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Hepatocyte growth factor (HGF) is a pleiotropic cytokine which exerts a variety of effects on several cells, being involved in the regulation of many biological processes, such as inflammation, tissue repair, morphogenesis, angiogenesis, tumour propagation, immunomodulation of viral infections and cardio-metabolic activities. Patients undergoing regular hemodialysis (HD) present elevated levels of HGF, mainly due to the leukocyte activation associated with HD treatment. High HGF levels might account for specific clinical features of HD patients, i.e. mild liver damage in course of HCV-infection and high cardiovascular risk profile. Moreover, in patients with acute kidney injury, the induction of HGF may represent a crucial step to promote renal recovery, which can have important prognostic consequences in the short and long-term. In this review we discuss the mechanisms underlying HGF production in HD patients, the role of HGF in this particular patient population and the potential clinical implications derived from the study of HGF in HD patients.

Although mushroom poisoning is a rare cause of acute renal injury, in some cases it may lead to the development of a severe and irreversible renal failure. Orellanus syndrome is the most important example of organic renal damage related to mushroom consumption. It is caused by the ingestion of orellanine, the main toxin of different types of Cortinarius mushrooms (Cortinarius speciosissimus, C. orellanus, C. orellanoides, etc.), and it is characterized by progressive clinical phases with a predominant kidney involvement, finally requiring renal replacement therapy in about 10% of cases. Renal damage is often late and associated with a histological picture of interstitial nephritis. Diagnosis is essentially clinical and no specific therapy has been shown to be effective in preventing and treating renal damage. Here, we describe the case of a patient with mixed wild mushroom poisoning, presenting the typical clinical signs and course of the Orellanus syndrome. This case offers us the opportunity to review the main clinical features of this severe and little-known intoxication., (© 2015 International Society for Hemodialysis.)

Background: Mineral and bone disorders (MBD) in patients undergoing hemodialysis (HD) are a major clinical complication. Current therapeutic strategies do not attain the expected results. The Italian audit on mineral metabolism was implemented to investigate MBD management through a "patient-oriented" approach., Methods: Clinical and laboratory data pertinent to MBD from 509 prevalent adult patients on chronic HD were recorded and examined (audit), after which individual strategies were elaborated to improve MBD control. Their effectiveness was evaluated 6 months after the audit (Post-6)., Results: The audit disclosed poor MBD control in a high percentage of patients (56 %). Low compliance to treatment was the major determinant of failure (in 43.5 % of cases). Logistic regression showed a direct correlation between high degree of compliance and the achievement of therapeutic targets, e.g. parathyroid hormone: odds ratio (OR) 2.48, p = 0.015. In contrast, a minority of the proposed interventions (14.7 %) included strategies to improve patient compliance. At Post-6, despite a significant increase in drug prescription (p < 0.05 vs. audit), the rate of successful MBD control was unchanged., Conclusions: Low compliance with treatment is a major, but still neglected, cause of failure in the achievement of MBD control in HD patients.

Heparin has remained the most commonly used anticoagulant in hemodialysis patients (HD). Its use is usually safe but, in some cases, important adverse effects can occur. Heparin-induced thrombocytopenia (HIT) is an immuno-mediated condition due to the formation of PF4/heparin/IgG complex leading to the activation of platelets and coagulative cascade. The consequent prothrombotic hypercoagulable state may cause venous or arterial thrombosis, skin gangrene and acute platelet activation syndrome. Clinical and laboratory findings may be suggestive for HIT, but formal diagnosis requires the demonstration of the presence of circulating antibodies. Clinical management is complex including the withdrawal of any form of heparin and the administration of anticoagulants. In addition, since anticoagulation is routinely required to prevent clotting of the dialysis lines and membranes, in HD patients presenting HIT it is mandatory to establish heparin-free anticoagulation strategies. Thus, the use of citrate, direct thrombin inhibitors or eparinods have been proposed as alternative anticoagulation approaches in HIT. Here, we review the most important pathogenic factors and clinical features of HIT occurring in HD patients.

Haemophilia A and B are genetic X-linked bleeding disorders, caused by mutations in genes encoding factors VIII and IX, respectively. Clinical manifestations of haemophilia are spontaneous haemorrhage or acute bleeding caused by minor trauma, resulting in severe functional consequences that can culminate in a debilitating arthropathy. Life expectancy and quality of life of patients with haemophilia have dramatically improved over the last years, mainly for new therapeutic options and the awareness to the risk of HCV and HIV infections. Different clinical problems arise from this important change in history of patients with haemophilia. In particular, ageing-related diseases, such as diabetes, hypertension and cancer, and chronic viral infections are emerging as new challenges in this patient population. Among the different types of chronic illnesses, renal diseases are of special interest as they involve some difficult management issues. In fact, decisions regarding adequate preventive strategies and viral infection treatment, the choice of the dialytic modality, placement of vascular access and prescription of dialytic treatments are particularly complicated, because only few data are available. In this review, we discuss the pathogenesis of renal damage in patients with haemophilia, especially in those with blood-transmitted viral infections, and the major issues about the management of renal diseases, including problems related to dialytic treatment and kidney transplantation, providing practical algorithms to guide the clinical decision-making process., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In patients on hemodialysis (HD), hypertension is a risk factor for cardiovascular disease. In this study we tested the effectiveness of a clinical audit in improving blood pressure (BP) control in HD patients. 
, Methods: 177 adult, prevalent patients undergoing dialysis in NephroCare centers in Italy were audited. At the conclusion of the audit, individual strategies were developed in order to improve BP control. Patient data was collected and examined at months -1 (Pre), 0 (the date of the audit- Audit), and +1 and +6 after the audit (Post-1 and Post-6, respectively).
We recorded BP, information on factors affecting BP, and anti-hypertensive drug regimen. The primary outcome of the study was to decrease prevalence of hypertension (BP ≥ 140/90 mmHg). Secondary outcomes were a reduction in average BP in hypertensive patients and/or a decrease in drug delivery associated with lower or unchanged BP.
, Results: 104 patients out of 177 (58.7%) were hypertensive at Audit. BP levels were directly related to comorbidity and male sex, and inversely related to dialysate sodium concentration. The announcement of the audit alone was associated with a decreased prevalence of hypertension (Pre 64.4% to Audit 58.7%); a further decrease followed the audit (Post-1 51.1%, Post-6 47.6%, p<0.05 vs. Audit). Systolic BP in hypertensive patients also decreased (mean decrease was -8.5 and -14.1; p = 0.007 and p<0.001 at Post-1 and Post-6). Number of drugs assumed was significantly lower at Post-1 and Post-6 vs. Audit (p = 0.005 and p<0.001, respectively).
, Conclusions: A clinical audit is an effective tool to improve BP control in HD patients.

Objectives: Acute kidney injury (AKI) is associated with a high mortality and morbidity rate. In this study we investigated whether dialysis membranes influence the recovery of renal function, through the regulation of hepatocyte growth factor (HGF)., Design and Methods: 21 patients were enrolled and assigned to hemodialysis (HD) with cellulose (CE, N=11) versus polymethylacrylate (PMMA, N=10) membranes in alternating order. HGF and IL-1 were measured in serum and in peripheral blood mononuclear cells (PBMC) supernatants collected immediately before the first HD session (T0), at 15 minutes (T15), at 240 minutes (T240) and after the last HD, when renal recovery occurred. Eight healthy volunteers were the controls (CON)., Results: Time to renal function recovery was lower in CE than in PMMA patients. Serum HGF in HD patients was significantly higher than in CON. HGF levels were higher in CE than in PMMA patients at T15 (13.4±2.7 vs 8.9±3.0 ng/mL, P=0.004) and T240. At recovery, HGF levels decreased. IL-1 serum levels showed a similar trend (at T15 CE: 20.5±2.9 vs PMMA: 16.9±3.2 pg/mL, P=0.005). HGF release significantly increased in the course of HD, resulting in higher levels in CE than that in PMMA patients. Considering all the patients, basal HGF release negatively correlated with time to renal recovery (r2=0.42, P<0.01)., Conclusions: Here we demonstrated that dialysis membranes influence the cytokine profile in AKI patients, HGF release being higher in patients treated with the CE membrane, in comparison to PMMA. Our results suggest that treatment with CE might improve clinical outcomes, possibly through increased release of HGF., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

This paper reports the analysis of the second part of the data obtained from the second SIN census and illustrates the management model of the Italian dialysis centers, highlighting its strengths but also its limits. The census was carried out between March and December 2008 with a webbased survey using fillable PDF forms. The survey was validated by comparing the data with those sent to the Italian Dialysis and Transplant Register (Registro Italiano di Dialisi e Trapianti, RIDT) and hence it refers to December 31, 2008, the date of the last RIDT report. Forty-two percent of dialysis centers, which altogether take care of 50% of Italian dialysis patients, participated in the census. The participation percentage was very variable among Italian regions (from 5% to 100% of dialysis centers). By excluding the three regions with a participation rate below 10%, the survey reached a participation rate of 68% of all Italian dialysis centers and is therefore sufficient to give an estimate of the Italian dialysis situation. However, because of this variability it was not possible to compare regional situations, and the data were evaluated only by analyzing the ''complex'' and ''simple'' dialysis centers separately. The state of affairs of dialysis in Italy on the whole proved to be complicated. It is striking, for example, that 15% of the ''complex'' dialysis centers do not have their own hospital beds and some of them lack traceability programs. Noteworthy are also the increasing use of central venous catheters and the number of patients that need an ambulance to get to the dialysis center. Despite its limits due to the reduced participation in the census, this work offers a fair description of the state of affairs of dialysis in Italy, where there is certainly space for qualitative improvement. First of all, however, every effort should be made to implement and improve the use of the existing structures and to standardize protocols and behaviors in all Italian dialysis centers.

Oxidative response and inflammation constitute a major defense against infections, but if not properly regulated they could also lead to a number of deleterious effects. Patients affected by different stages of acute and chronic kidney disease, particularly patients on hemodialysis, present a marked activation of oxidative and inflammatory processes. This condition exposes these patients to an elevated risk of morbidity and mortality. This Review is up to date and it analyses the newest notions about pathophysiological mechanisms of oxidative stress and inflammation in patients with renal diseases, also considering the different strategies studied to counterbalance this high risk state., (Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: In the aftermath of large natural and manmade disasters, the need for continuing maintenance haemodialysis (HD) in end-stage renal disease patients of the disaster area and care including dialysis for patients suffering from acute kidney injury (AKI) due to crush syndrome are the two most important nephrological problems., Methods: We report on how renal patients and renal care personnel faced emergency in the aftermath of the earthquake that struck the Italian town of L'Aquila and a surrounding district, on Monday 6 April 2009, causing 308 deaths, some 1500 injured and 66,000 people to be displaced., Results: The Dialysis Centre in the town did not collapse but was seriously damaged and out of action, making it necessary to move 88 patients on regular dialysis treatment to the closest available facilities to continue treatment. This was all the more urgent in that 45 patients of the Monday-Wednesday-Friday batch were coming off the long interdialytic interval, with possible medical problems (i.e. high increase in weight gain, blood pressure, etc.). In spite of manifold difficulties (including road interruption and shortage of means of transportation, problems in establishing contact between patients and care personnel due to failure of phone and electronic communication and the limited number of available dialysis posts), no patient missed any scheduled HD session. This was obtained thanks to the transfer of patients to neighbouring functioning units, often with extra dialysis shifts. In 3 days, a provisional Dialysis Centre was set up in an inflatable military-style tent, enabling 780 dialysis sessions to be performed safely on patients who had opted to return to L'Aquila. The tent facility was replaced by a rigid modular structure, insulated as living accommodation, containing 13 dialysis machines (20 from 17 November) functioning in HD or on-line haemodiafiltration. Ten cases of crush-related AKI needing dialysis treatment were recorded, the ratio of dialysed victims to number of deaths (32.4: 10 cases/308 deaths, 1000×) being the highest value yet reported. Fasciotomy was performed in six patients but none of the patients had to be amputated. Intermittent HD was used in most cases as the single modality of renal replacement therapy. All patients survived and recovered renal function on discontinuing dialysis treatment. Serum creatinine returned to normal values upon discharge from hospital or during the follow-up period., Conclusions: Each earthquake is different and may pose issues that will require unanticipated response efforts. Advance planning and rescue coordination, flexibility and creativity in the emergency situation, as well as the hard work and dedication of the entire dialysis care community, contributed to the remarkably positive outcome of dialysis-needing patients in the aftermath of the Aquila earthquake.

Autoimmunity to heat shock protein 60 (HSP60) has been related to atherosclerosis. Chlamydia pneumoniae (CP), the most studied infectious agent implicated in promoting atherosclerosis, produces a form of HSP60, which can induce an autoimmune response, due to high antigenic homology with human HSP60 (hHSP60). In this study, we evaluated the correlations among anti-hHSP60 antibodies, CP infection, and cardiovascular disease (CVD) in a high-risk population, such as patients undergoing hemodialysis (HD). Thirty-two patients (67.9 ± 13.9 years; male/female, 23:9) on regular HD were enrolled. Global absolute cardiovascular risk (GCR) was assessed using the Italian CUORE Project's risk charts, which evaluate age, gender, smoking habits, diabetes, systolic blood pressure, and serum cholesterol. The occurrence of cardiovascular events during a 24-month follow-up was recorded. Seropositivity to CP and the presence of anti-hHSP60 antibodies were tested by specific enzyme-linked immunosorbent assays. Inflammation was assessed by measurement of C-reactive protein (CRP) serum levels. Fifteen healthy sex and age-matched (61.9 ± 9.5 years; male/female, 11:4) subjects were the control group. Fifteen of 32 patients resulted seropositive for CP. CP + patients were older than CP-, while they did not differ for GCR, CRP, and dialytic parameters. CVD incidence was significantly higher in CP+ (9 CP+ vs 2 CP-, p < 0.05). Cox analysis recognized that the incidence of CVD was independently correlated with seropositivity to CP (HR, 7.59; p = 0.01; 95% CI = 1.63-35.4). On the other hand, there were no significant differences in anti-hHSP60 levels among CP+, CP- and healthy subjects: 18.11 μg/mL (14.8-47.8), 31.4 μg/mL (23.2-75.3), and 24.72 μg/mL (17.7-41.1), respectively. Anti-hHSP60 did not correlate to GCR, CRP, and incidence of CVD. In conclusion, our data suggest that anti-hHSP60 autoimmune response is not related to CP infection and CP-related CVD risk in HD patients.

Long-term hemodialysis treatment results in chronic monocyte activation with cytokine release. It generates Treg induction with potential immune dysfunction and associated clinical complications. Recent immunological data and preliminary clinical evidence suggest that synthetic polymers and vitamin E coated membranes are associated with a significant improvement in hemodialysis tolerance when compared to cellulose membranes. The aim of this review is to update cytokine release, T-cell polarization, and its clinical impact in patients under extracorporeal hemodialysis comparing traditional cellulose to synthetic/vitamin E coated membranes.

Background: Automatic systems for stabilizing blood pressure (BP) during dialysis are few and only control those variables indirectly related to BP. Due to complex BP regulation under dynamic dialysis conditions, BP itself appears to be the most consistent input parameter for a device addressed to preventing dialysis hypotension (DH)., Methods: An automatic system (ABPS, automatic blood pressure stabilization) for BP control by fluid removal feedback regulation is implemented on a dialysis machine (Dialog Advanced, Braun). A fuzzy logic (FL) control runs in the system, using instantaneous BP as the input variable governing the ultrafiltration rate (UFR) according to the BP trend. The system is user-friendly and just requires the input of two data: critical BP (individually defined as the possible level of DH risk) and the highest UFR applicable (percentage of the mean UFR). We evaluated this system's capacity to prevent DH in 55 RDT hypotension-prone patients. Sessions with (treatment A) and without (treatment B) ABPS were alternated one-by-one for 30 dialysis sessions per patient (674 with ABPS vs 698 without)., Results: Despite comparable treatment times and UF volumes, severe DH appeared in 8.3% of sessions in treatment A vs 13.8% in treatment B (-39%, P=0.01). Mild DH fell non-significantly (-12.3%). There was a similar percentage of sessions in which the planned body weight loss was not achieved and dialysis time was prolonged., Conclusions: In conclusion, FL may be suited to interpreting and controlling the trend of a determined multi-variable parameter like BP. The medical knowledge of the patient and the consequent updating of input parameters depending on the patient's clinical conditions seem to be the main factors for obtaining optimal results.

Background: In hemodialysis patients the activity of stimulated Th1 lymphocytes is depressed, while Th2 cells are constitutively primed. Such phenomena may depend on monocyte activation and altered release of interleukin (IL)-12 and IL-18, which regulate Th cell differentiation. Reactive oxygen species (ROS) activate monocytes; therefore, a hemodialyzer with antioxidant activity would contrast ROS, prevent monocyte activation, reset IL-12 and IL-18 release, and restore Th1/Th2 balance., Methods: Ten patients on regular dialysis treatment (RDT) with cellulosic membrane (CM) were shifted to vitamin E-coated dialyzer (VE). During treatment with CM and after 3, 6, and 12 months of treatment with VE, peripheral blood mononuclear cells (PBMC) and purified CD4+ cells were isolated, and cultured, resting, mitogen-stimulated, and interferon gamma (IFNgamma), IL-4, IL-10, IL-12, and IL-18 release was measured. Vitamin E and A plasma levels and the effects of a single dialysis session on peripheral blood NO levels were assayed., Results: The constitutive release of IL-4 and IL-10 by CD4+ cells was abated significantly by treatment with VE (nadir -77.8% and -55.3%, respectively, at 12 months). INFgamma release by mitogen-stimulated CD4+ recovered with VE (zenith +501% at 12 months). PBMC constitutive production of IL-12 and IL-18 was significantly reduced by VE (nadir at 12 months -64.7% and -51.3%, respectively). VE increased plasma levels of vitamins E and A. NO plasma levels fell after a single dialysis treatment with VE (-17%, P < 0.05) in contrast with CU (+27.1%, P < 0.05)., Conclusion: The network of cytokines released by monocytes and Th cells is reset toward normality by treatment with vitamin E-coated dialyzer.