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Acute kidney injury (AKI) affects about half of patients admitted to the intensive care unit (ICU), and worsens their short- and long-term outcomes. Apparently self-limiting AKI episodes initiate a progression toward chronic kidney disease (CKD) through cellular and molecular mechanisms that are yet to be explained. In particular, persistent AKI, defined in 2016 by the Acute Dialysis Quality Initiative as an AKI which lasts more than 48 h from its onset, has been correlated with higher morbidity and mortality, and with a higher progression to acute kidney disease (AKD) and CKD than transient AKI (i.e. AKI with a reversal within 48 h). This classification has been also used in the setting of solid organ transplantation, demonstrating similar outcomes. Due to its incidence and poor prognosis and because prompt interventions seem to change its course, persistent AKI should be recognized early and followed-up also after its recovery. However, while AKI and CKD are well-described syndromes, persistent AKI and AKD are relatively new entities. The purpose of this review is to highlight the key phases of persistent AKI in ICU patients in terms of both clinical and mechanistic features in order to offer to clinicians and researchers an updated basis from which to start improving patients' care and direct future research. [ABSTRACT FROM AUTHOR]

Several studies investigated the role of fibroblast growth factor 23 (FGF23) in the regulation of renal phosphate excretion in chronic kidney disease (CKD). However, patients with residual urine output (UO) seem to control their serum phosphorus levels better. Our aim was to determine whether FGF23 levels are influenced by dialysis modality and UO. We performed a cross-sectional study in hemodialysis (HD) and peritoneal dialysis (PD) patients. The C-terminal FGF23 (cFGF23) levels were determined in plasma with a two-site enzyme-linked immunosorbent assay. The UO collection referred to an mL/day measurement. All p values were two-sided, and the statistical significance was set at p < 0.05. We enrolled 133 patients (58 HD, 75 PD, UO 70%). The median cFGF23 was significantly higher in HD vs. PD patients (p = 0.0017) and not significantly higher in patients without UO (p = 0.12). We found a negative correlation between cFGF23 and the UO volume (p = 0.0250), but the correlation was not significant when considering the type of dialysis treatment. Phosphorus (ß = 0.21677; p = 0.0007), type of dialysis (ß = −0.68392; p = 0.0003), and creatinine (ß = 0.08130; p = 0.0133) were significant and independent predictors of cFGF23 levels. In conclusion, cFGF23 was significantly higher in HD than in PD patients. We found a significant negative correlation between cFGF23 and the residual UO volume, but the correlation was not significant considering the type of dialysis. Our study reveals that dialysis modality is an independent predictor of FGF23 levels. In particular, PD is associated with lower FGF23 levels than HD. [ABSTRACT FROM AUTHOR]

Interest in palliative care has increased in recent times, particularly in its multidisciplinary approach developed to meet the needs of patients with a life-threatening disease and their families. Although the modern concept of palliative simultaneous care postulates the adoption of these qualitative treatments early on during the life-threatening disease (and potentially just after the diagnosis), palliative care is still reserved for patients at the end of their life in most of the clinical realities, and thus is consequently mistaken for hospice care. Patients with acute or chronic kidney disease (CKD) usually experience poor quality of life and decreased survival expectancy and thus may benefit from palliative care. Palliative care requires close collaboration among multiple health care providers, patients, and their families to share the diagnosis, prognosis, realistic treatment goals, and treatment decisions. Several approaches, such as conservative management, extracorporeal, and peritoneal palliative dialysis, can be attempted to globally meet the needs of patients with kidney disease (e.g., physical, social, psychological, or spiritual needs). Particularly for frail patients, pharmacologic management or peritoneal dialysis may be more appropriate than extracorporeal treatment. Extracorporeal dialysis treatment may be disproportionate in these patients and associated with a high burden of symptoms correlated with this invasive procedure. For those patients undergoing extracorporeal dialysis, individualized goal setting and a broader concept of adequacy should be considered as the foundations of extracorporeal palliative dialysis. Interestingly, little evidence is available on palliative and end of life care for acute kidney injury (AKI) patients. In this review, the main variables influencing medical decision-making about palliative care in patients with kidney disease are described, as well as the different approaches that can fulfill the needs of patients with CKD and AKI. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication in patients undergoing cardiac surgery. Preoperative renal functional reserve (RFR) has been demonstrated to be highly predictive of CSA-AKI. We have previously demonstrated that intraparenchymal renal resistive index variation (IRRIV) measured by ultrasound (US) can identify the presence of RFR in healthy individuals. This study aimed (1) to examine the correlation between the US IRRIV test and RFR measured through the protein loading test in patients undergoing elective cardiac surgery and (2) to determine the value of the 2 methods for predicting occurrence of AKI or subclinical AKI after cardiac surgery. Methods: Consecutive patients scheduled for cardiac surgery were enrolled for this pilot study. The protein loading test and the IRRIV test were performed in all patients 2 days before cardiac surgery. Correlation between IRRIV and RFR was tested using Pearson correlation analysis. Association between presence of RFR and positive IRRIV test, presence of RFR and AKI and subclinical AKI, and positive IRRIV test and AKI and subclinical AKI was evaluated using logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the values of IRRIV for predicting RFR, RFR for predicting AKI and subclinical AKI, and IRRIV for predicting AKI and subclinical AKI. Results: Among the 31 patients enrolled, significant association was found between IRRIV and RFR (r = 0.81; 95% CI: 0.63–0.90; p < 0.01). The association between RFR and IRRIV was described in 27/31 (87.1%) patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the IRRIV test were 100, 84, 60, and 100%, respectively. In ROC curve analysis, the area under the curve (AUC) was 0.80 (95% CI: 0.64–0.96). After cardiac surgery, 1/31 (3.2%) patient had AKI and 12/31 (38.7%) had subclinical AKI. RFR predicted subclinical AKI (odds ratio [OR] = 0.93; 95% CI: 0.87–0.98; p = 0.02). The sensitivity, specificity, PPV, and NPV of the RFR were 61, 88.8, 80, and 76%, respectively; the AUC was 0.75 (95% CI: 0.59–0.91). IRRIV predicts subclinical AKI (OR = 0.79; 95% CI: 0.67–0.93; p = 0.005). The sensitivity, specificity, PPV, and NPV of the IRRIV test were 46.1, 100, 100, and 72%, respectively; the AUC was 0.73 (95% CI: 0.58–0.87). Conclusion: This pilot study suggests that a positive IRRIV test can significantly predict the presence of RFR in patients scheduled for cardiac surgery. RFR measured by the protein loading test or by the US IRRIV test can predict the occurrence of subclinical postoperative AKI. The findings of this study need to be confirmed in large patient cohorts. [ABSTRACT FROM AUTHOR]

Periodic dose assessment is quintessential for dynamic dose adjustment and quality control of continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury (AKI). The flows‐based methods to estimate dose are easy and reproducible methods to quantify (estimate) CRRT dose at the bedside. In particular, quantification of effluent flow and, mainly, the current dose (adjusted for dialysate, replacement, blood flows, and net ultrafiltration) is routinely used in clinical practice. Unfortunately, these methods are critically influenced by several external unpredictable factors; the estimated dose often overestimates the real biological delivered dose quantified through the measurement of urea clearance (the current effective delivered dose). Although the current effective delivered dose is undoubtedly more precise than the flows‐based dose estimation in quantifying CRRT efficacy, some limitations are reported for the urea‐based measurement of dose. This article aims to describe the standard of practice for dose quantification in critically ill patients with AKI undergoing CRRT in the intensive care unit. Pitfalls of current methods will be underlined, along with solutions potentially applicable to obtain more precise results in terms of (a) adequate marker solutes that should be used in accordance with the clinical scenario, (b) correct sampling procedures depending on the chosen indicator of transmembrane removal, (c) formulas for calculations, and (d) quality controls and benchmark indicators. [ABSTRACT FROM AUTHOR]

We report a 49-year-old man, without prior medical history, consulted in the emergency department with a 5 day history of cough, fever, and dysuria. He was admitted to the intensive care unit due to septic shock. Critical care management was initiated, including mechanical ventilation and vasopressors. Endotoxic shock was suspected (endotoxin activity assay [EAA] 0.75), and 2 treatments with Polymyxin B hemoperfusion (Toraymyxin®, Toray Medical Co., Ltd., Tokyo, Japan) were performed in 48 h, alternate with high-volume hemofiltration sessions. Initial blood cultures were positive for Neisseria meningitidis (serogroup B), and a lumbar puncture was deferred because of the coagulopathy and a bleeding risk. The circulatory efficiency significantly improved after the second procedure of hemoperfusion, and the treatment resulted in a marked decrease in the serum endotoxin level (EAA <0.4). However, after 48 h, tachycardia did not improve, left ventricular ejection fraction was 20%, and circulatory insufficiency progressed. Therefore, considering the involvement of septic cardiomyopathy and cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated for circulation assistance on day 3 from admission. Continuous cytokine hemoadsorption (Cytosorb®, Cytosorbent Corporation, Monmouth Junction, NJ, USA) was incorporated into a VA-ECMO circuit for 48 h without a considerable improvement. For this reason, a 72-h continuous veno-venous hemodialysis session was started in which a high cutoff filter was used. Tachycardia and myocardial dysfunction improved by day 6, and VA-ECMO was withdrawn on the tenth day. Subsequently, nutrition management and rehabilitation were performed, and the patient was transferred to the department of respiratory medicine on day 80, he was discharged from our hospital on day 113. Sequential extracorporeal therapy may be beneficial when concomitant with circulatory assistance in uncontrollable cases of septic shock using catecholamines and blockers. [ABSTRACT FROM AUTHOR]

Background: ACUsmart (Medica S.P.A., Italy) is a new-generation, continuous renal replacement therapy (CRRT) machine for critically ill patients with acute kidney injury. We designed a multicenter international pilot study to provide a description of outlines of the ACUsmart system, evaluation aspects of functionality, usability, and feasibility, discriminating reasons of possible treatment's withdrawals or discontinuations and highlighting strong and weak points of the machine. Methods: Data of 23 CRRT (and 11 plasma exchange) treatments were collected from 4 intensive care units. Parameters such as treatment duration, downtime, delivered dose, and number and type of alarms were recorded. The general perception of the machine was quantified through the administration of a survey to each component of the evaluating staff. Results: A total treatment time of 447 h was carried with ACUsmart. Eleven continuous veno-venous hemofiltration, 4 continuous veno-venous hemodialysis , and 8 continuous veno-venous hemodiafiltration were performed. The average percentage of net treatment duration with respect to total treatment duration was 92.37%. The mean prescribed dose and delivered dose were 26.33 and 24.10 mL/kg/h, respectively. In general, the machine was rated by users involved as practical and easy to use, although few components need to be slightly improved. Conclusion: ACUsmart is a new multifunctional machine that meets most of the features required in a fourth-generation CRRT equipment. [ABSTRACT FROM AUTHOR]

Worldwide, the widespread use of extracorporeal blood purification therapies (EBPTs) is progressively increasing in everyday clinical practice, particularly in critical care settings. The efficacy of EBPTs on removal of inflammatory mediators is already well established in the literature. Nonetheless, clinical research is particularly cumbersome in this setting, and many clinical trials aiming at exploring the effect of EBPTs on outcomes have failed in demonstrating consistent results regarding 28-day- or hospital-mortality rates. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of EBPTs. The philosophy behind this Italian Registry is a renewal of the concept of "clinical research" in the field of EBPTs applied to critically ill, septic patients with or without acute kidney injury. The platform used for the registry – specifically designed for research purposes and fed by clinical data prospectively observed – promotes good practice with a positive and active interaction with the physician/researcher. This interaction has favorable real-time effects for the specific patient, providing "bed-side clinical feedbacks," similarly to the decision support system. Examples of these issues are bundles reminders, suggestions for drug adjustment according to the extracorporeal clearance, clinical calculator for body mass index, or mechanical ventilation setting. The platform-physician interaction has additional useful effects on the single utilizing center, providing "mid-term, center-specific clinical feedbacks." These generally consist of clusters of data taken over a certain period, for example, regarding patients' outcome, microbiological data, or use of disposable for EBPTs. [ABSTRACT FROM AUTHOR]

Background Cardiac surgery is a leading cause of acute kidney injury (AKI). Such AKI patients may develop progressive chronic kidney disease (CKD). Others, who appear to have sustained no permanent loss of function (normal serum creatinine), may still lose renal functional reserve (RFR). Methods We extended the follow-up in the observational 'Preoperative RFR Predicts Risk of AKI after Cardiac Surgery' study from hospital discharge to 3 months after surgery for 86 (78.2%) patients with normal baseline estimated glomerular filtration rate (eGFR), and re-measured RFR with a high oral protein load. The primary study endpoint was change in RFR. Study registration at clinicaltrials.gov Identifier: NCT03092947, ISRCTN Registry: ISRCTN16109759. Results At 3 months, three patients developed new CKD. All remaining patients continued to have a normal eGFR (93.3 ± 15.1 mL/min/1.73 m2). However, when stratified by post-operative AKI and cell cycle arrest (CCA) biomarkers, AKI patients displayed a significant decrease in RFR {from 14.4 [interquartile range (IQR) 9.5 − 24.3] to 9.1 (IQR 7.1 − 12.5) mL/min/1.73 m2; P < 0.001} and patients without AKI but with positive post-operative CCA biomarkers also experienced a similar decrease of RFR [from 26.7 (IQR 22.9 − 31.5) to 19.7 (IQR 15.8 − 22.8) mL/min/1.73 m2; P < 0.001]. In contrast, patients with neither clinical AKI nor positive biomarkers had no such decrease of RFR. Finally, of the three patients who developed new CKD, two sustained AKI and one had positive CCA biomarkers but without AKI. Conclusions Among elective cardiac surgery patients, AKI or elevated post-operative CCA biomarkers were associated with decreased RFR at 3 months despite normalization of serum creatinine. Larger prospective studies to validate the use of RFR to assess renal recovery in combination with biochemical biomarkers are warranted. [ABSTRACT FROM AUTHOR]

Background: Convective therapies with high cut-off membranes (HCO) are usually not recommended because of theoretical excessive albumin loss. The aim of this in vitro study is to demonstrate the noninferior safety of pre-dilution hemodiafiltration with HCO (HCO-CVVHDF) with isotonic citrate anticoagulation (18 mmol/L) with respect to heparin anticoagulated hemodialysis with HCO (HCO-CVVHD) in terms of albumin removal and citrate load. Method: ­Albumin removal was compared in vitro between 3 pre-­dilution-HCO-CVVHDF with citrate anticoagulation and 3 ­HCO-CVVHD with heparin anticoagulation during 30-min single-pass and 180-min recirculation phases. Results: Considering concentrations and flows in the extracorporeal circuit, the transmembrane albumin removal was 2.06 (1.51; 2.09) g and 2.09 (1.9; 2.8) g respectively for HCO-CVVHDF and HCO-CVVHD, during the single-pass phase; 2.8 (2.67; 4.59) g and 2.54 (2.35; 4.67) g, respectively, for HCO-CVVHDF and HCO-CVVHD during the recirculation phase. Based on the citrate saturation coefficients, a citrate metabolic load of 8.86 mmol/h has been calculated for HCO-CVVHDF. Conclusion: HCO-CVVHDF performed with regional anticoagulation with 18 mmol/L citrate solution does not induce higher ­albumin transmembrane removal compared to HCO-CVVHD. [ABSTRACT FROM AUTHOR]

Background Although acute kidney injury (AKI) frequently complicates cardiac operations, methods to determine AKI risk in patients without underlying kidney disease are lacking. Renal functional reserve (RFR) can be used to measure the capacity of the kidney to increase glomerular filtration rate under conditions of physiologic stress and may serve as a functional marker that assesses susceptibility to injury. We sought to determine whether preoperative RFR predicts postoperative AKI. Methods We enrolled 110 patients with normal resting glomerular filtration rates undergoing elective cardiac operation. Preoperative RFR was measured by using a high oral protein load test. The primary end point was the ability of preoperative RFR to predict AKI within 7 days of operation. Secondary end points included the ability of a risk prediction model, including demographic and comorbidity covariates, RFR, and intraoperative variables to predict AKI, and the ability of postoperative cell cycle arrest markers at various times to predict AKI. Results AKI occurred in 15 patients (13.6%). Preoperative RFR was lower in patients who experienced AKI ( p < 0.001) and predicted AKI with an area under the receiver operating characteristic curve (AUC) of 0.83 (95% confidence interval [CI]: 0.70 to 0.96). Patients with preoperative RFRs not greater than 15 mL · min −1 · 1.73 m −2 were 11.8 times more likely to experience AKI (95% CI: 4.62 to 29.89 times, p < 0.001). In addition, immediate postoperative cell cycle arrest biomarkers predicted AKI with an AUC of 0.87. Conclusions Among elective cardiac surgical patients with normal resting glomerular filtration rates, preoperative RFR was highly predictive of AKI. A reduced RFR appears to be a novel risk factor for AKI, and measurement of RFR preoperatively can identify patients who are likely to benefit from preventive measures or to select for use of biomarkers for early detection. Larger prospective studies to validate the use of RFR in strategies to prevent AKI are warranted. ClinicalTrials.gov identifier: NCT03092947 , ISRCTN Registry: ISRCTN16109759. [ABSTRACT FROM AUTHOR]

Introduction: Ultrasound and colorDoppler technique, which is relatively inexpensive, rapid, non-invasive and repeatable is a powerful tool used for early diagnosis of vascular access (VA) complications in hemodialysis patients. To date a standard and widely comprehensible echocolorDoppler (ECD) protocol is not available. Materials and Methods: A simple step-by-step protocol based on anatomical and hemodynamic parameters of VA has been developed during a 3-years VA ECD follow-up. It consists of an ECD study scheme. The algorithm created involves the calculation of brachial artery flow, description of artero-venous and/or graft-vascular anastomosis and efferent vessel and/or graft. Results: The algorithm allows to formulate a medical report that takes into account both anatomic and hemodynamic parameters of the VA. Reduction of complications and the prevention of chronic complications as well as the early detection of acute problems were achieved. Discussion and Conclusion: The creation of a step-by-step protocol may simplify the multidisciplinary management of VA, its monitoring and the early diagnosis of its complications. [ABSTRACT FROM AUTHOR]

Background: To evaluate the incidence of Acute Kidney Injury (AKI) during therapeutic hypothermia (TH) and rewarming in comatose patients resuscitated from Cardiac Arrest (CA). Methods: We have performed a pilot study of consecutive comatose patients resuscitated from CA and admitted to our Intensive Care Unit (ICU) from January 2013 to March 2015. The surface cooling devices used were: 1) Arctic Sun® 5000; 2) Blanketrol® III. Data obtained at baseline and during TH included: temperature trend and rate, serum creatinine, interleukin 1-beta, interleukin 6 (IL-6), urinary Interleukin-18 (uIL-18), diuretic use, urine output, fluid balance (FB). AKI was defined according to Kidney Diseases Improving Global Outcomes (KDIGO) criteria. Results: Thirty-six patients were treated with TH out of 46 ICU admissions (78%). According to KDIGO classification, 21 (58%) had no evidence of AKI while 15 (41.7%) presented AKI during TH. In particular, the incidence of AKI was 2.8% at 24 h, 33.33% at 48 h and 30.6% at 72 h from the onset of cooling. Slower rewarming (above 600 min) was associated with with a non-significant lower incidence of AKI and with a non-significant lower levels of IL-6 and IL-18u. Only two patients required renal replacement therapy during TH (7.6%). Median cumulative FB was 2441 [437-4043] ml for all patients; 3140 [1421-4347] and 1332 [−131-3772] specifically for AKI and not-AKI patients. Conclusions: The hypothermia treatment, if not well performed, could be a double-edged sword for kidneys: whereas hypothermia may confer protection by reducing metabolism and oxygen consumption, rapid rewarming could nullify benefits leading to a worsening of kidney function and AKI. Additional clinical studies are needed to determine the optimal rewarming rate and strategy. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) are at high risk for developing critical illness and for admission to intensive care units (ICU). 'Critically ill CKD patients' frequently develop an acute worsening of renal function (i.e. acute-on-chronic, AoC) that contributes to long-term kidney dysfunction, potentially leading to end-stage kidney disease (ESKD). An integrated multidisciplinary effort is thus necessary to adequately manage the multi-organ damage of those kidney patients and contemporaneously reduce the progression of kidney dysfunction when they are critically ill. The aim of this review is to describe (1) the pathophysiological mechanisms underlying the development of AoC kidney dysfunction and its role in the progression toward ESKD; (2) the most common clinical presentations of critical illness among CKD/ESKD patients; and (3) the continuum of care for CKD/ESKD patients from maintenance hemodialysis/peritoneal dialysis to acute renal replacement therapy performed in ICU and, vice-versa, for AoC patients who develop ESKD. [ABSTRACT FROM AUTHOR]

Fluid management during continuous renal replacement therapy (CRRT) in critically ill patients is a dynamic process that encompasses 3 inter-related goals: maintenance of the patency of the CRRT circuit, maintenance of plasma electrolyte and acid–base homeostasis and regulation of patient fluid balance. In this article, we report the consensus recommendations of the 2016 Acute Disease Quality Initiative XVII conference on ‘Precision Fluid Management in CRRT’. We discuss the principles of fluid management, describe various prescription methods to achieve circuit integrity and introduce the concept of integrated fluid balance for tailoring fluid balance to the needs of the individual patient. We suggest that these recommendations could serve to develop the best clinical practice and standards of care for fluid management in patients undergoing CRRT. Finally, we identify and highlight areas of uncertainty in fluid management and set an agenda for future research. [ABSTRACT FROM AUTHOR]