Giovani nefrologi che fanno ricerca: quando scienza e passione si incontrano

La ricerca scientifica rappresenta il futuro della nefrologia e la ricerca del domani appartiene ai nefrologi del domani. I giovani nefrologi possono avere diverse opportunità per coltivare la ricerca. Le buone idee e l'esperienza accumulata, tuttavia, non sono le sole chiavi per il successo. La scienza deve sempre incontrare la passione e la curiosità. Presentiamo qui la storia di un giovane nefrologo con le sue esperienze personali di ricerca, dai primi passi ai primi traguardi, come modo per dimostrare agli altri giovani colleghi che l'entusiasmo scientifico e la devozione alla scienza spesso rendono i sogni realizzabili

NGAL: a new missing link between inflammation and uremic anemia?

n/

Renal Concerns in the Treatment of Chronic Hepatitis B with Tenofovir

Tenofovir, a third generation oral nucleos(t)ide analogue, currently represents one of the first-line drugs recommended for treating chronic hepatitis B virus (HBV) infection. After oral administration, tenofovir is mostly excreted in the urine by glomerular filtration and proximal tubular secretion. Hence, an impaired kidney function may lead to an increased renal exposure to the drug in patients with coexistent renal damage. This could further worsen kidney disease through different mechanisms of nephrotoxicity such as mitochondrial DNA depletion and tubular cytotoxicity. Despite several studies performed so far to assess tenofovir-related renal toxicity, data in HBV patients are not yet conclusive. Screening of risk factors for kidney disease before starting therapy and a careful monitoring of serum creatinine, glomerular filtration rate, serum phosphate and urine analysis during treatment are advocated to adjust the dose or stop treatment if needed. New biomarkers of tubular injury, such as neutrophil gelatinase associated lipocalin, could become helpful in the future for the timely identification and risk stratification of renal damage induced by tenofovir

Effects of Vitamin E-Coated versus Conventional Membranes in Chronic Hemodialysis Patients: A Systematic Review and Meta-Analysis

Introduction: Accruing evidence suggests that vitamin E-coated membranes (ViE-m) might improve the clinical management of chronic hemodialysis (HD) patients. Methods: We conducted a systematic review and meta-analysis of RCTs comparing ViE-m to conventional HD. Endpoints of interest were a series of biomarkers pertaining to anemia status, inflammation, oxidative stress and dialysis efficacy/status. Results: Sixty studies were included. ViE-m significantly improved the Erythropoietin Resistance Index but had no impact on other anemia parameters. As for oxidative stress and inflammation, ViE-m produced a significant decrease in interleukin-6 levels, thiobarbituric acid reactive substances, plasma and red blood cell (RBC) malonylaldehyde and a significant increase in blood and RBC vitamin E. Conversely, ViE-m use had no impact on lipid profile, dialysis adequacy, blood pressure, albumin and uric acid. Conclusions: ViE-m might ameliorate anemia management by reducing oxidative stress and inflammation. Benefits of these bio-membranes on harder clinical outcomes are uncertain and need to be investigated by future, targeted trials

Alterations of lipid metabolism in chronic nephropathies: mechanisms, diagnosis and treatment.

Nephropathic subjects show an increased tendency to develop cardiovascular diseases, mainly as the consequence of several risk factors including increased oxidative stress, inflammation, physical inactivity, anemia, vascular calcification, and endothelial dysfunction. The alterations in lipid metabolism represent a relatively lesser important cause of genesis and progression of atherosclerosis. Unfortunately, in these patients the atherogenic potential of dyslipidemia may depend more on apolipoproteins than on lipid abnormalities, and may not always be recognized by measurement of plasma lipids alone. The aim of this review was therefore to analyze the main lipid alterations that can occur in nephropathic patients, as well as their causes and their effects on the cardiovascular system. The clinical evidence and recommendations for the use of lipid-regulating drugs in patients with chronic kidney disease, nephrotic syndrome, in patients undergoing hemo- and peritoneal dialysis and in transplanted patients was also reviewed. Moreover, we analyzed the link between dyslipidemia and kidney disease onset and progression and the role of statins in preventing it

Obestatin: a new element for mineral metabolism and inflammation in patients on hemodialysis.

Background: Obestatin plays a key role in the process of energy balance maintenance with an anorectic effect. The main aim of the study was to evaluate obestatin in uremic patients to determine whether it is correlated with nutritional and inflammatory status. Methods: We studied plasma obestatin in uremic patients (n = 50) undergoing hemodialysis therapy and in healthy subjects. Plasma obestatin was measured using an ELISA kit. Results: Obestatin levels in uremic patients were lower than in healthy subjects (p 23 had lower obestatin levels than those with a BMI Conclusions: Based on the present observational data, obestatin might be implicated in the inflammatory state and the disturbances of calcium/phosphate metabolism of hemodialysis patients. However, further studies are warranted to determine whether this hormone plays a key role in contributing to malnutrition and to the chronic inflammatory process

Short-term vascular hemodynamic responses to isometric exercise in young adults and in the elderly

Background: Vascular aging is known to induce progressive stiffening of the large elastic arteries, altering vascular hemodynamics under both rest and stress conditions. In this study, we aimed to investigate changes in vascular hemodynamics in response to isometric handgrip exercise across ages. Participants and methods: We included 62 participants, who were divided into three age categories: 20-40 (n=22), 41-60 (n=20), and 61-80 (n=20) years. Vascular hemodynamics were measured using the Mobil-o-Graph® based on the pulsatile pressure changes in the brachial artery. One-way ANOVA test was performed to analyze the changes induced by isometric handgrip exercise. Results: After isometric handgrip exercise, aortic pulse wave velocity (PWV) increased by 0.10 m/s in the youngest, 0.06 m/s in the middle-age, and 0.02 m/s in the oldest age category. Changes in PWV strongly correlated with those in central systolic blood pressure (cSBP) (r=0.878, P<0.01). After isometric exercise, the mean change of systolic blood pressure (SBP) was −1.9% in the youngest, 0.6% in the middle-aged, and 8.2% in the oldest subjects. Increasing handgrip strength was associated with an increase in SBP and cSBP (1.08 and 1.37 mmHg per 1 kg increase in handgrip strength, res

Parenteral versus oral iron therapy for adults and children with chronic kidney disease

Background The anaemia seen in chronic kidney disease (CKD) may be exacerbated by iron deficiency. Iron can be provided through different routes, with advantages and drawbacks of each route. It remains unclear whether the potential harms and additional costs of intravenous (IV) compared with oral iron are justified. This is an update of a review first published in 2012. Objectives To determine the benefits and harms of IV iron supplementation compared with oral iron for anaemia in adults and children with CKD, including participants on dialysis, with kidney transplants and CKD not requiring dialysis. Search methods We searched the Cochrane Kidney and Transplant Register of Studies up to 7 December 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. Selection criteria We included randomised controlled trials (RCTs) and quasi‐RCTs in which IV and oral routes of iron administration were compared in adults and children with CKD. Data collection and analysis Two authors independently assessed study eligibility, risk of bias, and extracted data. Results were reported as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) was used or standardised mean difference (SMD) if different scales had been used. Statistical analyses were performed using the random‐effects model. Subgroup analysis and univariate meta‐regression were performed to investigate between study differences. The certainty of the evidence was assessed using GRADE. Main results We included 39 studies (3852 participants), 11 of which were added in this update. A low risk of bias was attributed to 20 (51%) studies for sequence generation, 14 (36%) studies for allocation concealment, 22 (56%) studies for attrition bias and 20 (51%) for selective outcome reporting. All studies were at a high risk of performance bias. However, all studies were considered at low risk of detection bias because the primary outcome in all studies was laboratory‐based and unlikely to be influenced by lack of blinding. There is insufficient evidence to suggest that IV iron compared with oral iron makes any difference to death (all causes) (11 studies, 1952 participants: RR 1.12, 95% CI 0.64, 1.94) (absolute effect: 33 participants per 1000 with IV iron versus 31 per 1000 with oral iron), the number of participants needing to start dialysis (4 studies, 743 participants: RR 0.81, 95% CI 0.41, 1.61) or the number needing blood transfusions (5 studies, 774 participants: RR 0.86, 95% CI 0.55, 1.34) (absolute effect: 87 per 1,000 with IV iron versus 101 per 1,000 with oral iron). These analyses were assessed as having low certainty evidence. It is uncertain whether IV iron compared with oral iron reduces cardiovascular death because the certainty of this evidence was very low (3 studies, 206 participants: RR 1.71, 95% CI 0.41 to 7.18). Quality of life was reported in five studies with four reporting no difference between treatment groups and one reporting improvement in participants treated with IV iron. IV iron compared with oral iron may increase the numbers of participants, who experience allergic reactions or hypotension (15 studies, 2607 participants: RR 3.56, 95% CI 1.88 to 6.74) (absolute harm: 24 per 1000 with IV iron versus 7 per 1000) but may reduce the number of participants with all gastrointestinal adverse effects (14 studies, 1986 participants: RR 0.47, 95% CI 0.33 to 0.66) (absolute benefit: 150 per 1000 with IV iron versus 319 per 1000). These analyses were assessed as having low certainty evidence. IV iron compared with oral iron may increase the number of participants who achieve target haemoglobin (13 studies, 2206 participants: RR 1.71, 95% CI 1.43 to 2.04) (absolute benefit: 542 participants per 1,000 with IV iron versus 317 per 1000 with oral iron), increased haemoglobin (31 studies, 3373 participants: MD 0.72 g/dL, 95% CI 0.39 to 1.05); ferritin (33 studies, 3389 participants: MD 224.84 µg/L, 95% CI 165.85 to 283.83) and transferrin saturation (27 studies, 3089 participants: MD 7.69%, 95% CI 5.10 to 10.28), and may reduce the dose required of erythropoietin‐stimulating agents (ESAs) (11 studies, 522 participants: SMD ‐0.72, 95% CI ‐1.12 to ‐0.31) while making little or no difference to glomerular filtration rate (8 studies, 1052 participants: 0.83 mL/min, 95% CI ‐0.79 to 2.44). All analyses were assessed as having low certainty evidence. There were moderate to high degrees of heterogeneity in these analyses but in meta‐regression, definite reasons for this could not be determined. Authors' conclusions The included studies provide low certainty evidence that IV iron compared with oral iron increases haemoglobin, ferritin and transferrin levels in CKD participants, increases the number of participants who achieve target haemoglobin and reduces ESA requirements. However, there is insufficient evidence to determine whether IV iron compared with oral iron influences death (all causes), cardiovascular death and quality of life though most studies reported only short periods of follow‐up. Adverse effects were reported in only 50% of included studies. We therefore suggest that further studies that focus on patient‐centred outcomes with longer follow‐up periods are needed to determine if the use of IV iron is justified on the basis of reductions in ESA dose and cost, improvements in patient quality of life, and with few serious adverse effects

Arrhythmias and hemodialysis: role of potassium and new diagnostic tools.

Cardiovascular diseases represent the main causes of death in patients affected by renal failure, and arrhythmias are frequently observed in patients undergoing hemodialysis. Dialytic treatment per se can be considered as an arrhythmogenic stimulus; moreover, uraemic patients are characterized by a "pro-arrhythmic substrate" because of the high prevalence of ischaemic heart disease, left ventricular hypertrophy and autonomic neuropathy. One of the most important pathogenetic element involved in the onset of intra-dialytic arrhythmias is the alteration in electrolytes concentration, particularly calcium and potassium. It may be very useful to monitor the patient's cardiac activity during the whole hemodilaytic session. Nevertheless, the application of an extended intradialytic electrocardiographic monitoring is not simple because of several technical and structural impairments. We tried to overcome these difficulties using Whealthy, a wearable system consisting in a t-shirt composed of conductors and piezoresistive materials, integrated to form fibers and threads connected to tissutal sensors, electrodes, and connectors. ECG and pneumographic impedance signals are acquired by the electrodes in the tissue, and the data are registered by a small computer and transmitted via GPRS or Bluetooth