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1.
Sci Rep ; 12(1): 3474, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1721587

ABSTRACT

Acute kidney injury (AKI) is associated with increased mortality in most critical settings. However, it is unclear whether its mild form (i.e. AKI stage 1) is associated with increased mortality also in non-critical settings. Here we conducted an international study in patients hospitalized with SARS-CoV-2 infection aiming 1. to estimate the incidence of AKI at each stage and its impact on mortality 2. to identify AKI risk factors at admission (susceptibility) and during hospitalization (exposures) and factors contributing to AKI-associated mortality. We included 939 patients from medical departments in Moscow (Russia) and Padua (Italy). In-hospital AKI onset was identified in 140 (14.9%) patients, mainly with stage 1 (65%). Mortality was remarkably higher in patients with AKI compared to those without AKI (55 [39.3%] vs. 34 [4.3%], respectively). Such association remained significant after adjustment for other clinical conditions at admission (relative risk [RR] 5.6; CI 3.5- 8.8) or restricting to AKI stage 1 (RR 3.2; CI 1.8-5.5) or to subjects with AKI onset preceding deterioration of clinical conditions. After hospital admission, worsening of hypoxic damage, inflammation, hyperglycemia, and coagulopathy were identified as hospital-acquired risk factors predicting AKI onset. Following AKI onset, the AKI-associated worsening of respiratory function was identified as the main contributor to AKI-induced increase in mortality risk. In conclusion, AKI is a common complication of Sars-CoV2 infection in non-intensive care settings where it markedly increases mortality risk also at stage 1. The identification of hospital-acquired risk factors and exposures might help prevention of AKI onset and of its complications.


Subject(s)
Acute Kidney Injury/etiology , Acute Kidney Injury/mortality , Hospital Mortality , Hospitalization , Humans , Internationality , Length of Stay , Longitudinal Studies , Patient Admission , Risk Factors
2.
Clin Immunol ; 236: 108961, 2022 03.
Article in English | MEDLINE | ID: covidwho-1705130

ABSTRACT

Patients receiving maintenance dialysis (MD) are vulnerable to COVID-19-related morbidity and mortality. Currently, data on SARS-CoV-2-specific cellular and humoral immunity post-vaccination in this population are scarce. We conducted a prospective single-center study exploring the specific cellular (interferon-γ and interleukin-2 ELISpot assays) and humoral immune responses (dot plot array and chemiluminescent microparticle immunoassay [CMIA]) at 4 weeks and 6 weeks following a single dose or a complete homologous dual dose SARS-CoV-2 vaccine regimen in 60 MD patients (six with a history of COVID-19). Our results show that MD patients exhibit a high seroconversion rate (91.7%) but the anti-spike IgG antibodies (CMIA) tend to wane rapidly after full immunization. Only 51.7% of the patients developed T cell immune response. High anti-spike IgG antibodies may predict a better cellular immunity. While patients with prior COVID-19 showed the best response after one, SARS-CoV-2-naïve patients may benefit from a third vaccine injection.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , COVID-19/prevention & control , Humans , Immunity, Humoral , Prospective Studies , RNA, Messenger , Renal Dialysis , SARS-CoV-2
3.
Blood Purif ; : 1-6, 2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1691199

ABSTRACT

INTRODUCTION: Interleukin-6 (IL-6) is one of the most important mediators of inflammation. It is also the culprit for a severe disease course in COVID-19. While COVID-19 has higher mortality in hemodialysis (HD) patients, medium cutoff (MCO) membranes were previously suggested as promising tools for better patient outcomes by purging inflammatory mediators. The aim of this study was to analyze changes in IL-6 levels of HD patients who were dialyzed via MCO membranes during their COVID-19 treatments. METHODS: This is an observational study on a group of HD patients who were admitted with COVID-19 diagnosis in a university hospital and intermittently dialyzed using MCO membranes during their hospital stay. IL-6 levels of the patients were measured before and after consecutive dialysis sessions by a commercial kit. Measurements were interpreted together with the clinical data. RESULTS: Nine patients with a total of 54 measurements were evaluated. IL-6 levels were significantly higher in patients who died (median and interquartile ranges [IQRs] of IL-6 levels for patients who died and survived were 112.0 pg/mL [48.3-399.4] and 5.3 pg/mL [2.2-27.4], respectively; p < 0.001). In the comparison of changes in IL-6 levels with dialysis sessions, patients who survived had lower post-dialysis levels (median: 4.5 pg/mL; IQR: 2.2-7.6). However, IL-6 levels had a tendency to increase with dialysis sessions in patients who could not survive COVID-19 (median: 237.0 pg/mL; IQR: 53.8-418.2). CONCLUSION: This study describes over time variations in IL-6 levels of COVID-19 patients undergoing HD with MCO membranes. The trend for the changes of IL-6 levels during dialysis sessions was not uniform for all patients. Surviving patients had decreasing levels of IL-6 with consecutive dialysis sessions, while nonsurvivors had an increasing trend.

4.
Clin Kidney J ; 14(12): 2483-2489, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1599422

ABSTRACT

Remote patient management (RPM) programs are one of the most crucial innovations in the peritoneal dialysis (PD) field that have been developed in the last decade. RPM programs are associated with favourable clinical outcomes by increasing the adherence of the patients to PD prescription. The literature supports that RPM is associated with increased blood pressure control and technique survival, and decreased hospitalization rate, length of hospital stay and health costs. RPM programs also facilitate patient follow-up during the coronavirus disease 2019 pandemic, increase treatment adherence and lead to better clinical outcomes. However, published data remain scarce and mainly consist of observational or retrospective studies with relatively low numbers of patients. Therefore, randomized controlled trial results will be more informative to demonstrate the effect of RPM programs on clinical outcomes.

5.
Lancet Diabetes Endocrinol ; 10(2): 97-98, 2022 02.
Article in English | MEDLINE | ID: covidwho-1569157
7.
Contrib Nephrol ; 199: 229-243, 2021.
Article in English | MEDLINE | ID: covidwho-1338891

ABSTRACT

Clinical Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread globally from late 2019, reaching pandemic proportions. Epidemiology: The related disease, COVID-19, exacerbates and progresses due to patients' abnormal inflammatory/immune responses, widespread endothelial damage, and complement-induced blood clotting with microangiopathy. COVID-19 manifests mainly as a respiratory illness. In cases of severe viral pneumonia, it may lead to acute respiratory distress syndrome, respiratory failure, and death. Challenges: Many extrapulmonary manifestations commonly occur, and a substantial proportion of patients with severe COVID-19 exhibit signs of kidney damage. Clinically, kidney involvement ranges from mild/moderate proteinuria and hematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT). The pathophysiologic mechanisms of kidney damage and AKI in patients with COVID-19 remain unclear but are known to be multifactorial. Current knowledge implies direct SARS-CoV-2-dependent effects on kidney cells (tubular epithelial cells and podocytes) and indirect mechanisms through the systemic effect of viral infection secondary to the critical pulmonary illness and its management. Prevention and Treatment: Standard-of-care strategies apply, as there is no specific evidence to suggest that COVID-19 AKI should be managed differently from other types in severely ill patients. If conservative management fails, RRT should be considered. The choice of RRT approaches and sequential extracorporeal therapies depends on local availability, resources, and expertise. The focus should now be on the long-term follow-up of COVID-19 patients, especially those who developed kidney injury and dysfunction. This represents an opportunity for integrated multidisciplinary research to clarify the natural history of COVID-19 renal sequelae and the best therapeutic interventions to mitigate them.


Subject(s)
Acute Kidney Injury/therapy , Acute Kidney Injury/virology , COVID-19/complications , COVID-19/therapy , COVID-19/epidemiology , Hematuria/virology , Humans , Nephrologists , Proteinuria/virology , Renal Replacement Therapy , SARS-CoV-2
9.
Blood Purif ; 51(4): 309-316, 2022.
Article in English | MEDLINE | ID: covidwho-1317090

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) in patients with COVID-19 can be caused by multiple mechanisms. Renal resistive index (RRI) is a noninvasive instrument to evaluate kidney hemodynamics, and it is obtained by analysis of intrarenal arterial waves using Doppler ultrasound. This study aimed to determine the role of RRI in predicting AKI and adverse outcomes in critically ill patients with COVID-19. METHODS: This cross-sectional study included 65 patients with confirmed SARS-CoV-2 pneumonia admitted to the critical care unit from April 1, 2020, to June 20, 2020. Informed consent was obtained from all individual participants included in the study. Cardiac, pulmonary, and kidney ultrasonographic evaluations were performed in a protocolized way. RESULTS: In this cohort, 65 patients were included, mean age was 53.4 years, 79% were male, and 35% were diabetic. Thirty-four percent of patients developed AKI, 12% required RRT, and 35% died. Of the patients who developed AKI, 68% had RRI ≥ 0.7. Also, 75% of the patients who required RRT had RRI ≥ 0.7. In the adjusted Cox model, the RRI ≥ 0.7 was associated with higher mortality (HR 2.86, 95% CI: 1.19-6.82, p = 0.01). CONCLUSIONS: Critical care ultrasonography is a noninvasive, reproducible, and accurate bedside method that has proven its usefulness. An elevated RRI may have a role in predicting AKI, RRT initiation, and mortality in patients with severe SARS-CoV-2 pneumonia.


Subject(s)
Acute Kidney Injury , COVID-19 , Acute Kidney Injury/etiology , COVID-19/complications , COVID-19/diagnostic imaging , Critical Illness , Cross-Sectional Studies , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2
11.
Perit Dial Int ; 41(3): 307-312, 2021 05.
Article in English | MEDLINE | ID: covidwho-916958

ABSTRACT

BACKGROUND: Peritoneal dialysis (PD) is a viable option for renal replacement therapy in acute kidney injury (AKI), especially in challenging times during disasters and pandemics when resources are limited. While PD techniques are well described, there is uncertainty about how to determine the amount of PD to be prescribed toward a target dose. The aim of this study is to derive practical equations to assist with the prescription of PD for AKI. METHODS: Using established physiological principles behind PD clearance and membrane transport, a primary determinant of dose delivery, equations were mathematically derived to estimate dialysate volume required to achieve a target dose of PD. RESULTS: The main derivative equation is VD = (1.2 × std-Kt/V × TBW)/(tdwell + 4), where VD is the total dialysate volume per day, std-Kt/V is the desired weekly dose, TBW is the total body water, and tdwell is the dwell time. VD can be expressed in terms of dwell volume, vdwell, by VD = (0.3 × std-Kt/V × TBW) - (6 × vdwell). Two further equations were derived which directly describe the mathematical relationship between tdwell and vdwell. A calculator is included as an Online Supplementary Material. CONCLUSIONS: The equations are intended as a practical tool to estimate solute clearances and guide prescription of continuous PD. The estimated dialysate volume required for any dose target can be calculated from cycle duration or dwell volume. However, the exact target dose of PD is uncertain and should be adjusted according to the clinical circumstances and response to treatment. The equations presented in this article facilitate the adjustment of PD prescription toward the targeted solute clearance.


Subject(s)
Acute Kidney Injury/therapy , Dialysis Solutions/administration & dosage , Peritoneal Dialysis/methods , COVID-19 , Disasters , Drug Dosage Calculations , Humans , Pandemics
12.
Kidney Int Rep ; 6(4): 872-874, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1117225
13.
Artif Organs ; 45(6): E187-E194, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1087949

ABSTRACT

The coronavirus disease 2019 (COVID-19) has been shown to involve the gastrointestinal tract, which implies bacterial translocation and endotoxemia. The aim of this study was to evaluate the role of extracorporeal endotoxin removal by Polymyxin B hemoperfusion (PMX-HP), in the treatment of patients with COVID-19 and secondary bacterial infection. We conducted a subgroup analysis of a multicenter, multinational, prospective, and observational web-based database (EUPHAS2 registry). We included 12 patients with severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction from nasal/oral swab, admitted to the intensive care unit between February and May 2020, who were affected by septic shock and received PMX-HP as per clinical indication of the attending physician. Septic shock was diagnosed in nine patients (75%), with a median time between symptoms onset and PMX-HP treatment of 16 (14-22) days. We identified Gram-negative bacteria in most of the microbiological cultures (N = 17, 65%), followed by Gram-positive bacteria in (N = 4, 15%), fungi (N = 3, 12%) and no growth (N = 2, 8%). Sequential Organ Failure Assessment (SOFA) score progressively improved over the next 120 hours following PMX-HP and it was associated with median endotoxin activity assay (EAA) decrease from 0.78 [0.70-0.92] at T0 to 0.60 [0.44-0.72] at T120 (P = .245). A direct correlation was observed between SOFA score and EAA. Lung Injury Score decreased and was associated with hemodynamic improvement over the same period. No statistically significant difference was observed for RIFLE score at each time point. Nine out of 12 patients (75%) required continuous renal replacement therapy because of acute kidney injury. In a series of consecutive COVID-19 patients with endotoxic shock, PMX-HP was associated with organ function recovery, hemodynamic improvement, and contemporary EAA level reduction. No PMX-HP-related complications were observed.


Subject(s)
Anti-Bacterial Agents/therapeutic use , COVID-19/complications , Endotoxemia/drug therapy , Endotoxemia/microbiology , Polymyxin B/therapeutic use , Shock, Septic/drug therapy , Shock, Septic/microbiology , Anti-Bacterial Agents/administration & dosage , Biomarkers/blood , COVID-19/mortality , Critical Illness , Endotoxemia/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Organ Dysfunction Scores , Prospective Studies , Registries , SARS-CoV-2 , Shock, Septic/mortality
14.
Blood Purif ; 50(6): 921-924, 2021.
Article in English | MEDLINE | ID: covidwho-1030460

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 may lead to high levels of expression of inflammatory cytokines. Medium cut-off (MCO) membranes may make greater clearances for large-middle molecules (including cytokines) than low-flux (LF) membranes. In this study, we aimed to evaluate the impact of MCO membranes on outcome of COVID-19 patients on hemodialysis (HD). METHODS: Sixty COVID-19 HD patients were included in this study. The patients were categorized into 2 groups regarding type of HD membranes. Clinical data were taken from medical records. RESULTS: Initial crp and ferritin levels, which are surragates of cytokine storm and severity of disease in COVID-19, were significantly higher in MCO membrane group compared to LF group (p = 0.037 and 0.000, respectively). Although there were more patients with severe disease in MCO group, there were no significant differences regarding need for intensive care unit and death. CONCLUSION: It may be an option to use MCO membranes in HD patients with COVID-19 in order to reduce cytokine levels and prevent cytokine storm.


Subject(s)
COVID-19/therapy , Membranes, Artificial , Renal Dialysis/instrumentation , Aged , COVID-19/complications , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/therapy , Cytokines/isolation & purification , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification , Treatment Outcome
16.
Blood Purif ; 50(4-5): 499-505, 2021.
Article in English | MEDLINE | ID: covidwho-962803

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). However, the epidemiological features and outcomes of AKI among COVID-19 patients with ARDS are unknown. METHODS: We retrospectively recruited consecutive adult COVID-19 patients who were diagnosed with ARDS according to Berlin definition from 13 designated intensive care units in the city of Wuhan, China. Potential risk factors of AKI as well as the relation between AKI and in-hospital mortality were investigated. RESULTS: A total of 275 COVID-19 patients with ARDS were included in the study, and 49.5% of them developed AKI during their hospital stay. In comparison with patients without AKI, patients who developed AKI were older, tended to have chronic kidney disease, had higher Sepsis-Related Organ Failure Assessment score on day 1, and were more likely to receive invasive ventilation and develop acute organ dysfunction. Multivariate analysis showed that age, history of chronic kidney disease, neutrophil-to-lymphocyte ratio, and albumin level were independently associated with the occurrence of AKI. Importantly, increasing AKI severity was associated with increased in-hospital mortality when adjusted for other potential variables: odds ratio of stage 1 = 5.374 (95% CI: 2.147-13.452; p < 0.001), stage 2 = 6.216 (95% CI: 2.011-19.210; p = 0.002), and stage 3 = 34.033 (95% CI: 9.723-119.129; p < 0.001). CONCLUSION: In this multicenter retrospective study, we found that nearly half of COVID-19 patients with ARDS experienced AKI during their hospital stay. The coexistence of AKI significantly increased the mortality of these patients.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/complications , Hospital Mortality , Respiratory Distress Syndrome/etiology , SARS-CoV-2 , Acute Kidney Injury/blood , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Aged , China/epidemiology , Comorbidity , Creatinine/blood , Female , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Renal Insufficiency, Chronic/complications , Respiration, Artificial/adverse effects , Respiration, Artificial/statistics & numerical data , Respiratory Distress Syndrome/therapy , Retrospective Studies , Risk Factors
17.
Front Med (Lausanne) ; 7: 598379, 2020.
Article in English | MEDLINE | ID: covidwho-954188

ABSTRACT

Coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) is associated with high mortality. Lung-protective ventilation is the current standard of care in patients with ARDS, but it might lead to hypercapnia, which is independently associated with worse outcomes. Extracorporeal carbon dioxide removal (ECCO2R) has been proposed as an adjuvant therapy to avoid progression of clinical severity and limit further ventilator-induced lung injury, but its use in COVID-19 has not been described yet. Acute kidney injury requiring renal replacement therapy (RRT) is common among critically ill COVID-19 patients. In centers with available dialysis, low-flow ECCO2R (<500 mL/min) using RRT platforms could be carried out by dialysis specialists and might be an option to efficiently allocate resources during the COVID-19 pandemic for patients with hypercapnia as the main indication. Here, we report the feasibility, safety, and efficacy of ECCO2R using an RRT platform to provide either standalone ECCO2R or ECCO2R combined with RRT in four hypercapnic patients with moderate ARDS. A randomized clinical trial is required to assess the overall benefit and harm. Clinical Trial Registration: ClinicalTrials.gov. Unique identifier: NCT04351906.

18.
Am J Physiol Lung Cell Mol Physiol ; 320(4): L590-L599, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-945036

ABSTRACT

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.


Subject(s)
COVID-19/virology , Immunoglobulins/deficiency , SARS-CoV-2/pathogenicity , Severity of Illness Index , Cohort Studies , Female , Humans , Intensive Care Units , Male , Middle Aged , Risk Factors
19.
Minerva Anestesiol ; 86(11): 1214-1233, 2020 11.
Article in English | MEDLINE | ID: covidwho-941782

ABSTRACT

In December 2019, Coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread around the word. The immune response is essential to control and eliminate CoV infections, however, multiorgan damage might be due to direct SARS-CoV2 action against the infected organ cells, as well as an imbalanced host immune response. In effect, a "cytokines storm" and an impaired innate immunity were found in the COVID-19 critically ill patients. In this review, we summarized the virus immune response steps, underlying the relevance of introducing the measurement of plasma cytokine levels and of circulating lymphocyte subsets in clinical practice for the follow-up of critically ill COVID-19 patients and support new therapy.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Adaptive Immunity , Critical Care , Critical Illness , Cytokine Release Syndrome , Humans , Immunity, Innate , Immunotherapy
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