Minimal Change Disease: Pathogenetic Insights from Glomerular Proteomics.

The mechanism underlying podocyte dysfunction in minimal change disease (MCD) remains unknown. This study aimed to shed light on the potential pathophysiology of MCD using glomerular proteomic analysis. Shotgun proteomics using label-free quantitative mass spectrometry was performed on formalin-fixed, paraffin-embedded (FFPE) renal biopsies from two groups of samples: control (CTR) and MCD. Glomeruli were excised from FFPE renal biopsies using laser capture microdissection (LCM), and a single-pot solid-phase-enhanced sample preparation (SP3) digestion method was used to improve yield and protein identifications. Principal component analysis (PCA) revealed a distinct separation between the CTR and MCD groups. Forty-eight proteins with different abundance between the two groups (p-value ≤ 0.05 and |FC| ≥ 1.5) were identified. These may represent differences in podocyte structure, as well as changes in endothelial or mesangial cells and extracellular matrix, and some were indeed found in several of these structures. However, most differentially expressed proteins were linked to the podocyte cytoskeleton and its dynamics. Some of these proteins are known to be involved in focal adhesion (NID1 and ITGA3) or slit diaphragm signaling (ANXA2, TJP1 and MYO1C), while others are structural components of the actin and microtubule cytoskeleton of podocytes (ACTR3 and NES). This study suggests the potential of mass spectrometry-based shotgun proteomic analysis with LCM glomeruli to yield valuable insights into the pathogenesis of podocytopathies like MCD. The most significantly dysregulated proteins in MCD could be attributable to cytoskeleton dysfunction or may be a compensatory response to cytoskeleton malfunction caused by various triggers.

Chronic Kidney Disease and Periodontitis Interplay-A Narrative Review.

Periodontitis (PO), a chronic microbially-induced inflammation of the supporting tissues of the tooth, is linked to various systemic diseases. We analyze its bidirectional relationship to chronic kidney disease (CKD), a major health-care problem with impressive excess mortality. Overwhelming associative relationship between CKD and PO are analyzed. Major pathophysiologic mechanisms that link CKD to PO are then presented: systemic inflammation, endothelial dysfunction, and imbalance of oxidative stress characteristic of CKD have a role in PO development and might influence escape mechanisms of oral microbiota. Subclinical local and systemic inflammation induced by PO might influence in turn CKD outcomes. Homeostatic changes induced by CKD such as mineral bone disorders, acidosis, uremic milieu, or poor salivary flow are also relevant for the occurrence of PO. There is insufficient evidence to recommend a standardized diagnostic and therapeutic approach regarding association of PO to CKD.

The Use of Machine Learning Algorithms and the Mass Spectrometry Lipidomic Profile of Serum for the Evaluation of Tacrolimus Exposure and Toxicity in Kidney Transplant Recipients.

Tacrolimus has a narrow therapeutic window; a whole-blood trough target concentration of between 5 and 8 ng/mL is considered a safe level for stable kidney transplant recipients. Tacrolimus serum levels must be closely monitored to obtain a balance between maximizing efficacy and minimizing dose-related toxic effects. Currently, there is no specific tacrolimus toxicity biomarker except a graft biopsy. Our study aimed to identify specific serum metabolites correlated with tacrolinemia levels using serum high-precision liquid chromatography-mass spectrometry and standard laboratory evaluation. Three machine learning algorithms were used (Naïve Bayes, logistic regression, and Random Forest) in 19 patients with high tacrolinemia (8 ng/mL) and 23 patients with low tacrolinemia (5 ng/mL). Using a selected panel of five lipid metabolites (phosphatidylserine, phosphatidylglycerol, phosphatidylethanolamine, arachidyl palmitoleate, and ceramide), Mg2+, and uric acid, all three machine learning algorithms yielded excellent classification accuracies between the two groups. The highest classification accuracy was obtained by Naïve Bayes, with an area under the curve of 0.799 and a classification accuracy of 0.756. Our results show that using our identified five lipid metabolites combined with Mg2+ and uric acid serum levels may provide a novel tool for diagnosing tacrolimus toxicity in kidney transplant recipients. Further validation with targeted MS and biopsy-proven TAC toxicity is needed.

Relationship between vascular cell adhesion molecule-1 (VCAM-1), soluble receptor for advanced glycation end products (sRAGE) and functional hemodynamic parameters of arteriovenous fistula.

BACKGROUND: The preferred vascular access for hemodialysis is represented by arteriovenous fistula (AVF) due to fewer complications and more prolonged survival. Considerable efforts have been made to identify biomarkers associated with AVF dysfunction, but results are conflicting. Vascular cell adhesion molecule (VCAM-1) and advanced glycation end products are involved in atherogenesis, vascular calcification, peripheral artery disease, and neointimal hyperplasia in renal and non-renal patients. The objective of this study was to evaluate whether there is an association between VCAM-1, soluble receptor for advanced glycation end products (sRAGE), NcarboxymethylLysine (CML), and arteriovenous fistula dysfunction (AVF). METHODS: VCAM-1, sRAGE, and CML were performed using the ELISA technique in 88 HD patients. Ultrasound assessment of AVF reports brachial artery blood flow (Qa), brachial resistivity index (RI), presence of calcification, and the diameter. AVF dysfunction was defined as a brachial artery Qa ⩽ 500 ml/min or RI ⩾ 0.5. RESULTS: The median level of VCAM-1 [2676.5(2206.8-4203.9) versus 2613.2(1885.7-3161.8), p 0.026] was significantly higher in patients with AVF dysfunction compared to the rest of the patients. sRAGE and CML were higher in this group but without statistical significance. In patients with AVF dysfunction, significant positive correlations were found between VCAM-1and sRAGE (r = 0.417, p = 0.001), RI (r = 0.313, p = 0.046), dialysis vintage (r = 0.540, p < 0.001), AVF vintage (r = 0.336, p = 0.032), intima-media thickness (r = 0.423, p = 0.006) and C-reactive protein (r = 0.315, p = 0.045). VCAM-1 correlated inversely with cholesterol (r = -0.312, p = 0.047), triglycerides (r = -0.358, p = 0.021), body mass index (r = -0.388, p = 0.012). In multivariate regression analysis, VCAM-1 (p = 0.013) and sRAGE (p = 0.01) remained significant predictors of RI and Qa. Logistic regression disclosed calcification, VCAM-1, as risks factors for AVF dysfunction. CONCLUSION: The results we obtained showed that patients with AVF dysfunction had a significantly higher level of VCAM-l. A positive correlation between VCAM-1 and sRAGE was identified in this group.

Hemodialysis Patients with Higher Serum Levels of Soluble Receptor for Advanced Glycation End Products Have an Increased Risk for Arteriovenous Fistula Failure.

BACKGROUND: Arteriovenous fistula (AVF) failure due to thrombosis is a major cause of morbidity in patients undergoing regular hemodialysis (HD). Advanced glycation end products (AGEs) and their receptor (RAGE) might contribute to inflammation, neointimal hyperplasia, and thrombosis. RAGE has a C-truncated secretory receptor form, called soluble RAGE (sRAGE). In this study, we aimed to evaluate the association of serum sRAGE with AVF failure due to thrombosis in HD patients. METHODS: Eighty-eight prevalent HD patients with functional AVF were included in the study. The presence of stenosis, clinical and laboratory data, and serum sRAGE was evaluated at inclusion. sRAGE concentration was measured by a competitive enzyme-linked immunosorbent assay, and stenosis was detected by ultrasound. Patients were prospectively followed up for 36 months. During this period, AVF failure (defined as the absence of blast or palpable thrill and impossible cannulation with 2 needles because of complete thrombosis) was noted and thrombosis was certified by ultrasound examination. RESULTS: During follow-up, 16 (18.18%) patients lost their vascular access due to thrombosis. In multivariate Cox regression analysis, sRAGE was a significant predictor of vascular access thrombosis (hazard ratio = 1.15, 95% confidence interval: 1.03-1.25, p = 0.012). Kaplan-Meier analysis showed a significantly lower AVF patency time in patients with sRAGE >16.78 ng/mL than those with sRAGE <16.78 ng/mL (p = 0.02). In the subgroup of patients with stenosis at baseline, sRAGE, serum albumin, obesity, and ischemic heart disease were associated with thrombosis. CONCLUSION: In our study, baseline, systemic sRAGE is associated with the occurrence of thrombosis of AVF, and this marker has a significant impact on AVF survival.

The role of Contrast-Enhanced Ultrasound for evaluating renal perfusion dynamics in partially reversible acute cortical kidney ischemia in a patient with sepsis.

We report the case of a sepsis-induced acute kidney injury accompanied by disseminated intravascular coagulation and thrombotic microangiopathy, responsible for subsequent renal microvascular thrombosis. Contrast-enhanced ultrasound was used to assess the thrombotic cortical kidney ischemia and its evolution over time.

Pentosidine in chronic hemodialysis patients: relation with arteriovenous fistula morphology and function.

PURPOSE: It has been suggested that advanced glycation end products (AGEs) are involved in atherogenesis, vascular calcification and remodeling, including neointimal hyperplasia, in renal and non-renal patients. Their relevance for arteriovenous fistula (AVF) function has been poorly studied to date, with only one clinical study addressing the issue of thrombosis of vascular access in relation to AGEs in dialysis patients. We aimed to evaluate the relationship between serum pentosidine and AVF morphology and function. METHODS: Eighty-eighth hemodialysis patients with patent native AVF were included. Ultrasound examination of AVF evaluated blood flow in the brachial artery, resistivity index (RI), the diameter of the vessels and the presence of stenosis. AVF and cardiovascular history were recorded, routine clinical and laboratory evaluation was performed and serum pentosidine was assessed. RESULTS: Forty-eight patients (54.54%) had AVF stenosis. Pentosidine correlated in univariate analysis with cholesterol (r = 0.270, p = 0.01), triglycerides (r = 0.309, p = 0.003), calcium (r = 0.040, p < 0.001) and inversely to dialysis vintage (r = - 0.453, p < 0.001), access vintage (r = - 0.432, p = 0.001), phosphate (r = - 0.211, p = 0.04), parathyroid hormone (r = - 0.211, p = 0.04), urea (r = - 0.230, p = 0.03), residual diameter of AVF (r = - 0.023, p = 0.03). In multivariate regression calcium (p = 0.006), access vintage (p = 0.03), and residual diameter of AVF vein (p = 0.02) remain significantly linked to pentosidine. Patients with pentosidine above median had higher cholesterol (179.91 vs. 160.97, p = 0.04), triglycerides (187.18 vs. 129.31, p = 0.002) and higher prevalence of hypertension (93.70% vs. 84.10%, p = 0.02). CONCLUSIONS: Our study suggests that pentosidine could be associated to vascular access morphology and function in dialysis patients.

Ghrelin and acyl ghrelin levels are associated with inflammatory and nutritional markers and with cardiac and vascular dysfunction parameters in hemodialysis patients.

PURPOSE: Exogenous ghrelin is associated with cardiovascular protection in experimental and human studies. Nevertheless ESRD patients have increased ghrelin levels and severe cardiovascular comorbidities. This study aims to elucidate the metabolic factors influencing endogenous ghrelin/acyl ghrelin levels and to analyze the relation between endogenous ghrelin/acyl ghrelin levels and cardiac and vascular function markers in hemodialysis patients. METHODS: The cross-sectional study was conducted in hemodialysis patients (n = 88); 50 of them were men, mean age 61.1 ± 13.5 years, 17% had diabetes. We assessed nutritional and inflammatory status and analyzed the determinants of ghrelin/acyl ghrelin and their relation with cardiac and vascular function. RESULTS: Ghrelin is correlated with IL-1ß (r = 0.88, p < 0.0001), triglycerides, total cholesterol (TC), and Kt/V. IL-1ß is the strongest predictor of ghrelin levels (p < 0.0001). Acyl ghrelin is correlated with TC (r = 0.36, p = 0.001), LDL-cholesterol, serum bicarbonate, body mass index. TC is the strongest predictor for acyl ghrelin levels (p = 0.038). Patients with high ghrelin levels had significantly decreased nitroglycerin-mediated dilation (p = 0.05) and higher IL-1ß levels (p < 0.001); increased NT-proBNP is associated with lower levels of acyl ghrelin (r = - 0.33, p = 0.02) in male patients. CONCLUSION: The inflammatory marker IL-1ß is in our study the strongest predictor of ghrelin levels while the nutritional marker-total cholesterol is the strongest predictor for acyl ghrelin levels in HD patients. High endogenous ghrelin level is associated with high IL-1ß and with vascular smooth muscle cell dysfunction. Low acyl ghrelin level is associated with high NT-proBNP (a cardiac dysfunction marker) in male HD patients. There is a direct correlation between endogenous ghrelin level and inflammatory markers, which is not related with cardiovascular protection.

Matrix-Metalloproteinase-2 Predicts Arteriovenous Fistula Failure in Hemodialysis Patients.

In hemodialysis patients the principal cause of arteriovenous fistula dysfunction is stenosis. Matrix-metalloproteinase-2 is implicated in the pathophysiological mechanism of stenosis development. Our study tried to assess the clinical impact of this protease on arteriovenous fistula survival. Seventy-nine prevalent dialysis patients with functional arteriovenous fistulas were included in the study. The presence of stenosis and the serum levels of matrix-metalloproteinase-2 were determined at the beginning of the study. The patency of the arteriovenous fistulas was followed- up for two years. In multivariate regression; matrix-metalloproteinase-2 was a significant predictor of vascular access loss (HR = 1.104, 95%CI 1.033-1.179, P = 0.003). Patients with a level of matrix-metalloproteinase-2 lower than 50 ng/mL had a better survival of the arteriovenous fistulas. Matrix-metalloproteinase-2 was an even stronger predictor of fistula failure in the stenosis group (HR = 1.076, 95%CI 1.027-1.127, P = 0.002). In our study matrix-metalloproteinase-2 has a predictive value for arteriovenous fistula failure.

Insomnia, muscular cramps and pruritus have low intensity in hemodialysis patients with good dialysis efficiency, low inflammation and arteriovenous fistula.

INTRODUCTION: Insomnia, muscular cramps, pruritus and postdialysis recovery time (RT) are quality-of-life parameters that affect hemodialysis (HD) patients physically and mentally. METHODS: We included 171 end-stage renal disease patients: 115 on high-flux HD and 56 on online hemodiafiltration (HDF). Patients were asked "How long does it take you to recover from a dialysis session?" and they evaluated intensity (absent, mild, medium and severe) of insomnia, muscular cramps and pruritus in the past 4 weeks. We sought associations of RT, insomnia, muscular cramps and pruritus with themselves and age, dialysis vintage, sex, body mass index, hemoglobin, albumin, C-reactive protein (CRP), Daugirdas single-pool Kt/V (Kt/V), ultrafiltration volume, blood processed volume and vascular access type. RESULTS: Insomnia absence correlated with muscular cramps absence (p = 0.01), arteriovenous fistula (AVF) presence (p = 0.02) and lower CRP (p = 0.003). Muscular cramps absence associated pruritus absence (p = 0.007) and AVF (p = 0.001). Absent pruritus patients were younger (p = 0.04), had higher Kt/V (p = 0.01) and more AVF (p = 0.02). Men insomnia was more severe in HD than HDF and albumin related (p = 0.007), while CRP was lower in absent pruritus. Women insomnia associated with muscular cramps (p = 0.04) and vascular access (p = 0.03), as was pruritus (p = 0.03). RT had no relations with any parameter. CONCLUSIONS: HD patients with AVF have less insomnia, muscular cramps and pruritus. Insomnia is associated with muscular cramps and inflammation. Pruritus is worse in older patients, is diminished with increased dialysis efficiency and is associated with higher CRP in men. There is no difference between HD and HDF patients, except more severe insomnia for HD in men.

Osteoprotegerin and uremic osteoporosis in chronic hemodialysis patients.

INTRODUCTION: Osteoprotegerin (OPG) is a powerful inhibitor of osteoclast activity, and it plays an important role in bone metabolism. In hemodialysis (HD) patients, the relationship between OPG and bone mineral density (BMD) is important, but remains unclear yet. The study objective was to assess the OPG role related to uremic osteoporosis in HD patients. METHODS: This cross-sectional study has been realized on a cohort of 63 chronic HD patients. INCLUSION CRITERIA: elderly prevalent HD patients with an age over 55 years old. EXCLUSION CRITERIA: previous bone disease or previous renal transplant; neoplasia; parathyroidectomy, hormone replacement therapy. The data regarding demographical and clinical characteristics, including treatments for mineral and cardiovascular complications, were recorded. Serum OPG and mineral markers levels were measured. BMD was assessed by calcaneus quantitative ultrasound; it measured broadband ultrasound attenuation, speed of sound (SOS) and stiffness index (STI). RESULTS: The high OPG levels were associated with higher bone mineral density (OPG-SOS P = 0.003; R = 0.37; OPG-STI P = 0.03; R = 0.28). Malnutrition, anemia and advanced age correlated with bone demineralization. Males had higher bone density parameters than females. In patients treated with vitamin D (P = 0.005), the BMD was increased comparing to patients without these treatments. CONCLUSIONS: OPG levels had directly correlated with bone mineral density parameters. Our study further confirms the critical role of OPG in the pathogenesis of uremic osteoporosis in ESRD. Whether the increased circulant OPG protect against bone loss in patients undergoing HD remains to be established.

Soluble CD40 ligand in haemodialysis patients: survival impact and cardiovascular prognostic role.

CONTEXT: Soluble CD40 ligand (sCD40l) can predict cardiovascular events (CVE) and mortality in haemodialysis (HD) patients (short-, medium-term follow-up studies). OBJECTIVE: To evaluate the relationship between sCD40l and survival, CVE and mortality in HD patients on long-term follow-up. METHODS: We registered 46 HD patients' baseline characteristics, mortality and CVE for 108 months. RESULTS: SCD40l correlated positively with C-reactive protein, was higher in survivors, but had no impact on survival and was not predictive for CVE or CV mortality. CONCLUSION: The levels of sCD40l have no influence on survival or CVE and mortality in HD patients in a long-term follow-up.

The metabolic hormone FGF21 is associated with endothelial dysfunction in hemodialysis patients.

PURPOSE: Finding new, reliable biomarkers of cardiovascular risk in hemodialysis (HD) patients is of utmost importance. Fibroblast growth factor 21 (FGF21) has been recently associated with atherosclerosis in the general population. The relationship between markedly elevated FGF21 levels in HD patients and endothelial dysfunction is unknown. The aim of the study was to assess the determinants of FGF21, the correlation between FGF21 and tumor necrosis factor TNF-like weak inducer of apoptosis (sTWEAK) and the correlation between FGF21 and endothelial dysfunction in HD patients. METHODS: A cross-sectional observational study was conducted in 70 HD patients (mean age 59.9 ± 12.5 years, 14.3% diabetes mellitus, 57.1% male) from Nefromed Dialysis Center Cluj. We registered clinical and biological data, and serum FGF21 levels were measured by ELISA. Endothelial function was evaluated by brachial flow-mediated dilation (FMD). An analysis based on stratification of FGF21 values into quartiles was performed. RESULTS: FGF21 levels were directly correlated with sTWEAK, tricipital skinfold thickness (TST), systolic blood pressure (SBP), total cholesterol and triglycerides. In multivariate linear analysis, only sTWEAK and SBP remained significantly associated with FGF21. FGF21 values in the inferior quartile were directly correlated with HDL-cholesterol, while FGF21 values in the superior quartile were directly correlated with SBP, pulse pressure and sTWEAK. FMD was significantly higher in the inferior quartile as compared to the superior quartile. CONCLUSIONS: High FGF21 values in our patients are correlated with atherosclerosis risk factors: hypercholesterolemia, hypertriglyceridemia, hypertension, increased TST and increased levels of sTWEAK. Endothelial dysfunction is associated with high FGF21 in HD patients.

Ultrasonographic diagnosis of stenosis of native arteriovenous fistulas in haemodialysis patients.

AIMS: Ultrasound (US) examination is an important tool in the diagnosis of arteriovenous (AVF) stenoses; different US measures are available for assessing the severity of stenoses. The aim of our study was to analyse risk factors and consequences of AVF stenosis and its severity and to compare the usefulness of different US measures of stenoses' severity. MATERIAL AND METHODS: Ninety-seven prevalent patients from a single dialysis centre with patent AVF were included. We recorded history of disease, clinical and laboratory data. US was used to diagnosis the stenosis and to measure blood flow in the brachial artery, resistivity index (RI), and the diameter of the vessels (arteries, anastomosis, venous outflow). RESULTS: Stenosis was present in 54.64% of the patients (59.6% juxtaanastomotic). Stenosis patients had higher age, lower diameter of the brachial artery, lower anastomosis diameter, and lower diastolic blood pressure (DBP). Atherosclerosis, delayed maturation of AVF, and statin treatment were more prominent in the stenosis group. Logistic regression disclosed delayed maturation, cholesterol, atherosclerosis, and DBP as significant predictors of stenosis. When severe stenosis was measured by the diameter reduction, stenosis patients had higher age, lower HDL cholesterol, and poorer dialysis efficacy. Flow in the brachial artery and RI were less useful for identifying risk factors or differences in outcome. CONCLUSIONS: Prevalence of stenosis was high in our cohort, more than half of the patients having some degree of stenosis. Risk factors for stenosis were related to atherosclerosis, low DBP, and delayed maturation of AVF. Diameter of stenosis is the most useful marker of severity.

Malondialdehyde can predict survival in hemodialysis patients.

BACKGROUND AND AIMS: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in hemodialysis (HD) patients. Kidney disease is associated with increased oxidative stress (OS), a nontraditional CV risk factor. Few studies evaluate the effect of OS markers on CV events (CVE) and survival in HD patients. The aim of this study is to examine potential determinants of OS markers and their predictive role on survival and CV morbidity and mortality in HD patients during a long-term follow-up (108 months). METHODS: We conducted an analytical cross-sectional prospective observational study, carried on a cohort of randomly selected HD patients. We registered in 44 HD patients baseline characteristics, OS markers, mortality and CVE over a period of 108 months and we used statistical analysis (descriptive, Kaplan-Meier, univariate and multivariate Cox model) for interpretation. RESULTS: Bound malondialdehyde (bMDA) was positively correlated with serum calcium, protein carbonyls (PC) were inversely correlated with diastolic blood pressure (DBP) and directly correlated with ferritin, NOx was directly correlated with ceruloplasmin) and serum albumin. Of the measured OS markers only bMDA was related to survival (HR=3.29 95% CI (1.28-8.44), p=0.01), and approached statistical significance in the effect on CV mortality (HR=2.85 95% CI (0.88-9.22), p=0.07). None of the measured OS markers was associated with CVE. CONCLUSIONS: bMDA has a strong predictive value on survival in HD patients in a long-term follow-up (9 years). Its value is correlated with CV mortality but is not a predictor of CV events. Regular assessment of MDA in HD patients and the development of strategies aimed at reducing oxidative stress in these patients might be beneficial.

Mineral and bone disorders, morbidity and mortality in end-stage renal failure patients on chronic dialysis.

BACKGROUND AND AIM: In spite of numerous interventions, the control of mineral disturbances remains poor in end-stage renal failure (ESRF) patients. Chronic kidney disease - mineral and bone disorders (CKD-MBD) represent an important cause of mortality and morbidity. The aim of this study is to analyze the relationship between mineral and bone disorders (MBD) and their components impact on all-cause mortality and cardiovascular (CDV) mortality and morbidity in chronic dialysis patients. METHODS: This prospective study was carried out in a cohort of 92 randomly selected patients with ESRF treated with hemodialysis (HD) and peritoneal dialysis (PD). The data regarding demographic and clinical characteristics were recorded, including vascular disease (coronary, cerebral, peripheral). The follow-up lasted 40 months and the final evaluation included the number and causes of deaths, CDV events and disease. Serum Ca, P, ALP, iPTH, albumin, cholesterol, urea and creatinine levels were measured. The plain radiographic films of hands and pelvis evaluated all bone abnormalities suggestive of renal osteodystrophy (ROD) and peripheral vascular calcification (VC). RESULTS: All-cause annual mortality represented 9.25% in HD and 9.09% in PD patients. The CDV mortality represented almost 44% in HD patients and 66% in PD patients from all deaths. There was a high prevalence of CDV diseases and events. High and low serum P levels were associated with a worse survival rate. Hypercalcaemia was associated with high risk for CDV events in HD patients. In PD patients, the relationship between increased ALP levels and all-cause mortality was significant. Other mineral markers were not predictive of the outcome in the studied patients. In the HD patients the severity of VC was associated with all-cause and CDV mortality, and with CDV events. Male gender, hypercholesterolemia, decreased URR, albumin and creatinine were identified as risk factors for all-cause mortality. The diabetics had higher death rates. Low dialysis efficacy represented a risk factor for mortality and CDV diseases and events. In PD patients, low albumin induced a higher death rate. In PD patients the death rate was similar to HD patients. CONCLUSION: All-cause mortality was higher than in general population, but lower than the chronic dialysis patients' mortality reported in other studies. The death rates in HD and PD patients were similar. VC and serum P levels influenced the outcome in the HD patients - increased the risk for all-cause and CDV mortality, but also for CDV events. ALP levels influenced outcome in PD patients. There were no significant differences between HD and PD patients regarding outcome.

The association of high sCD163/sTWEAK ratio with cardiovascular disease in hemodialysis patients.

PURPOSE: Cardiovascular disease (CVD) is the most common cause of death in hemodialysis (HD) patients. Transmembrane proteins that circulate as soluble form such as tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and CD163 have been proposed in previous studies as CVD biomarkers in chronic kidney disease patients. In HD patients, since studies are scarce, the role of these proteins is not completely understood. We tested the hypothesis that sTWEAK, sCD163 or sCD163/sTWEAK ratio could be associated with cardiovascular disease in HD patients. METHODS: We recorded current clinical and biological data, and we measured sTWEAK and sCD163 serum levels by ELISA in 70 hemodialysis patients. Univariate analysis and multivariate (logistic regression) analysis were used to identify the relation between sTWEAK, sCD163 and sCD163/sTWEAK ratio and CVD. RESULTS: In univariate analysis, CVD in HD patients is associated with higher sCD163/sTWEAK ratio (p = 0.04), sCD163 (p = 0.07), CRP (p = 0.04), age (p = 0.07), smoking (p = 0.09) and vascular calcifications (p = 0.10). In multivariate analysis, only logarithm of sCD163/sTWEAK ratio (p = 0.04) and smoking (p = 0.03) was significantly associated with CVD. The levels of these molecules and their ratio were correlated with atherosclerosis risk factors: diabetes mellitus, high fasting glucose, tricipital skinfold thickness and CRP as well as (for sCD163/sTWEAK) intravenous iron therapy. CONCLUSIONS: Cardiovascular disease is associated with increased sCD163/sTWEAK ratio. To our knowledge, this is the first report about this relationship in HD patients.

ESAM predicts cardiovascular mortality in diabetic hemodialysis patients.

AIM: To assess endothelial cell selective adhesion molecule (ESAM) as predictor of cardiovascular mortality in diabetic dialysis patients (DDPs). METHODS: ESAM, clinical and laboratory parameters were assessed in 73 DDP. Cardiovascular mortality was recorded in a 2 years' prospective observational study. RESULTS: Baseline ESAM was 17.1 (10.05-24.8) ng/ml and was correlated to phosphate (r = -0.42, p = 0.008), parathormone (r = -0.36, p = 0.048), albumin (r = -0.24, p = 0.048). ESAM significantly predicted cardiovascular death in univariate [HR = 1.03, 95% CI (1.006-1.054), p = 0.01] and multivariate [HR = 1.034, 95% CI (1.003-1.066), p = 0.03] Cox analysis. Time to cardiovascular death was shorter for patients with ESAM >12.44 ng/ml, p = 0.0045. CONCLUSION: ESAM is an independent predictor of cardiovascular mortality in DDP.

Survival after parathyroidectomy in chronic hemodialysis patients with severe secondary hyperparathyroidism.

INTRODUCTION: The life for end-stage renal disease patients has remarkably improved in the last years. Although mineral and bone disorders remain as unsolved complication, in severe secondary hyperparathyroidism (sHPT), the ultimate treatment is parathyroidectomy (PTX). It is an old treatment, but there are still insufficient data regarding survival after PTX. The study goals were to compare 2-year mortality and morbidity after PTX in surgically versus medically treated sHPT and to compare the efficacy and safety in subtotal versus total PTX in a cohort of patients receiving hemodialysis (HD). METHODS: This prospective, longitudinal study was carried out on a cohort of chronic HD patients with severe sHPT (iPTH over 700 pg/ml). Among the overall HD population, 26 patients underwent PTX. This group was compared to a control group treated with specific drugs. Laboratory parameters, specific symptoms and mortality were registered after 24 months of follow-up for each group. The subgroups of subtotal and total PTX patients were also compared. RESULTS: All average values of mineral markers were significantly reduced after PTX, as a proof that surgical treatment was effective. The reduction in mineral markers and the improvement in symptoms and mortality rates were similar after total and subtotal PTX. Bone pain was significantly lower in patients after PTX than in those drug treated (p = 0.0005), but not muscle weakness and itching. Survival at 2 years was better in patients surgically treated (PTX) despite significantly higher mean baseline values of iPTH, Ca and ALP compared to patients medically treated (p = 0.03). CONCLUSIONS: We compared clinical and laboratory outcomes in HD patients with severe sHPT. Mortality, bone pain and mineral markers were improved by PTX. Total and subtotal PTX had similar clinical outcomes.