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.

Retrospective analysis of the perioperative outcome in living donor kidney transplantation with multiple renal arteries: does accessory vessel ligation affect the outcome?

PURPOSE: Accurate surgical reconstruction of arterial vascular supply is a crucial part of living kidney transplantation (LDKT). The presence of multiple renal arteries (MRA) in grafts can be challenging. In the present study, we investigated the impact of ligation versus anastomosis of small accessory graft arteries on the perioperative outcome. METHODS: Clinical and radiological outcomes of 51 patients with MRA out of a total of 308 patients who underwent LDKT with MRA between 2011 and 2020 were stratified in two groups and analyzed. In group 1 (20 patients), ligation of accessory arteries (ARAs) and group 2 (31 patients) anastomosis of ARAs was performed. RESULTS: Significant differences were observed in the anastomosis-, surgery-, and warm ischemia time (WIT) in favor of group 1. Students t-test showed comparable serum creatinine levels of 2.33 (± 1.75) to 1.68 (± 0.83) mg/dL in group 1 and 2.63 (± 2.47) to 1.50 (± 0.41) mg/dL in group 2, were seen from 1 week to 1 year after transplant. No increased rates of Delayed graft function (DGF), primary transplant dysfunction and transplant rejection were seen, but graft loss and revision rates were slightly higher when the ARAs were ligated. Analysis of Doppler sonography revealed that segmental perfusion deficits tend to regenerate during the clinical course. CONCLUSION: Ligation of smaller accessory renal arteries may not affect the outcome of living kidney transplantation, except for a minor increase in the reoperation rate. Segmental perfusion deficits of the graft seem to regenerate in most cases as seen in Doppler sonography.

Food to Prevent Vascular Calcification in Chronic Kidney Disease.

Vascular calcification (VC) is a consequence of chronic kidney disease (CKD) which is of paramount importance regarding the survival of CKD patients. VC is far from being controlled with actual medication; as a result, in recent years, diet modulation has become more compelling. The concept of medical nutritional therapy points out the idea that food may prevent or treat diseases. The aim of this review was to evaluate the influence of food habits and nutritional intervention in the occurrence and progression of VC in CKD. Evidence reports the harmfulness of ultra-processed food, food additives, and animal-based proteins due to the increased intake of high absorbable phosphorus, the scarcity of fibers, and the increased production of uremic toxins. Available data are more supportive of a plant-dominant diet, especially for the impact on gut microbiota composition, which varies significantly depending on VC presence. Magnesium has been shown to prevent VC but only in experimental and small clinical studies. Vitamin K has drawn considerable attention due to its activation of VC inhibitors. There are positive studies; unfortunately, recent trials failed to prove its efficacy in preventing VC. Future research is needed and should aim to transform food into a medical intervention to eliminate VC danger in CKD.

Triiodothyronine and Protein Malnutrition Could Influence Pulse Wave Velocity in Pre-Dialysis Chronic Kidney Disease Patients.

Cardiovascular diseases (CVD) are the first cause of chronic kidney disease (CKD) mortality. For personalized improved medicine, detecting correctable markers of CVD can be considered a priority. The aim of this study was the evaluation of the impact of nutritional, hormonal and inflammatory markers on brachial-ankle Pulse Wave Velocity (PWV) in pre-dialysis CKD patients. A cross-sectional observational study was conducted on 68 pre-dialysis CKD patients (median age of 69 years, 41.2% with diabetes mellitus, 52.9% male). Laboratory data were collected, including levels of prolactin, triiodothyronine, TGF α, IL-6, and IL-1ß. The high values of brachial-ankle PWV were associated with reduced muscle mass (p = 0.001, r = -0.44), low levels of total cholesterol (p = 0.04, r = -0.26), triglycerides (p = 0.03, r = -0.31), triiodothyronine (p = 0.04, r = -0.24), and prolactin (p = 0.02, r = -0.27). High PWV was associated with advanced age (p < 0.001, r = 0.19). In the multivariate analysis, reduced muscle mass (p = 0.018), low levels of triiodothyronine (p = 0.002), and triglycerides (p = 0.049) were significant predictors of PWV, but age (p < 0.001) remained an important factor. In conclusion, reduced triiodothyronine together with markers of malnutrition and age were associated with PWV in pre-dialysis CKD patients.

Platelet-to-Albumin Ratio: The Prognostic Utility in the Prediction of 2-Month Postoperative Heart Transplant Complications.

BACKGROUND: The platelet-to-albumin ratio (PAR), leucocyte-to-albumin ratio (LAR), neutrophil percentage-to-albumin ratio (NPAR), and monocyte-to-albumin ratio (MAR) represent easily reproducible markers, which may predict the outcomes in various diseases. Early postoperative complications might appear after heart transplantation, such as infections, diabetes mellitus type 2 (DM2), acute graft rejection, and atrial fibrillation (AFib). OBJECTIVE: The aim of our study was to investigate the PAR, LAR, NPAR, and MAR values before and after heart transplantation, and the associations of the preoperative levels of these markers with the presence of postoperative complications in first two months after surgery. METHODS: Our retrospective research was directed from May 2014 to January 2021, with a total number of 38 patients being included. We used cut-off values for the ratios from previously published studies, as well as our own determination of these levels by using a receiver operating characteristic (ROC) curve. RESULTS: By ROC analysis, the optimal preoperative PAR cut-off value was 38.84 (AUC: 0.771, p = 0.0039), with 83.3% sensitivity, and 75.0% specificity. Applying a Chi square (χ2) test, PAR > 38.84 represented an independent risk factor for complications, regardless of cause, and postoperative infections. CONCLUSIONS: Preoperative PAR > 38.84 was a risk factor of developing complications of any cause, and postoperative infections in the first two months after heart transplantation.

Robot-Assisted Laparoscopic Prostatectomy Experience and Pathological Quality: Are They Always Linked?

Objective: We investigated whether pathological outcomes improved with experience and surgeon generation after robot-assisted laparoscopic prostatectomy (RALP). Materials and Methods: The study included 1338 patients who underwent RALP between February 2010 and April 2020. We created learning curves for pelvic lymph node dissection (PLND), number of lymph nodes (LNs) removed, and positive surgical margin (PSM) after adjustment for confounders. We compared the outcomes between the first and second generation of surgeons in regression models. Results: The learning curve regarding PLND indications showed a significant increase with experience for the first generation, whereas the second generation had a learning curve that remained flat at a higher level (92.3%) and significantly better than the first generation (p < 0.001). Similarly, the number of LN removed showed a significant increase with experience in both generations, but the overall median number of LN removed was significantly higher in the second generation compared with the first generation (12 vs 10, p < 0.001). However, the learning curve for PSM remained flat at ∼20% after adjustment and did not show improvement with experience in both generations of surgeons (p = 0.794). Conclusions: Surgeons showed improvement with experience and education with RALP with respect to the indications for PLND and number of LNs removed. However, there was no improvement over time and generations for PSM. Experience based solely on the number of patients operated on is not an intrinsic factor in the pathological quality of RALP. Factors other than experience may also play a role in oncologic improvement.

FIP1L1-PDGFRα-Positive Loeffler Endocarditis-A Distinct Cause of Heart Failure in a Young Male: The Role of Multimodal Diagnostic Tools.

The presence of the Fip1-Like1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRα) fusion gene represents a rare cause of hypereosinophilic syndrome (HES), which is associated with organ damage. The aim of this paper is to emphasize the pivotal role of multimodal diagnostic tools in the accurate diagnosis and management of heart failure (HF) associated with HES. We present the case of a young male patient who was admitted with clinical features of congestive HF and laboratory findings of hypereosinophilia (HE). After hematological evaluation, genetic tests, and ruling out reactive causes of HE, a diagnosis of positive FIP1L1-PDGFRα myeloid leukemia was established. Multimodal cardiac imaging identified biventricular thrombi and cardiac impairment, thereby raising suspicion of Loeffler endocarditis (LE) as the cause of HF; this was later confirmed by a pathological examination. Despite hematological improvement under corticosteroid and imatinib therapy, anticoagulant, and patient-oriented HF treatment, there was further clinical progression and subsequent multiple complications (including embolization), which led to patient death. HF is a severe complication that diminishes the demonstrated effectiveness of imatinib in the advanced phases of Loeffler endocarditis. Therefore, the need for an accurate identification of heart failure etiology in the absence of endomyocardial biopsy is particularly important for ensuring effective treatment.

The Role of Preoperative Chronic Statin Therapy in Heart Transplant Receipts-A Retrospective Single-Center Cohort Study.

BACKGROUND: Statin therapy has been proven to reduce the risk of cardiovascular events. The objective of our retrospective study was to investigate the relationship between preoperative chronic administration of statins to postoperative 2-month heart transplantation complications. METHODS: A total number of 38 heart transplantation recipients from the Cardiovascular and Transplant Emergency Institute of Târgu Mureș between May 2014 and January 2021 were included in our study. RESULTS: In logistic regression, we found a statistical significance between statin treatment and the presence of postoperative complications of any cause (OR: 0.06, 95% CI: 0.008-0.56; p = 0.0128), simultaneously presenting an elevated risk for early-postoperative acute kidney injury (AKI). From the statin group, atorvastatin therapy had a higher risk of type 2 diabetes mellitus (T2DM) development (OR: 29.73, 95% CI: 1.19-741.76; p = 0.0387) and AKI (OR: 29.73, 95% CI: 1.19-741.76; p = 0.0387). C-reactive protein (CRP), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) represented risk factors, atorvastatin administration being independently associated with lower CRP values. CONCLUSIONS: Chronic previous administration of statins represented a protective factor to the development of 2-month postoperative complications of any cause in heart transplant receipts.

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.

Arterial calcifications and osteoprotegerin in chronic hemodialysis patients: impact on 6-year survival.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Acute severe paediatric asthma: study protocol for the development of a core outcome set, a Pediatric Emergency Reserarch Networks (PERN) study.

BACKGROUND: Acute severe childhood asthma is an infrequent, but potentially life-threatening emergency condition. There is a wide range of different approaches to this condition, with very little supporting evidence, leading to significant variation in practice. To improve knowledge in this area, there must first be consensus on how to conduct clinical trials, so that valid comparisons can be made between future studies. We have formed an international working group comprising paediatricians and emergency physicians from North America, Europe, Asia, the Middle East, Africa, South America, Central America, Australasia and the United Kingdom. METHODS/DESIGN: A 5-stage approach will be used: (1) a comprehensive list of outcomes relevant to stakeholders will be compiled through systematic reviews and qualitative interviews with patients, families, and clinicians; (2) Delphi methodology will be applied to reduce the comprehensive list to a core outcome set; (3) we will review current clinical practice guidelines, existing clinical trials, and literature on bedside assessment of asthma severity. We will then identify practice differences in tne clinical assessment of asthma severity, and determine whether further prospective work is needed to achieve agreement on inclusion criteria for clinical trials in acute paediatric asthma in the emergency department (ED) setting; (4) a retrospective chart review in Australia and New Zealand will identify the incidence of serious clinical complications such as intubation, ICU admission, and death in children hospitalized with acute severe asthma. Understanding the incidence of such outcomes will allow us to understand how common (and therefore how feasible) particular outcomes are in asthma in the ED setting; and finally (5) a meeting of the Pediatric Emergency Research Networks (PERN) asthma working group will be held, with invitation of other clinicians interested in acute asthma research, and patients/families. The group will be asked to achieve consensus on a core set of outcomes and to make recommendations for the conduct of clinical trials in acute severe asthma. If this is not possible, the group will agree on a series of prioritized steps to achieve this aim. DISCUSSION: The development of an international consensus on core outcomes is an important first step towards the development of consensus guidelines and standardised protocols for randomized controlled trials (RCTs) in this population. This will enable us to better interpret and compare future studies, reduce risks of study heterogeneity and outcome reporting bias, and improve the evidence base for the management of this important condition.

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.

[Female urology: review of the development in the past 5 decades]. / Urologie der Frau ­ Rückblick auf die Entwicklung in den letzten 5 Jahrzehnten.

Urogynaecology is a highly specialised interdisciplinary medical field. It aims to investigate and treat functional, static, endocrine and sexual disorders of the genitourinary system and pelvic area in a sustainable and holistic manner.The "Urological Functional Diagnostics and Female Urology" working group of the German Urologist Academy was founded in 1977. It focuses on developing and updating diagnostics and clinical therapy, contributing to urogynaecological guidelines as well as establishing programmes for further education.Urinary incontinence and other pelvic floor disorders are increasing for demographic reasons. Rising socio-cultural expectations of women require more effective treatments using methods that guarantee success and a low level of complications.Milestones in urogynaecology include the introduction and further development of minimally-invasive surgical procedures such as tension-free vaginal tape (TVT) systems, laparoscopic and robot-assisted techniques, the development of a modern complication management, more targeted drug therapies, and the possibilities of modern functional diagnostics including pelvic floor sonography and MRI examinations.Classic surgical techniques such as colposuspension or colposacropexy and vaginal native tissue repair continue to be very important. In special cases, e. g. recurrent pelvic organ prolapse, mesh-based repair has proven to be superior to conventional procedures because of good long-term success and low recurrence rates. However, this method requires an anatomically correct surgical technique, critical selection of textile implants, and adequate patient education. Suturing devices and robot-assisted surgery may be helpful due to the narrow access and limited surgical spaces. For apical direct fixations, the elevation angle of the vagina is the therapeutically relevant outcome. Tried-and-tested anatomical fixation points should be preferred.Education and training in the field of urogynaecology and harmonisation with European standards (European Board & College of Obstetrics and Gynaecology) should be implemented. Skills for highly specialised mesh-based surgery and effective techniques for managing complications should be taught in the same interdisciplinary manner as diagnostic procedures such as pelvic floor sonography, which are easy to learn and use.Only an interdisciplinary urogynecological sub-specialisation can guarantee the development of required professional competences. Interdisciplinary education should be organised by the participating societies (urology, surgery and gynaecology) together.

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.

Adiponectin is related to markers of endothelial dysfunction and neoangiogenesis in diabetic patients.

PURPOSE: Adiponectin an adipokine, produced by mature adipocyte, has an important effect on several aspects of endothelial function, including leukocyte adhesion (mediated by adhesion molecules like intercellular adhesion molecule 1 (ICAM1) endothelial cell selective adhesion molecule ESAM). Recently, it has been linked to vascular endothelial growth factor (VEGF)-modulated angiogenesis. ESAM might also be involved in modulating VEGF-dependent actions. We studied relationship of adiponectin to ESAM, ICAM1, and VEGF in type 2 diabetic patients (T2DP) with or without microvascular complications. METHODS: Incident T2DP referred for nephrologic evaluation were included (patients with no nephropathy or stage 1-4 nephropathy). T2DP with stage 5 chronic kidney disease (CKD) were selected from a dialysis center. Clinical, standard laboratory assessment and adiponectin, ESAM, ICAM1, and VEGF (ELISA) were recorded. RESULTS: Eighty-seven patients were included, 15 had no CKD, 30 with stage 1 or 2 CKD, 20 with stage 3 or 4 CKD and 22 patients on dialysis. ESAM was higher in patients with CKD than in those without CKD (p = 0.02), adiponectin, ICAM1, and VEGF were similar. Adiponectin correlated in univariate analysis to ESAM (r = 0.32, p = 0.002), ICAM1 (r = 0.23, p = 0.038), and CRP (r = 0.31, p = 0.012), and inversely to serum albumin (r = - 0.57, < 0.0001). In predialysis patients, adiponectin also correlated to albuminuria (r = 0.54, p < 0.0001) and glomerular filtration rate (r = - 0.46, p = 0.0001). In multivariate regression ESAM (p = 0.04), VEGF (p = 0.03), and albumin (p < 0.0001) are significant predictors of adiponectin. None of these cytokines were different when comparing patients with and without retinopathy. CONCLUSION: Adiponectin is directly linked to adhesion molecules and VEGF in T2DP.

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.