Bioimpedance analysis (BIA) is a validated non-invasive technique already proven to be useful for the diagnosis, prognosis, and management of body fluids in subjects with heart failure (HF) and chronic kidney disease (CKD). Although BIA has been widely employed for research purposes, its clinical application is still not fully widespread. The aim of this review is to provide a comprehensive overview of the state of the art of BIA utilization by analyzing the clinical benefits, limitations, and potential future developments in this clinically unexplored field.

COVID-19 is strongly influenced by age and comorbidities. Acute kidney injury (AKI) is a frequent finding in COVID-19 patients and seems to be associated to mortality and severity. On the other hand, the role of kidney dysfunction in COVID-19 is still debated. We performed a retrospective study in a cohort of 174 hospitalized COVID-19 patients in Italy from March 3rd to May 21st 2020, to investigate the role of kidney dysfunction on COVID-19 severity and mortality. Moreover, we examined in depth the relationship between kidney function, age, and progression of COVID-19, also using different equations to estimate the glomerular filtration rate (GFR). We performed logistic regressions, while a predictive analysis was made through a machine learning approach. AKI and death occurred respectively in 10.2% and 19.5%, in our population. The major risk factors for mortality in our cohort were age [adjusted HR, 6.2; 95% confidence interval (CI) 1.8–21.4] and AKI [3.36 (1.44–7.87)], while, in these relationships, GFR at baseline mitigated the role of age. The occurrence of AKI was influenced by baseline kidney function, D-dimer, procalcitonin and hypertension. Our predictive analysis for AKI and mortality reached an accuracy of ≥ 94% and ≥ 91%, respectively. Our study scales down the role of kidney function impairment on hospital admission , especially in elderly patients. BIS-1 formula demonstrated a worse performance to predict the outcomes in COVID-19 patients when compared with MDRD and CKD-EPI.

To the Editor: We read with great interest the systematic review and meta-analysis by Bonanni et al., recently published in Anesthesiology, in which the authors investigated how different anesthetic agents (volatile vs. propofol) affected outcomes in patients who had undergone cardiac surgery with cardiopulmonary bypass. The main finding—that volatile anesthetics were superior to propofol with regard to long-term mortality as well as cardioprotective effects—is clinically valuable information. Some methodologic issues should be further discussed and clarified, however, and there is a need for data validation, for three main reasons which we describe below. First, we are skeptical about the authors’ assertion that the majority of the studies were at low risk of bias (Supplemental Digital Content 2, http://links.lww.com/ALN/C280, in Bonanni et al.). It is almost impossible for anesthesiologists to perform either total intravenous anesthesia or volatile induction and maintenance anesthesia blindly. Performance bias is therefore unavoidable in trials comparing these anesthesia methods, and its potential influence will be stronger in some selected studies. A recent trial reported by Landoni et al. that was included in the Bonanni et al. meta-analysis was terminated early for the reason of futility, reducing the power of the study and leading to an underestimation of the treatment effect. This may have induced bias. Because appraisal of risk of bias in included studies is an integral part of systematic review methodology, the authors should clarify why most of the trials they assessed were deemed to have low risk of bias. Second, the positive results pertaining to improved longterm survival with volatile anesthetics are driven mainly by the study of Likhvantsev et al., but the long-term mortality rate in that study was considerably higher (18.8% in the propofol group) than it was in the other studies analyzed (4.2%), which Likhvantsev et al. acknowledged in their study. In addition, we assume that their study entailed high risk of attrition bias, not low risk of bias. In the funnel plot of Figure 2, there were 52 deaths in the volatile group (437 patients) and 81 in the propofol group (431 patients) in the study by Likhvantsev et al. However, the original study of Likhvantsev et al. reported that 1-yr mortality rates were 52 of 292 (17.8%) in the sevoflurane group and 81 of 326 (24.8%) in the total intravenous anesthesia group. No explanation of the lost to follow-up rate at 1 yr was provided, but with more than a quarter of patients lost to follow-up—resulting in substantially incomplete outcome data—high risk of attrition bias is arguably inevitable. Accordingly, the authors should clearly state any assumptions or imputation methods to handle missing data, and the effects of imputation should be investigated via sensitivity analyses, which may change interpretations of the results. Last, we would like to see the overall quality of the evidence assessed via the grading of recommendations assessment, development, and evaluation (GRADE) framework for relevant outcomes. The information thus derived would be valuable to the readers of Anesthesiology.

BACKGROUND:The aim of this systematic review and meta-analysis was to assess the effect of anesthesia maintenance with volatile agents compared with propofol on both short- and long-term mortality (primary outcomes) and major clinical events in adults undergoing cardiac surgery with cardiopulmonary bypass.METHODS:Randomized clinical trials on the effects of current volatile anesthetics versus propofol in adults undergoing cardiac surgery with cardiopulmonary bypass were searched (1965 to September 30, 2019) in PubMed, the Cochrane Library, and article reference lists. A random effect model on standardized mean difference for continuous outcomes and odds ratio for dichotomous outcomes were used to meta-analyze data.RESULTS:In total, 37 full-text articles (42 studies, 8,197 participants) were included. The class of volatile anesthetics compared with propofol was associated with lower 1-yr mortality (5.5 vs. 6.8%; odds ratio, 0.76 [95% CI, 0.60 to 0.96]; P = 0.023), myocardial infarction (odds ratio, 0.60 [95% CI, 0.39 to 0.92]; P = 0.023), cardiac troponin release (standardized mean difference, -0.39 [95% CI, -0.59 to -0.18], P = 0.0002), need for inotropic medications (odds ratio, 0.40 [95% CI, 0.24 to 0.67]; P = 0.0004), extubation time (standardized mean difference, -0.35 [95% CI, -0.68 to -0.02]; P = 0.038), and with higher cardiac index/output (standardized mean difference, 0.70 [95% CI, 0.37 to 1.04]; P < 0.0001). The class of volatile anesthetics was not associated with changes in short-term mortality (1.63 vs. 1.65%; odds ratio, 1.04 [95% CI, 0.73 to 1.49]; P = 0.820) and acute kidney injury (odds ratio, 1.25 [95% CI, 0.77 to 2.03]; P = 0.358).CONCLUSIONS:In adults undergoing cardiac surgery with cardiopulmonary bypass, the class of volatile anesthetics was superior to propofol with regard to long-term mortality, as well as to many secondary outcomes indicating myocardial protection.

AbstractAmino acids are classically considered as the building blocks for the synthesis of proteins. The unique characteristics of amino acids are the presence of a free amino group in the α‐carbon and a free carboxyl group. The amino acids differ from each other with respect to their side‐chains and are classified into subgroups according to their similarity in carbon skeleton, substituent groups or a common metabolic pathway. The biosynthesis of amino acids involves several biochemical pathways in which amino acids are assembled from other precursors and is distinct from that involving lipids or carbohydrates because it includes the use of nitrogen. In addition to the 20 canonical amino acids that serve as the primary basis of protein structure and function, many noncanonical amino acids are either found in nature or are chemically created by man. Noncanonical amino acids are used as synthetic intermediates or therapeutics and may also be encoded directly into proteins to obtain useful new features, including better protein stability and increased activity.Key ConceptsAmino acids are classically considered as the building blocks from which proteins are synthesised.In addition to their structural role in proteins, the amino acid sequence dictates protein tertiary structure and affects protein function, localisation, recognition and posttranslational modification. In addition, selected amino acids serve as regulators of gene expression and the protein phosphorylation cascade, and play a role in the regulation of protein turnover, signal transduction, transport of nitrogen and carbon across the organs, and neurotransmission.The biosynthesis of amino acids involves several biochemical pathways in which amino acids are assembled from other precursors and is distinct from that involving lipids or carbohydrates because it includes the use of nitrogen.The fixation of nitrogen is a process that converts atmospheric nitrogen to a form that can be used biologically.The pathways for the synthesis of essential amino acids are present only in microorganisms and plants.Nine of 12 nonessential amino acids are synthesised from amphibolic intermediates, whereas three amino acids (tyrosine, cysteine and hydroxylysine) derive from essential amino acids. Amino acid transaminases, glutamate dehydrogenase and glutamine synthetase play a central role in the synthesis of nonessential amino acids.In the human adult, as much as 200–250 g of proteins are degraded daily, and their constituent amino acids are in large part reutilised in protein synthesis.Amino acid deficiency states can result if any of the essential amino acid is present in inadequate amounts or omitted from the diet.Alanine, glutamate and glutamine are crucial links between energy and protein metabolism. Moreover, glutamine and alanine biosynthesis in muscle provides a means for the transport of carbon from peripheral tissues to the liver for gluconeogenesis and nitrogen for ureagenesis.Besides the 20 canonical amino acids, many noncanonical amino acids are either found in nature or are chemically created by man. Noncanonical amino acids are used as synthetic intermediates or therapeutics and may also be encoded directly into proteins to obtain useful new features, including better protein stability and increased activity.

BackgroundThe main aim of this systematic review was to assess whether remote ischaemic preconditioning (RIPC) protects kidneys and the heart in cardiac surgery with cardiopulmonary bypass (CPB) and to investigate a possible role of anaesthetic agents.MethodsRandomized clinical trials (RCTs) on the effects of RIPC through limb ischaemia in adult patients undergoing cardiac surgery with CPB were searched (1965-October 2016) in PubMed, Cochrane Library and article reference lists. A random effects model on standardized mean difference (SMD) for continuous outcomes and the Peto odds ratio (OR) for dichotomous outcomes were used to meta-analyse data. Subgroup analyses to evaluate the effects of different anaesthetic regimens were pre-planned.ResultsThirty-three RCTs (5999 participants) were included. In the whole group, RIPC did not significantly reduce the incidence of acute kidney injury (AKI), acute myocardial infarction, atrial fibrillation, mortality or length of intensive care unit (ICU) and hospital stays. On the contrary, RIPC significantly reduced the area under the curve for myocardial injury biomarkers (MIBs) {SMD -0.37 [95% confidence interval (CI) -0.53 to - 0.21]} and the composite endpoint incidence [OR 0.85 (95% CI 0.74-0.97)]. In the volatile anaesthetic group, RIPC significantly reduced AKI incidence [OR 0.57 (95% CI 0.41-0.79)] and marginally reduced ICU stay. Conversely, except for MIBs, RIPC had fewer non-significant effects under propofol with or without volatile anaesthetics.ConclusionsRIPC did not consistently reduce morbidity and mortality in adults undergoing cardiac surgery with CPB. In the subgroup on volatile anaesthetics only, RIPC markedly and significantly reduced the incidence of AKI and composite endpoint as well as myocardial injury.

Background and aims: The independent role of serum uric acid (SUA) as a marker of cardio-renal risk is debated. The aim of this study was to assess the relationship between SUA, metabolic syndrome (MS), and other cardiovascular (CV) risk factors in an Italian population of hypertensive patients with a high prevalence of diabetes.Methods and results: A total of 2429 patients (mean age 62 +/- 11 years) among those enrolled in the I-DEMAND study were stratified on the basis of SUA gender specific quartiles. MS was defined according to the NCEP-ATP III criteria, chronic kidney disease (CKD) as an estimated GFR (CKD-Epi) < 60 ml/min/1.73 m(2) or as the presence of microalbuminuria (albumin-to-creatinine ratio >= 2.5 mg/mmol in men and >= 3.5 mg/mmol in women).The prevalence of MS, CKD, and positive history for CV events was 72%, 43%, and 20%, respectively. SUA levels correlated with the presence of MS, its components, signs of renal damage and worse CV risk profile. Multivariate logistic regression analysis revealed that SUA was associated with a positive history of CV events and high Framingham risk score even after adjusting for MS and its components (OR 1.10, 95% CI 1.03-1.18; P = 0.0060; OR 1.28, 95% CI 1.15-1.42; P < 0.0001). These associations were stronger in patients without diabetes and with normal renal function.Conclusions: Mild hyperuricemia is a strong, independent marker of MS and high cardio-renal risk profile in hypertensive patients under specialist care. Intervention trials are needed to investigate whether the reduction of SUA levels favorably impacts outcome in patients at high CV risk. (C) 2014 Elsevier B.V. All rights reserved.

Objective:The aim of this study was to assess the accuracy of a risk calculator that includes renal function as compared with that of the traditional Framingham Risk Score (FRS) in predicting the risk of mortality of hypertensive individuals managed in primary care.Methods:From the databases of British and Italian General Practitioners, we retrieved demographic and clinical data for 35101 UK and 27818 Italian individuals aged 35-74 years with a diagnosis of hypertension. Then, the 5-year incidence of cardiovascular events as well as all-cause and cardiovascular mortality were recorded for both samples. A comparison analysis of the performance of the Individual Data Analysis of Antihypertensive Intervention Trials (INDANA) calculator with that of FRS in predicting 5-year all-cause and cardiovascular mortality risk was made.Results:The INDANA calculator was more accurate than the FRS in predicting all-cause [c 0.038, 95% confidence interval (CI) 0.026-0.051 for United Kingdom, and 0.018, 95% CI 0.010-0.027 for Italy, both P<0.0001] and cardiovascular mortality (c 0.050, 95% CI 0.027-0.074 for United Kingdom, and 0.080, 95% CI 0.059-0.101 for Italy, both P<0.0001). By using the INDANA calculator, 20% of the UK and 10% of the Italian patients were reclassified to higher risk classes for all-cause mortality, and 25 and 28%, respectively were reclassified when cardiovascular mortality was assessed (P<0.0001 for all).Conclusion:The INDANA calculator proved to be more accurate than the FRS in predicting the risk of mortality in hypertensive patients and should be considered for systematic adoption for risk stratification of hypertensive individuals managed in primary care.

BACKGROUNDSubclinical cardiac damage has recently emerged as a potential predictor of adverse renal outcome. We therefore retrospectively evaluated the effect of left-ventricular hypertrophy (LVH), diagnosed electrocardiographically, on the renal outcome of hypertensive patients managed in primary care.METHODSFrom a historical cohort of 39,525 hypertensive individuals evaluated in 2005, we retrieved 5-year data of the 18,510 surviving subjects for whom renal follow-up was available.RESULTSThe baseline prevalences of chronic kidney disease (CKD) and LVH in the study cohort were 25.6% and 5.6%, respectively. During the 5-year follow-up, 1.4% of patients with LVH and 0.5% of those without LVH progressed to end-stage renal disease (ESRD) requiring dialysis (P < 0.01). Moreover, 25.6% of patients with LVH and 17% without LVH progressed from each stage of CKD to a more advanced stage (P < 0.01), whereas 0.9% of patients with LVH and 0.4% without LVH reached stage 5 CKD (P < 0.01). Multivariate Cox regression analysis showed that besides estimated glomerular filtration rate (eGFR) and male gender, LVH was the most significant modifiable predictor of progression to dialysis (hazard ratio (HR), 1.82; 95% CI, 1.05-3.17; P = 0.03). Multivariate logistic regression analysis also revealed LVH as a significant predictor of the risk of progression from each stage of CKD to a more advanced stage (OR, 1.24; 95% CI, 1.07-1.45; P < 0.01), as well as of progression to stage 5 CKD (OR, 1.86; 95% CI, 1.17-2.95; P < 0.01).CONCLUSIONSLeft-ventricular hypertrophy proved to be a significant predictor of adverse renal outcome in hypertensive patients managed with primary care, and systematic screening for LVH should be adopted for assessing renal risk in these patients.

Organ damage (OD) is an indicator of increased cardiovascular risk. Blood pressure variability (BPV) is related to greater incidence of events, regardless of the severity of hypertension. We investigated the relationship between ambulatory blood pressure monitoring (ABPM)-derived indices of BPV and the presence of multiple OD in primary hypertension (PH). One hundred and sixty-nine untreated patients with PH were evaluated. Systolic (SBP) and diastolic blood pressure (DBP) variability were assessed as the crude and weighted (w.) standard deviation (s.d.), and average real variability (ARV) of the mean value of 24-h, awake and asleep ABPM recordings. Left ventricular mass index, intima-media thickness, estimated-glomerular filtration rate and urinary albumin excretion were assessed as indices of cardiac, vascular and renal damage, respectively. Risk profile progressively increased starting from patients without OD to patients with only one sign of OD, and then to those with multiple OD. In addition to greater severity of the organ involvement, the only variables that were found to significantly differ between subjects with multiple and single OD were office SBP (160±14 vs 154±11 mm Hg, P=0.0423) and DBP (101±7 vs 97±8 mm Hg, P=0.0291), ambulatory arterial stiffness index (AASI) (0.60±0.10 vs 0.50±0.17, P=0.0158) and indices of BPV (24-h SBP s.d., 23±5 vs 20±6 mm Hg, P=0.0300; awake SBP s.d., 22±6 vs 19±6 mm Hg, P=0.0366; 24-h SBP w.s.d., 20±5 vs 17±5 mm Hg, P=0.0385; and 24-h SBP ARV, 18±4 vs 15±5 mm Hg, P=0.0420). All the above mentioned BPV parameters turned out to be determinants of multiple OD, regardless of several confounding variables, including BP levels. Therefore, in hypertensive patients increased SBP variability is associated with multiple signs of OD, regardless of BP values.

Background: Mixed diffusive-convective dialysis therapies offer greater removal capabilities than conventional dialysis. The aim of this study was to compare two different on-line, post-dilution hemodiafiltration (HDF) treatments with regard to achieved convective volume and middle-molecule dialysis efficiency: standard volume control (sOL-HDF) and automated control of the transmembrane pressure (TMP) (UC-HDF). Methods: We enrolled 30 ESRD patients (55.9 ± 14.0 years, 20/10 M/F) in a randomized, prospective, crossover study. The patients received a 3-month period of sOL-HDF followed by UC-HDF for a further 3 months, or vice versa, using the same dialysis machine. In sOL-HDF, fixed exchange volumes were set according to a filtration fraction greater than or equal to 25%. In UC-HDF therapy, the exchanged volume was driven by a biofeedback system controlling the TMP and its set point in a double loop. Patients maintained their treatment time, dialyzer, blood flow rate, and anticoagulant regimen unchanged throughout the study. Results: Greater convective volumes were achieved in UC-HDF than in sOL-HDF (23.8 ± 3.9 vs.19.8 ± 4.8 L; p<0.001) with high pre-dialysis Ht value (sOL-HDF 34.0 ± 4.5% and UC-HDF 34.0 ± 4.4%; p = 0.91). The average clearance values of β2m and P were higher in UC-HDF than in sOL-HDF (respectively 123 ± 24 vs. 111 ± 22 ml/min, p<0.002 and 158 ± 26 vs. 152 ± 25 ml/min, p<0.05). Moreover, the UC-HDF mode led to a significantly increased rate of call-free sessions from 88% to 97% (p<0.0001). Conclusions: This study showed that the biofeedback module, applied to the automatic control of TMP in on-line HDF, results in higher convective volumes and correspondingly higher β2m and P clearances. By making the HDF treatment more automated and less complex to perform, it significantly reduced the staff workload.

Recent studies suggest a close relationship between renal dysfunction and new onset diabetes (NOD). The aim of the study was to investigate the association between subclinical functional and structural renal abnormalities and NOD in primary hypertension (PH). This observational prospective study (9.1±2.2 years follow-up) includes 231 consecutive untreated non-diabetic patients with PH and without overt nephropathy. The primary end point was NOD. Albuminuria (albumin to creatinine ratio, ACR), glomerular filtration rate (eGFR), and renal structure and hemodynamics (ultrasound scan and Doppler) were evaluated at baseline. During 2106 person-years of follow-up, 10 patients developed diabetes (incidence rate 4.7/1000 person-years). Patients with NOD showed a higher body mass index, serum uric acid, serum creatinine and ACR, and lower eGFR and renal volume (RV) to resistive index (RI) ratio (RV/RI) at baseline, as compared with the 221 controls that did not develop diabetes. When all renal variables were taken into consideration, RV/RI was the only variable significantly related to diabetes (hazard ratio 1.04, P=0.0342). Patients in the lowest tertile of RV/RI were more likely to develop diabetes (10.4 vs 2.6 vs 0%, P=0.0044). For each s.d. decrease of RV/RI, the risk of NOD increased by 68% (P=0.0012). Subclinical functional and structural renal abnormalities are independent predictors of diabetes in PH.

BACKGROUND:Metabolic syndrome (MS) and chronic kidney disease (CKD) are well-known, independent predictors of increased cardiovascular risk. Both conditions are fairly prevalent in the general population. The aim of this study was to assess the relationship between MS or its individual components and CKD in an Italian population of hypertensive patients with normal or mildly to moderately impaired renal function under specialist care.METHODS:A total of 2,916 patients (mean age 62 ± 11 years) among those enrolled in the I-DEMAND study were taken into consideration for this analysis. MS was defined according to the NCEP-ATP III criteria. CKD was defined as an estimated GFR (abbreviated MDRD equation) <60 ml/min/1.73m2 or as the presence of microalbuminuria (mean albumin-to-creatinine ratio =2.5 mg/mmol in men and =3.5 mg/mmol in women).RESULTS:MS was present in 59% of our study patients. The prevalence of microalbuminuria, reduced GFR and CKD was 26%, 25%, and 41%, respectively. Patients with MS had higher urinary albumin excretion (p<0.0001), lower GFR (p=0.0077), and a greater prevalence of CKD (p<0.0001), even after adjusting for age and gender. Multivariate logistic regression analysis revealed that MS was significantly associated with CKD, even after adjusting for several potential confounders including its individual components (OR 1.33, 95%CI 1.03-1.71, p=0.0268). The association between MS and CKD was stronger in nondiabetic patients.CONCLUSIONS:Renal abnormalities and MS are frequently associated in hypertensive patients under specialist care. This relationship is independent of several potential confounding factors including the components of MS.