Correlation between preoperative vein and artery diameters and arteriovenous fistula outcome in patients with end-stage renal disease.

BACKGROUND AND AIMS: Arteriovenous fistula (AVF) maturation failure rates remain high in patients with end-stage renal disease (ESRD). Although preoperative morphological and functional assessment of blood vessels by duplex ultrasonography (DUS) has been shown to improve AVF maturation, there is no consensus regarding the optimal vein (VD) and artery (AD) diameters to be universally used for AVF creation. To improve patient selection, set out to investigate if there is a correlation between preoperative VD/AD and clinical covariates, and postoperative AVF outcome. METHODS: This was a prospective cohort study conducted during January-August 2014. ESRD patients referred to "Niculae Stancioiu" Heart Institute Cluj-Napoca, who had a VD ≥1.9 mm and AD ≥1.5 mm, as measured by DUS, and underwent AVF creation were enrolled. We assessed whether preoperative VD/AD and clinical covariates were associated with AVF maturation rate and primary patency at 2 years after AVF creation. RESULTS: Of 115 patients referred for AVF creation, 93 were included in the study. Mean (± standard deviation) VD was 3.3 ± 1.1 mm and VDs were distributed in quartile Q1 <2.55 mm, Q2: 2.56-3.10 mm, Q3: 3.11-3.70 mm and Q4: >3.71 mm. Mean AD was 3.3 ± 1.4 mm and ADs were distributed in Q1 <2.55 mm, Q2: 2.56-3.10 mm, Q3: 3.11-3.70 mm, and Q4, >3.71 mm. AVF maturation rate increased proportionally with VD from Q1 (62%) to Q2 (70%), Q3 (82%) to Q4 (96%) (p=0.03). Based on AD, a higher AVF maturation rate was observed in Q3 (86%), Q4 (83%) vs Q1 (71%) and Q2 (67%). Long-term primary patency of AVFs seemed not to be influenced by VD and AD. In older patients and those with peripheral arterial disease, AVF maturation failure tended to be higher. CONCLUSIONS: Our findings suggest that a preoperative VD ≥1.9 mm and AD ≥1.5 mm have a successful maturation rate of AVF greater than 60% in ESRD patients. The maturation rate of surgical AVF increases proportionally with the size of VD used for AVF creation.

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.

Effect of the veins histopathological characteristics and preexisting medical conditions on arteriovenous fistula maturation and primary patency in patients with end-stage renal disease: an observational, prospective study.

We assessed the veins histopathological characteristics and preexisting medical conditions before arteriovenous fistula (AVF) creation, and their correlation with AVF outcome and primary patency in patients with end-stage renal disease (ESRD). In this observational, prospective, mono-center study in Romania, patients with artery and venous diameters =2 mm and =2.5 mm, respectively, were enrolled. Vein specimens were harvested at AVF creation and evaluated by Hematoxylin and Eosin, Masson's trichrome and Orcein stainings, in terms of intimal hyperplasia, elastic fibers disposition, medial hypertrophy and smooth muscle cell disorganization and fibrosis (graded from mild to severe). Venous diameters and blood flow one÷two-months post-AVF creation, AVF maturation at dialysis start, two-year primary patency were assessed. Of 115 examined patients, 50 were enrolled and underwent AVF creation. Of six (12%) patients with no vein morphological changes, 11 (22%) with mild histopathological changes, 19 (38%) with moderate and 14 (28%) with severe histopathological changes, four (67%), eight (73%), 17 (89%) and 12 (86%), respectively, had mature AVF. Regardless of histopathological characteristics, non-mature AVF were recorded in older patients and with smaller venous diameter. One÷two-months post-AVF creation, in all patients with mature AVF, venous diameter and ultrasonographic blood flow were similar. Two years post-AVF creation, 26 patients had functional AVF; non-functional AVFs were recorded more likely in women and functional AVFs were most likely located on forearm. The veins histopathological modifications may not negatively influence AVF maturation in ESRD patients. AVF maturation failure may most likely be related to age and venous diameter at AVF creation.

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.

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.

Urinary angiotensin converting enzyme 2 is strongly related to urinary nephrin in type 2 diabetes patients.

PURPOSE: Podocyte lesion is recently recognized as an early event in diabetic kidney disease (DKD) and is reflected by urinary (u) nephrin (Neph) shedding. Angiotensin II plays an important role in podocyte dysfunction of diabetes. Angiotensin converting enzyme 2 (ACE2) is the main ACE variant in podocytes and counteracts deleterious angiotensin II effects. We assessed for the first time the relation of uACE2 and uNeph in type 2 diabetes subjects. MATERIAL AND METHOD: Seventy-five type 2 diabetes patients were included in a transversal study. History, clinical and laboratory data, urinary albumin-to-creatinine ratio (uACR), and ELISA determination of uNeph and uACE2 were obtained. RESULTS: uNeph was 349.00 ± 133.42 pg/ml, and uACE2 was 45.50 (36.35-62.60) pg/ml. uNeph correlated to uACE2 (r = 0.44, p < 0.001) and to uACR (r = 0.25, p = 0.032). In multivariate regression, introducing parameters that are known to be related to DKD, uACE2 (p < 0.0001), LDL cholesterol (p = 0.02) and glycated hemoglobin (p = 0.03) remained significant predictors of uNeph. Normoalbuminuric patients had lower uNeph than patients with uACR > 30 mg/g (325.50 ± 135.45 vs 391.03 ± 121.40 pg/ml, p = 0.04); they also had a tendency versus lower uACE2 [41.40 (34.30-60.65) vs 52.57 (37.95-69.85) pg/ml, p = 0.06]. A cutoff for uNeph of 451.6 pg/ml was derived from the ROC curve analysis; uACE2 was the main determinant for uNeph being above or below this cutoff-OR = 1.09; 95 %CI (1.04-1.15), p = 0.001. Patients taking blockers of the renin angiotensin system had similar uNeph and uACE2. uNeph and uACE2 were not influenced by renal function. CONCLUSION: uNeph is significantly correlated to uACE2 and uACR in type 2 diabetes patients.

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.

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.

Prevalence of chronic kidney disease and its association with cardio-metabolic risk factors in the adult Romanian population: the PREDATORR study.

PURPOSE: PREDATORR is the first national study analyzing the prevalence of chronic kidney disease and its prognosis and association with socio-demographic, cardio-metabolic and lifestyle risk factors in the adult Romanian population. METHODS: Chronic kidney disease was defined according to the KDIGO 2012 criteria as an estimated glomerular filtration rate <60 mL/min/1.73 m(2) and/or urinary albumin-to-creatinine ratio ≥30 mg/g. The socio-demographic, lifestyle and anamnestic data were collected through interviewer-administered questionnaires. Physical examination and biochemical assays were also performed. RESULTS: This cross-sectional study conducted between December 2012 and February 2014 in Romania included 2717 adults. The overall age- and sex-adjusted prevalence of chronic kidney disease was 6.74 % (95 %CI 5.60-7.88 %), of which 3.31 % (2.50-4.13 %) had only reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m(2)), 2.98 % (2.21-3.76 %) had only albuminuria, and 0.45 % (0.14-0.74 %) had both. The prevalence of chronic kidney disease increased with age and was similar in women and in men. Age, hyperuricemia, impaired glucose regulation (diabetes/prediabetes), hypertriglyceridemia and a family history of renal disease were independent risk factors for the presence of chronic kidney disease. CONCLUSIONS: The PREDATORR study showed a high prevalence of chronic kidney disease in the adult Romanian population providing data on its prognosis and association with several cardio-metabolic risk factors.

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.

Relationship of adiponectin to markers of oxidative stress in type 2 diabetic patients: influence of incipient diabetes-associated kidney disease.

PURPOSE: 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. METHODS: 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. RESULTS: 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, p < 0.0001. 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, p < 0.0001) and glycated hemoglobin (r = -0.5, p < 0.0001). 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 (GFR < 60 ml/min or UACR > 30 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. CONCLUSION: 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.

Role of osteoprotegerin in vascular disorders of the end-stage renal disease patients.

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.