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The key role of oxidative stress (OxSt) and inflammation for the induction of cardiovascular disease, the leading cause of excess morbidity/mortality in chronic kidney disease and dialysis patients, is known and both the activations of NADPH oxidase and RhoA/Rho kinase (ROCK) pathway are pivotal for their effects. While specific hemodialysis procedures, such as hemodiafiltration with on‐line reinfusion of ultrafiltrate and/or the use of vitamin E‐coated dialyzers, are beneficial for OxSt and inflammation, studies in peritoneal dialysis (PD) are instead scarce and results seem not favorable. In nine patients under PD OxSt in terms of mononuclear cell protein level of p22phox (Western blot), subunit of NADPH oxidase, essential for the generation of OxSt, and MYPT‐1 phosphorylation state (Western blot), a marker of ROCK activity, have been measured at the beginning and after 3 and 6 months of PD. Blood levels of interleukin 6 (IL‐6), ferritin, and albumin have been considered for evaluating the inflammatory state. p22phox protein expression, MYPT‐1‐phosphorylation, and ferritin level were increased both at baseline vs healthy subjects (P = .02, P, Oxidative stress (OxSt) and inflammation increase during peritoneal dialysis (PD) confirming via molecular biology approach a biochemical report. They may lead to structural/functional damage of the peritoneal membrane, in addition to increase cardiovascular risk, the leading cause of excess morbidity/mortality in dialysis patients.To improve OxSt in PD a multitarget approach is necessary. It might include the use of more physiologic pH, low glucose degradation products, low lactate and iso‐osmolar PD solutions, patients’ strict glycemic control, optimal volume management.Studies in our laboratory are ongoing to evaluate with a molecular biology approach in PD patients, the effect of more biocompatible solutions on OxSt and its signaling.

Critical patients with Acute Kidney Injury (AKI) requiring renal replacement therapy are in most cases eligible only for continuous modalities where the electrolyte balance control is a critical issue. The standard solutions used for hemodiafiltration, containing potassium at 2 mmol/L and no phosphorus, determines during the extended renal replacement therapy hypokalemia and hypophosphatemia. Therefore, solutions containing potassium and phosphate in physiological concentrations were formulated to avoid electrolyte imbalances and reduce ion alterations in prolonged treatments, these solutions are not routinely used in the standard clinical practice. To avoid electrolyte imbalances, we have first introduced in our practice two different solutions and then we have retrospectively analyzed the electrolyte balance upon these two solutions in order to identity the impact of these solutions on potassium and phosphate according to our clinical practice. We retrospectively analyzed 96 patients treated with Continuous Renal Replacement Therapy (CRRT) in the intensive care units (ICU) at Padua’s University Hospital to evaluate the role on electrolyte balance of Phoxilium® and Prismasol 2® that differ in their composition and the need for electrolytes infusions. In the Phoxilium group the frequency of hypokalemia, hypophosphatemia, and the need of potassium and phosphate replacement were significantly reduced resulting in a reduction in complications, workload, and clinical risk associated with infusions of electrolytes. Our data demonstrated that the use of these two different hemodiafiltration solutions can reduce the occurrence of hypokalemia and hypophosphatemia during CRRT performing personalized treatments without the use of potassium and phosphate infusions.

The excessive activation of the renin-angiotensin system in kidney disease leads to alteration of intracellular pathways which concur altogether to the induction of cardiovascular and renal remodeling, exposing these patients since the very beginning of the renal injury to chronic kidney disease and progression to end stage renal disease, a very harmful and life threatening clinical condition. Oxidative stress plays a pivotal role in the pathophysiology of renal injury and cardiovascular-renal remodeling, the long-term consequence of its effect. This review will examine the role of oxidative stress in the most significant pathways involved in cardiovascular and renal remodeling with a focus on the detrimental effects of oxidative stress-mediated renal abnormalities on the progression of the disease and of its complications. Food for thoughts on possible therapeutic target are proposed on the basis of experimental evidences.

Background and Aims Cardiovascular disease is the leading cause of excess mortality in chronic kidney disease (CKD) and dialysis patients with oxidative stress (OxSt) and inflammation playing a pivotal role, as non-traditional risk factors and OxSt and inflammation have been shown to increase in peritoneal dialysis. Rho kinase (ROCK) activation is deeply involved in the induction of OxSt and inflammation and is closely linked to cardiovascular-renal remodeling. We aimed to evaluate in peritoneal dialysis patients with a molecular biology approach OxSt, in terms of phosphorylation state of MYPT-1 (marker of ROCK activity), the protein expression of p22phox (subunit of NADPH oxidase, essential for the generation of ROS), and inflammation state, in terms of acute-phase proteins level (Interleukin 6 (IL-6), ultra-sensitive C-reactive protein (US-CRP), Ferritin, Albumin and Transferrin). Method 9 male ESRD patients (39-81 years old) were enrolled and analyzed before (baseline) and after three and six months of peritoneal dialysis treatment (CAPD 7 patients, APD 2 patients). Mononuclear cells (PBMCs) MYPT-1 phosphorylation state and p22phox protein expression were determined by Western Blot. Specific acute-phase proteins as IL-6, US-CRP, Ferritin, Albumin and Transferrin were assessed through blood chemistry tests. Results MYPT-1 phosphorylation was increased after six months of treatment with peritoneal dialysis compared with three months and predialysis (1.03±0.07 vs 1.02±0.04 vs 1.57±0.16 d.u., p Conclusion The increase of OxSt and inflammation during peritoneal dialysis is confirmed also at molecular biology level and may lead in the medium-long term to dangerous consequences. The necessary improvement of OxSt status in peritoneal dialysis needs a multitarget approach. It might include the use of neutral pH, low glucose degradation products, low lactate and iso-osmolar peritoneal dialysis solutions, strict glycemic control, optimal volume management and, likely, a supplementation with antioxidants as N-acetylcysteine.

A native arteriovenous fistula (AVF) is the vascular access of choice for hemodialysis (HD) treatment. Compared with other types of vascular access such as grafts and central venous catheters, it functions longer and is associated with a lower risk of complications. The aim of the study described here was to assess, in an HD population, the position of the fistula needles during an HD session and evaluate the role of ultrasound in the management of AVF puncture. Forty-five consecutive chronic HD patients with an AVF or an arteriovenous vascular graft were included in the study for ultrasound evaluation. Each patient underwent an ultrasound evaluation during HD treatment to assess the position of the needles inside the vascular access. The ultrasound evaluation revealed that 81.8% of the traditional needles were incorrectly adjacent to the vessel walls, in the absence of clinical symptoms or hemodynamic alterations detectable on the dialysis monitor. A greater frequency of malpositioning has been observed for needles in the arterial portion of the vascular access, closer to the anastomosis. The absence of clinically detectable signs of venipuncture-related complications does not ensure correct positioning of the needles within the AVF. Ultrasound evaluation may not only resolve suboptimal cannulation problems of new or complicated vascular accesses but may also be useful in the prevention of acute and chronic damage to the AVF.

Introduction: Mortality in dialysis patients is higher than in the general population, and cardiovascular disease represents the leading cause of death. Hypertension and volume overload are important risk factors for the development of left ventricular hypertrophy (LVH) in hemodialysis (HD) and peritoneal dialysis (PD) patients. Other factors are mainly represented by hyperparathyroidism, vascular calcification, arterial stiffness and inflammation. The aim of this study was to compare blood pressure (BP) and metabolic parameters with cardiovascular changes [cardiothoracic ratio (CTR), aortic arch calcification (AAC) and LV mass index (LVMI)] between PD and HD patients. Materials and Methods: 45 patients (23 HD and 22 PD patients) were enrolled. BP measurements, echocardiography and chest X-ray were performed in each patient to determine the LVMI and to evaluate the CTR and AAC. Inflammatory indexes, intact parathyroid hormone (iPTH) and arterial blood gas analysis were also evaluated. Results: LVMI was higher in PD than HD patients (139 ± 19 vs. 104 ± 22; p = 0.04). In PD patients, a significant correlation between iPTH, C-reactive protein and the presence of LVH was observed (r = 0.70, p = 0.04; r = 0.70, p = 0.03, respectively). The CTR was increased in PD patients as compared to HD patients, while no significant differences in cardiac calcifications were determined. Conclusions: Our data indicate that HD patients present more effective BP control than PD patients. Adequate fluid and metabolic control are necessary to assess the adequacy of BP, which is strongly correlated with the increase in LVMI and with the increased CTR in dialysis patients. PD is a home therapy and allows a better quality of life, but PD patients may present a further increased cardiovascular risk if not adequately monitored. © 2014 S. Karger AG, Basel

Introduction: Most forms of human glomerulonephritis (GN) result from immunologic mechanisms that are mediated by the actions of multiple elements of both the innate and adaptive immune systems, thereby resulting in different clinical manifestations. The treatment of immune-mediated kidney disease is based on steroids and immunosuppressive drugs that interfere with the immune processes. These groups of drugs have led to significant benefits, but severe side effects are still frequent. Monoclonal antibodies directed against molecules of inflammation or several cellular components have emerged in clinical practice. Plasmapheresis and new methods to reduce the risks associated with the procedure with standard therapies may be combined. Moreover new therapeutic options have been proposed, as the use of natural anti-inflammatory cytokines or intracellular signaling reducing inflammation. Materials and Methods: We conducted a systematic review on the pathogenetic mechanisms of glomerulonephritis and their therapies. Results: We analized all RCTs and quasi-RCTs evaluating the current knowledge about pathogenetic mechanisms of glomerulonephritis and related therapy were considered. Conclusion: The pathogenetic mechanisms of glomerulonephritis are complex and strongly influenced by immunogenetic factors. Several clinical trials to identify the best therapeutic options for glomerulonephritis have been conducted, but currently, although significant advancements over the last 10 years have been obtained, important questions are still unanswered. Moreover, we need to consider many and important side effects that have the main therapies for glomerulonephritis. Therefore the development of a web enabled data base to assist nephrologists for the treatment of patients with glomerulonephritis is strongly suggested.