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De Rosa S.,International Renal Research Institute of Vicenza IRRIV | De Rosa S.,Catholic University | De Rosa S.,San Bortolo Hospital | Antonelli M.,Catholic University | And 2 more authors.
Nephrology Dialysis Transplantation | Year: 2017

Cellular damage after reperfusion of ischaemic tissue is defined as ischaemia-reperfusion injury (IRI). Hypothermia is able to decrease oxygen consumption, preventing a rapid loss of mitochondrial activity. However, even though cooling can help to decrease the deleterious effects of ischaemia, the consequences are not exclusively beneficial, such that hypothermic storage is a compromise between benefits and harm. The present review details the relationship between renal IRI and hypothermia, describing the pathophysiology of IRI and hypothermic protection through experimental evidence. Although experimental models of renal IRI are a valuable tool for understanding the pathophysiology of renal ischaemia-reperfusion, the clinical transfer of experimental results has several limitations, particularly because of anatomical and physiological differences. In this review limitations of animal models but also hypothermia as a strategy to protect the kidney from IRI are discussed. We also attempt to describe three clinical scenarios where hypothermia is used in clinical settings of IRI: transplantation, deceased donors and post-cardiac arrest. © The Author 2017.


PubMed | International Renal Research Institute of Vicenza IRRIV, Ospedale Belcolle and L Parodi Delfino Hospital
Type: Journal Article | Journal: Heart failure reviews | Year: 2015

Cardiorenal syndrome type 5 (CRS-5) includes conditions where there is a simultaneous involvement of the heart and kidney from a systemic disorder. This is a bilateral organ cross talk. Fabrys disease (FD) is a devastating progressive inborn error of metabolism with lysosomal glycosphingolipid deposition in variety of cell types, capillary endothelial cells, renal, cardiac and nerve cells. Basic effect is absent or deficient activity of lysosomal exoglycohydrolase a-galactosidase A. Renal involvement consists of proteinuria, isosthenuria, altered tubular function, presenting in second or third decade leading to azotemia and end-stage renal disease in third to fifth decade mainly due to irreversible changes to glomerular, tubular and vascular structures, especially highlighted by podocytes foot process effacement. Cardiac involvement consists of left ventricular hypertrophy, right ventricular hypertrophy, arrhythmias (sinus node and conduction system impairment), diastolic dysfunction, myocardial ischemia, infarction, transmural replacement fibrosis, congestive heart failure and cardiac death. Management of FD is based on enzymatic replacement therapy and control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors-and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statin to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).


Sartori M.,International Renal Research Institute of Vicenza IRRIV | Sartori M.,St Bortolo Hospital | Sartori M.,University of Padua | Sharma A.,International Renal Research Institute of Vicenza IRRIV | And 12 more authors.
International Journal of Artificial Organs | Year: 2014

Purpose: Limited options are available to treat critically ill patients with acute liver failure (ALF) and acute-on-chronic liver failure (AoCLF), therefore we set up an in vitro study in order to test the bilirubin adsorption capacity of the Lixelle S-35 cartridge by direct hemoperfusion (DHP).Methods: Mock DHP was performed for 120 min using hyperbilirubinic human plasma and blood obtained from a plasmapheresis and exchange transfusion, respectively. The total bilirubin (TBIL) and direct bilirubin (DBIL) baseline concentrations were 17.57 ± 0.53, 12.57 ± 0.23 mg/dl for plasma and 23.10 ± 0.47, 15.37 ± 0.24 mg/dl for blood. Plasma and blood were separately circulated in a closed circuit simulating DHP using an adsorption column (Lixelle S-35) at flow rate of 100 ml/min. TBIL and DBIL levels were measured at 10, 30, 60, and 120 min from arterial and venous ports and assessed with the Jendrassik-Grof method. All tests were performed in triplicate.Results: The total removal subsequent to DHP (120 min) was seen as TBIL in plasma 55.60%, TBIL in blood 62.16%, DBIL plasma 58.87%, DBIL in blood 64.41%, respectively. The estimated mass adsorption of TBIL in plasma 958.20 ± 5.72 mg, TBIL in blood 1233.60 ± 10.22 mg, DBIL in plasma 680.70 ± 10.68, DBIL in blood 818.10 ± 4.68, respectively. Conclusions: The bilirubin adsorption rates after DHP were very promising for both hyperbilirubinic plasma and blood. Although further in vitro investigations are required, including comparisons with other techniques, these findings have shown that the Lexille S-35 should represent an option for the management of hyperbilirubinemia in ALF or AoCLF. © 2014 Wichtig Publishing.


Virzi G.M.,San Bortolo Hospital | Virzi G.M.,International Renal Research Institute of Vicenza IRRIV | Clementi A.,International Renal Research Institute of Vicenza IRRIV | Clementi A.,San Giovanni Of Dio Hospital | And 15 more authors.
Oxidative Medicine and Cellular Longevity | Year: 2015

Cardiorenal Syndrome Type 1 (Type 1) is a specific condition which is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Even though its pathophysiology is complex and not still completely understood, oxidative stress seems to play a pivotal role. In this study, we examined the putative role of oxidative stress in the pathogenesis of CRS Type 1. Twenty-three patients with acute heart failure (AHF) were included in the study. Subsequently, 11 patients who developed AKI due to AHF were classified as CRS Type 1. Quantitative determinations for IL-6, myeloperoxidase (MPO), nitric oxide (NO), copper/zinc superoxide dismutase (Cu/ZnSOD), and endogenous peroxidase activity (EPA) were performed. CRS Type 1 patients displayed significant augmentation in circulating ROS and RNS, as well as expression of IL-6. Quantitative analysis of all oxidative stress markers showed significantly lower oxidative stress levels in controls and AHF compared to CRS Type 1 patients (P < 0.05). This pilot study demonstrates the significantly heightened presence of dual oxidative stress pathway induction in CRS Type 1 compared to AHF patients. Our findings indicate that oxidative stress is a potential therapeutic target, as it promotes inflammation by ROS/RNS-linked pathogenesis. Copyright © 2015 Grazia Maria Virzì et al.


Cerda J.,Albany Medical College | Cerda J.,Physicians Capital | Sheinfeld G.,University of Maryland, Baltimore | Ronco C.,St Bortolo Hospital | Ronco C.,International Renal Research Institute of Vicenza IRRIV
Blood Purification | Year: 2010

Fluid overload may occur in critically ill patients as a result of aggressive resuscitation therapies. In such circumstances, persistent fluid overload must be avoided since it does not benefit the patient while it may be harmful. In the septic patient, early volume expansion seems to be beneficial. Beyond that threshold, when organ failure develops, fluid overload has been shown to be associated with worse outcomes in multiple disparate studies. One well-designed randomized controlled trial showed the benefit of a conservative fluid management strategy based on limited fluid intake and use of furosemide in such patients. Use of diuretics should be only short term as long as it is effective, generally at high doses, while avoiding simultaneous utilization of nephrotoxins such as aminoglycosides. Multiple randomized controlled trials have not shown benefit in the use of diuretics, either to prevent AKI or to treat established AKI. If fluid overload (defined as fluid accumulation >10% over baseline) develops and the patient does not respond to diuretics, persistent use of these drugs will only lead to a delay in the initiation of dialysis or ultrafiltration and an increased risk of negative patient outcomes. In that setting, early initiation of continuous renal replacement therapies may be preferable. Copyright © 2010 S. Karger AG, Basel.


Sartori M.,International Renal Research Institute of Vicenza IRRIV | Sartori M.,University of Padua | Day S.,International Renal Research Institute of Vicenza IRRIV | De Rosa S.,International Renal Research Institute of Vicenza IRRIV | And 6 more authors.
International Journal of Artificial Organs | Year: 2015

Purpose: The pharmacokinetic properties of vancomycin (VAN) and teicoplanin (TEC) may be affected by adsorption during hemofiltration as well as hemoperfusion therapies. The aim of this in vitro study was to investigate VAN and TEC removal adsorption kinetics with mass balance analysis by direct hemoperfusion (DHP) with the Lixelle S-35 cartridge (Lixelle, Kaneka Corporation, Tokyo). Methods: Mock DHP was performed for 120 min using VAN and TEC solutions (46.08 ± 0.81 and 74.79 ± 1.24 mg/l per N = 6). Clinical plasma antibiotic concentrations were circulated in a closed circuit simulating DHP using an adsorption column (Lixelle S-35) at flow rate of 250 ml/min. Samples were collected at 10, 60, and 120 min through both arterial and venous ports; drug levels were measured with particle enhanced turbidimetric inhibition immunoassay and fluorescence polarization immunoassay. All tests were performed in triplicate. Results: Results subsequent to DHP at the primary assessment interval for VAN mass was 49.06 ± 1.47 mg, indicating a significant reduction of the starting mass (94.74 ± 1.63 mg). The observed reduction of TEC levels greatly exceeded that of VAN at the first interval (10 min). At 120 min of DHP, the estimated mass adsorption of VAN was 45.68 ± 2.26 mg, while the mesured total TEC mass adsorbed was 126.86 ± 0.91 mg. Conclusions: A VAN adsorption plateau indicating the VAN loading dose may be required in patients receiving DHP with the Lixelle S-35. The total TEC mass was adsorbed subsequent to 60 min of circulation, so the loading dose should be closely considered. In addition, the Lixelle S-35 may represent an option as a rescue therapy in accidental overdose of TEC. © 2015, Wichtig Publishing.


Bagshaw S.M.,University of Alberta | Chakravarthi M.R.,Star Hospitals | Ricci Z.,Ospedale Pediatrico Bambino Gesu | Tolwani A.,University of Alabama at Birmingham | And 6 more authors.
Blood Purification | Year: 2016

Continuous renal replacement therapy (CRRT) remains the dominant form of renal support among critically ill patients worldwide. Current clinical practice on CRRT prescription mostly relies on high quality studies suggesting no impact of CRRT dose on critically ill patients' outcomes. Recent clinical practice guidelines have been developed based on these studies recommending a static prescribed CRRT dose of 20-25 ml/kg/h. There is a rationale for renewed attention to CRRT prescription/practice based on the concept of dynamic solute control adapted to the changing clinical needs of critically ill patients. In response, Acute Disease Quality Initiative convened a 17th consensus meeting centered on re-evaluation of CRRT. This work group developed 4 themes focused specifically on CRRT dose prescription, delivery and solute control that were summarized in a series of consensus statements, along with the identification of critical knowledge gaps. CRRT dose prescription and delivery can be based on effluent flow rate. Delivered dose should be routinely monitored to ensure coherence with prescribed dose. CRRT dose should be dynamic, in recognition of between- and within-patient variation in targeted solute control or unintended solute clearance. Quality measures specific for monitoring delivered CRRT dose have been proposed that require further validation, prior to implementation, into the practice of guiding optimal CRRT dosage. © 2016 S. Karger AG, Basel. Copyright: All rights reserved.


Zaragoza J.J.,International Renal Research Institute of Vicenza IRRIV
Blood Purification | Year: 2015

Introduction: One of the top research priorities in acute kidney injury is related to the timing of renal replacement therapy (RRT) initiation. The purpose was to develop an index that might serve as a standardized concept of timing of initiation of RRT. Methods: A previously described database was used. We applied a multivariable Cox regression model with backward selection to characterize parameters present in those patients who received RRT compared with those who did not receive RRT. Results: We studied 590 patients. We identified independent risk factors for RRT and a risk score was devised. The Area Under the Curve of the receiver operating characteristic curve was 0.81 (95% CI 0.74-0.86) for predicting the need for RRT. Conclusions: We have developed a simple Score (IRRIV Score) to identify patients at high risk of requiring RRT. This score may serve as a standardized definition of the timing of initiation of RRT. © 2015 S. Karger AG, Basel Copyright © 2015, S. Karger AG. All rights reserved.


Sharma A.,International Renal Research Institute of Vicenza IRRIV | Sharma A.,Indraprastha Apollo Hospitals | Mucino M.J.,International Renal Research Institute of Vicenza IRRIV | Mucino M.J.,Intensive Care Unit | And 2 more authors.
Nephron - Clinical Practice | Year: 2014

Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak 'stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use. © 2014 S. Karger AG, Basel.


PubMed | University of Padua, International Renal Research Institute of Vicenza IRRIV, Dialysis And Transplantation G Brotzu Hospital, Cincinnati Childrens Hospital and 2 more.
Type: Journal Article | Journal: Pediatric nephrology (Berlin, Germany) | Year: 2016

The CARdiorenal PEDIatric EMergency (CARPEDIEM) machine was originally designed to perform only continuous venovenous hemofiltration (CVVH) in neonatal and pediatric patients. In some cases, adequate convective clearance may not be reached because of a limited blood flow. In such conditions, the application of diffusive clearance [continuous venovenous hemodialysis (CVVHD)] would help optimize blood purification. In this study, the CARPEDIEM machine was modified to enable the circulation of dialysis through the filter allowing testing of the performance of CARPEDIEM machine in CVVHD.Three different polyethersulfone hemodialyzers (surface area=0.1m(2), 0.2m(2), and 0.35m(2), respectively) were tested in vitro with a scheduled combination of plasma flow rates (Qp=10-20-30ml/min) and dialysis fluid flow rate (Qd=5-10-15ml/min). Three sessions were performed in co-current and one in counter-current configuration (as control) for each filter size. Clearance was measured from the blood and dialysate sides and results with mass balance error greater than 5% were discarded.Urea and creatinine clearances for each plasma/dialysate combination are reported: clearance increase progressively for every filter proportionally to plasma flow rates. Similarly, clearances increase progressively with dialysate flow rates at a given plasma flow. The clearance curve tends to present a steep increase for small increases in plasma flow in the range below 10ml/min, while the curve tends to plateau for values averaging 30ml/min. As expected, the plateau is reached earlier with the smaller filter showing the effect of membrane surface-area limitation. At every plasma flow, the effect of dialysate flow increase is evident and well defined, showing that saturation of effluent was not achieved completely in any of the experimental conditions explored. No differences (p>0.05 for all values) were obtained in experiments using whole blood instead of plasma or using co-current versus counter-current dialysate flow configuration.Although plasma flow and filter surface give an important contribution to the level of clearance urea and creatinine, it appears evident that dialysate flow plays an essential role in the blood purification process, justifying the use of CVVHD versus CVVH in case of high dialysis dose requirement and/or limited blood flow rate.

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