A retrospective analysis of the hemolysis occurrence during extracorporeal membrane oxygenation in a single center.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO)-associated hemolysis still represents a serious complication. The present study aimed to investigate those predictive factors, such as flow rates, the use of anticoagulants, and circuit connected dialysis, that might play a pivotal role in hemolysis in adult patients. METHODS: This is a retrospective single-center case series of 35 consecutive adult patients undergoing veno-venous ECMO support at our center between April 2014 and February 2020. Daily plasma-free hemoglobin (pfHb) and haptoglobin (Hpt) levels were chosen as hemolysis markers and they were analyzed along with patients' characteristics, daily laboratory findings, and corresponding ECMO system variables, as well as continuous renal replacement therapy (CRRT) when administered, looking for factors influencing their trends over time. RESULTS: Among the many settings related to the ECMO support, the presence of CRRT connected to the ECMO circuit has been found associated with both higher daily pfHb levels and lower Hpt levels. After correction for potential confounders, hemolysis was ascribable to circuit-related variables, in particular the membrane oxygenation dead space was associated with an Hpt reduction (B = -215.307, p = 0.004). Moreover, a reduction of ECMO blood flow by 1 L/min has been associated with a daily Hpt consumption of 93.371 mg/dL (p = 0.001). CONCLUSIONS: Technical-induced hemolysis during ECMO should be monitored not only when suspected but also during quotidian management and check-ups. While considering the clinical complexity of patients on ECMO support, clinicians should not only be aware of and anticipate possible circuitry malfunctions or inadequate flow settings, but they should also take into account the effects of an ECMO circuit-connected CRRT, as an equally important key factor triggering hemolysis.

Effects of preoperative high-oral protein loading on short- and long-term renal outcomes following cardiac surgery: a cohort study.

BACKGROUND: Post-cardiac surgery acute kidney injury (AKI) is associated with increased mortality. A high-protein meal enhances the renal blood flow and glomerular filtration rate (GFR) and might protect the kidneys from acute ischemic insults. Hence, we assessed the effect of a preoperative high-oral protein load on post-cardiac surgery renal function and used experimental models to elucidate mechanisms by which protein might stimulate kidney-protective effects. METHODS: The prospective "Preoperative Renal Functional Reserve Predicts Risk of AKI after Cardiac Operation" study follow-up was extended to postoperative 12 months for 109 patients. A 1:2 ratio propensity score matching method was used to identify a control group (n = 214) to comparatively evaluate the effects of a preoperative protein load and standard care. The primary endpoints were AKI development and postoperative estimated GFR (eGFR) loss at 3 and 12 months. We also assessed the secretion of tissue inhibitor of metalloproteases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), biomarkers implicated in mediating kidney-protective mechanisms in human kidney tubular cells that we exposed to varying protein concentrations. RESULTS: The AKI rate did not differ between the protein loading and control groups (13.6 vs. 12.3%; p = 0.5). However, the mean eGFR loss was lower in the former after 3 months (0.1 [95% CI - 1.4, - 1.7] vs. - 3.3 [95% CI - 4.4, - 2.2] ml/min/1.73 m2) and 12 months (- 2.7 [95% CI - 4.2, - 1.2] vs - 10.2 [95% CI - 11.3, - 9.1] ml/min/1.73 m2; p < 0.001 for both). On stratification based on AKI development, the eGFR loss after 12 months was also found to be lower in the former (- 8.0 [95% CI - 14.1, - 1.9] vs. - 18.6 [95% CI - 23.3, - 14.0] ml/min/1.73 m2; p = 0.008). A dose-response analysis of the protein treatment of the primary human proximal and distal tubule epithelial cells in culture showed significantly increased IGFBP7 and TIMP-2 expression. CONCLUSIONS: A preoperative high-oral protein load did not reduce AKI development but was associated with greater renal function preservation in patients with and without AKI at 12 months post-cardiac surgery. The potential mechanisms of action by which protein loading may induce a kidney-protective response might include cell cycle inhibition of renal tubular epithelial cells. Clinical trial registration ClinicalTrials.gov: NCT03102541 (retrospectively registered on April 5, 2017) and ClinicalTrials.gov: NCT03092947 (retrospectively registered on March 28, 2017).

Renal Outcomes of Dialysis-Dependent Acute Kidney Injury in Noncritically Ill Patients: A Retrospective Study.

INTRODUCTION: Acute kidney injury (AKI) is a common complication among hospitalized patients, potentially affecting short- and long-term clinical outcomes. In this retrospective study, we evaluated renal outcomes in noncritically ill patients who required acute hemodialysis (HD) because of an AKI episode occurring during hospitalization. METHODS: Sixty-three hemodynamically stable patients with AKI undergoing acute intermittent HD were included. Kidney function was evaluated at baseline control (pre-AKI), at AKI diagnosis and during the follow-up. According to serum creatinine and the estimated glomerular filtration rate (eGFR), we defined three clinical conditions: renal recovery, different stages of acute kidney disease (AKD), and chronic kidney disease (CKD). RESULTS: Among the 63 patients evaluated, 34 patients (54%) had a history of CKD. Six patients (10%) presented early full renal recovery. HD treatment was stopped in 38 patients (60%), while 25 patients (40%) required maintenance HD. Dialysis-independent patients presented lower comorbidity and higher baseline eGFR and delta creatinine, compared to dialysis-dependent patients. Baseline CKD, previous AKI episodes, and parenchymal causes of AKI were associated with a significant risk of dialysis dependence. At 1-month control, 15 patients (39%) presented AKD stage 0, 6 patients (16%) AKD stage 1, and 17 patients (44%) AKD stage 2-3. At 3-month control, 29 out of 38 patients recovering from AKI (76%) presented CKD. AKD stage was significantly correlated with the risk of CKD development, which, resulted higher in patients with lower baseline eGFR. CONCLUSIONS: AKI might represent a risk factor for the development of chronic kidney damage, even in noncritically ill patients.

A Role of Circuit Clotting and Strategies to Prevent It during Blood Purification Therapy with oXiris Membrane: An Observational Multicenter Study.

INTRODUCTION: Membrane fouling is a significant complication potentially reducing clinical effects of extracorporeal blood purification (EBP) in critically ill septic patients with acute kidney injury. Although fascinating, the effect of heparin coating in preventing membrane fouling is currently unknown. This multicenter prospective study aims to preliminary describe the incidence, associated factors, and clinical consequences of premature circuit clotting in a cohort of adult critically ill septic patients treated with EBP using a high biocompatible heparin-coated hemodiafilter characterized by advanced adsorption properties. METHODS: This study was a retrospective analysis of prospectively entered data in the oXirisNet Registry; overall, 97 septic patients undergoing EBP with oXiris between May 2019 and March 2020 were enrolled in this study. Patients were divided into two groups according to the occurrence of filter clotting (premature vs. nonpremature). Logistic regression analysis was used to identify factors associated with premature circuit clotting. RESULTS: Premature clotting occurred in 18 (18.6%) patients. Results of the multivariate logistic regression analysis demonstrated that hematocrit (p = 0.02, odds ratio [OR] 1.15 [1.05; 1.30]), serum procalcitonin (PCT) (p = 0.03, OR 1.1 [1.05; 1.2]), and anticoagulation strategy (p = 0.05 at Wald's test) were independent predictors of circuit clotting. Systemic anticoagulation (p = 0.02, OR 0.03 [0.01; 0.52]) and regional citrate anticoagulation (p = 0.10, OR 0.23 [0.04; 1.50]) were both protective factors if compared to no-anticoagulation strategy. Patients with nonpremature circuit clotting showed more rapid recovery from hemodynamic instability, pulmonary hypo-oxygenation, and electrolyte disorders and greater improvement of inflammatory markers and SOFA scores. CONCLUSION: Although in this study the incidence of premature circuit clotting was relatively low (18.6%) compared to previously reported values (54%), membrane clotting in adult critically ill septic patients could cause clinically relevant interferences with treatment performances. Prevention of clotting should be based on avoiding higher patients' hematocrit, high serum PCT, and no-anticoagulation strategy which resulted as independent predictors of circuit clotting.

Clinical Assessment of Continuous Hemodialysis with the Medium Cutoff EMiC®2 Membrane in Patients with Septic Shock.

INTRODUCTION: At the time of renal replacement therapy, approximately 20% of critically ill patients have septic shock. In this study, medium cutoff (MCO) continuous venovenous hemodialysis (CVVHD) was compared to high-flux membrane continuous venovenous hemodiafiltration (CVVHDF) in terms of hemodynamic improvement, efficiency, middle molecule removal, and inflammatory system activation. METHODS: This is a monocenter crossover randomized study. Between December 31, 2017, and December 31, 2019, 20 patients with septic shock and stage 3 acute kidney injury (AKI) admitted to 2 Italian ICUs were enrolled. All patients underwent CVVHD with Ultraflux® EMiC®2 and CVVHDF with AV1000S® without washout. Each treatment lasted 24 h. RESULTS: Compared to AV1000S®-CVVHDF, EMIC®2-CVVHD normalized cardiac index (ß = -0.64; p = 0.02) and heart rate (ß = 5.72; p = 0.01). Interleukin-8 and myeloperoxidase removal were greater with AV1000S®-CVVHDF than with EMiC®2-CVVHD (ß = 0.35; p < 0.001; ß = 0.43; p = 0.03, respectively). Leukocytosis improved over 24 h in EMiC®2-CVVHD-treated patients (ß = 4.13; p = 0.03), whereas procalcitonin levels decreased regardless of the modality (ß = 0.89; p = 0.01) over a 48-h treatment period. Reduction rates, instantaneous plasmatic clearance of urea, creatinine, and ß2-microglobulin were similar across modalities. ß2-Microglobulin removal efficacy was greater in the EMiC®2 group (ß = 0-2.88; p = 0.002), while albumin levels did not differ. Albumin was undetectable in the effluent in both treatments. DISCUSSION: In patients with septic shock and severe AKI, the efficacy of uremic toxin removal was comparable between MCO-CVVHD and CVVHDF. Further, MCO-CVVHD was associated with improved hemodynamics. Fraction of filtration and transmembrane pressure reduction and the maintenance of equal efficacy might be the key features of CVVHD with MCO membranes in critically ill patients.

Vancomycin concentrations during cardiopulmonary bypass in pediatric cardiac surgery: a prospective study.

INTRODUCTION: Few data are available regarding intraoperative plasma concentrations of vancomycin administered as prophylaxis in pediatric cardiac surgery. The aims of this study were to investigate during pediatric cardiac surgery with cardiopulmonary bypass(CPB) the attainment of the area-under-the-curve of the vancomycin serum concentrations versus time over surgery to minimum inhibitory concentration ratio(AUCintra/MIC) of 400 (mg × h)/l and/or a target concentration of 15-20 mg/l. METHODS: In a prospective study, 40 patients divided into four subgroups (neonates, infants, children <10 years-old, ⩾10 years-old) undergoing cardiac surgery with cardiopulmonary bypass (CPB) were enrolled. A slow vancomycin bolus of 20 mg/kg, up to a maximum dose of 1000 mg was administered before skin incision and a further dose of 10 mg/kg (up to 500 mg) at CPB start. Vancomycin samples were collected intraoperatively at four time points. RESULTS: The median (interquartile range) age was 241.5 days (47-3898) and the median weight was 7.1 kg (3.1-37). The median AUCintra/MIC was 254.73 (165.89-508.06). In 11 patients the AUCintra/MIC target was not reached. Neonates displayed the lowest AUCintra/MIC values, and these were significantly lower than those of children ⩾10 years old (p = 0.02). Vancomycin concentrations were above the maximal target of 20 mg/l in 82.5% and 80% of patients at surgery and CPB start, respectively. At CPB and surgery end, 42.5% of patients showed vancomycin concentrations above 20 mg/l and 42.5% below 15 mg/l. Patients⩾10 years old showed the highest peak values whereas neonates were those with the lowest troughs. AUCintra/MIC correlated with age(r:0.36, p = 0.02), weight(r:0.35, p = 0.03), intraoperative protein value(r:0.40, p = 0.01), CPB priming volume/kg(r:-0.33, p = 0.04), CPB duration(r:0.36, p = 0.02) and vancomycin troughs(r:0.35, p = 0.04). CONCLUSIONS: An AUCintra/MIC ⩾400 target was not reached in one-quarter of children undergoing heart surgery. Vancomycin peaked before the start of surgery and neonates were those with the lowest troughs. Vancomycin concentrations are affected by CPB hemodilution and by patients' age and weight.

Immunoglobulin deficiency as an indicator of disease severity in patients with COVID-19.

Despite the pandemic status of COVID-19, there is limited information about host risk factors and treatment beyond supportive care. Immunoglobulin G (IgG) could be a potential treatment target. Our aim was to determine the incidence of IgG deficiency and associated risk factors in a cohort of 62 critically ill patients with COVID-19 admitted to two German ICUs (72.6% male, median age: 61 yr). Thirteen (21.0%) of the patients displayed IgG deficiency (IgG < 7 g/L) at baseline (predominant for the IgG1, IgG2, and IgG4 subclasses). Patients who were IgG-deficient had worse measures of clinical disease severity than those with normal IgG levels (shorter duration from disease onset to ICU admission, lower ratio of [Formula: see text] to [Formula: see text], higher Sequential Organ Failure Assessment score, and higher levels of ferritin, neutrophil-to-lymphocyte ratio, and serum creatinine). Patients who were IgG-deficient were also more likely to have sustained lower levels of lymphocyte counts and higher levels of ferritin throughout the hospital stay. Furthermore, patients who were IgG-deficient compared with those with normal IgG levels displayed higher rates of acute kidney injury (76.9% vs. 26.5%; P = 0.001) and death (46.2% vs. 14.3%; P = 0.012), longer ICU [28 (6-48) vs. 12 (3-18) days; P = 0.012] and hospital length of stay [30 (22-50) vs. 18 (9-24) days; P = 0.004]. Univariable logistic regression showed increasing odds of 90-day overall mortality associated with IgG-deficiency (odds ratio 5.14, 95% confidence interval 1.3-19.9; P = 0.018). IgG deficiency might be common in patients with COVID-19 who are critically ill, and warrants investigation as both a marker of disease severity as well as a potential therapeutic target.

Hemoperfusion with CytoSorb as Adjuvant Therapy in Critically Ill Patients with SARS-CoV2 Pneumonia.

We report a preliminary experience of adjuvant therapy with Hemoperfusion (HP) in patients with Severe Acute Respiratory Syndrome-CoronaVirus 2 (SARS-CoV2) pneumonia. Currently, there are no approved treatments for CoronaVirus Disease 19 (COVID-19); however, therapeutic strategies based on the preclinical evidence include supportive measures, such as oxygen supplementation, antiviral, and anticoagulant agents. Despite these treatments, 10% of patients worsen and develop severe acute respiratory distress syndrome (ARDS). Since the pathogenic mechanism of ARDS is an uncontrolled inflammatory state, we speculate that removing inflammation effectors from blood may contrast tissue injury and improve clinical outcome. In a scenario of dramatic medical emergency, we conducted an observational study on 9 consecutive patients hospitalized in COVID Intensive Care Unit, where 5 of 9 consecutive patients were treated with HP, due to the emergency overload made it impossible to deliver blood purification in the other 4 patients. COVID-19 was diagnosed through the identification of virus sequences by reverse transcription-PCR on respiratory specimens. All patients had severe pneumonia requiring continuous positive airway pressure. HP was started in all patients 6-7 days after hospital admission. The treated patients (T) received 2 consecutive sessions of HP using CytoSorb cartridge. Our results show a better clinical course of T compared to control patients (C), in fact all T except 1 survived, and only 2 of them were intubated, while all C required intubation and died. Lymphocytopenia worsened in C but not in T. C-reactive protein decreased in both patients, but to a greater extent in T. IL-6, IL-8, and TNF-α decreased after HP, IL-10 did not change. Respiratory function remained stable and did not worsen in T compared to C. The limited sample size and observational study design preclude a sound statement about the potential effectiveness of HP in COVID-19 patients, but our experience suggests a potential therapeutic role of adjuvant CytoSorb HP in the early course of CO-VID-19 pneumonia. A randomized clinical trial is ongoing.

Blood purification therapy with a hemodiafilter featuring enhanced adsorptive properties for cytokine removal in patients presenting COVID-19: a pilot study.

BACKGROUND: Systemic inflammation in COVID-19 often leads to multiple organ failure, including acute kidney injury (AKI). Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBP) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions in COVID-19. AIM: Describe overtime variations of clinical and biochemical features of critically ill patients with COVID-19 treated with EBP with a hemodiafilter characterized by enhanced cytokine adsorption properties. METHODS: An observational prospective study assessing the outcome of patients with COVID-19 admitted to the ICU (February to April 2020) treated with EBP according to local practice. Main endpoints included overtime variation of IL-6 and multiorgan function-scores, mortality, and occurrence of technical complications or adverse events. RESULTS: The study evaluated 37 patients. Median baseline IL-6 was 1230 pg/ml (IQR 895) and decreased overtime (p < 0.001 Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 24 h (p = 0.001). The reduction in serum IL-6 concentrations correlated with the improvement in organ function, as measured in the decrease of SOFA score (rho = 0.48, p = 0.0003). Median baseline SOFA was 13 (IQR 6) and decreased significantly overtime (p < 0.001 at Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 48 h (median 8 IQR 5, p = 0.001). Compared to the expected mortality rates, as calculated by APACHE IV, the mean observed rates were 8.3% lower after treatment. The best improvement in mortality rate was observed in patients receiving EBP early on during the ICU stay. Premature clotting (running < 24 h) occurred in patients (18.9% of total) which featured higher effluent dose (median 33.6 ml/kg/h, IQR 9) and higher filtration fraction (median 31%, IQR 7.4). No electrolyte disorders, catheter displacement, circuit disconnection, unexpected bleeding, air, or thromboembolisms due to venous cannulation of EBP were recorded during the treatment. In one case, infection of vascular access occurred during RRT, requiring replacement. CONCLUSIONS: EBP with heparin-coated hemodiafilter featuring cytokine adsorption properties administered to patients with COVID-19 showed to be feasible and with no adverse events. During the treatment, patients experienced serum IL-6 level reduction, attenuation of systemic inflammation, multiorgan dysfunction improvement, and reduction in expected ICU mortality rate.

Brief Report: A Case of Tramadol Overdose: Extracorporeal Life Support and Hemoperfusion as Life-Saving Treatment.

We describe the case of a 49-year-old woman with a Tramadol intoxication associated with multiorgan failure. Veno-arterial femoro-femoral extracorporeal life support (VA-ECLS) and hemoperfusion (HP) were used as rescue treatments. The emergency medical service found a woman at home unconscious. Once in the hospital, she was intubated and catecholamines support was immediately started for a severe shock. Brain CT was normal, whereas EEG revealed a metabolic encephalopathy pattern. Toxic levels of Tramadol and Quetiapine were detected. VA-ECLS was implanted due to persistent multiorgan failure, and HP with a charcoal cartridge was set to increase the Tramadol clearance. To quantify the charcoal cartridge's removal efficiency of Tramadol, Tramadol concentration was measured before and after the cartridge and before and after the treatment in the patient's blood. The charcoal cartridge showed good extraction ratio during the treatment and no significant rebound effect. VA-ECLS and HP allowed the patient to be weaned from vasoconstrictors and the resolution of the organ failures. These treatments might be lifesaving in the Tramadol intoxication.

Tissue inhibitor metalloproteinase-2 (TIMP-2) • IGF-binding protein-7 (IGFBP7) levels are associated with adverse outcomes in patients in the intensive care unit with acute kidney injury.

The G1 cell cycle inhibitors tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as novel biomarkers for the prediction of moderate to severe acute kidney injury (AKI) risk. However, the prognostic value of [TIMP-2]•[IGFBP7] in predicting adverse outcomes in intensive care unit (ICU) patients with AKI was not previously described. To evaluate this, we conducted a cohort study, measuring [TIMP2]•[IGFBP7] levels in critically ill patients admitted to the ICU and classified the patients as NephroCheck (NC) (+) or NC (-) according to [TIMP-2]•[IGFBP7] values and AKI (+) or AKI (-) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We then evaluated the incidence of continuous renal replacement therapy initiation, all-cause mortality and a composite endpoint of both in the four groups. Baseline [TIMP-2]•[IGFBP7] values were available for 719 patients, of whom 239 developed AKI and 151 met the composite endpoint. Compared to NC (-)/AKI (+) patients, NC (+)/AKI (+) patients had a significant risk of ICU mortality and the composite endpoint. Kaplan-Meier curves showed that the survival estimate for the composite endpoint of NC (+)/AKI (+) patients was 34.4%; significantly worse than NC (-)/AKI (+) patients (67.4%). Multivariate analyses showed strong association between NC positivity and the composite endpoint. The inflammatory marker, procalcitonin, was an additional prognostic biomarker to compare and confirm the incremental value of NephroCheck. No association between procalcitonin and the composite endpoint was found, especially in patients with AKI, suggesting that NephroCheck may be more kidney specific. Thus, the [TIMP-2]•[IGFBP7] values can serve to identify patients with AKI at increased risk for adverse outcomes in the ICU.

Alterations in Doppler-derived renal venous stasis index during recompensation of right heart failure and fluid overload in a patient with pulmonary hypertension.

Renal congestion is becoming recognized as a potential contributor to cardiorenal syndromes. Adequate control of congestion with simultaneous preservation of renal function has been proposed as a central goal of the management of heart failure. We report our care of a 48-year-old woman suffering from right heart failure and massive fluid overload due to severe pulmonary hypertension secondary to a combination of left-heart disease and status after recurrent pulmonary embolisms. Alterations in Doppler-derived intrarenal venous flow patterns and a novel renal venous stasis index were used to evaluate improvement in renal venous congestion during recompensation. Due to refractory congestion despite optimal medical treatment and continuous veno-venous hemodialysis, a peritoneal dialysis catheter was placed to relieve the massive ascites. The paracentesis of ascites led to a significant loss of weight, normalization of hydration status with subsequent termination of continuous veno-venous hemodialysis, and a significant improvement in clinical and echocardiographic parameters. Renal Doppler ultrasonography showed continuous improvement in intrarenal venous flow patterns and the renal venous stasis index indicative of effective decongestion up to a normal intrarenal venous flow pattern and renal venous stasis index. Furthermore, residual renal function increased during follow-up. This case demonstrates the feasibility of renal Doppler ultrasonography as a simple, non-invasive, and integrative measure of renal congestion. The renal venous stasis index and intrarenal venous flow patterns may be useful to evaluate the treatment response and to guide therapy in patients with right heart failure.

Persistent decrease of renal functional reserve in patients after cardiac surgery-associated acute kidney injury despite clinical recovery.

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.

Persistent pollutants: focus on perfluorinated compounds and kidney.

PURPOSE OF REVIEW: There is increasing interest in the environmental and human damage caused by pollutants. Big efforts are continuously made to monitor their levels and identify safe thresholds. For this purpose, an essential step is to prioritize harmful substances and understand their effect on human body. Perfluorinated compounds (PFCs) deserve particular attention because of their wide diffusion and potential correlation with different diseases including glucose intolerance, hyperlipidaemia, thyroid diseases, gestational diabetes mellitus and hypertension, testicular and genitourinary cancer as well as impaired kidney function. This review focuses on the renal effects of PFCs, with the attempt to clarify their occurrence and pathogenetic mechanisms. RECENT FINDINGS: We reviewed MEDLINE and EMBASE citations between 31 October 2017 and 31 May 2019 and selected human studies measuring PFCs exposure, kidney function markers and the ability of haemodialysis to remove PFCs from the circulating blood. It has been currently clarified that exposure to PFCs is linked with an impaired kidney function and that they can be removed by blood purification. SUMMARY: Further studies are required on the potential synergic negative effect of PFCs co-exposure with other pollutants as well as animal studies about the removal capacity of different haemodialysis membranes.

Predicting Acute Kidney Injury in Intensive Care Unit Patients: The Role of Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor-Binding Protein-7 Biomarkers.

BACKGROUND: Acute kidney injury (AKI) diagnosis is based on a rise in serum creatinine and/or fall in urine output. It has been shown that there are patients that fulfill AKI definition but do not have AKI, and there are also patients with evidence of renal injury who do not meet any criteria for AKI. Recently the innovative and emerging proteomic technology has enabled the identification of novel biomarkers that allow improved risk stratification. METHODS: Tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7) were measured to a cohort of 719 consecutive patients admitted to Intensive Care Unit (ICU). The primary endpoint was the evaluation of clinical performances of the biomarkers focusing on the probability do develop AKI in the first 7 days. RESULTS: The Kaplan-Meier analysis considering the first 7 days of ICU stay suggested a lower risk of developing AKI (p < 0.0001) for patients with a negative (<0.3; TIMP-2*IGFBP7) test. CONCLUSION: (TIMP-2*IGFBP7) at ICU admission has a good performance in predicting AKI, especially in the first 4 days in ICU.

Kinetics of Linezolid in Continuous Renal Replacement Therapy: An In Vitro Study.

BACKGROUND: Continuous veno-venous hemofiltration (CVVH) could affect the pharmacokinetic profile of linezolid (LZD). The aim of this study was to evaluate the LZD extracorporeal clearance using an in vitro CVVH model. METHODS: A sham miniaturized CVVH circuit (CARPEDIEM; Bellco, Mirandola, Italy) was set up with a polysulfone hemofilter (0.25 m; cutoff 50,000 Da) for 240 minutes using normal saline solution (0.9% wt/vol NaCl) and blood (n = 6) spiked with LZD. Drug solution samples were collected during CVVH at 10, 30, 60, 120, and 240 minutes. LZD levels were measured by high-performance liquid chromatography. RESULTS: Results were used to estimate pharmacokinetic parameters. The LZD baseline level decreased from 17.24 ± 0.54 to 9.73 ± 4.85 mg/L and from 11.75 ± 0.08 to 5.01 ± 0.67 mg/L in the first 10 minutes, and then increased to 13.2 ± 3.10 and 7.4 ± 0.71 mg/L in normal saline solution and blood, respectively. Mass balance analysis reported a rapid adsorption of LZD onto a polysulfone membrane followed by its release: a rebound phenomenon occurred. CONCLUSIONS: Although further studies are necessary to clarify this phenomenon, LZD level variations observed in our study should be considered to avoid antimicrobial underexposure. Several strategies are available for adjusting the dosage regimen of LZD, but therapeutic drug monitoring is highly recommended when it is used.

Impact of hyperhydration on the mortality risk in critically ill patients admitted in intensive care units: comparison between bioelectrical impedance vector analysis and cumulative fluid balance recording.

BACKGROUND: Studies have demonstrated a positive correlation between fluid overload (FO) and adverse outcomes in critically ill patients. The present study aims at defining the impact of hyperhydration on the Intensive Care Unit (ICU) mortality risk, comparing Bioelectrical Impedance Vector Analysis (BIVA) assessment with cumulative fluid balance (CFB) recording. METHODS: We performed a prospective, dual-centre, clinician-blinded, observational study of consecutive patients admitted to ICU with an expected length of ICU stay of at least 72 hours. During observational period (72-120 hours), CFB was recorded and cumulative FO was calculated. At the admission and daily during the observational period, BIVA was performed. We considered FO between 5% and 9.99% as moderate and a FO ≥ 10% as severe. According to BIVA hydration scale of lean body mass, patients were classified as normohydrated (>72.7%-74.3%), mild (>71%-72.7%), moderate (>69%-71%) and severe (≤ 69%) dehydrated and mild (>74.3%-81%), moderate (>81%-87%) and severe (>87%) hyperhydrated. Two multivariate logistic regression models were performed: the ICU mortality was the response variable, while the predictor variables were hyperhydration, measured by BIVA (BIVA model), and FO (FO model). A p-value <0.05 was considered to indicate statistical significance. RESULTS: One hundred and twenty-five patients were enrolled (mean age 64.8 ± 16.0 years, 65.6% male). Five hundred and fifteen BIVA measurements were performed. The mean CFB recorded at the end of the observational period was 2.7 ± 4.1 L, while the maximum hydration of lean body mass estimated by BIVA was 83.67 ± 6.39%. Severe hyperhydration measured by BIVA was the only variable found to be significantly associated with ICU mortality (OR 22.91; 95% CI 2.38-220.07; p < 0.01). CONCLUSIONS: The hydration status measured by BIVA seems to predict mortality risk in ICU patients better than the conventional method of fluid balance recording. Moreover, it appears to be safe, easy to use and adequate for bedside evaluation. Randomized clinical trials with an adequate sample size are needed to validate the diagnostic properties of BIVA in the goal-directed fluid management of critically ill patients in ICU.

Nomenclature for renal replacement therapy in acute kidney injury: basic principles.

This article reports the conclusions of a consensus expert conference on the basic principles and nomenclature of renal replacement therapy (RRT) currently utilized to manage acute kidney injury (AKI). This multidisciplinary consensus conference discusses common definitions, components, techniques, and operations of the machines and platforms used to deliver extracorporeal therapies, utilizing a "machine-centric" rather than a "patient-centric" approach. We provide a detailed description of the performance characteristics of membranes, filters, transmembrane transport of solutes and fluid, flows, and methods of measurement of delivered treatment, focusing on continuous renal replacement therapies (CRRT) which are utilized in the management of critically ill patients with AKI. This is a consensus report on nomenclature harmonization for principles of extracorporeal renal replacement therapies. Devices and operations are classified and defined in detail to serve as guidelines for future use of terminology in papers and research.

Copeptin levels and kidney function in ADPKD: case-control study.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Studies have suggested a possible prognostic role of copeptin in determining the rate of progressive kidney function decline in ADPKD patients. However, it remains unresolved whether the changes in copeptin levels are specific for ADPKD or merely reflect a decline in glomerular filtration rate (GFR) regardless of the etiology of chronic kidney disease (CKD). METHODS: We performed a case-control study in ADPKD and non-ADPKD (control) patients. Patients were categorized based on the GFR-category (G-stage, KDIGO). We evaluated urea, creatinine, cystatin C, and copeptin in plasma and correlated these levels with estimated glomerular filtration rate (eGFR) (CKD-EPI). All p-values were two sided, and p < 0.05 was considered as statistically significant. RESULTS: We enrolled 112 ADPKD and 112 control patients. The median copeptin level was 10.72 (interquartile range (IQR) 5.21 - 26.21) pmol/L in the ADPKD group and 12.32 (IQR 4.47 - 30.73) pmol/L in the control group. The median copeptin level increased according to the G-stage in a progressive fashion and remained statistically significant across all G-stages and in both groups. Copeptin levels were not significantly different between ADPKD and control groups. We found a significant inverse correlation between copeptin level and eGFR (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) in the ADPKD, r = -0.81 (p < 0.001), and in the control group, r = -0.76 (p < 0.001). CONCLUSIONS: Copeptin levels seem to be strongly correlated with renal function rather than the presence of ADPKD. Further prospective studies need to evaluate its role as a prognostic marker in the early stage of CKD for ADPKD progression.

The Influence of Hemodialysis on T Regulatory Cells: A Meta-Analysis and Systematic Review.

AIMS: The study aimed to determine whether the available literature supports a positive or negative influence of dialysis on regulatory T-cells (Tregs). METHODS: We performed a systematic search and a meta-analysis. Mean differences in Tregs number of chronic kidney disease stages G5 on dialysis patients (CKD G5D) and healthy controls (HCs) were compared. Random effects model was applied. The software used was general package for meta-analysis (version 4.3-0, depends R (≥2.9.1)). RESULTS: Five studies were included in the meta-analysis. The mean difference in percentage of Tregs on CD4+ T-cells between CKD G5D and HCs was not statistically different. Moreover, CKD GFR stages G5 not on dialysis (CKD G5) versus HC (p = 0.002; mean difference in Treg percentage was -2.47% in CKD G5 vs. HC) and CKD G5 versus CKD G5D (not significant). CONCLUSION: This meta-analysis demonstrates an association between the uremic state and lower Tregs, and supports the hypothesis that hemodialysis alter Tregs. Our findings highlight the need for new clinical studies. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=449242.