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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.

BACKGROUND AND AIMS Magnesium (Mg) is the second cation in the intracellular space and the fourth prevalent cation in the body. It contributes to DNA and protein synthesis, infiammatory processes and cardiac excitability, while Mg deficiency leads to increased cardiovascular risk, atherosclerosis and diabetes [1]. In addition to gastrointestinal losses, loop or thiazide diuretics induce renal wasting, volume expansion and nephrotoxins including antibiotics Hypomagnesemia (HypoMg) is observed early after kidney transplantation and is associated with a faster decline of allograft function. Main determinants are calcineurin inhibitors (CNIs), protonic pump inhibitors (PPI), low Mg intake and diuretics. CNIs, in particular, induce HypoMg with mechanisms not fully understood, likely via downregulation of the Mg channel TRPM6 in the distal collecting tubule [2]. HypoMg should be corrected with oral supplements. Recently, in order to increase magnesium bioavailability and tolerance not shown by convetional oral magnesium supplements, a new sucrosomial magnesium formulation has been developed. Its innovative preparation encapsulates magnesium oxide in a phospholipid membrane covered by a sucrester matrix, which enhances Mg passage through the gastric and intestinal environment without any interaction with the intestinal mucosa [3]. This study evaluates magnesium bioavailability, tolerance and effectiveness after administration of sucrosomial magnesium compared with magnesium pidolate. METHOD We recruited 32 adult single, double or combined kidney-pancreas transplant recipients within 1 year from transplantation, who developed CNI-induced hypomagnesemia. Exclusion criteria include: HypoMg due to PPI or gastrointestinal losses. A total of 13 patients received magnesium pidolate, and 19 patients received sucrosomial magnesium. Venous blood samples were taken at baseline (T0) and after 10 days of magnesium supplement (T1). RESULTS Sucrosomial magnesium increased Mg bioavailability and tolerance: 0.60 ± 0.02 T0 mmoL/L versus 0.69 ± 0.05 T1; P < .0001 versus magnesium pidolate: 0.61 ± 0.05 T0 versus 0.64 ± 0.05 T1; P = .72 N.S. (Fig. 1A). Sucrosomial magnesium provided an increase of Mg over magnesium pidolate in terms of $\Delta \% $ increase: 12.4% for sucrosomial Mg versus 5.4%, P = .04 (Fig. 1B). CONCLUSION Our data, although obtained by a small cohort of transplant patients, shows that sucrosomial Mg is more efficient and better tolerated compared with magnesium pidolate. On the one hand, the fact that our study is the first in transplant patients to evaluate the impact of sucrosomial Mg for the correction of HypoMg might justify the limited number of patients enrolled and the short observation time; on the other hand, our results could serve as a working hypothesis for further studies with a larger number of transplant patients and for extended study duration to confirm the benefit of sucrosomial Mg.

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.

Objectives Kidney transplant (KTx) recipients frequently have deficient or insufficient levels of serum vitamin D. Few studies have investigated the effect of cholecalciferol in these patients. We evaluated the efficacy of weekly cholecalciferol administration on parathyroid hormone (PTH) levels in stable KTx patients with chronic kidney disease stage 1–3. Methods In this retrospective cohort study, 48 stable KTx recipients (37 males, 11 females, aged 52 ± 11 years and 26 months post-transplantation) were treated weekly with oral cholecalciferol (7500–8750 IU) for 12 months and compared to 44 untreated age- and gender-matched recipients. Changes in levels of PTH, 25(OH) vitamin D (25[OH]D), serum calcium, phosphate, creatinine and estimated glomerular filtration rate (eGFR) were measured at baseline, 6 and 12 months. Results At baseline, clinical characteristics were similar between treated and untreated patients. Considering the entire cohort, 87 (94.6%) were deficient in vitamin D and 64 (69.6%) had PTH ≥130 pg/mL. Serum calcium, phosphate, creatinine and eGFR did not differ between groups over the follow-up period. However, 25(OH)D levels were significantly higher at both 6 (63.5 vs. 30.3 nmol/L, p Conclusions Weekly administration of cholecalciferol can significantly and stably reduce PTH levels, without any adverse effects on serum calcium and renal function.

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.

BACKGROUND: Sunitinib, a tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF), is approved for first and second line treatment of advanced renal cell carcinoma (RCC). Knowledge on the effects of sunitinib on cardiovascular (CV) risk and renal damage is limited. AIM: To evaluate possible renal and CV damage in patients with RCC treated with sunitinib. MATERIALS AND METHODS: Patients with metastatic RCC treated with sunitinib were enrolled. This population was evaluated before starting treatment (T0) and after 3 months (T1). Laboratory and instrumental parameters, including interventricular septum (IVS) and left ventricular mass index (LVMI) were recorded before and after treatment. RESULTS: Thirty-two patients (13 female, 19 male, mean age 62.7±9.9 years) were enrolled. We observed overtime, a significant reduction in estimated glomerular filtration rate (eGFR) (p=0.01), haemoglobin (Hb) (p=0.04) and 25-hydroxyvitamin D (25-OH-VitD) (p=0.002), in association with a significant increase in serum phosphorus (p

Chronic kidney disease (CKD) is associated with markedly increased cardiovascular (CV) risk. This increase is not fully explained by traditional CV risk factors but may in part be mediated by nontraditional risk factors, such as inadequate vitamin D (vit D) levels and insulin resistance (IR). Although IR is shown in nondiabetic CKD, its association with vit D deficiency and vascular disease in this population is unknown and what this study aims to investigate.The study comprised 67 patients with CKD (eGFR ≥ 30 mL/min) and 15 healthy controls matched for age and sex. The phlogosis indexes, vit D levels, IR, carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI) were measured.In our study, the mean value of LVMI and cIMT was significantly higher in patients with eGFR ≥ 30 mL/min compared with controls (p = 0.037 and p 0.001). The IR and intact parathyroid hormone (iPTH) levels were increased in CKD patients, whereas the serum levels of vit D were significantly reduced (p = 0.044, p = 0.012, p = 0.038). A positive correlation was found between LVMI and IR (r = 0.704, p = 0.041) and a negative correlation was found between IR and vit D levels (r = -0.238, p = 0.031).In our study, IR and vit D deficiency were found to be independent predictors of left ventricular hypertrophy and atherosclerotic disease. Vitamin D deficiency and IR are thus associated with increased CV risk. More novel approaches to improving IR and vit D supplementation in the CKD population might lead to potential strategies for preventing excess CV mortality.

Patients with chronic kidney disease (CKD) present a markedly increased cardiovascular (CV) morbidity and mortality since the early stages and have a high prevalence of accelerated atherosclerosis, inflammation and endothelial dysfunction. Nontraditional cardiovascular risk factors and serum cardiac biomarkers would contribute to explain this increased morbidity.The aim is to investigate the relation among serum cardiac biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), nontraditional cardiovascular risk factors (serum uric acid, homocysteine), inflammatory indexes (C-reactive protein (CRP) serum ferritin, fibrinogen) and noninvasive predictors of atherosclerosis (carotid intima-media thickness (cIMT), brachial artery flow mediated dilation (baFMD), and left ventricular mass index (LVMI)) in CKD patients.In 50 patients with CKD in stage 2/3 kidney disease outcomes quality initiative (KDOQI) and 18 age- and sex-matched healthy controls, the following parameters were measured: cardiac markers (cTnT and NT-proBNP), renal function, inflammatory markers (CRP, serum ferritin and fibrinogen), serum uric acid and homocysteine. We have also evaluated LVMIs, cIMT and baFMD.In our study, we showed an increase of NT-proBNP and the serum cTnT, of serum uric acid and homocysteine with a positive correlation with the increase of cIMT and LVMI and reduced baFMD compared with the controls.Serum cardiac biomarkers and nontraditional cardiovascular risk factors increase already in the stage 2/3 KDOQI contributing to explain the high cardiovascular morbidity and mortality of these patients. The NT-proBNP seems to have a rise earlier compared with serum cTnT; however, both seemed to be a useful clinical biomarker for evaluating noninvasive predictors of atherosclerosis in CKD patients.

Autoimmune polyglandular syndromes (APS) are constellations of symptoms and signs of multiple glandular insufficiencies. We report a rare case of type III APS in a female patient.A 51-year-old woman was treated with radiotherapy because of thymus hyperplasia when she was two years old; she was diagnosed with celiac disease and autoimmune hypothyroidism at 41 years old and with sicca syndrome and myasthenia gravis seronegative a few years later.Our patient demonstrates a previous constellation of diseases of APS, which may be a random association but may also indicate a common immunological and genetic disturbance. The APS is an expression of a system impairment of immune tolerance to autoreactive clones, and this is necessary because the phenomena can become aggressive and expressed clinically. We suppose that the development of thymic hyperplasia or its radiotherapy in childhood may have compromise the patient's immune system.

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.

Introduction The incidence and spectrum of kidney disease in Human Immunodeficiency Virus-infected patients have been altered by the diffused use of highly active antiretroviral therapy; indeed, acute and chronic kidney disease has emerged as a significant cause of morbidity and mortality among Human Immunodeficiency Virus-infected population. Risk factors associated with kidney disease in such Human Immunodeficiency Virus-infected population include aging, hypertension, diabetes mellitus, co-infection with hepatitis C virus, low CD4 cell count, and high Human Immunodeficiency Virus viral load. The aim of this review was to discuss nephropathies in Human Immunodeficiency Virus-infected patients. Materials and Methods We conduct a review on the actual knowledge of acute and chronic Human Immunodeficiency Virus-associated renal disease, metabolic alterations and related nephropathies, and the side effects of highly active antiretroviral therapy. Results We examined all the randomised controlled trials and quasi-randomised controlled trials that evaluate the current knowledge on acute and chronic HIV and highly active antiretroviral therapy associated renal disease. After quality appraisal, 170 met the inclusion criteria for the review. The studies included in the review were grouped into two areas: nephropathy HIV associated and nephropathy highly active antiretroviral therapy associated. Conclusion Early identification and treatment of kidney disease is imperative for preventing further renal damage in Human Immunodeficiency Virusinfected populations and for instituting appropriate management efficiently. The Infectious Diseases Society of America guidelines recommend urinalysis and estimation of kidney function for all Human Immunodeficiency Virus-infected persons at the time of Human Immunodeficiency Virus diagnosis. Periodic monitoring of albuminuria, tubular parameters such as low-molecularweight proteinuria, and the estimated glomerular filtration rate may be useful for early diagnosis of patients at risk for acute or chronic renal disease.