Valentina Pistolesi

Hemorrhagic complications have been reported in up to 30% of critically ill patients with AKI undergoing RRT with systemic anticoagulation. Because bleeding is associated with significantly increased mortality risk, strategies aimed at reducing hemorrhagic complications while maintaining extracorporeal circulation should be implemented. Among the alternatives to systemic anticoagulation, regional citrate anticoagulation has been shown to prolong circuit life while reducing the incidence of hemorrhagic complications and lowering transfusion needs. For these reasons, the recently published Kidney Disease Improving Global Outcomes Clinical Practice Guidelines for Acute Kidney Injury have recommended regional citrate anticoagulation as the preferred anticoagulation modality for continuous RRT in critically ill patients in whom it is not contraindicated. However, the use of regional citrate anticoagulation is still limited because of concerns related to the risk of metabolic complications, the complexity of the proposed protocols, and the need for customized solutions. The introduction of simplified anticoagulation protocols based on citrate and the development of dialysis monitors with integrated infusion systems and dedicated software could lead to the wider use of regional citrate anticoagulation in upcoming years.

BACKGROUND AND AIMS: Contrast-induced acute kidney injury (CI-AKI) is the third leading cause of hospital-acquired acute kidney injury. It is more commonly observed following intra-arterial administration of iodinated contrast media (CM) for cardiac procedures in patients with pre-existing chronic kidney disease (CKD), and is associated with increased short- and long-term morbidity and mortality. This review investigates the key current evidence on CI-AKI definition, epidemiology and pathogenesis, as a basis for recommending preventive measures that can be implemented in clinical practice. METHODS: An extensive literature search was performed to identify the relevant studies describing the epidemiology, pathogenesis, outcome and prevention of CI-AKI. RESULTS AND CONCLUSION: Pre-existing CKD, intra-arterial administration and CM volume are the most important risk factors for CI-AKI. Since risk factors for CI-AKI are well defined, and the timing of renal insult is known, patients should be carefully stratified before the administration of CM, in order to reduce the negative impact of modifiable risk factors on renal function. The intravenous administration of moderate amounts of isotonic saline solution or bicarbonate solution still represents the principal intervention with documented and acceptable effectiveness for CI-AKI prevention. More data are needed on aggressive volume expansion strategies along with diuretics, targeting forced diuresis with high urinary output. The role of antioxidant agents remains controversial, and only moderate evidence exists in favour of N-acetylcysteine. Statins could contribute to reducing the incidence of CI-AKI, although their mechanism of action is not fully ascertained. No robust data demonstrate a reduction of CI-AKI incidence by peri-procedural hemodialysis/hemofiltration; renal replacement therapies may carry instead unnecessary risks. Remote ischemic preconditioning might represent a simple, non-invasive and cost effective preventive measure for CI-AKI prevention, but few data are currently available about its clinical application in patients at high risk of CI-AKI.

to clinically significant modifications of drugs' pharmacokinetic parameters, and the need for renal replacement therapy represents a further variable that should be considered to avoid inappropriate antimicrobial therapy. The most important pharmacokinetic parameters, useful to determine the significance of extracorporeal removal of a given drug, are molecular weight, protein binding, and distribution volume. In many cases, the extracorporeal removal of antimicrobials can be relevant, with a consistent risk of underdosing-related treatment failure and/or potential onset of bacterial resistance. It should also be taken into account that renal replacement therapies are often not standardized in critically ill patients, and their impact on plasma drug concentrations may substantially vary in relation to membrane characteristics, treatment modality, and delivered dialysis dose. Thus, in this clinical scenario, the knowledge of the pharmacokinetic and pharmacodynamic properties of different antimicrobial classes is crucial to tailor maintenance dose and/or time interval according to clinical needs. Finally, especially for antimicrobials known for a tight therapeutic range, therapeutic drug monitoring is strongly suggested to guide dosing adjustment in complex clinical settings, such as septic patients with acute kidney injury undergoing renal replacement therapy.

INTRODUCTION: Regional citrate anticoagulation (RCA) is a valid option in patients at high risk of bleeding who are undergoing continuous renal replacement therapy (CRRT). The aim of this study was to evaluate, in critically ill patients with severe acute kidney injury following cardiac surgery, the efficacy and safety of RCA-continuous veno-venous hemofiltration (CVVH) using a low concentration citrate solution. METHODS: In high bleeding-risk cardiac surgery patients, we adopted, as an alternative to heparin or no anticoagulation, RCA-CVVH using a 12 mmol/l citrate solution. For RCA-CVVH settings, we developed a mathematical model to roughly estimate citrate load and calcium loss. In order to minimize calcium chloride supplementation, a calcium-containing solution was used as post-dilution replacement fluid. RESULTS: Thirty-three patients (age 70.8 ± 9.5, Sequential Organ Failure Assessment (SOFA) score 13.9 ± 2.5) were switched to RCA-CVVH from no anticoagulation CRRT. Among them, 16 patients had been previously switched from heparin to no anticoagulation because of bleeding or heparin-related complications. RCA-CVVH filter life (49.8 ± 35.4 hours, median 41, 152 circuits) was significantly longer (P < 0.0001) when compared with heparin (30.6 ± 24.3 hours, median 22, 73 circuits) or no anticoagulation (25.7 ± 21.2 hours, median 20, 77 circuits). Target circuit and systemic Ca(++) were easily maintained (0.37 ± 0.09 and 1.18 ± 0.13 mmol/l), while the persistence of a mild metabolic acidosis required bicarbonate supplementation (5.8 ± 5.9 mmol/hours) in 27 patients. The probability of circuit running at 24, 48, 72 hours was higher during RCA-CVVH (P < 0.0001), with a lower discrepancy between delivered and prescribed CRRT dose (P < 0.0001). RCA was associated with a lower transfusion rate (P < 0.02). Platelet count (P = 0.012) and antithrombin III activity (P = 0.004) increased throughout RCA-CVVH, reducing the need for supplementation. CONCLUSIONS: RCA safely prolonged filter life while decreasing CRRT downtime, transfusion rates and supplementation needs for antithrombin III and platelets. In cardiac surgery patients with severe multiple organ dysfunction syndrome, the adoption of a 12 mmol/l citrate solution may provide a suboptimal buffers supply, easily overwhelmed by bicarbonate supplementation.

BACKGROUND AND AIM OF THE STUDY: In hemodialysis patients, sedentarism is a potentially modifiable mortality risk factor. We explored whether healthcare staff's attitude towards exercise interacts with patient-perceived barriers in modifying the level of physical activity in this population. METHODS: In this prospective, cross-sectional, multicenter study we recruited 608 adult patients and 330 members of the healthcare staff in 16 hemodialysis units in Italy. We assessed patient-perceived barriers to, and healthcare staff's attitude towards, exercise by specific questionnaires. We fitted multilevel linear models to analyze the relationships of either barriers or staff's attitude, and their interaction, with a measure of patient self-reported physical activity (the Human Activity Profile-Adjusted Activity Score [HAP-AAS]), adjusting for multiple confounders. We also employed latent class analysis to dichotomize patients into those endorsing or not endorsing barriers. RESULTS: Most barriers were negatively associated with the HAP-AAS (adjusted change attributable to a given barrier ranging between -5.1 ["Feeling too old", 95% Confidence Interval: -9.4 to -0.8] and -15.6 ["Ulcers on legs and feet", 95%CI: -24.8 to -6.5]. We found a significant interaction between staff's attitude and barriers (adjusted P values ranging between 0.03 ["I do not believe that it is physician's or nurse's role providing advice on exercise to patients on dialysis"] and 0.001 ["I do not often ask patients about exercise"]). A beneficial effect of a proactive staff's attitude was evident only in patients not endorsing barriers. CONCLUSIONS: Barriers and non-proactive staff's attitude reduce physical activity in hemodialysis patients. Patients not endorsing barriers benefit the most from a proactive staff's attitude.