St Bortolo Hospital

Vicenza, Italy

St Bortolo Hospital

Vicenza, Italy
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Cardio-Renal syndrome (CRS) is a common and complex clinical condition in which multiple causative factors are involved. The time window between renal insult and development of acute kidney injury (AKI) in acute heart failure (AHF) can be varied in different patients and AKI often is diagnosed too late, only when the effects of the insult become evident with a loss or decline of renal function. For this reason, pharmaceutical interventions for AKI that have been shown to be renoprotective or beneficial when tested in experimental conditions do not display similar results in the clinical setting. In most cases patients with AHF are admitted with clinical signs and symptoms of congestion and fluid overload. Loop diuretics, typically used to induce an enhanced diuresis in these congested patients, often are associated with a subsequent significant decrease in glomerular filtration rate and cause a creatinine increase that is apparent within 72 hours. Early detection of AKI is not possible with the use of serum creatinine and there is a need for a timely diagnostic tool able to address renal damage while it is happening. We need to define the diagnosis of both AHF and AKI in the early phases of CRS type 1 by coupling a kidney damage marker such as neutrophil gelatinase-associated lipocalin (NGAL) with B-type natriuretic peptide (BNP). Indeed, it would be ideal to make available a panel including whole blood or plasma cardiac and renal biomarkers building specific, pathophysiologically based, molecular profiles. Based on current knowledge and consensus, we can use kidney damage biomarkers such as plasma NGAL for an early diagnosis of AKI. However, differences in individual patient values and uncertainties about the ideal cut-off values may currently limit the application of these biomarkers. We propose that NGAL may increase its usefulness in the diagnosis and prevention of CRS if a curve of plasma values rather than a single plasma measurement is determined. To apply the concept of measuring an NGAL curve in AHF patients, however, assay performance in the lower-range values becomes a critical factor. For this reason, we propose the use of the new extended-range plasma NGAL assay that may contribute to remarkably improve the sensitivity of AKI diagnosis in AHF and lead to more effective intervention strategies. © 2012 Elsevier Inc.

Ricci Z.,Bambino Gesu Childrens Hospital | Ronco C.,St Bortolo Hospital | Ronco C.,International Renal Research Institute
Current Opinion in Critical Care | Year: 2011

Purpose of review: In the past 3 years substantial progress has been made in the field of renal replacement therapy (RRT) for critically ill patients. Recent findings: Two important multicenter randomized clinical trials have been recently published and extensively discussed: the randomized evaluation of normal versus augmented level (RENAL) replacement therapy study and the VA/NIH Acute Renal Failure Trial Network (ATN) study. The RENAL and ATN studies were designed to compare 'normal' or 'less intensive' renal support to an 'augmented' or 'intensive' therapy: both studies showed no benefit in outcomes by increases in intensity of RRT dose. The definition of 'normal dose' is now recommended in a range of 20-30 ml/kg per h for continuous therapies and/or thrice weekly intermittent hemodialysis. On the contrary, the complex issue of RRT optimal timing still remains uncertain and controversial. Summary: Wide variations in clinical practice still require RRT for critically ill patients to be optimized. The ideal prescription does not exist; however, continuous hemofiltration at a dose of 30 ml/kg/h meets many requirements of optimal care. In order to shed some light in the issue of RRT timing, furthermore, in the near future a standardized and clinically relevant definition of 'early' RRT should be provided. Great expectations currently rely on the utilization of acute kidney injury severity classifications and on new biomarkers of renal function. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Ronco C.,St Bortolo Hospital
Blood Purification | Year: 2013

The second law of thermodynamics applies with local exceptions to patient history and therapy interventions. Living things preserve their low level of entropy throughout time because they receive energy from their surroundings in the form of food. They gain their order at the expense of disordering the nutrients they consume. Death is the thermodynamically favored state: it represents a large increase in entropy as molecular structure yields to chaos. The kidney is an organ dissipating large amounts of energy to maintain the level of entropy of the organism as low as possible. Diseases, and in particular uremia, represent conditions of rapid increase in entropy. Therapeutic strategies are oriented towards a reduction in entropy or at least a decrease in the speed of entropy increase. Uremia is a process accelerating the trend towards randomness and disorder (increase in entropy). Dialysis is a factor external to the patient that tends to reduce the level of entropy caused by kidney disease. Since entropy can only increase in closed systems, energy and work must be spent to limit the entropy of uremia. This energy should be adapted to the system (patient) and be specifically oriented and personalized. This includes a multidimensional effort to achieve an adequate dialysis that goes beyond small molecular weight solute clearance. It includes a biological plan for recovery of homeostasis and a strategy towards long-term rehabilitation of the patient. Such objectives can be achieved with a combination of technology and innovation to answer specific questions that are still present after 60 years of dialysis history. This change in the individual bioentropy may represent a local exception to natural trends as the patient could be considered an isolated universe responding to the classic laws of thermodynamics. Copyright © 2013 S. Karger AG, Basel.

Giavarina D.,St Bortolo Hospital
Autoimmunity Reviews | Year: 2012

Studies of accuracy are often more complex to understand than clinical trials, since there can be more than one outcome and scope (screening, diagnosis, and prognosis) and because results have to be reported in more than one way, than in clinical trials (relative risk or odds ratio). Sensitivity and specificity are common terms for practitioners, but to remember that sensitivity is the "ratio between true positive rate and true positive rate plus false negative rate" may sometime cause some frustration. Moreover, likelihood ratio, predictive values, diagnostic odds ratio, and pre- and post-test probability complicate the framework. To summarize these indexes from multiple studies can be also a little more difficult. However, understanding diagnostic test accuracy from different study results and how to interpret systematic reviews and meta-analysis can help every practitioner improve critical appraisal of evidence about the best use of diagnostic tests. Avoiding complicated mathematical formulas, this paper attempts to explain the meaning of the most important diagnostic indexes and how to read a Forest plot and a summary Receiver Operative Characteristic curve. © 2012 Elsevier B.V.

Costanzo M.R.,Edward Heart Hospital | Ronco C.,St Bortolo Hospital
Current Cardiology Reports | Year: 2012

Most heart failure hospitalizations are due to volume overload, which contributes to disease progression. Heart failure decompensation is typically treated with intravenous diuretics, which are of limited efficacy especially in patients with underlying chronic kidney disease. Since the introduction of hemodialysis, ultrafiltration has been used to remove excess body fluid. Newer, simplified isolated ultrafiltration devices make ultrafiltration feasible at most hospitals and in less acute care settings. Veno-venous ultrafiltration is characterized by transport of solutes and water across a semipermeable membrane in response to a transmembrane pressure gradient generated by a peristaltic pump. Monitoring of ultrafiltration requires a combination of clinical and biomarkers values. Hemodynamic instability due to overaggressive fluid removal must be avoided. Based on recent clinical trials, practice guidelines state that ultrafiltration is reasonable for patients with congestion refractory to medical therapy (Class IIa, Level of Evidence B). Unanswered questions regarding ultrafiltration in heart failure patients include optimal fluid removal rates, effect on long-term survival, and cost. © Springer Science+Business Media, LLC 2012.

Perini F.,St Bortolo Hospital | De Boni A.,St Bortolo Hospital
Neurological Sciences | Year: 2012

Patients with chronic migraines are often refractory to medical treatment. Therefore, they might need other strategies to modulate their pain, according to their level of disability. Neuromodulation can be achieved with several tools: meditation, biofeedback, physical therapy, drugs and electric neurostimulation (ENS). ENS can be applied to the central nervous system (brain and spinal cord), either invasively (cortical or deep brain) or non-invasively [cranial electrotherapy stimulation, transcranial direct current stimulation and transcranial magnetic stimulation]. Among chronic primary headaches, cluster headaches are most often treated either through deep brain stimulation or occipital nerve stimulation because there is a high level of disability related to this condition. ENS, employed through several modalities such as transcutaneous electrical nerve stimulation, interferential currents and pulsed radiofrequency, has been applied to the peripheral nervous system at several sites. We briefly review the indications for the use of peripheral ENS at the site of the occipital nerves for the treatment of chronic migraine. © Springer-Verlag 2012.

Palazzuoli A.,University of Siena | Masson S.,Instituto Of Ricerche Farmacologiche Mario Negri | Ronco C.,St Bortolo Hospital | Maisel A.,University of California at San Diego
Heart Failure Reviews | Year: 2014

In recent years, numerous biomarkers have been studied in heart failure to improve diagnostic accuracy and identify patients at higher risk. The overall outcome remains fairish despite improvements in therapy, with mean survival after first hospitalization, around 5 years. We therefore need surrogate end points to better understand the pathogenetic mechanisms of the disease, including interplays with other organs. The kidney plays an important role in the initiation and progression of HF, and around one-third of patients with HF show some degree of renal dysfunction. In addition, treatment for HF often worsens renal function, consequently to hemodynamic and clinical improvement do not correspond an effective improvement in HF prognosis. Association between HF and renal impairment (RI) is now classified as cardiorenal syndrome (CRS) pointing out the bidirectional nature of this vicious circle leading to a mutual and progressive damage of both organs. The clinicians can rely on circulating biomarkers that give insights into the underlying pathogenetic mechanisms and help in risk stratification. Recently, a multimarker strategy including biomarker tool to traditional risk scores has been purposed and applied: Although each biomarker provided incremental outcome benefit, the combination of multiple biomarkers should offer the greatest improvement in risk prediction. Natriuretic peptides (NP) and cardiac troponins (TN) are the two biomarkers most studied in this setting, probably because of their organ-specific nature. However, both NP and TN cutoffs in presence of renal dysfunction need to be revised and discussed in relation to age, gender and stage of RI. In this context, the biomarkers are a unique opportunity to elucidate pathophysiological mechanisms, tailor clinical management to the single patient and improve outcomes. Specific studies about the exact role of biomarkers as in HF as in CRS should be planned and considered for future trials. © 2013 Springer Science+Business Media New York.

Ricci Z.,Bambino Gesu Childrens Hospital | Cruz D.N.,International Renal Research Institute Vicenza | Ronco C.,St Bortolo Hospital
Nature Reviews Nephrology | Year: 2011

Acute kidney injury (AKI) is often overlooked in hospitalized patients, despite the fact that even mild forms are strongly associated with poor clinical outcomes such as increased mortality, morbidity, cardiovascular failure and infections. Research endorsed by the Acute Dialysis Quality Initiative led to the publication of a consensus definition for AKIg-the RIFLE criteria (Risk, Injury, Failure, Loss of function, and End-stage renal disease)g-which was designed to standardize and classify renal dysfunction. These criteria, along with revised versions developed by the AKI Network (AKIN), can detect AKI with high sensitivity and high specificity and describe different severity levels that aim to predict the prognosis of affected patients. The RIFLE and AKIN criteria are easy to use in a variety of clinical and research settings, but have several limitations: both utilize an increase in serum creatinine level from a hypothetical baseline value and a decrease in urine output, but these surrogate markers of renal impairment manifest relatively late after injury has occurred and do not consider the nature or site of the kidney injury. New biomarkers for AKI have shown promise for early diagnosis and prediction of the prognosis of AKI. As more data become available, they could, in the future, be incorporated into improved definitions or criteria for AKI. © 2011 Macmillan Publishers Limited. All rights reserved.

Ronco C.,St Bortolo Hospital
Contributions to Nephrology | Year: 2011

Technological developments in the fields of membranes, machines and fluids have contributed to making hemodiafiltration (HDF) a safe and effective technique. Synthetic membranes with combined hydrophilic-hydrophobic structure and reduced wall thickness allowed to combine diffusion and convection into a unique technique. Accurate volumetric ultrafiltration control systems in dialysis machines reduce the risk for fluid balance errors and allow to perform safe and efficient online HDF. In fact, modern dialysis machines are equipped with specific balancing systems to manage fluid reinfusion and ultrafiltration simultaneously. Online preparation of sterile and pyrogen-free solutions for infusion is today possible, allowing the safe infusion of large fluid volumes during a HDF session. Dedicated software and enhanced user interfaces of modern dialysis machines simplify the procedures and reduce both operator workload and error. Emerging evidence suggests that these therapies may be superior to classic diffusive hemodialysis in terms of morbidity, and perhaps even mortality. There is a need for better understanding of the mechanisms involved, as well as further confirmation of these encouraging findings with prospective controlled trials. Nevertheless, HDF appears a promising therapy that likely will improve patient outcomes. Based on these considerations, HDF has the potential to become the new gold standard for dialysis in the years to come. Copyright © 2011 S. Karger AG, Basel.

Ronco C.,St Bortolo Hospital | Ronco C.,International Renal Research Institute | Cicoira M.,University of Verona | McCullough P.A.,St John Providence Health System | And 3 more authors.
Journal of the American College of Cardiology | Year: 2012

Cardiorenal syndrome (CRS) type 1 is characterized as the development of acute kidney injury (AKI) and dysfunction in the patient with acute cardiac illness, most commonly acute decompensated heart failure (ADHF). There is evidence in the literature supporting multiple pathophysiological mechanisms operating simultaneously and sequentially to result in the clinical syndrome characterized by a rise in serum creatinine, oliguria, diuretic resistance, and in many cases, worsening of ADHF symptoms. The milieu of chronic kidney disease has associated factors including obesity, cachexia, hypertension, diabetes, proteinuria, uremic solute retention, anemia, and repeated subclinical AKI events all work to escalate individual risk of CRS in the setting of ADHF. All of these conditions have been linked to cardiac and renal fibrosis. In the hospitalized patient, hemodynamic changes leading to venous renal congestion, neurohormonal activation, hypothalamic-pituitary stress reaction, inflammation and immune cell signaling, systemic endotoxemic exposure from the gut, superimposed infection, and iatrogenesis all contribute to CRS type 1. The final common pathway of bidirectional organ injury appears to be cellular, tissue, and systemic oxidative stress that exacerbate organ function. This review explores in detail the pathophysiological pathways that put a patient at risk and then effectuate the vicious cycle now recognized as CRS type 1. © 2012 American College of Cardiology Foundation.

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