Extracorporeal blood purification in patients with liver failure: Considerations for the low-and-middle income countries of Latin America.

Severe liver failure is common in Low-and-Medium Income Countries (LMIC) and is associated with a high morbidity, mortality and represents an important burden to the healthcare system. In its most severe state, liver failure is a medical emergency, that requires supportive care until either the liver recovers or a liver transplant is performed. Frequently the patient requires intensive support until their liver recovers or they receive a liver transplant. Extracorporeal blood purification techniques can be employed as a strategy for bridging to transplantation or recovery. The most common type of extracorporeal support provided to these patients is kidney replacement therapy (KRT), as acute kidney injury is very common in these patients and KRT devices more readily available. However, because most of the substances that the liver clears are lipophilic and albumin-bound, they are not cleared effectively by KRT. Hence, there has been much effort in developing devices that more closely resemble the clearance function of the liver. This article provides a review of various non-biologic extracorporeal liver support devices that can be used to support these patients, and our perspective keeping in mind the needs and unique challenges present in the LMIC of Latin America.

Use of hepatic support with MARS in a patient with SARS-CoV-2 Pneumonia, in treatment with ECMO and CRRT therapies: Case Report.

Extracorporeal Membrane Oxygenation (ECMO) therapy had an important role in the treatment of severe COVID-19 pneumonia, where invasive mechanical ventilation was not enough to provide correct oxygenation to various organ systems. However, there are other extracorporeal technologies, such as the Molecular Absorbent Recirculation System (MARS) and Continuous Renal Replacement Therapy (CRRT), that provide temporal support for any critical patient. The following case describes a 60-year-old man with severe Acute Respiratory Distress Syndrome (ARDS), who needed ECMO therapy. During the critical days of hospitalization, CRRT was used, but a sudden hyperbilirubinemia ensued. Consequently, MARS therapy was initiated; followed by an improvement of bilirubin levels. Additional studies are needed to establish the possible benefits of the combination of MARS therapy and ECMO; however, we detected that concomitantly, there was a decrease in other laboratory parameters such as acute phase reactants. Even though, no change in clinical course was observed, as shown in some studies.

Neurogenic diabetes insipidus in a critical patient with COVID-19 pneumonia in treatment with extracorporeal membrane oxygenation: a case report.

The following case report analyses a patient with extracorporeal membrane oxygenation (ECMO), who suffered from a severe Acute Respiratory Distress Syndrome (ARDS) due to COVID-19 pneumonia. ARDS is defined as a diffuse and inflammatory injury of the lungs; classifying this as severe when the ratio of arterial oxygen tension to a fraction of inspired oxygen (PaO2/FiO2) is equal to or lower than 100 mmHg. To decide if the patient was suitable for the use of ECMO therapy, the ELSO criteria were used; and in this case, the patient matched with the criteria of hypoxemic respiratory failure (with a PaO2/FiO2 < 80 mmHg) after optimal medical management, including, in the absence of contraindications, a trial of prone positioning. During hospitalization, the patient presented a Central Diabetes Insipidus (CDI), probably explained by the damage hypoxia generated on the central nervous system. There are few reports of this complication produced by COVID-19. The case is about a 39-year-old woman, who started with ECMO 6 days after the beginning of Invasive Mechanical Ventilation (IMV), because of a severe ARDS. On the fifth day of ECMO, the patient started with a polyuria of 7 L in 24 h. A series of paraclinical studies were made, but no evidence of central nervous system lesions was found. After treatment with desmopressin was initiated and the ARDS was solved, polyuria stopped; with this, CDI was diagnosed. There are many complications secondary to the evolution of COVID-19 infection, and some of them are not yet well explained.

Association of Country Income Level With the Characteristics and Outcomes of Critically Ill Patients Hospitalized With Acute Kidney Injury and COVID-19.

Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods: This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results: Among patients with COVID-19 admitted to the intensive care unit, AKI incidence was highest in patients in LLMIC, followed by patients in upper-middle income countries (UMIC) and high-income countries (HIC) (53%, 38%, and 30%, respectively), whereas dialysis rates were lowest among patients with AKI from LLMIC and highest among those from HIC (27% vs. 45%). Patients with AKI in LLMIC had the largest proportion of community-acquired AKI (CA-AKI) and highest rate of in-hospital death (79% vs. 54% in HIC and 66% in UMIC). The association between AKI, being from LLMIC and in-hospital death persisted even after adjusting for disease severity. Conclusions: AKI is a particularly devastating complication of COVID-19 among patients from poorer nations where the gaps in accessibility and quality of healthcare delivery have a major impact on patient outcomes.

Urea Reduction in Acute Kidney Injury and Mortality Risk.

INTRODUCTION: Urea is a toxin present in acute kidney injury (AKI). We hypothesize that reduction in serum urea levels might improve clinical outcomes. We examined the association between the reduction in urea and mortality. METHODS: Patients with AKI admitted to the Hospital Civil de Guadalajara were enrolled in this retrospective cohort study. We create 4 groups of urea reduction ratio (UXR) stratified by their decrease in urea from the highest index value in comparison to the value on day 10 (0%, 1-25%, 26-50%, and >50%), or at the time of death or discharge if prior to 10 days. Our primary endpoint was to observe the association between UXR and mortality. Secondary observations included determination of which types of patients achieved a UXR >50%, whether the modality of kidney replacement therapy (KRT) effected changes in UXR, and if serum creatinine (sCr) value changes were similarly associated with patient mortality. RESULTS: A total of 651 AKI patients were enrolled. The mean age was 54.1 years, and 58.6% were male. AKI 3 was present in 58.5%; the mean admission urea was 154 mg/dL. KRT was started in 32.4%, and 18.9% died. A trend toward decreased risk of death was observed in association with the magnitude of UXR. The best survival (94.3%) was observed in patients with a UXR >50%, and the highest mortality (72.1%) was observed in patients achieving a UXR of 0%. After adjusting for age, sex, diabetes mellitus, CKD, antibiotics, sepsis, hypovolemia, cardio-renal syndrome, shock, and AKI stage, the 10-day mortality was higher in groups that did not achieve a UXR of at least 25% (OR: 1.20). Patients achieving a UXR >50% were most likely initiated on dialysis due to a diagnosis of the uremic syndrome or had a diagnosis of obstructive nephropathy. Percentage change in sCr was also associated with increased mortality risk. CONCLUSIONS: In our retrospective cohort of AKI patients, the percent decrease in UXR from admission was associated with a stratified risk of death. Patients with a UXR >25% had the best associated outcomes. Overall, a greater magnitude in UXR was associated with improved patient survival.

What Did We Learn about Coronavirus Disease-19-Associated Acute Kidney Injury During the Pandemic?

ABSTRACT Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.

What did we learn about coronavirus disease-19-associated acute kidney injury during the pandemic?

Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.

Continuous Renal Replacement Therapy in Acute Brain Injury.

Acute brain injury is the sudden and reversible loss of brain self regulation capacity as a disruption of the blood-brain barrier that conditions metabolic and inflammatory disorders that can exacerbate acute kidney injury in a critical setting; specifically it has been described that the alterations of the internal environment that come from the severity of the acute kidney injury increases the risk of endocranial hypertension and cerebral edema; in this context, injuries should be identified and treated in a timely manner with a comprehensive approach. Continuous renal replacement therapy is an extracorporeal purification technique that has been gaining ground in the management of acute kidney injury in critically ill patients. Within its modalities, continuous venous venous hemofiltration is described as the therapy of choice in patients with acute brain injury due to its advantages in maintaining hemodynamic stability and reducing the risk of cerebral edema. Optimal control of variables such as timing to start renal replacement therapy, the prescribed dose, the composition of the replacement fluid and the anticoagulation of the extracorporeal circuit will have a significant impact on the evolution of the neurocritical patient with acute kidney injury. There are limited studies evaluating the role of hemofiltration in this context.

Removal of middle molecules with medium cutoff dialyzer in patients on short frequent hemodialysis.

INTRODUCTION: Medium cutoff (MCO) membranes for hemodialysis (HD) remove more effectively large middle molecules than high-flux (HF) membranes. In patients on in-center short frequent HD regimen (5 sessions per week, 2 hours and 30 minutes per session) the effect of MCO on middle weight uremic toxins has not been elucidated. METHODS: This retrospective study included 15 patients previously performing short frequent HD with HF dialyzer (HF-HD), that were switched to short frequent HD with MCO dialyzer (MCO-HD) for 2 months, and returned to HF-HD. The primary endpoint was the predialysis concentration of α1-acid glycoprotein during the different study phases. Secondary endpoints were predialysis concentration of other middle molecules, albumin, and assessment of the quality of life using the 36-item short-form health survey (SF-36). FINDINGS: During MCO-HD phase there was a reduction in mean ± SD α1-acid glycoprotein concentration (98.71 ± 25.2 vs. 88.6 ± 24.6 mg/dL, P = 0.107), followed by an increment 2 months after returning to HF-HD (89.18 ± 26.12 vs. 97.33 ± 31.29 mg/dL, P = 0.002); however, only the second variation was statistically significant. MCO-HD provided lower median predialysis concentration of prolactin (16 [10.2-25.6] vs. 14.1 [11.7-34.8] ng/mL, P = 0.036). Single-pool Kt/V, standard Kt/V, predialysis ß2-microglobulin, myoglobin, and SF-36 questionnaire remained stable during the first two phases (pre-MCO and MCO). ß2-Microglobulin increased in the post-MCO phase (20.02 ± 8.14 vs. 21.27 ± 7.64 µg/mL, P = 0.000). Mean predialysis concentration of albumin reduced significantly from pre-MCO vs. MCO phases (39.9 ± 3.7 vs. 38.3 ± 3.3 g/L, P = 0.020) and rebounded significantly from MCO vs. post-MCO phases (38.7 ± 3.1 vs. 41.3 ± 3.0 g/L, P = 0.007). DISCUSSION: In this retrospective analysis, short frequent MCO-HD promotes a reduction in prolactin, a middle weight uremic toxin, and trends toward a reduction in α1-acid glycoprotein. No patients developed hypoalbuminemia. These findings are encouraging and deserve investigation in prospective studies.

Neutrophil gelatinase-associated lipocalin does not predict acute kidney injury in heart failure.

BACKGROUND: Acute cardiorenal syndrome type 1 (CRS-1) is defined by a rapid cardiac dysfunction leading to acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) is expressed on the surface of human neutrophils and epithelial cells, such as renal tubule cells, and its serum (sNGAL) and urinary have been used to predict AKI in different clinical settings. AIM: To characterize CRS-1 in a cohort of patients with acute heart diseases, evaluating the potentiality of sNGAL as an early marker of CRS-1. METHODS: We performed a retrospective cohort, multi-centre study. From January 2010 to December 2011, we recruited 202 adult patients admitted to the coronary intensive care unit (CICU) with a diagnosis of acute heart failure or acute coronary syndrome. We monitored the renal function to evaluate CRS-1 development and measured sNGAL levels within 24 h and after 72 h of CICU admission. RESULTS: Overall, enrolled patients were hemodynamically stable with a mean arterial pressure of 92 (82-107) mmHg, 55/202 (27.2%) of the patients developed CRS-1, but none of them required dialysis. Neither the NGAL delta value (AUC 0.40, 95%CI: 0.25-0.55) nor the NGAL peak (AUC 0.45, 95%CI: 0.36-0.54) or NGAL cut-off (≥ 140 ng/mL) values were statistically significant between the two groups (CRS-1 vs no-CRS1 patients). The area under the ROC curve for the prediction of CRS-1 was 0.40 (95%CI: 0.25-0.55) for the delta NGAL value and 0.45 (95%CI: 0.36-0.54) for the NGAL peak value. Finally, in multivariate analysis, the risk of developing CRS-1 was correlated with age > 60 years, urea nitrogen at admission and 24 h-urine output (AUC 0.83, SE = 60.5% SP = 93%), while sNGAL was not significantly correlated. CONCLUSION: In our population, sNGAL does not predict CRS-1, probably as a consequence of the mild renal injury and the low severity of heart disease. So, these data might suggest that patient selection should be taken into account when considering the utility of NGAL measurement as a biomarker of kidney damage.

Development and validation of quick Acute Kidney Injury-score (q-AKI) to predict acute kidney injury at admission to a multidisciplinary intensive care unit.

AKI is associated with increased risk of death, prolonged length of stay and development of de-novo chronic kidney disease. The aim of our study is the development and validation of prediction models to identify the risk of AKI in ICU patients up to 7 days. We retrospectively recruited 692 consecutive patients admitted to the ICU at San Bortolo Hospital (Vicenza, Italy) from 1 June 2016 to 31 March 2017: 455 patients were treated as the derivation group and 237 as the validation group. Candidate variables were selected based on a literature review and expert opinion. Admission eGFR< 90 ml/min /1.73 mq (OR 2.78; 95% CI 1.78-4.35; p<0.001); SOFAcv ≥ 2 (OR 2.23; 95% CI 1.48-3.37; p<0.001); lactate ≥ 2 mmol/L (OR 1.81; 95% CI 1.19-2.74; p = 0.005) and (TIMP-2)•(IGFBP7) ≥ 0.3 (OR 1.65; 95% CI 1.08-2.52; p = 0.019) were significantly associated with AKI. For the q-AKI score, we stratified patients into different AKI Risk score levels: 0-2; 3-4; 5-6; 7-8 and 9-10. In both cohorts, we observed that the proportion of AKI patients was higher in the higher score levels.

[Anticoagulación en terapia de reemplazo renal continua].

La terapia de reemplazo renal continua (TRRC) se desarrolló para cubrir los inconvenientes de la terapia intermitente en pacientes críticos. Cuando la TRRC es verdaderamente continua, puede proveer de un control metabólico y de volumen sumamente efectivo. Sin embargo, el fallo prematuro o la coagulación del circuito extracorpóreo durante las terapias continúa siendo un obstáculo común que contribuye a tratamientos inadecuados, perdidas sanguíneas, altos costos y una gran cantidad de tiempo invertido por el personal de enfermería dedicado a instalar los equipos en lugar de la atención directa al paciente. El fallo temprano de los circuitos está relacionado a diversos factores, incluyendo aquellos relacionados a) con el paciente (p. ej., el paciente críticamente enfermo con lesión renal aguda (LRA) desarrolla un estado procoagulable), b) con las terapias utilizadas en estos pacientes (p. ej., transfusiones), y c) con factores relacionados a la prescripción de TRRC. Por lo tanto, estrategias destinadas a prevenir el fallo del circuito deben tener en cuenta todos estos factores e incluir la optimización del funcionamiento del catéter, circuito y prescripción de TRRC. Mientras las optimizaciones de todos estos factores mejoran la vida media del circuito, la anticoagulación es generalmente también requerida para maximizar la vida del circuito. Estas estrategias de anticoagulación pueden administrarse por vía sistémica o regional (intracircuito). El objetivo de esta revisión es ofrecer un panorama general de las medidas de anticoagulación más utilizadas en TRRC.Continuous renal replacement therapies (CRRT) were developed to overcome shortcomings of intermittent haemodialysis in critically ill patients. When CRRT is truly continuous, it provides very effective volume and metabolic control. However, premature loss of extracorporeal circuit patency during CRRT remains a common obstacle and contributes to inadequate treatment, and increased blood loss, costs in nursing time dedicated to CRRT instead of direct patient care. Early loss of circuit patency is related to numerous factors including (a) patient related factors (e.g. critically ill patients with acute kidney injury develop a pro-coagulant state), (b) therapy-related factors (e.g. blood transfusions), and (c) factors related to the CRRT prescription. Thus, strategies implemented to prolong circuit patency must take all these factors into account, particularly those related to CRRT; that is, to optimize the circuit life of the CRRT circuit, one must implement a comprehensive strategy that includes optimization of the catheter, circuit, and CRRT prescription. While optimization of these factors will improve circuit life, anticoagulation is generally also required to maximize it. This can be accomplished via systemic or regional (intra-circuit) anticoagulation strategies. This paper provides an overview of the most commonly used anticoagulation strategies being used in CRRT.

Pro: Prevention of acute kidney injury: time for teamwork and new biomarkers.

Acute kidney injury (AKI) is a common condition in critically ill patients. Multiple studies have identified AKI as a strong independent risk factor for higher morbidity and mortality. AKI is often multifactorial, asymptomatic and difficult to predict. In recent years, the discovery of several AKI biomarkers, including the recent validation and approval of cell cycle arrest biomarkers (NephroCheck, Astute Medical, San Diego, CA, USA), has provided additional tools to detect patients at high risk of AKI and improve their outcomes. We propose a protocol to integrate the use of NephroCheck into a multidisciplinary rapid clinical response team to potentially reduce AKI development, severity and the number of patients who need dialysis. We have designed a stepped alarm system for nephrologists and critical care physicians that starts with the recognition of high-risk patients in the clinical setting. The evaluation of patients' clinical situation together with the NephroCheck value will lead to a list of recommendations to prevent the development of AKI or progression to acute kidney stress or injury. We propose that the routine clinical application of a NephroCheck Rapid Response Team (RRT), where the NephroCheck RRT acts under the principle of improving safety and avoiding deterioration of patients, can impact patients' well-being in a positive way.