Corrigendum. The influence of body mass index on the accumulation of advanced glycation end products in hemodialysis patients.

Correction to: European Journal of Clinical Nutrition (2015) 69, 309­313; 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. The .html and online PDF versions have also been amended. The authors apologise for any inconvenience caused.

The influence of body mass index on the accumulation of advanced glycation end products in hemodialysis patients.

BACKGROUND/OBJECTIVES: The level of skin autofluorescence (AF) at a given moment is an independent predictor of mortality in hemodialysis (HD) patients. Skin AF is a measure of the accumulation of advanced glycation end products (AGEs). The aim of the study was to estimate the influence of nutrition on the 1-year increase of skin AF (ΔAF) in HD patients. SUBJECTS/METHODS: A total of 156 HD patients were enrolled in this study. Skin AF, body mass index (BMI), superoxide dismutase, myeloperoxidase, C-reactive protein, inter-cellular adhesion molecule-1, von Willebrand factor and heart-type fatty acid-binding protein were measured four times at intervals of approximately half a year. Data from the monthly routine blood analysis were also used. Daily calorie, protein and AGE intakes were assessed from food recordings over a period of 1 week. RESULTS: A J-shaped relation was found between baseline BMI and ΔAF (P=0.01). The lowest point of the J-shaped curve is found for BMI=24.3 kg/m(2). In the univariate analysis of the contributors to the 1-year ΔAF, we found that beside BMI=24.3 kg/m(2), AGE and calorie intakes, as well as myeloperoxidase and HD vintage, had a P <0.10. The sole independent predictor of the 1-year ΔAF was BMI=24.3 kg/m(2) (P=0.01). CONCLUSIONS: It appears that calorie, protein and AGE intakes hardly influence the 1-year ΔAF in HD patients. BMI of HD patients of around 24 kg/m(2) resulted in a lower 1-year ΔAF.

Brain natriuretic peptide between traditional and nontraditional risk factors in hemodialysis patients: analysis of cardiovascular mortality in a two-year follow-up.

BACKGROUND: The ability of brain natriuretic peptide (BNP) together with other traditional and nontraditional risk factors to predict cardiovascular (CV) mortality in hemodialysis (HD) patients has not been well established. The aim of this prospective study was to determine the predictive cutoff values of baseline measurement of BNP along with the known CV disease risk factors to predict all-cause and CV mortality in HD patients. METHODS: BNP concentration before HD was measured in 125 prevalent HD patients (age 53.0 ± 13.5 years, HD vintage 75.2 ± 61.0 months). In addition, several traditional CV risk factors (blood pressure, dyslipidemia, diabetes mellitus, body mass index, left ventricular hypertrophy) and uremia/dialysis-related CV risk factors (anemia, calcium and phosphate impairment, malnutrition, inflammation, ultrafiltration, HD duration, Kt/V) were examined. RESULTS: During the 2-year follow-up, we lost 28 out of 125 patients (22.5%), with CV disease (65.7%) being the main cause of mortality. The cutoff point for BNP, as predictor of the clinical outcome, according to the ROC curve was 1,194 pg/ml for CV mortality with sensitivity and specificity of 63 and 65%, respectively (AUC 0.61 and confidence interval (CI) 95% 0.47-0.75). Kaplan-Meier analysis showed that all-cause (log-rank, p = 0.002) and CV mortality (log-rank, p = 0.001) were the cause of a significantly lower survival in patients with a mean BNP >1,200 pg/ml. The univariate Cox regression analysis found the following factors to be predictors of all-cause mortality: hemoglobin (<110 g/l), phosphorus (>1.78 mmol/l), albumin (<40 g/l), C-reactive protein (CRP ≥ 10 mg/l), BNP (>1,200 pg/ml) and cardiac ejection fraction (≤ 55%). The multivariate Cox regression analyses demonstrated that only CRP ≥ 10 mg/l with a hazard ratio (HR) 6.82 (CI 95% 1.86-24.9, p = 0.004) and BNP >1,200 pg/ml with HR 5.79 (CI 95% 1.58-21.3, p = 0.004) were predictors of all-cause mortality. BNP >1,200 pg/ml with HR 13.52 (CI 95% 1.68-108.9, p = 0.014) was found to be an even stronger predictor of CV mortality than CRP ≥ 10 mg/l with HR 6.53 (CI 95% 1.35-31.6, p = 0.020). CONCLUSIONS: Our study pointed out that BNP >1,200 pg/ml as a marker of cardiac dysfunction and CRP ≥ 10 mg/l as a marker of inflammation identify HD patients at increased risk of CV mortality.

New approaches in the therapy of hepatitis C in dialysis patients.

Patients with renal disease are at increased risk of acquiring hepatitis C virus (HCV) infection because of their frequent exposure to blood from transfusions or exposure to HCV-contaminated medical equipment during hemodialysis. The prevalence of anti-HCV antibodies among hemodialysis patients varies between 5-10% in the developed world, and 10-70% in developing countries. Acute hepatitis C is often mild and associated with few, if any symptoms. The major complication of acute HCV infection is chronic hepatitis, which occurs in up to 80% of the cases, the long-term outcome being cirrhosis, portal hypertension, hepatic failure, and hepatocellular carcinoma. Interferon alpha (IFN-alpha) has shown activity against HCV. Twenty four to 48 week course of therapy with interferon could lead to a sustained loss of HCV RNA, normalization of alanine aminotrasferase (ALT) levels, and resolution of the liver disease. Sustained viral response was achieved in approximately half of the treated patients. Therapy with interferon was associated with a number of adverse events such as: "flu-like" symptoms, neurological, gastrointestinal symptoms, anemia, fatigue, thrombocytopenia, leucopenia. A major advance in therapy came with the addition of ribavirin to interferon therapy. Peginterferon-alpha-2a (40KD) is a new 'pegylated' subcutaneous formulation of interferon-alpha-2a, that was developed to improve the pharmacokinetic profile and therapeutic efficacy of interferon-alpha-2a. In our study, fourteen hemodialysis patients with chronic hepatitis C received 135 microg PEG-IFN alpha-2a subcutaneously, once a week, after dialysis session for a period of 48 weeks. In the intention-to-treat analysis, sustained viral response was present in 36% of the patients (five out of fourteen patients) at the end of the follow up period. The biochemical response with normalization of serum ALT levels during the treatment was observed in all treated patients (83 +/- 20.1 U/L at base line vs. 23.4 +/- 4.6 U/L after the 48 weeks; p < 0.01). At present, therapy for hepatitis C should be considered in hemodialysis patients with significant liver disease, minimal other co morbidities, and a reasonable likelihood of prolonged survival or if renal transplantation is planned.

Factors associated with various arterial calcifications in haemodialysis patients.

BACKGROUND: Haemodialysis (HD) patients are at increased risk of the development of arterial intimal (AIC) and medial calcification (AMC). The aim of our study was to analyze the association between the pre-defined potential risk factors and the status of various arterial calcifications in our HD patients. METHODS: In a cross-sectional study of 150 patients (91 male, mean age 54.55 +/- 12.46 yrs, HD duration 104.77 +/- 68.02 mths) we first determined the presence of AIC and AMC using plain radiography of the pelvis. We then compared the percentages of different radiogram findings in patients stratified according to various cut-off levels or the codes of each clinical and biochemical parameter (mean value of one year laboratory data recorded in the files). RESULTS: We determined arterial calcifications in 77.3% of our patients (AIC in 45.3%, AMC in 32%). The significantly higher frequencies of arterial calcifications of both groups (AIC and/or AMC) and isolated AIC presence were found in patients older than 55 at inclusion and 45 at the start of treatment with HD, with a serum C-reactive protein (CRP) > 4.5 mg/L, predominantly of male gender with diabetes. The patients with a significantly higher occurrence of arterial calcifications had lower percentages of total serum calcium (Ca) levels but within the K/DOQI guideline recommendations. Also, we found a significantly higher proportion of isolated AIC presence in the group of patients with corrected total serum Ca levels > 2.35 mmol/L and serum intact parathyroid hormone (iPTH) levels out of the range proposed by K/DOQI guidelines. In parallel, a significantly higher percentage of absence of arterial calcifications (ACA) was obtained in the patients with corrected total serum Ca levels < 2.35 mmol/L, body mass index (BMI) < 23 kg/m(2), mean pulse pressure < 60 mmHg, blood leucocytes < 6.5 x 10(9)L and serum triglycerides < 1.8 mmol/L. Finally, we found a significantly higher presence of isolated AMC in patients with mean Kt/V < 1.3 (poor dialysis adequacy), serum triglycerides > 1.8 mmol/L and outside K/DOQI guideline achievements for corrected total serum Ca. In the 12 month period data analyzed, there were no significant differences in other risk factors such as the dose of prescribed calcium carbonate and vitamin D3, serum levels of albumin, cholesterol, phosphate (P) and Ca x P product. CONCLUSIONS: AIC and AMC were frequently present in our HD population. Age, gender, BMI, diabetes, pulse pressure, dialysis adequacy, serum CRP, triglycerides, Ca and iPTH, as well as blood leucocyte levels were associated with the occurrence of arterial calcifications in our HD patients.

Hepatitis C in dialysis patients.

Hepatitis C virus (HCV) remains prevalent in dialysis patients and is an important cause of liver disease in this population. A number of risk factors have been identified for spreading the HCV infection among dialysis patients, including the number of blood transfusions, the duration of dialysis, the mode of dialysis, and the prevalence of HCV infection in the dialysis unit. Difficulties in formulating policies regarding HCV infection in dialysis units arise because of the high prevalence of HCV infection in dialysis patients, the limitations of current tests in identifying these patients, and the uncertainties regarding the modes of transmission within dialysis unit. Little is known concerning the natural history of HCV infection in patients undergoing dialysis. This is due in part to an unrecognized onset of infection, the slow progression of hepatitis C viral disease, and the fact that infected dialysis patients may not have the time to become clinically apparent because of the overall shortened life-expectancy. The clinical course of HCV infection in dialysis patients is generally asymptomatic, and the progression of the disease is apparently benign. The mortality rate of infected dialysis patients is higher than in non-infected subjects, and this is not only due to the liver disease itself but also to cardiovascular disorders. Interferon alpha (standard or pegylated) is the current treatment of HCV infection in dialysis patients, with careful patient selection together with a close follow-up of the main side effect. HCV infected dialysis patients who are candidates for renal transplantation have to be treated before transplantation, since HCV infection has a negative impact on graft and patient survival and interferon therapy remains contraindicated after transplantation because of the serious risk of graft rejection.

Survival of patients on maintenance haemodialysis over a twenty-year period.

Patient survival is a key index of the overall adequacy of treatment in most chronic diseases. Analyses of survival of patients undergoing haemodialysis is very important, as it may offer clues and ideas for prolonging survival of patients with end-stage renal disease (ESRD). The aims of this study were to describe the characteristics of the patients on maintenance haemodialysis therapy over a period of 20 years, to determine the survival rate of these patients according to ages at the onset of haemodialysis, the primary renal diseases, and the cause of death, and to determine the survival rate at five, ten, fifteen and twenty years of haemodialysis treatment at our centre. The charts of 518 unselected patients, 282 male and 236 female, treated with maintenance haemodialysis therapy in a period of 20 years (1985-2005) were reviewed. At the time of evaluation, 164 patients were currently being treated, and 354 patients overall had been diseased. Statistical analysis was performed to evaluate the relationship between survival and patient characteristics such as age, gender, primary renal disease, and age at dialysis onset. Actual survival rates were determined by the Kaplan-Meier method. The survival rate of our patients treated with maintenance haemodialysis was 60% at 5 years, 37% at 10 years, 25% at 15 years and 9% at 20 years. Female patient survival was superior to male. Patients aged under 40 at the start of dialysis had a better survival probability compared to older patients. Patients with diabetes mellitus and nephroangiosclerosis, had a lower survival rate compared to patients with glomerulonephritis and with adult dominant polycystic kidney disease. Cardiac death was the most common cause of death in patients involved in the study. About 52% of the patients died from cardiovascular disease. Death is the most severe consequence of inadequate dialysis and can be used as an index of the adequacy of the dialysis therapy. Treatment factors that may improve outcomes include an early start of dialysis therapy, a high dose of dialysis (Kt/V over 1.2), correction of anemia, adequate protein and caloric intake, control of calcium and phosphate metabolism, and the use of biocompatible dialyzers.

Effect of nephrology referral on the initiation of haemodyalisis and mortality in ESRD patients.

Late nephrology referral of patients with chronic kidney disease (CKD) has been suggested as increasing mortality after the initiation of dialysis. The aim of this study was to assess the impact of nephrology referral on the initiation of haemodyalisis (HD) and mortality during HD treatment in end-stage renal disease (ESRD) patients who have died in our institution over a five-year period. We studied data from all 117 patients on HD treatment in our institution who died (after 90 days of HD treatment) in the period between 01.01. 2002 and 31.12. 2006. Early (ER) and late referral (LR) were defined by the time of follow-up by a nephrologist greater than or less than 6 months, respectively, before the initiation of haemodialysis. Out of a total of 117 patients, 37.6% (44 patients) started HD in the ER group and 62.4% (73 patients) in the LR group. At the start of HD, LR patients were older, had a higher proportion of temporary catheters and had a significantly lower levels of haemoglobin and diuresis. Creatinine clearance was less in the LR (7.67 +/- 3.86 ml/min/1.73 m2) vs. the ER group (8.70 +/- 3.62 ml/min/1.73 m2), but not significantly different. Cardiovascular disease (CVD), defined by a history of myocardial infarction, cerebral vascular disease, peripheral arteriopathy, and/or heart failure, was also significantly more common among LR patients compared to ER (56%; 27%, p = 0.002). During the haemodyalisis treatment, the LR group had significantly lower levels of haemoglobin and haematocrit. CVD accounted for about 64% of deaths observed in the LR group. According to echocardiography data, there were no significant differences in the left ventricular mass index (LVMI) between the LR and ER groups at the time of dialysis initiation, but during haemodialysis treatment the LR group had significantly greater LVMI than the ER group (232,96 +/- 92,48 g/m2 vs.184,09 +/- 51,74 g/m2; p = 0,031). The time until death in months during dialysis treatment was significantly different between the LR and ER group, (69.51 +/- 64.03 vs.113.27 +/- 89.03, p = 0.0025). LR patients experienced a greater degree of anaemia and a high prevalence of CVD at the time of dialysis initiation. Our data suggest that the anaemia, CV damage and progression of left ventricular hypertrophy (LVH) in the LR patients during haemodialysis treatment are associated with poor survival on haemodialysis.

Inflammation predicts all-cause and cardiovascular mortality in haemodialysis patients.

Among non-traditional cardiovascular risk factors both malnutrition and inflammation appear to be strong predictors of mortality and morbidity in haemodialysis (HD) patients. Our study objective was to determine predictors of all-cause and cardiovascular mortality, considering the nutritional and immunologic parameters, in a cohort of HD patients treated in a single haemodialysis centre. 216 patients on HD were analyzed for clinical, nutritional-serum albumen and BMI, immunologic-serum CRP (C-reactive protein) and fibrinogen and dialysis parameters -- ultrafiltration, length of dialysis in hours, HD dose (using spKt/V and eKt/V). Mortality was monitored prospectively over a two-year period. Fifty-five of the 216 HD patients died during the follow-up period and the main cause of death was cardiovascular disease (CVD) -- 33 patients out of 55 (60%), followed by infection/sepsis (13 pts, 24%). The patients who died were significantly older, had a significantly shorter duration of HD in hours, ultrafiltration was significantly less, HD doses were significantly lower, as were serum levels of albumin (36.06 +/- 4.17 vs. 39.74 +/- 3.31; p=0.000) and Hg (93.14 +/- 15.43 vs. 109,16 +/- 12,08; p=0.000), but they had significantly higher serum levels of CRP (40.26 +/- 34.75 vs. 8.71 +/- 7.68, p=0.000) and fibrinogen (5.28 +/- 1.28 vs. 4.42 +/- 0.97, p=0.000). Kaplan-Meier survival estimates showed that the group with the lowest levels of albumin (< 3.5 g/L), and with the greatest levels of CRP (>20 mg/l) and fibrinogen (>5 g/L) had the lowest survival (log-rank test p=0.0008, p=0.00000, p=0.0000). However, in the Cox proportional hazards model, a high CRP and low Hg level (chi-square=96.467, p=0.0000) were predictors of all-cause mortality, whereas serum level of albumin did not show to be predictive. When only cardiovascular mortality is entered into the Cox model, CRP and Hg levels are still more important in predicting mortality (chi-square=70.055, p=0.0000) and only if CRP is not taken into account in the multivariate analysis, serum albumin level remains, after Hg, the strongest predictor for both overall and cardiovascular mortality (chi-square=76,564, p=0.0000; chi-square 50.619 p=0.0000). It can be concluded that inflammation predicted all-cause and cardiovascular mortality in our study group, because high CRP, as a marker of inflammation and low haemoglobin, as a result of inflammation, remained powerful predictors of both overall and cardiovascular death.

Malnutrition inflammation complex syndrome in maintenance haemodialysis patients.

Malnutrition inflammation complex syndrome (MICS) occurs in maintenance haemodialysis (MHD) patients and is a strong predictor of morbidity and mortality in these patients. The aim of our study was to evaluate the influence of inflammation on the biochemical and anthropometrical parameters of the nutritional status in MHD patients. Our study was made on 154 patients (93 men and 61 women, mean age=54.7 yrs. and mean time on dialysis 84 months) over a period of 6 months. The indicator of inflammation, C-reactive protein (CRP), was measured monthly at the central laboratory by nephelometry. The assessment tools used to evaluate the influence of inflammation on the nutritional status in MHD patients were: serum albumin and cholesterol level, midarm circumference (MAC), midarm muscle circumference (MAMC), triceps skin fold thickness (TSF) and body mass index (BMI). Student's t-test was used for group mean comparison between men and women. Person's correlation r was used to determine the significance and the strength of associations. The CRP level was significantly greater in men than in women (12.9 vs. 7.97, p < 0.04). The CRP level showed a strong correlation only with the serum concentration of cholesterol (r=0.49, p < 0.000), and did not correlate with the serum albumin of the MHD patients. There was no correlation between the CRP level and the anthropometrical parameters of the MHD patients in our study. Two separate processes, inflammation and reduced protein intake, each separately contributed to causing a decrease in serum albumin concentration and anthropometrical measurements. The levels of acute phase proteins vary widely as opposed to the serum albumin level; for that reason, changes in the albumin catabolic rate or synthesis require a considerable time to become visible. The average value of the protein catabolic rate of the patients in our study was 1.01 g/kg/d, a value that showed adequate protein intake. These findings would suggest that clinical attention to the maintenance of adequate nutrition could blunt the effects of inflammation on both somatic and visceral protein stores.

Histomorphometric analysis of fibrosis in the renal interstitial compartment.

The interstitium is the extravascular intertubular space of the renal parenchyma, which provides structural support to the functional renal units and is included at the same time in nearly all renal functions. Alterations to this renal compartment have been found in almost all glomerular diseases. During the last thirty years the studies of a few groups of investigators have shown that the degree of the renal dysfunction is strongly correlated with the changes in the tubulointerstitial compartment. We made a morphometric study of a group of 10 renal biopsies, previously diagnosed as IgA nephropathy or membranoproliferative glomerulonephritis. For morphometric analysis we made colour extraction of the interstitial area on tissue sections stained with trichrom Masson using the LUCIA M-NIKON image analysing system with integrated software for statistical analysis of the data. We measured the surface of the marked fields and the results were expressed as a percentage of the total scanned area. The results were correlated with the serum creatinine at the time of biopsy. We found fibrosis occupying more than 10% of the tubulointerstitial surface in all 10 patients. Six of them had a moderate level of fibrosis, occupying more that 20% of the tubulointerstitial space. The statistical analysis of these results showed a significant correlation between the degree of the interstitial expansion and the serum creatinine. The results showing the correlation between these parameters will enable the quantitative histological analyses to be included in the process of the nephropathological diagnosis in order to evaluate the histological risk factors in glomerular diseases.