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The association between end-stage renal disease and cardiovascular mortality may be influenced through vascular alterations, in particular atherosclerosis and vascular calcification. The study goal was to assess the impact of each type of arterial intimal calcifications (AIC) and arterial medial calcifications (AMC), of osteoprotegerin (OPG), mineral metabolism markers and other features on all-cause and cardiovascular mortality in chronic hemodialysis patients. Ultrasound was performed in 87 patients on the carotid and femoral arteries, and the severity of AIC and AMC was assessed calculating a score according to the extension of calcification. We analyzed the link between AIC, AMC, OPG, mineral markers and mortality after 6 years of follow-up. The cutoff value for OPG determined using ROC was 4.9 pmol/l for all-cause and cardiovascular mortality. Patients with higher serum OPG levels presented higher mortality rates. Our study revealed that AIC, high OPG, low ankle-arm index, presence of diabetes, smoking status, and lack of arteriovenous fistula are associated with all-cause and cardiovascular mortality in univariate regression analysis. Multivariate analysis identified AIC scoring based on the segmentation method as an independent predictor of all-cause and cardiovascular mortality, along with increased OPG levels. AMC scoring was not a predictor of mortality. Identifying and scoring AIC on ultrasound and measuring OPG levels, as a basis of the HD patient assessment may become valuable tools in clinical work, as these have an impact on death toll.

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 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.

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.

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. 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. 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

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 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 study goal was to assess the impact of each type of arterial intimal calcifications (AIC) and arterial medial calcifications (AMC) identified on ultrasound, of osteoprotegerin (OPG), mineral metabolism markers and other features on all-cause and cardiovascular mortality in chronic hemodialysis patients. Ultrasound was performed in 87 patients on the carotid and femoral arteries, and the severity of AIC and AMC was assessed calculating a score according to the extension of calcification. The cut-off value for OPG determined using ROC was 4.9 pmol/L for all-cause and cardiovascular mortality. Patients with higher serum OPG levels presented higher mortality rates. Our results revealed that AIC, high OPG, low ankle-arm index, presence of diabetes, smoking status, and lack of arteriovenous fistula are associated with all-cause and cardiovascular mortality in univariate regression analysis. Multivariate analysis identified AIC scoring based on the segmentation method as an independent predictor of all-cause and cardiovascular mortality, along with increased OPG levels. AMC scoring was not a predictor of mortality. Identifying and scoring AIC on ultrasound and measuring OPG levels, as a basis of the HD patient assessment may become valuable tools in clinical work, as these have an impact on death toll.

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. 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. Ghrelin is correlated with IL-1β (r = 0.88, p

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, pruritus and postdialysis recovery time (RT) are quality-of-life parameters that affect hemodialysis (HD) patients physically and mentally. 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. 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. 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 (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. 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). 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. 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.

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.

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.

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.

CONTEXT: Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and cleaves angiotensin II to Angiotensin (1–7), annihilating the deleterious effects of angiotensin II which is known to be a strong activator of oxidative stress. OBJECTIVE: We aimed to evaluate the relationship of oxidative stress to urinary ACE2 (uACE2) in type 2 diabetes mellitus (T2DM) patients. DESIGN: We included consecutive normo or microalbuminuric T2DM patients in an observational transversal study. Routine laboratory investigations, plasma malondialdehyde (MDA, fluorimetric thiobarbituric method) as a marker of prooxidant capacity and superoxide dismutase (SOD, cytochrome reduction method) and catalase (CAT) activity (in erythrocyte lysate by the modification of absorbance method) as two measures of serum antioxidant capacity and uACE2 (ELISA method) were assessed. RESULTS: MDA showed a negative correlation with SOD (r=-0.44, p=0.001), CAT (r=-0.37, p=0.006), uACE2 (r=-0.33, p=0.016) and a positive correlation with glycated haemoglobin (HbA1c) (r=0.49, p

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). 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. 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). 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.

Aim: To assess the osteoprotegerin (OPG) relationship with cardiovascular complications in hemodialysis (HD) patients.Methods: The study included 87 HD patients. Clinical characteristics, ankle-arm index (AAI), OPG and mineral markers levels were recorded. Arterial intimal calcification (AIC) and arterial medial calcification (AMC) were registered.Results: OPG levels were increased in HD patients. Patients with AIC (p = 0.006)/ AMC (p = 0.01) had higher OPG levels. OPG did not have any relation with cardiovascular diseases. OPG correlated positively with age, increased HD vintage and inversely with albumin and AAI. OPG has not been a risk factor for VC or cardiovascular disease.Conclusion: OPG rising could be a reaction in defense to vascular aggression, because OPG was associated with VC, but not with vascular disease.

Aim: The aim of our study was to investigate the understanding of statistical terms commonly used in lectures presented at summer schools for residents and young specialists. Material and Method: A survey was distributed to all the participants at the “Diabetic neuropathy from theory to practice” Summer School, 2014. The program was addressed to residents or young specialists in diabetes, neurology, surgery, and orthopedic from Romania. The survey consists of 6 multiple-choice questions and the first four questions evaluate the understanding of statistical terms. Results: There were 51 (42.5%) participants who completed the questionnaires. From 204 total questions 81 (39.7%) had correct answers. At the question 1, where relative risk was evaluated, only 3 (5.9%) respondents answered correctly while at the question 2 (number need to treat) about 78.4% (40) of answers were correct. At the question 3 (sensitivity), 22 (43.1%) respondents answer correct while at the question 4 (Receiver Operating Characteristic curves) only 16 (31.4%) respondents provided a correct answer. The overall mean score of correct answers was 1.56±0.91. Conclusion: Our study showed that young specialists who participated to the survey were not familiarized with simple statistical terms commonly used in presentations.

Endothelial dysfunction is an important contributor to micro and macrovascular complications of type 2 diabetes (T2D) and is reflected by increased systemic oxidative stress. Endothelial cell selective adhesion molecule (ESAM) influences endothelial function. We aimed to assess, for the first time to our knowledge, the relationship of soluble ESAM to markers of systemic oxidative stress.ESAM, malondialdehyde (MDA) level and catalase activity were determined in 54 T2D patients and 43 controls.T2D patients had significantly higher ESAM when compared to controls (16.07 ± 5.77 μg/L versus 8.57 ± 5.28 μg/L, p0.0001), they also had higher MDA level (3.88 ± 1.50 μmol/L vs. 1.58 ± 0.72 μmol/L, p0.0001) and lower catalase activity (3.07 (2.63-3.44) U/mg vs. 8.72 (4.55-10.46) U/mg, p0.0001). In T2D patients ESAM was inversely related to catalase activity (r = -0.27, p = 0.04), relationship to MDA level was direct but not significant (r = 0.16, p = 0.24). MDA concentration correlated inversely to catalase activity (r = -0.28, p = 0.04). In multiple regression catalase activity remained significantly correlated to ESAM (p = 0.02) and MDA level was significantly related to glycated hemoglobin (p = 0.01); there was trend towards a positive correlation of MDA level to ESAM (p = 0.08). When patients were divided according to oxidative stress, those with increased oxidative stress (defined as MDA concentration2.98 μmol/L and catalase activity3.38 U/mg) had higher ESAM than the rest of the patients (17.99 ± 5.02 μg/L vs. 14.29 ± 5.94 μg/L p = 0.01).ESAM is higher in T2D than in controls and parallels oxidative stress: ESAM is inversely related to catalase activity and higher ESAM is found in T2D patients with increased oxidative stress.

Obiectiv. La pacienţii cu diabet zaharat de tip 2, natura progresivă a afectării renale reprezintă un risc crescut de mobiditate şi mortalitate. Scopul studiului nostru a fost acela de a evalua valoarea predictivă a molecului de adeziune intercelulară (ICAM 1) pentru creşterea albuminuriei în stadiile timpurii ale afectării renale la pacienţii cu diabet zaharat de tip 2. Metodă. S-au inclus în studiu pacienţi consecutivi cu diabet zaharat de tip 2, urmăriţi prospectiv timp de 1 an. Progresia bolii renale a fost evaluată prin modificarea în timp a raportului albumină urinară pe creatinină urinară (ΔuACR). Rezultate. 93 de pacienţi cu diabet zaharat tip 2 au fost incluşi în studiu, dintre aceştia 58 fiind normoalbuminurici, iar 35 albuminurici. Media excreţiei urinare de albumină a fost în stadiu microalbuminuric şi au avut a valoare a filtrării glomerulare aproape normală. ΔuACR a prezentat o corelaţie pozitivă cu nivelul seric iniţial al ICAM 1 (p=0.003, r= 0.31) şi cu creatinina serică. În regresie multiplă, ICAM 1 a rămas singurul determinant al ΔuACR (p= 0.002). La pacienţii albuminurici, ΔuACR a prezentat o corelaţie şi mai puternică cu nivelul seric iniţial al ICAM 1 (p=0.0003, r=0.57). Concluzii. La pacienţii noştri cu diabet zaharat tip 2, principalul predictor al creşterii albuminuriei pe parcusul unui an de urmărire a fost nivelul seric iniţial al ICAM 1, în special la pacienţii albuminurici. ICAM 1 ar putea fi un biomarker non-invaziv cu utilitate clinică în prezicerea progresiei albuminuriei la pacienţii cu diabet zaharat tip 2.

Chronic hemodialysis (HD) patients have bad prognosis and cardiovascular diseases (CVD) represent their main threatening complication. Fibroblast growth factor (FGF-23) has been associated with all kinds of evil consequences, including cardiovascular morbidity, but some studies demonstrated the contrary. Therefore, it is important to know whether FGF-23 is associated with cardiovascular risk or protection. The purpose of this study was to assess the links between FGF-23 and intimal vascular calcification (VC) and with the presence of CVD in chronic HD patients. This study was carried out on a cohort of randomly selected 88 prevalent HD patients. We recorded demographical, clinical, and biochemical data, including FGF-23. VC was evaluated on carotid ultrasound. CVD were registered. The mean age was 59.68 ± 14.49 years, HD vintage was 59.61 ± 52.39 months, and 20 patients were diabetic (22.72 %). VC was present in 54 patients (61.4 %) and 25 patients (28.4 %) had CVD. FGF-23 correlated positively with HD vintage (r = 0.37; p

The newly discovered endothelial cell-selective adhesion molecule (ESAM) stabilizes the interendothelial tight junction; it circulates in serum as a soluble fraction. In experimental diabetes, reduced ESAM expression in the kidney is associated with albuminuria. We investigated, for the first time, serum ESAM as a predictor of progression of kidney disease in type 2 diabetes (T2D).T2D non-nephrotic patients with glomerular filtration rate (GFR)30 ml/min were included. History, medication and laboratory evaluation were assessed at inclusion and the end of study; ESAM was determined at baseline.Eighty-eight patients--mean age 63 ± 10.84 years, 49 (55.68 %) males--were prospectively followed up for 20 months. Baseline GFR was 76.37 ± 29.56 ml/min, and urinary albumin/creatinine ratio (UACR) 21.63(7.08-94.52) mg/g; ESAM was 12.85(6.13-19.83) ng/ml. Difference (Δ) in UACR between end of study and baseline was inversely related to serum albumin (r = -0.27, p = 0.017) and ESAM (r = -0.21, p = 0.047); ΔGFR correlated to glycated hemoglobin (r = 0.22, p = 0.05). In multiple regression, introducing variables susceptible to influence progression of kidney disease, ΔUACR was significantly related to log ESAM (p = 0.005) and ΔGFR to glycated hemoglobin (p = 0.016).Serum ESAM is a predictor of worsening of albuminuria in T2D patients without advanced kidney disease.

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. 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. 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. 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.

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.

Eur J Clin Invest 2012; 42 (11): 1227–1234 Abstract Background Endothelial cell–selective adhesion molecule (ESAM) contributes to the integrity of tight junctions and modulates endothelial function. ESAM has been linked to experimental diabetic nephropathy; its soluble fraction is related to atherosclerosis in humans. In this cross-sectional observational study, we describe for the first time serum ESAM in type 2 diabetic patients with different stages of chronic kidney disease (CKD) and its relationship to vascular endothelial growth factor-A (VEGF-A). Materials and methods We included diabetic patients with different stages of CKD and controls. History, laboratory evaluation, serum ESAM and VEGF-A and urinary albumin/creatinine ratio were obtained. Results Endothelial cell–selective adhesion molecule was higher in non-CKD diabetic patients 13·80 (6·15–18·70) ng/mL (n = 45) than controls 7·30 (4·60–9·40) ng/mL (n = 48), P = 0·001. VEGF-A had a similar pattern: 71·3 (54·75–120·70) vs. 43·20 (30·1–65·90) pg/mL, P

Adiponectin, an anti-inflammatory and insulin-sensitizing cytokine, has been shown to reduce proteinuria and glomerulosclerosis in experimental models. We assessed the relationship of plasma adiponectin to the progression of kidney disease in type 2 diabetes (T2D) patients.T2D nonnephrotic patients with glomerular filtration rate (GFR)30 ml/min and without acute cardiovascular/inflammatory conditions were included. Laboratory standard evaluation, urinary albumin/creatinine ratio (UACR), total plasma adiponectin, and CRP (C-reactive protein) were determined at inclusion and the end of study.Eighty-six patients (62.79% male) were followed up for 20.53±5.46 months. Baseline GFR was 72.85±26.29 ml/min and UACR was 20.53 (interquartile range 6.82-86.39) mg/g. At baseline adiponectin was significantly correlated to UACR (r =0.40, p =0.0001), HDL cholesterol (r =0.30, p =0.005), GFR (r =- 0.23, P =0.04), body mass index (BMI) (r =- 0.26, P =0.02) and waist circumference (r =-0.27, p =0.01). In multiple regression UACR (p =0.0003) and BMI (p =0.03) were significantly related to baseline adiponectin. The progression of kidney disease was estimated as the difference (D) between end and baseline UACR/month and between end and baseline GFR/month. None of the baseline parameters correlated to ΔGFR, but adiponectin inversely (r =- 0.26, p =0.02) correlated to ΔUACR. In multiple regression only adiponectin (p0.0001) predicted ΔUACR. A computed progression index (PI) resulting from a linear combination of GFR and UACR was also used to assess progression. Baseline adiponectin was significantly correlated to ΔPI between end of study and baseline (r =- 0.43, p0.0001), and predicted ΔPI in multiple regression (p =0.009).Low plasma adiponectin predicts progression of kidney disease in T2D patients.

The 276GT polymorphism of the adiponectin (ADIPOQ) gene has been correlated with plasma adiponectin, type 2 diabetes (T2D) and its complications. Studies of the role of 276GT polymorphism in the prevalence of T2D kidney disease are few and contradictory; ethnic differences might play a role. We aimed to assess the relationship of this polymorphism with albuminuria in a cohort of Caucasian T2D patients.Consecutive T2D outclinic patients were screened and included upon informed consent; exclusion criteria were glomerular filtration rate (GFR)30 ml/min, acute intercurrent illness and urinary tract infection. History, standard laboratory evaluation, total plasma adiponectin and genotyping for the 276 ADIPOQ locus were obtained.One hundred and three T2D patients were included. Forty-three (41.7%) of them had GG genotype, 50 (48.5%) had GT and 10 (9.7%) had TT genotype. Plasma adiponectin was significantly higher in TT-allele carriers (19.03±3.46 μg/ml) than in GT (10.14±1.78 μg/ml) and GG carriers (8.71±1.60 μg/ml), P=0.003. Adiponectin was higher in albuminuric (13.97±2.07 μg/ml) than in normoalbuminuric patients (6.91±0.88 μg/ml), P=0.004. The prevalence of T allele was higher in normoalbuminuric patients [36 (69.2%) GT+TT carriers] than in albuminuric ones [24 (47.1%)], P=0.02. Logistic regression identified the following as predictors of albuminuria: GG genotype: P=0.003 (OR 4.2; CI 1.61-10.96); low GFR: P=0.003 (OR 0.97; CI 0.95-0.99); and high plasma adiponectin: P=0.012 (OR 1.07; CI 1.01-1.14).Our data suggest that 276GT polymorphism of the ADIPOQ gene is associated with plasma adiponectin levels. By influencing adiponectinemia, 276GT polymorphism might predict the presence of albuminuria in Caucasian T2D 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.

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. 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. 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. Cardiovascular disease is associated with increased sCD163/sTWEAK ratio. To our knowledge, this is the first report about this relationship in HD patients.

Objectives Adiponectin is an insulin-sensitizing, anti-inflammatory adipokine with anti-atherogenic actions in the general population. In dialysis patients it is unclear whether adiponectin conserves its protective value or is, on the contrary, associated to worse prognosis. We assessed the predictive value of adiponectin for atherosclerosis related cardiovascular events in type 2 diabetic dialysis patients. Design and methods Prevalent diabetic dialysis patients from three dialysis units (n = 77) were enrolled in a 3 years' prospective observational study. Serum adiponectin, clinical and laboratory parameters were determined at baseline; new occurrence of atherosclerosis related events (coronary events, atherosclerosis obliterans, and stroke) was recorded. Results Baseline adiponectin was 17.25(9.53–31.97) μg/mL and significantly correlated to HDL cholesterol (r = 0.29, p = 0.01), triglycerides (r = −0.40, p = 0.0004), ferritin (r = − 0.29, p = 0.02), transferrin (r = − 0.28, p = 0.02), and uric acid (r = − 0.24, p = 0.04). In multivariate analysis association to triglycerides (p = 0.001), HDL cholesterol (p = 0.01) and ferritin (p = 0.04) remained significant. 36 new fatal and non-fatal new cardiovascular events occurred, 29 patient died. Cox proportional regression analysis showed that adiponectin below or above a ROC-derived cut-off of 27.33 μg/mL significantly influenced event-free survival: hazard ratio (HR) 2.48, 95% confidence interval (CI) (1.09–5.66), p = 0.031 along with fasting glucose HR 1.01, 95%CI(1.00–1.02), p = 0.01 and history of cardiovascular events at inclusion HR 3.16, 95%CI(1.36–7.32), p = 0.007. In multivariate analysis baseline adiponectin HR 5.02, 95%CI(0.98–25.06), p = 0.05 and glycemia HR 1.01, 95%CI(1.00–1.02), p = 0.01 influenced event-free survival. Adiponectin also predicted cardiovascular events in patients without cardiovascular disease at inclusion but was not associated to overall mortality. Conclusions In diabetes dialysis patients low adiponectin favors occurrence of atherosclerosis related cardiovascular events.

Adiponectin may be beneficial in incipient chronic kidney disease by antagonizing oxidative stress. We evaluated adiponectin, malondialdehyde (MDA), and superoxide dismutase (SOD), in type 2 diabetes mellitus patients (T2DP) with and without incipient nephropathy.T2DP with glomerular filtration rate (GFR)30 ml/min were compared with 20 healthy controls. Clinical and laboratory evaluations, levels of MDA (fluorimetric thiobarbituric test), SOD (cytochrome reduction method) and adiponectin (ELISA) were obtained.Sixty-four patients (GFR 91.44 ± 38.50 ml/min, urinary albumin-to-creatinine ratio [UACR] 20.81 [4.64-72.88 mg/g]) were included. MDA was higher in T2DP than in controls: 3.97 (2.43-4.59) versus 1.35 (1.16-1.81) nmol/ml, p0.0001. MDA correlated with glycated hemoglobin (r = 0.40, p = 0.001), adiponectin (r = -0.28, p = 0.03), systolic blood pressure (r = -0.28, p = 0.03) and SOD (r = -0.35, p = 0.005); adiponectin (p = 0.01) and glycated hemoglobin (p = 0.02) remained significant predictors of MDA in multiple regression analysis. SOD was negatively correlated with glycemia (r = -0.71, p0.0001) and glycated hemoglobin (r = -0.5, p0.0001). When patients were divided according to a ROC-derived adiponectin cutoff of 8.9 µg/ml, patients with higher adiponectin had lower MDA, [2.55 (2.35-3.60) vs. 4.10 (2.89-5.31) nmol/ml, p = 0.005] but similar SOD levels. In T2DP with nephropathy (GFR60 ml/min or UACR30 mg/g), the correlation of adiponectin with MDA was stronger, (r = -0.51, p = 0.004) confirmed in multiple regression analysis (p = 0.03). Adiponectin was not correlated with MDA, and SOD was inversely related to MDA in patients without nephropathy.Adiponectin is a significant predictor of MDA in early diabetic nephropathy, whereas SOD strongly depends only on glycemic control and is not directly related to adiponectin.

Background: Monocytes and granulocytes, activated by contact with hemodialysis membranes, generate increased cytokine secretion, an important key in pathogenesis of anemia and erythropoietin (rHuEPO) resistance. We aimed to examine the correlation of IL-17 and pro-hepcidin with anemia of chronic kidney disease (CKD) patients treated with hemodialysis(HD). Method: 69 HD patients were included. Exclusion criteria were: neoplasia, acute infections, blood loss, absolute iron deficiency. IL-17 and pro-hepcidin were determined. Hemoglobin, ferritin, transferrin and transferrin saturation were measured. rHuEPO responsiveness index was calculated. A poor response to rHuEPO was defined as rHuEPO responsiveness index>200. Results: Mean level of IL-17 was 33.3 ± 5.1 pg/ml and pro-hepcidin was 336.6 ± 23.7 pg/ml. IL-17 and pro-hepcidinnegatively correlated with hemoglobin (R0.503, p 200 had higher pro-hepcidin (432.5 ± 25 vs. 157.5 ± 12 pg/ml, p

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.

The study of online hemodiafiltration (HDF) benefits over high-flux hemodialysis (HD) raises great interest. The purpose was to compare clinical and laboratory parameters in patients treated with HD who were switched to HDF. Forty-eight HD patients (study group) were switched to HDF, while other 521 patients remained on HD as a control group. During last 6 HD months and during first year of HDF, we determined in both groups the following parameters: monthly–weekly dialysis time, systolic and diastolic blood pressure, body mass index (BMI), interdialytic body weight gain (IBWG), blood flow rate (Qb), weekly erythropoietin-stimulating agents dose (EPO), single-pool Kt/V, calcium, phosphorus (P), hemoglobin and normalized protein catabolic ration (nPCR), plus every 3 months—albumin, parathormone (PTH), ferritin and transferrin saturation (TSAT). In both groups, parameters in the last 6 HD months were compared to those in the first 6 months and, respectively, to those in the first year of HDF. In the study group, albumin and nPCR were significantly higher in the HD period not only compared to the first 6 months of HDF, but also compared to the first year of HDF. IBWG and P were higher with HD compared to the first year of HDF, but not with the first 6 months. PTH, Kt/V, Qb and EPO were higher in both HDF periods. In the control group, albumin was significantly higher in the first 6 months after the switch, but it was significantly lower in the first year. BMI, ferritin, PTH, Kt/V, Qb, TSAT and weekly dialysis time were higher in both HDF periods, while nPCR, EPO, SBP and DBP were lower. IBWG and Hb rose only during the first year after the switch, while P was lower in the first year, but not in the first 6 months. Nutrition, assessed by albumin, nPCR and BMI, was not improved by HDF compared to HD. With HDF, Kt/V and phosphorus control were better, similar results were observed in the control group. A larger EPO dose was needed with HDF for maintaining a similar hemoglobin level.

Diabetic kidney disease is a significant complication of type 2 diabetes mellitus and has a significant impact on quality of life and patient survival, both due to progression towards endstage kidney disease and associated atherosclerosis. Identification of the risk factors, especially in incipient kidney disease, is an important focus of research. The aim of our study was to rank the risk factors of two separate criteria for renal function: albumin excretion — quantified as urinary albumin/creatinine ratio (UACR) and GFR (glomerural filtration rate) in type 2 diabetes patients. Data from 53 type 2 diabetic patients were analyzed first with TOPSIS method and then compared with relative risk of each factor for UACR and GFR separately. 18 possible risk factors were taken in consideration. In the top of the TOPSIS method hierarchy was serum adiponectin (RR=2.06 for UACR and RR=1.65 for GFR) followed by C reactive protein (RR=1.74 for UACR and RR=1.02 for GFR), systolic blood pressure (RR=1.69 for UACR and RR=1.03 for GFR) and triglycerides (RR=1.57 for UACR and RR=0.96 for GFR). The Spearman coefficient of correlation between hierarchy provided by RR for UACR and TOPSIS method hierarchy was r=0.53, p=0.03. The Spearman coefficient of correlation between hierarchy provided by RR for GFR and TOPSIS method hierarchy was r=0.73, p=0.001. In conclusion, using TOPSIS method in this case brought new information about factors that may influence the occurrence of diabetic kidney disease.

Both kidney expression and soluble serum Klotho are influenced by chronic kidney disease (CKD) and diabetes. Serum Klotho is a yet poorly explored biomarker. We describe, for the first time to our knowledge, serum Klotho in diabetic patients with CKD and its relationship to vascular endothelial growth factor A (VEGF-A).We included 43 controls and 146 diabetic patients with different stages of CKD. Laboratory evaluation, urinary albumin/creatinine ratio (UACR), Klotho (ELISA), VEGF-A (ELISA) were performed.Klotho was 0.40(0.10-1.30)ng/mL in diabetic patients without CKD and 0.80(0.30-1.30)ng/mL in controls, p=0.20; VEGF-A was higher in diabetic patients 73.85(57.32-119.00)pg/mL than in controls 43.20(30.1-65.9)pg/mL, p0.0001. Klotho increased with CKD stage: 0.2(0.10-0.40)ng/mL in CKD 1/2, 0.60(0.20-1.1)ng/mL in CKD 3/4 and 1.45(0.425-2.90)ng/mL in dialysis patients, p0.0001; it also increased with decreasing glomerular filtration rate (GFR). Klotho was lower in albuminuric (UACR30 mg/g) patients 0.20(0.10-0.70)ng/mL than in normoalbuminuric (UACR30 mg/g) ones 0.50(0.20-1.30)ng/mL, p=0.03; lowest Klotho was found in microalbuminuric (UACR 30-300 mg/g) patients, p=0.07. VEGF was lower in microalbuminuric patients but was not influenced by GFR. In diabetic patients but not in controls, Klotho correlated to VEGF-A (r=0.29, p=0.0003); in multiple regression VEGF-A was the only significant predictor of Klotho: b=0.27, 95%CI (0.01-0.04), p=0.001.In diabetic patients, Klotho is decreased in early CKD and increases thereafter, paralleling reduced GFR. VEGF-A is higher in diabetic patients than in controls. Both Klotho and VEGF-A are decreased in the presence of microalbuminuria. In diabetes, Klotho strongly correlates to VEGF-A.

About 12-15 % of hemodialysis patients have a poor response to recombinant human erythropoietin (rHuEPO). The aim of this prospective study was to examine the influence of oxidative stress and vitamin E supplementation on rHuEPO responsiveness in chronic hemodialysis patients. Sixty-five hemodialysis patients treated with rHuEPO were studied. Those with iron deficiency, blood loss, malignancy, vitamin B12 and folate deficiency, severe hyperparathyroidism, liver cirrhosis, and congestive heart failure were excluded. Twenty-one healthy volunteers served as a control group. Malondialdehyde, carbonyl proteins, erythrocyte superoxide dismutase (SOD), ceruloplasmin, and serum antioxidant capacity were measured. Values of SOD150 U/ml were considered as normal. Patients with SOD150 U/ml were divided in two groups: group A (n = 11): treated with vitamin E 400 mg/day (600 IU/day) for 8 weeks; group B (n = 13): not treated. A third, group C consisted of patients with normal SOD. rHuEPO doses (U/kg/week) were recorded. rHuEPO responsiveness index was calculated as rHuEPO U/week/hematocrit. A poor response was defined as a rHuEPO responsiveness index200. SOD positively correlated with hemoglobin (p = 0.0018, R = 0.337) and negatively with rHuEPO responsiveness index (p = 0.0122, R = 0.319). Vitamin E-treated patients from group A exhibited significantly increased hemoglobin levels as compared to initial values (10.5 ± 0.3 vs. 8.6±0.4, p = 0.002). In comparison with group B, the vitamin E-treated patients displayed a higher hemoglobin (10.5 ± 0.3 vs. 9.4 ± 0.3, p = 0.04), had a lower rHuEPO dose (85.7 ± 7.4 vs. 136.8 ± 13.8, p = 0.025), and a significantly improved rHuEPO responsiveness (rHuEPO responsiveness index 177.9 ± 28.6 vs. 314.1 ± 34.0, p = 0.006). Patients from group A significantly improved their rHuEPO responsiveness after vitamin E therapy as compared to baseline (rHuEPO responsiveness index 177.9 ± 28.6 vs. 271.7 ± 30.3, p = 0.034). We conclude that lower values of SOD correlate with lower hemoglobin, higher rHuEPO dose and poor response to rHuEPO in chronic hemodialysis patients. Vitamin E supplementation significantly improves rHuEPO responsiveness, increases hemoglobin level, and decreases rHuEPO dose.

Experimental studies have shown that adiponectin has antiproteinuric and nephroprotective effects. The purpose of the study was to assess the value of plasma adiponectin as a predictor of proteinuria in type 2 diabetes (T2D) patients.In this one-year prospective follow-up study, we included T2D patients with positive visual test for microalbuminuria (Micral) and negative visual test for proteinuria. Exclusion criteria were: glomerular filtration ratio (GFR)30 ml/min, acute infection/inflammation, uncontrolled hypertension, and atherosclerotic complications. The main outcome measure was the change in urinary albumin/creatinine ratio (UACR) after 1 year follow-up (Δ UACR).Fifty-six patients (66% males) completed the study. Their initial mean UACR was 81.58 ± 26.42 mg/g and mean GFR was 81.15 ± 3.96 ml/min. At baseline, simple regression disclosed significant correlations between UACR and plasma adiponectin (r = 0.54, P = 0.00002) and GFR (r = -0.28, P = 0.03); in multiple regression analysis, plasma adiponectin remained the only predictor of UACR (P = 0.00007). Baseline plasma adiponectin was significantly correlated to body mass index (r = -0.28, P = 0.04), waist circumference (r = -0.27, P = 0.05), HDL cholesterol (r = 0.35, P = 0.01), and LDL cholesterol (r = 0.27, P = 0.04). Baseline plasma adiponectin significantly correlated in simple (r = -0.38, P = 0.004) and multiple regression (P = 0.04) to Δ UACR. When patients were divided according to Δ UACR in nonprogressors (Δ UACR0) and progressors (Δ UACR0), logistic regression showed that baseline GFR (OR = 1.04, CI95%: 1.00-1.09, P = 0.04) and plasma adiponectin (OR = 1.16, CI95%: 1.02-1.32, P = 0.02) were the only factors that predicted whether the patient would be a progressor or not.In T2D patients, lower plasma adiponectin levels seem to be predictive of increased UACR.

Our study addressed the influence of early inflammatory stages of diabetic kidney disease: leukocyte adhesion and monocyte activation (as assessed by intercellular leukocyte adhesion molecule-ICAM-1 and monocyte chemoatractant protein-MCP-1) on the degree of albuminuria. Plasma levels of adiponectin, a possible anti-inflammatory counteracting mechanism, were also studied in correlation to the above-mentioned cytokines.79 consecutive type 2 diabetic outpatients and 46 controls were included. Routine laboratory analysis, urinary albumin to creatinine ratio (uACR), plasma adiponectin, plasma ICAM-1 and urinary MPC-1 were assessed.In multiple regression ICAM-1 (p=0.004) and adiponectin (p=0.04) were the main determinants of uACR. Plasma adiponectin positively correlated to ICAM-1 (p=0.03, r=0.24). In albuminuric patients (uACR ≥30 mg/g) plasma adiponectin was significantly higher compared to normoalbuminuric ones (uACR30 mg/g). In albuminuric patients the main determinants of uACR were plasma ICAM-1 and adiponectin. In multiple regression ICAM-1 is the only one that retains statistical significance (p=0.02). Urinary MCP-1 did not correlate to uACR.In our type 2 diabetic patients, plasma levels of ICAM-1 and adiponectin are predictive for albuminuria. Urinary MCP-1 does not correlated to uACR. Plasma adiponectin positively correlates to adhesion molecule ICAM-1 in our cohort.

Vascular calcifications (VCs) and renal osteodystrophy (ROD) are frequently seen together and represent the major causes of morbidity and mortality in hemodialysis (HD) patients. Some studies suggest a pathogenic link between them, but there is no consensus as yet regarding this issue. The main objective of our study was to establish whether there is any relation between VCs and ROD in our HD patients. We evaluated the prevalence of VCs and ROD and the relationship between VCs and some clinical and biochemical characteristics of HD patients. We examined radiological signs of VCs and ROD on hands and pelvis bone radiographs in 81 chronic HD patients, and we calculated a VC score on this basis. We found a significant relation between radiological signs of ROD and those of VC (P = 0.019). The patients with ROD had a higher mean VC score (P = 0.02). By linear regression, the VC score correlated directly with serum calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH) and CaxP product and inversely with serum albumin. The logistic regression model revealed that ROD, male gender and treatment with calcium salts were predictive of VCs development. There were no associations between VCs and age, HD vintage, diabetes, dialysate Ca concentration, vitamin D treatment, spKt/V, URR and C-reactive protein (CRP) levels. There seems to be a pathogenetic link between bone and artery diseases in chronic HD patients. Both VCs and ROD have a high prevalence. ROD, male gender and treatment with calcium salts are risk factors for VCs.