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1.
Theranostics ; 12(6): 2963-2986, 2022.
Article in English | MEDLINE | ID: covidwho-1780235

ABSTRACT

Many factors such as trauma and COVID-19 cause acute kidney injury (AKI). Late AKI have a very high incidence and mortality rate. Early diagnosis of AKI provides a critical therapeutic time window for AKI treatment to prevent progression to chronic renal failure. However, the current clinical detection based on creatinine and urine output isn't effective in diagnosing early AKI. In recent years, the early diagnosis of AKI has made great progress with the advancement of information technology, nanotechnology, and biomedicine. These emerging methods are mainly divided into two aspects: First, predicting AKI through models construct by machine learning; Second, early diagnosis of AKI through detection of newly-discovered early biomarkers. Currently, these methods have shown great potential and become an attractive tool for the early diagnosis of AKI. Therefore, it is very important to discuss and summarize these methods for the early diagnosis of AKI. In this review, we first systematically summarize the application of machine learning in AKI prediction algorithms and specific scenarios. In addition, we introduce the key role of early biomarkers in the progress of AKI, and then comprehensively summarize the application of emerging detection technologies for early AKI. Finally, we discuss current challenges and prospects of machine learning and biomarker detection. The review is expected to provide new insights for early diagnosis of AKI, and provided important inspiration for the design of early diagnosis of other major diseases.


Subject(s)
Acute Kidney Injury , COVID-19 , Acute Kidney Injury/diagnosis , Biomarkers/urine , COVID-19/diagnosis , Creatinine , Early Diagnosis , Humans , Lipocalin-2
2.
Int J Infect Dis ; 117: 302-311, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1693388

ABSTRACT

BACKGROUND: Acute renal injury is an important complication of coronavirus disease 2019 (COVID-19). Both COVID-19-specific mechanisms, such as damage to the renal parenchyma by direct infection, and non-specific mechanisms, such as the pre-renal injury factors, have been proposed to be involved in COVID-19-associated renal injuries. In this study, we aimed to elucidate the characteristics of COVID-19-associated renal injuries, focusing mainly on urine sediment findings. METHODS: We compared the urine sediment findings and their associations with renal functions or urinary clinical parameters between subjects with COVID-19 and subjects without COVID-19 with acute renal injuries. RESULTS: We found that the number of urine sediment particles and the levels of N-acetyl-ß-D-glucosaminidase, α1-microglobulin, liver type fatty acid-binding protein, and neutrophil gelatinase-associated lipocalin were associated with the severity of COVID-19. In addition, we observed that the number of granular casts, epithelial casts, waxy casts, and urinary chemical marker levels were lower in the subjects with COVID-19 than subjects without COVID-19 with acute renal injuries when the subjects were classified according to their renal function. CONCLUSIONS: These results suggest that pre-renal injury factors might be largely involved in the pathogenesis of COVID-19-associated renal injuries compared with non-COVID-19-associated renal injuries arising from surgery or sepsis.


Subject(s)
Acute Kidney Injury , COVID-19 , Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Biomarkers/urine , COVID-19/complications , Humans , Kidney/metabolism , Urinalysis/adverse effects
3.
Biomolecules ; 12(2)2022 02 08.
Article in English | MEDLINE | ID: covidwho-1674482

ABSTRACT

A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. The early recognition of subclinical AKI could contribute to AKI prevention. Therefore, this study was aimed at exploring the role of the urinary biomarkers NGAL and [TIMP-2] × [IGFBP7] for the early detection of AKI in this population. This prospective, longitudinal cohort study included critically ill COVID-19 patients without AKI at study entry. Urine samples were collected on admission to critical care areas for determination of NGAL and [TIMP-2] × [IGFBP7] concentrations. The demographic information, comorbidities, clinical, and laboratory data were recorded. The study outcomes were the development of AKI and mortality during hospitalization. Of the 51 individuals that were studied, 25 developed AKI during hospitalization (49%). Of those, 12 had persistent AKI (23.5%). The risk factors for AKI were male gender (HR = 7.57, 95% CI: 1.28-44.8; p = 0.026) and [TIMP-2] × [IGFBP7] ≥ 0.2 (ng/mL)2/1000 (HR = 7.23, 95% CI: 0.99-52.4; p = 0.050). Mortality during hospitalization was significantly higher in the group with AKI than in the group without AKI (p = 0.004). Persistent AKI was a risk factor for mortality (HR = 7.42, 95% CI: 1.04-53.04; p = 0.046). AKI was frequent in critically ill COVID-19 patients. The combination of [TIMP-2] × [IGFBP7] together with clinical information, were useful for the identification of subclinical AKI in critically ill COVID-19 patients. The role of additional biomarkers and their possible combinations for detection of AKI in ritically ill COVID-19 patients remains to be explored in large clinical trials.


Subject(s)
Acute Kidney Injury/diagnosis , Acute Kidney Injury/urine , COVID-19/diagnosis , COVID-19/urine , Critical Illness/mortality , Acute Kidney Injury/complications , Acute Kidney Injury/mortality , Adult , Aged , Biomarkers/urine , COVID-19/complications , COVID-19/mortality , Female , Humans , Insulin-Like Growth Factor Binding Proteins/urine , Kaplan-Meier Estimate , Lipocalin-2/urine , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Risk Factors , Tissue Inhibitor of Metalloproteinase-2/urine
4.
Nutrients ; 13(11)2021 Nov 20.
Article in English | MEDLINE | ID: covidwho-1573692

ABSTRACT

This study examines the correlation of acute and habitual dietary intake of flavan-3-ol monomers, proanthocyanidins, theaflavins, and their main food sources with the urinary concentrations of (+)-catechin and (-)-epicatechin in the European Prospective Investigation into Cancer and Nutrition study (EPIC). Participants (N = 419, men and women) provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day. Acute and habitual dietary data were collected using a standardized 24-HDR software and a validated dietary questionnaire, respectively. Intake of flavan-3-ols was estimated using the Phenol-Explorer database. Concentrations of (+)-catechin and (-)-epicatechin in 24-h urine were analyzed using tandem mass spectrometry after enzymatic deconjugation. Simple and partial Spearman's correlations showed that urinary concentrations of (+)-catechin, (-)-epicatechin and their sum were more strongly correlated with acute than with habitual intake of individual and total monomers (acute rpartial = 0.13-0.54, p < 0.05; and habitual rpartial = 0.14-0.28, p < 0.01), proanthocyanidins (acute rpartial = 0.24-0.49, p < 0.001; and habitual rpartial = 0.10-0.15, p < 0.05), theaflavins (acute rpartial = 0.22-0.31, p < 0.001; and habitual rpartial = 0.20-0.26, p < 0.01), and total flavan-3-ols (acute rpartial = 0.40-0.48, p < 0.001; and habitual rpartial = 0.23-0.33, p < 0.001). Similarly, urinary concentrations of flavan-3-ols were weakly correlated with both acute (rpartial = 0.12-0.30, p < 0.05) and habitual intake (rpartial = 0.10-0.27, p < 0.05) of apple and pear, stone fruits, berries, chocolate and chocolate products, cakes and pastries, tea, herbal tea, wine, red wine, and beer and cider. Moreover, all comparable correlations were stronger for urinary (-)-epicatechin than for (+)-catechin. In conclusion, our data support the use of urinary concentrations of (+)-catechin and (-)-epicatechin, especially as short-term nutritional biomarkers of dietary catechin, epicatechin and total flavan-3-ol monomers.


Subject(s)
Biflavonoids/analysis , Catechin/urine , Diet/statistics & numerical data , Flavonoids/analysis , Proanthocyanidins/analysis , Adult , Aged , Biomarkers/urine , Catechin/analysis , Diet Surveys , Eating , Europe , Female , Humans , Male , Middle Aged , Nutrition Assessment , Prospective Studies , Statistics, Nonparametric
5.
Sci Rep ; 11(1): 19675, 2021 10 04.
Article in English | MEDLINE | ID: covidwho-1450292

ABSTRACT

Kidney function is affected in COVID-19, while kidney itself modulates the immune response. Here, hypothesize if COVID-19 urine biomarkers level can assess immune activation vs. clinical trajectory. Considering the kidney's critical role in modulating the immune response, we sought to analyze activation markers in patients with pre-existing dysfunction. This was a cross-sectional study of 68 patients. Blood and urine were collected within 48 h of hospital admission (H1), followed by 96 h (H2), seven days (H3), and up to 25 days (H4) from admission. Serum level ferritin, procalcitonin, IL-6 assessed immune activation overall, while the response to viral burden was gauged with serum level of spike protein and αspike IgM and IgG. 39 markers correlated highly between urine and blood. Age and race, and to a lesser extend gender, differentiated several urine markers. The burden of pre-existing conditions correlated with urine DCN, CAIX and PTN, but inversely with IL-5 or MCP-4. Higher urinary IL-12 and lower CAIX, CCL23, IL-15, IL-18, MCP-1, MCP-3, MUC-16, PD-L1, TNFRS12A, and TNFRS21 signified non-survivors. APACHE correlated with urine TNFRS12, PGF, CAIX, DCN, CXCL6, and EGF. Admission urine LAG-3 and IL-2 predicted death. Pre-existing kidney disease had a unique pattern of urinary inflammatory markers. Acute kidney injury was associated, and to a certain degree, predicted by IFNg, TWEAK, MMP7, and MUC-16. Remdesavir had a more profound effect on the urine biomarkers than steroids. Urinary biomarkers correlated with clinical status, kidney function, markers of the immune system activation, and probability of demise in COVID-19.


Subject(s)
Acute Kidney Injury/pathology , Biomarkers/urine , COVID-19/immunology , Renal Insufficiency, Chronic/pathology , Acute Kidney Injury/complications , Adult , Aged , Antigens, CD/urine , Biomarkers/blood , CA-125 Antigen/urine , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Chemokines, CC/blood , Cross-Sectional Studies , Female , Humans , Interleukin-12/urine , Interleukin-6/blood , Male , Membrane Proteins/urine , Middle Aged , Procalcitonin/blood , Renal Insufficiency, Chronic/complications , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Severity of Illness Index , Spike Glycoprotein, Coronavirus/blood
6.
PLoS One ; 16(9): e0257615, 2021.
Article in English | MEDLINE | ID: covidwho-1435618

ABSTRACT

The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of tuberculosis (TB) at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker that can be detected in urine, an easily collected sample matrix. For obtaining optimal sensitivity, we and others have shown that some form of sample pretreatment is necessary to remove background from patient urine samples. A number of systems are paper-based often destined for resource limited settings. Our current work presents incorporation of one such sample pretreatment, proteinase K (ProK) immobilized on paper (IPK) and test its performance in comparison to standard proteinase K (SPK) treatment that involves addition and deactivation at high temperature prior to performing a capture ELISA. Herein, a simple and economical method was developed for using ProK immobilized strips to pretreat urine samples. Simplification and cost reduction of the proposed pretreatment strip were achieved by using Whatman no.1 paper and by minimizing the concentration of ProK (an expensive but necessary reagent) used to pretreat the clinical samples prior to ELISA. To test the applicability of IPK, capture ELISA was carried out on either LAM-spiked urine or the clinical samples after pretreatment with ProK at 400 µg/mL for 30 minutes at room temperature. The optimal conditions and stability of the IPK were tested and validation was performed on a set of 25 previously analyzed archived clinical urine samples with known TB and HIV status. The results of IPK and SPK treated samples were in agreement showing that the urine LAM test currently under development has the potential to reach adult and pediatric patients regardless of HIV status or site of infection, and to facilitate global TB control to improve assay performance and ultimately treatment outcomes.


Subject(s)
Biomarkers/urine , Endopeptidase K/metabolism , Enzyme-Linked Immunosorbent Assay/methods , Tuberculosis/diagnosis , Endopeptidase K/chemistry , Enzyme-Linked Immunosorbent Assay/instrumentation , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Humans , Lipopolysaccharides/urine , Paper , Temperature
8.
Clin Exp Nephrol ; 25(11): 1240-1246, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1303328

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome Coronavirus 2 has rapidly spread worldwide, with acute kidney injury (AKI) as one of the manifestations with unknown causal mechanisms. We aimed to investigate tubular injury by assessing tubular markers and their association with the severity of Coronavirus disease 2019 (COVID-19). METHODS: We examined the associations between laboratory markers and urinary levels of N-acetyl-ß-D-glucosaminidase (uNAG), ß2-microglobulin (u ß2MG), α1-microglobulin (u α1MG), and liver-type fatty acid binding protein (L-FABP). We studied 18 COVID-19 patients without previous chronic kidney disease and analyzed the relationship between the urinary biomarkers and inflammatory markers in patients with severe (n = 7) or non-severe (n = 11) COVID-19, defined by requirements of supplemental oxygen. RESULTS: Fourteen patients (78%) showed abnormal urinalysis findings and two (11%) developed AKI. Patients with severe COVID-19 had significantly higher levels of proteinuria, uNAG, uß2MG, uα 1MG, and L-FABP than those with non-severe disease. Serum levels of interleukin-6 (IL-6) were significantly higher on admission in all severe COVID-19 cases and correlated with the levels of L-FABP, uß2MG, uα1MG, uNAG, and proteinuria. Moreover, the changes in serum IL-6 (ΔIL-6) levels from baseline to 7 days after admission significantly correlated with ΔL-FABP and Δuß2MG. CONCLUSIONS: Levels of tubular injury markers, especially L-FABP and uß2MG, were significantly associated with IL-6 levels even in patients with no evident AKI. This suggests that L-FABP and uß2MG could be useful as early detective biomarkers for COVID-19 associated renal injury.


Subject(s)
Acute Kidney Injury/blood , COVID-19/blood , Cytokines/blood , Inflammation Mediators/blood , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/urine , Adult , Aged , Biomarkers/blood , Biomarkers/urine , COVID-19/complications , COVID-19/diagnosis , Fatty Acid-Binding Proteins/urine , Female , Humans , Interleukin-6/blood , Male , Middle Aged , Proteinuria/blood , Proteinuria/etiology , Proteinuria/urine , Retrospective Studies , Severity of Illness Index , Up-Regulation , beta 2-Microglobulin/urine
9.
Int Urol Nephrol ; 54(3): 627-636, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1293420

ABSTRACT

PURPOSE: To evaluate urinary kidney injury molecule-1 (uKIM-1), which is a proximal tubule injury biomarker in subclinical acute kidney injury (AKI) that may occur in COVID-19 infection. METHODS: The study included proteinuric (n = 30) and non-proteinuric (n = 30) patients diagnosed with mild/moderate COVID-19 infection between March and September 2020 and healthy individuals as a control group (n = 20). The uKIM-1, serum creatinine, cystatin C, spot urine protein, creatinine, and albumin levels of the patients were evaluated again after an average of 21 days. RESULTS: The median (interquartile range) uKIM-1 level at the time of presentation was 246 (141-347) pg/mL in the proteinuric group, 83 (29-217) pg/mL in the non-proteinuric group, and 55 (21-123) pg/mL in the control group and significantly high in the proteinuric group than the others (p < 0.001). Creatinine and cystatin C were significantly higher in the proteinuric group than in the group without proteinuria, but none of the patients met the KDIGO-AKI criteria. uKIM-1 had a positive correlation with PCR, non-albumin proteinuria, creatinine, cystatin C, CRP, fibrinogen, LDH, and ferritin, and a negative correlation with eGFR and albumin (p < 0.05). In the multivariate regression analysis, non-albumin proteinuria (p = 0.048) and BUN (p = 0.034) were identified as independent factors predicting a high uKIM-1 level. After 21 ± 4 days, proteinuria regressed to normal levels in 20 (67%) patients in the proteinuric group. In addition, the uKIM-1 level, albuminuria, non-albumin proteinuria, and CRP significantly decreased. CONCLUSIONS: Our findings support that the kidney is one of the target organs of the COVID-19 and it may cause proximal tubule injury even in patients that do not present with AKI or critical/severe COVID-19 infection.


Subject(s)
Acute Kidney Injury , Biomarkers , COVID-19 , Hepatitis A Virus Cellular Receptor 1/analysis , Noncommunicable Diseases , Urinalysis , Acute Kidney Injury/blood , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/urine , Biomarkers/blood , Biomarkers/urine , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/physiopathology , Comorbidity , Correlation of Data , Creatinine/blood , Creatinine/urine , Cystatin C/blood , Female , Humans , Male , Middle Aged , Noncommunicable Diseases/drug therapy , Noncommunicable Diseases/epidemiology , Proteinuria , Reproducibility of Results , SARS-CoV-2 , Severity of Illness Index , Turkey/epidemiology , Urinalysis/methods , Urinalysis/statistics & numerical data
11.
Sci Rep ; 11(1): 11134, 2021 05 27.
Article in English | MEDLINE | ID: covidwho-1246397

ABSTRACT

Risk factors associated with severity and mortality attributable to COVID-19 have been reported in different cohorts, highlighting the occurrence of acute kidney injury (AKI) in 25% of them. Among other, SARS-CoV-2 targets renal tubular cells and can cause acute renal damage. The aim of the present study was to evaluate the usefulness of urinary parameters in predicting intensive care unit (ICU) admission, mortality and development of AKI in hospitalized patients with COVID-19. Retrospective observational study, in a tertiary care hospital, between March 1st and April 19th, 2020. We recruited adult patients admitted consecutively and positive for SARS-CoV-2. Urinary and serum biomarkers were correlated with clinical outcomes (AKI, ICU admission, hospital discharge and in-hospital mortality) and evaluated using a logistic regression model and ROC curves. A total of 199 COVID-19 hospitalized patients were included. In AKI, the logistic regression model with a highest area under the curve (AUC) was reached by the combination of urine blood and previous chronic kidney disease, with an AUC of 0.676 (95%CI 0.512-0.840; p = 0.023); urine specific weight, sodium and albumin in serum, with an AUC of 0.837 (95% CI 0.766-0.909; p < 0.001) for ICU admission; and age, urine blood and lactate dehydrogenase levels in serum, with an AUC of 0.923 (95%CI 0.866-0.979; p < 0.001) for mortality prediction. For hospitalized patients with COVID-19, renal involvement and early alterations of urinary and serum parameters are useful as prognostic factors of AKI, the need for ICU admission and death.


Subject(s)
Acute Kidney Injury/mortality , Acute Kidney Injury/urine , COVID-19/mortality , COVID-19/urine , Acute Kidney Injury/complications , Acute Kidney Injury/physiopathology , Adult , Aged , Area Under Curve , Biomarkers/urine , COVID-19/complications , COVID-19/physiopathology , Critical Care , Female , Hospitalization , Humans , Logistic Models , Male , Middle Aged , Observational Studies as Topic , Prognosis , ROC Curve , Retrospective Studies , Risk Factors , Severity of Illness Index , Urine/chemistry
12.
Cytokine ; 146: 155589, 2021 10.
Article in English | MEDLINE | ID: covidwho-1240276

ABSTRACT

BACKGROUND: Acute kidney injury is common in COVID-19 patients admitted to the ICU. Urinary biomarkers are a non-invasive way of assaying renal damage, and so far, urinary cytokines are not fully investigated. The current study aimed to assess urinary cytokine levels in COVID-19 patients. METHODS: Urine was collected from COVID-19 patients (n = 29) in intensive care and compared to a preoperative group of patients (n = 9) with no critical illness. 92 urinary cytokines were analyzed in multiplex using the Olink Target 96 inflammation panel and compared to clinical characteristics, and urinary markers of kidney injury. RESULTS: There were strong correlations between proinflammatory cytokines and between urinary cytokines and urinary kidney injury markers in 29 COVID-19 patients. Several cytokines were correlated to kidney injury, 31 cytokines to AKI stage and 19 cytokines correlated to maximal creatinine. CONCLUSIONS: Urinary inflammatory cytokines from a wide range of immune cell lineages were significantly upregulated during COVID-19 and the upregulation correlated with acute kidney injury as well as urinary markers of kidney tissue damage.


Subject(s)
Acute Kidney Injury/urine , Biomarkers/urine , COVID-19/urine , Critical Illness , Cytokines/urine , Aged , Albuminuria/urine , COVID-19/diagnosis , COVID-19/virology , Creatinine/blood , Creatinine/urine , Critical Care , Female , Humans , Male , Middle Aged , SARS-CoV-2/physiology
13.
J Nephrol ; 34(2): 355-364, 2021 04.
Article in English | MEDLINE | ID: covidwho-1042399

ABSTRACT

BACKGROUND: Proteinuria has been commonly reported in patients with COVID-19. However, only dipstick tests have been frequently used thus far. Here, the quantification and characterization of proteinuria were investigated and their association with mortality was assessed. METHODS: This retrospective, observational, single center study included 153 patients, hospitalized with COVID-19 between March 28th and April 30th, 2020, in whom total proteinuria and urinary α1-microglobulin (a marker of tubular injury) were measured. Association with mortality was evaluated, with a follow-up until May 7th, 2020. RESULTS: According to the Kidney Disease Improving Global Outcomes staging, 14% (n = 21) of the patients had category 1 proteinuria (< 150 mg/g of urine creatinine), 42% (n = 64) had category 2 (between 150 and 500 mg/g) and 44% (n = 68) had category 3 proteinuria (over 500 mg/g). Urine α1-microglobulin concentration was higher than 15 mg/g in 89% of patients. After a median follow-up of 27 [14;30] days, the mortality rate reached 18%. Total proteinuria and urinary α1-microglobulin were associated with mortality in unadjusted and adjusted models. This association was stronger in subgroups of patients with normal renal function and without a urinary catheter. CONCLUSIONS: Proteinuria is frequent in patients with COVID-19. Its characterization suggests a tubular origin, with increased urinary α1-microglobulin. Tubular proteinuria was associated with mortality in COVID-19 in our restropective, observational study.


Subject(s)
COVID-19/complications , Proteinuria/epidemiology , Aged , Aged, 80 and over , Belgium/epidemiology , Biomarkers/urine , COVID-19/epidemiology , COVID-19/urine , Female , Humans , Male , Middle Aged , Prevalence , Prognosis , Proteinuria/etiology , Proteinuria/urine , Retrospective Studies , Survival Rate/trends
14.
J Clin Apher ; 36(3): 313-321, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-978131

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX-DHP) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive pneumonia patients. METHODS: This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS-CoV-2-positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX-DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX-DHP was performed. PMX-DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated. RESULTS: On day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine ß2-microglobulin decreased on days 4 and 8. Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty-two PMX-DHPs were performed, of which seven and five PMX-DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D-dimer and fibrin degradation product levels were high before PMX-DHP. CONCLUSIONS: Future studies are expected to determine the therapeutic effect of PMX-DHP on COVID-19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.


Subject(s)
COVID-19/therapy , Hemoperfusion/instrumentation , Hemoperfusion/methods , Polymyxin B/chemistry , Polystyrenes/chemistry , Adult , Aged , Aged, 80 and over , Arteries/metabolism , Biomarkers/urine , Blood Gas Analysis , Cytokines/blood , Endothelium, Vascular/metabolism , Female , Hospitalization , Humans , Male , Middle Aged , Oxygen/metabolism , Respiration, Artificial , Retrospective Studies , Risk , beta 2-Microglobulin/urine
15.
Acta Anaesthesiol Scand ; 65(3): 364-372, 2021 03.
Article in English | MEDLINE | ID: covidwho-944614

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is a syndrome of reduced glomerular filtration rate and/or reduced urine flow associated with mortality in corona virus disease 2019 (COVID-19). AKI is often associated with renal tissue damage, which may lead to chronic kidney disease. Biomarkers of tissue damage may identify patients of particular risk. METHODS: In a prospective observational study of 57 patients admitted to intensive care, AKI incidence and characteristics was evaluated according to KDIGO criteria and related to days after admission. Urinary albumin, Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule 1 (KIM-1) and Plasma Tissue Inhibitor of MetalloProteinase 2 (TIMP-2) were analysed in 52 patients at admission. The majority (n = 51, 89%) of patients developed AKI, and 27 (47%) patients had predominantly oliguric AKI where oliguria was more severe than plasma Creatinine increase. Severe oliguria within first 2 days after admission was common (n = 37, 65%), whereas stage 2 and 3 AKI due to Creatinine occurred later than day 2 in 67% (12/18) of cases. Renal replacement therapy was started in 9 (16%) patients, and 30-day mortality was 28%. Urinary biomarkers were increased in a majority of patients, but did not robustly predict KDIGO stage. Most patients had microalbuminuria, and severe albuminuria (albumin Creatinine ratio > 30 mg/mmol) was found in n = 9 (17%) patients. CONCLUSIONS: A majority of patients with COVID-19 admitted to the ICU develop AKI. The functional deficit is often low urinary volume, and initial levels of biomarkers are generally increased without clear relation to final AKI stage.


Subject(s)
Acute Kidney Injury/etiology , COVID-19/complications , Critical Care/methods , Oliguria/etiology , Acute Kidney Injury/therapy , Acute Kidney Injury/urine , Biomarkers/urine , COVID-19/urine , Female , Humans , Intensive Care Units , Male , Middle Aged , Oliguria/therapy , Oliguria/urine , Prospective Studies , Renal Replacement Therapy/methods , SARS-CoV-2
16.
Nat Commun ; 11(1): 5859, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-933687

ABSTRACT

The outbreak of COVID-19 has become a worldwide pandemic. The pathogenesis of this infectious disease and how it differs from other drivers of pneumonia is unclear. Here we analyze urine samples from COVID-19 infection cases, healthy donors and non-COVID-19 pneumonia cases using quantitative proteomics. The molecular changes suggest that immunosuppression and tight junction impairment occur in the early stage of COVID-19 infection. Further subgrouping of COVID-19 patients into moderate and severe types shows that an activated immune response emerges in severely affected patients. We propose a two-stage mechanism of pathogenesis for this unusual viral infection. Our data advance our understanding of the clinical features of COVID-19 infections and provide a resource for future mechanistic and therapeutics studies.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/pathology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Betacoronavirus/pathogenicity , Biomarkers/urine , COVID-19 , Coronavirus Infections/urine , Disease Progression , Humans , Immune Tolerance , Pandemics , Pneumonia/immunology , Pneumonia/pathology , Pneumonia/urine , Pneumonia, Viral/urine , Proteome/analysis , SARS-CoV-2 , Tight Junctions/pathology
17.
Proteomics ; 20(24): e2000229, 2020 12.
Article in English | MEDLINE | ID: covidwho-897888

ABSTRACT

Proteins and peptides serve as biomarkers in the context of multiple pathologies. The hypothesis that protein or peptide biomarkers may also be of value in the context of the Covid-19 pandemic appears self-evident. Proteome based biomarkers are not expected to display significant added value in the detection of viral infection but appear well suited to address a major unmet need: the prognosis of the course of disease, to guide appropriate, timely intervention. Based on similar approaches in the context of other diseases and using a CE-MS platform, urinary peptides are investigated for their value as biomarkers to assess disease progression after SARS-CoV-2 infection. The manuscript presented in this issue of Proteomics reports first results, indicating that urine peptides may be of substantial value in the assessment and prediction of severity of the Covid-19 disease course on an individual level. While the findings are not entirely surprising, the report does stand out from all others by a well-defined context-of-use, and, what is more, by presenting an already initiated validation study that may, if successful, result in immediate implementation of this proteomics-based diagnostic test. This approach should serve as positive example for the planning and execution of clinical proteomics studies.


Subject(s)
COVID-19/urine , Peptides/urine , Proteome/genetics , Proteomics , Biomarkers/urine , COVID-19/genetics , COVID-19/therapy , COVID-19/virology , Humans , Pandemics , Peptides/genetics , SARS-CoV-2 , Severity of Illness Index
18.
Pediatrics ; 147(3)2021 03.
Article in English | MEDLINE | ID: covidwho-839707

ABSTRACT

The novel coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, has created a global pandemic, with many cases affecting the elderly. However, children have been affected as well, with ∼2.4% to 3.7% of cases reported. This case is the first published case of an adolescent presenting with rhabdomyolysis as the first sign of novel coronavirus disease 2019, with extremely elevated creatinine kinase levels, approaching almost 400 000 U/L. This case adds to the growing body of literature of a variety of life-threatening manifestations associated with severe acute respiratory syndrome coronavirus 2 infection and highlights the importance of how prompt recognition of these unique presentations of the disease is important to mitigate complications.


Subject(s)
COVID-19/complications , COVID-19/diagnosis , Rhabdomyolysis/etiology , Adolescent , Biomarkers/blood , Biomarkers/urine , COVID-19/therapy , Creatine Kinase/urine , Critical Care , Humans , Male , Pandemics , Rhabdomyolysis/diagnosis , Rhabdomyolysis/virology , SARS-CoV-2
20.
Clin Chem Lab Med ; 58(7): 1121-1124, 2020 06 25.
Article in English | MEDLINE | ID: covidwho-52616

ABSTRACT

Background Among patients with coronavirus disease 2019 (COVID-19), the cases of a significant proportion of patients are severe. A viral nucleic acid test is used for the diagnosis of COVID-19, and some hematological indicators have been used in the auxiliary diagnosis and identification of the severity of COVID-19. Regarding body fluid samples, except for being used for nucleic acid testing, the relationship between COVID-19 and routine body fluid parameters is not known. Our aim was to investigate the value of urine biochemical parameters in the prediction of the severity of COVID-19. Methods A total of 119 patients with COVID-19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID-19, the patients were divided into three groups (moderate 67, severe 42 and critical 10), and 45 healthy persons were enrolled in the same period as healthy controls. The relationship between the results of urine biochemical parameters and the severity of COVID-19 was analyzed. Results The positive rates of urine occult blood (BLOOD) and proteinuria (PRO) were higher in COVID-19 patients than in healthy controls (p < 0.05); the urine specific gravity (SG) value was lower in patients than in healthy controls (p < 0.05), and the urine potential of hydrogen (pH) value was higher in patients than in healthy controls (p < 0.01). The positive rates of urine glucose (GLU-U) and PRO in the severe and critical groups were higher than those in the moderate group (p < 0.01 and p < 0.05, respectively); other biochemical parameters of urine were not associated with the severity of COVID-19. Conclusions Some urine biochemical parameters are different between patients with severe acute respiratory syndrome (SARS)-CoV-2 and healthy controls, and GLU-U and PRO may be helpful for the differentiation of COVID-19 severity.


Subject(s)
Biomarkers/urine , Coronavirus Infections/urine , Pneumonia, Viral/urine , Urine/chemistry , Aged , Betacoronavirus/metabolism , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus/metabolism , Coronavirus/pathogenicity , Coronavirus Infections/metabolism , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/metabolism , SARS-CoV-2 , Severity of Illness Index
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