dialysis. Although only limited reduction in plasma fluorescence was observed, this was more pronounced when performing LF dialysis. These data are not in overwhelming support of the use of HF dialysis in the setting used in this study.
Chronic kidney disease (CKD), especially in its end stage, is marked by extremely high cardiovascular rates of morbidity and mortality; hemodialysis patients have a five-fold shorter life expectancy than healthy subjects of the same age. In CKD the metabolic products that accumulate in the body are so-called uremic toxins. These include advanced glycation end-products (AGE). AGE levels are markedly increased in CKD patients not only because of impaired excretion but also because of increased production. AGE formation has initially been described as a non-enzymatic reaction between proteins and glucose in the so-called Maillard reaction, but they are also more rapidly formed during oxidative stress and subsequent formation of reactive carbonyl compounds like (methyl) glyoxal. AGE accumulate in tissue where they cross-link with proteins, e. g., collagen, inducing tissue stiffening of blood vessels and skin. They may also interact with receptor of AGE (RAGE) and other receptors, which lead to activation of intracellular transduction mechanisms resulting in cytokine release and further tissue damage in CKD. The accumulation of AGE in the skin can be measured non-invasively using autofluorescence. The skin autofluorescence is a strong marker of cardiovascular mortality in CKD. The focus of this review is on the role of tissue and plasma AGE, and of skin autofluorescence as a proxy of tissue AGE accumulation, in the increase in cardiovascular disease in end stage renal disease (ESRD). This review will also present the possibility of reducing the AGE accumulation in ESRD patients using the following five methods: 1) use of low AGE peritoneal dialysis solutions; 2) use of advanced hemodialysis techniques; 3) use of AGE reducing drugs; 4) optimizing the nutrition of hemodialysis patients; and 5) renal transplantation.
Abstract Chronic kidney disease (CKD), especially in its end stage, is marked by extremely high cardiovascular rates of morbidity and mortality; hemodialysis patients have a five-fold shorter life expectancy than healthy subjects of the same age. In CKD the metabolic products that accumulate in the body are so-called uremic toxins. These include advanced glycation end-products (AGE). AGE levels are markedly increased in CKD patients not only because of impaired excretion but also because of increased production. AGE formation has initially been described as a non-enzymatic reaction between proteins and glucose in the so-called Maillard reaction, but they are also more rapidly formed during oxidative stress and subsequent formation of reactive carbonyl compounds like (methyl)glyoxal. AGE accumulate in tissue where they cross-link with proteins, e.g., collagen, inducing tissue stiffening of blood vessels and skin. They may also interact with receptor of AGE (RAGE) and other receptors, which lead to activation of intracellular transduction mechanisms resulting in cytokine release and further tissue damage in CKD. The accumulation of AGE in the skin can be measured non-invasively using autofluorescence. The skin autofluorescence is a strong marker of cardiovascular mortality in CKD. The focus of this review is on the role of tissue and plasma AGE, and of skin autofluorescence as a proxy of tissue AGE accumulation, in the increase in cardiovascular disease in end stage renal disease (ESRD). This review will also present the possibility of reducing the AGE accumulation in ESRD patients using the following five methods: 1) use of low AGE peritoneal dialysis solutions; 2) use of advanced hemodialysis techniques; 3) use of AGE reducing drugs; 4) optimizing the nutrition of hemodialysis patients; and 5) renal transplantation.
Advanced glycation end-products (AGEs) are uremic toxins that accumulate progressively in hemodialysis (HD) patients. The aim of this study was to assess the 1-year increase in skin autofluorescence (ΔAF), a measure of AGEs accumulation and plasma markers, as predictors of mortality in HD patients. One hundred sixty-nine HD patients were enrolled in this study. Skin autofluorescence was measured twice, 1 year apart using an AGE Reader (DiagnOptics Technologies BV, Groningen, The Netherlands). Besides routine blood chemistry, additional plasma markers including superoxide dismutase, myeloperoxydase, intercellular adhesion molecule 1 (ICAM-1), C-reactive protein (hs-CRP), heart-type fatty acid binding protein (H-FABP), and von Willebrand factor were measured at baseline. The mortality of HD patients was followed for 36 months. Skin autofluorescence values of the HD patients at the two time points were significantly higher (P < 0.001) than those of healthy subjects of the same age. Mean 1-year ΔAF of HD patients was 0.16 ± 0.06, which was around seven- to ninefold higher than 1-year ΔAF in healthy subjects. Multivariate Cox regression showed that age, hypertension, 1-year ΔAF, hs-CRP, ICAM-1, and H-FABP were independent predictors of overall mortality. Hypertension, 1-year ΔAF, hs-CRP, and H-FABP were also independent predictors of cardiovascular mortality. One-year ΔAF and plasma H-FABP, used separately and in combination, are strong predictors of overall and cardiovascular mortality in HD patients.
Skin autofluorescence (AF) is related to the accumulation of advanced glycation end products (AGEs) and is one of the strongest prognostic markers of mortality in hemodialysis (HD) patients. The aim of this pilot study was to investigate whether changes in skin AF appear after a single HD session and if they might be related to changes in plasma AF. Skin and plasma AF were measured before and after HD in 35 patients on maintenance HD therapy (nine women and 26 men, median age 68 years, range 33-83). Median dialysis time was 4 h (range 3-5.5). Skin AF was measured noninvasively with an AGE Reader, and plasma AF was measured before and after HD at 460 nm after excitation at 370 nm. The HD patients had on average a 65% higher skin AF value than age-matched healthy persons (P < 0.001). Plasma AF was reduced by 14% (P < 0.001), whereas skin AF was not changed after a single HD treatment. No significant influence of the reduced plasma AF on skin AF levels was found. This suggests that the measurement of skin AF can be performed during the whole dialysis period and is not directly influenced by the changes in plasma AF during HD.
Introduction and Aims: Higher creatinine levels in dialysis patients are associated with higher muscle mass, insufficient dialysis adequacy or a decline in residual renal function (RRF).We aimed to understand association between changes in creatinine levels and patient outcomes in incident hemodialysis patients with no RRF.Methods: We studied all incident hemodialysis (HD) patients treated in RRI clinics who had their first in-center treatment between 1/2000 and 12/2010.Only patients who survived the first 12 months on HD were included.Patients' baseline serum creatinine was computed as an average over the first 3 months.Slope of serum creatinine was computed on a per patient basis using simple linear regression of available creatinine values between months 4 and 12 from the start of treatment.Patients were stratified based on (a) their baseline creatinine (group 1: < 5 mg/dL; group 2: 5 to 8 mg/dL; group 3: > 8 mg/dL) and (b) the average rate of change in creatinine computed by simple linear regression (declined: < -2 mg/dL/year; stable: -2 to 2 mg/dL/year; increased: > 2 mg/dL/year).Patients were then stratified into 9 groups of baseline creatinine levels and creatinine changes.Only patients with no RRF at the start of dialysis were included.Further, for patients whose creatinine increased or declined, only patients with a significant p-value for the slope were included.Patient survival was assessed in months 13 to 18 from the start of dialysis.Cox proportional hazards model adjusted for age, gender, race, ethnicity, diabetic status, access type, BMI, albumin, systolic blood pressure, body temperature, nPCR, eKt/V, interdialytic weight gain, urea distribution volume, and slope of interdialytic weight gain in months 4 to 12 were constructed to compute associations of creatinine as well as creatinine changes and survival.Results: We studied 2333 patients.In a Cox model that includes only the baseline creatinine levels and not its trend, patients with creatinine < 5 ml/dL had a borderline significant association with poorest survival (HR = 1.43, 95% CI: 0.99-2.06,p = 0.06) compared to reference group (creatinine 5 to 8 mg/dL); no difference between creatinine 5 to 8 mg/dL and > 8 mg/dL was observed.In a model that includes the creatinine trend but not the baseline values, an increase of creatinine in months 4 to 12 was borderline significantly associated with improved survival (HR = 0.67, 95% CI: 0.45-1.02,p = 0.06) compared to the reference group (stable creatinine); no difference between declining and stable levels was observed.Lowest HRs were observed in patients with baseline creatinine 5 to 8 mg/dL and > 8 mg/dL and in who the serum creatinine increased (HR = 0.50, p < 0.05; HR = 0.13, p < 0.05, respectively).Creatinine in the first 3 months was positively associated with nPCR ( p < 0.05); slope of creatinine was positively associated with slope of interdialytic weight gain ( p < 0.05); both alluding to higher creatinine values associated with improved nutrition.Conclusions: In incident HD patients lower creatinine levels at baseline ( < 5 mg/dL) are associated with poorer survival.Increases in creatinine levels in patients with baseline creatinine > 5 mg/dL are associated with improved outcomes ( particularly in patients starting with creatinine > 8 mg/dL).It appears that increases in muscle mass ( possibly due to better nutrition) are primarily responsible for increases in creatinine.
K1 (EI0154) AGES IN HEMODIALYSIS: TISSUEAND PLASMAAUTOFLUORESCENCE R. Graaff1, S. Arsov1, L. Trajceska4, P. Dzekova4, G.E. Engels1, M. Koetsier1, W. van Oeveren1, L Lundberg5, S. Assa2, C.F.M. Franssen2, A.J. Smit3, G. Rakhorst1, A. Sikole2, B. Stegmayr5 1Dept. of Biomedical Engineering, 2Internal Medicine, Div. Nephrology and 3Div. Vascular Medicine, University Medical Center Groningen, Groningen, The Netherlands; 4Department of Nephrology, University Clinic of Nephrology, Skopje, R. Macedonia; 5Department of Internal Medicine, University Hospital, Umea, Sweden
K1 (EI0154) AGES IN HEMODIALYSIS: TISSUEAND PLASMAAUTOFLUORESCENCE R. Graaff1, S. Arsov1, L. Trajceska4, P. Dzekova4, G.E. Engels1, M. Koetsier1, W. van Oeveren1, L Lundberg5, S. Assa2, C.F.M. Franssen2, A.J. Smit3, G. Rakhorst1, A. Sikole2, B. Stegmayr5 1Dept. of Biomedical Engineering, 2Internal Medicine, Div. Nephrology and 3Div. Vascular Medicine, University Medical Center Groningen, Groningen, The Netherlands; 4Department of Nephrology, University Clinic of Nephrology, Skopje, R. Macedonia; 5Department of Internal Medicine, University Hospital, Umea, Sweden
Does the advanced glycation end-products (ages) food intake influence mortality in dialysis patients?