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1.
Cytokine ; 149: 155727, 2022 01.
Article in English | MEDLINE | ID: covidwho-1506763

ABSTRACT

BACKGROUND: Although pneumonia is the hallmark of coronavirus disease 2019 (COVID-19), multiple organ failure may develop in severe disease. TNFα receptors in their soluble form (sTNFR) are involved in the immune cascade in other systemic inflammatory processes such as septic shock, and could mediate the inflammatory activation of distant organs. The aim of this study is to analyse plasma levels of sTNFR 1 and 2 in association with organ failure and outcome in critically ill patients with COVID-19. METHODS: After informed consent, we included 122 adult patients with PCR-confirmed COVID-19 at ICU admission. Demographic data, illness severity scores, organ failure and survival at 30 days were collected. Plasma sTNFR 1 and 2 levels were quantified during the first days after ICU admission. Twenty-five healthy blood donors were used as control group. RESULTS: Levels of sTNFR were higher in severe COVID-19 patients compared to controls (p < 0.001). Plasma levels of sTNFR were associated to illness severity scores (SAPS 3 and SOFA), inflammation biomarkers such as IL-6, ferritin and PCT as well as development of AKI during ICU stay. sTNFR 1 higher than 2.29 ng/mL and? sTNFR 2 higher than 11.7 ng/mL were identified as optimal cut-offs to discriminate survivors and non-survivors 30 days after ICU admission and had an area under the curve in receiver operating characteristic curve of 0.75 and 0.67 respectively. CONCLUSION: Plasma levels of sTNFR 1 and 2 were higher in COVID-19 patients compared to controls and were strongly associated with other inflammatory biomarkers, severity of illness and acute kidney injury development during ICU stay. In addition, sTNFR 1 was an independent predictor of 30-day mortality after adjustment for age and respiratory failure.


Subject(s)
Acute Kidney Injury/blood , Acute Kidney Injury/mortality , COVID-19/blood , COVID-19/mortality , Critical Illness/mortality , Receptors, Tumor Necrosis Factor/blood , Biomarkers/blood , Female , Hospital Mortality , Humans , Intensive Care Units , Male , Middle Aged , Multiple Organ Failure/blood , Multiple Organ Failure/mortality , Organ Dysfunction Scores , Prospective Studies , SARS-CoV-2/pathogenicity , Severity of Illness Index
2.
Ther Drug Monit ; 43(4): 451-454, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1501177

ABSTRACT

OBJECTIVE: The authors report on a case of a 59-year-old man hospitalized in the intensive care unit because of severe SARS-COV-2 infection (COVID-19). BACKGROUND: The patient had several comorbidities, including liver cirrhosis. He developed ventilation-associated bacterial pneumonia for which he was administered cefepime at an initial dose of 2 g/8 hours. Therapeutic drug monitoring was performed, showing overexposure with an initial trough concentration of >60 mg/L. METHODS: Analysis of pharmacokinetic data and model-based dose adjustment was performed using BestDose software. RESULTS: The patient had unexpected pharmacokinetic parameter values. Serum creatinine was only moderately increased, whereas measured creatinine clearance based on urine collection showed impaired renal function. Bacterial minimum inhibitory concentration was also considered in the dosing decisions. After dose reduction to 0.5 g/8 hours, the cefepime trough concentration progressively declined and reached the target values by the end of the therapy. A post-hoc analysis provided a different interpretation of drug overexposure. CONCLUSION: This case report illustrates how physiological, microbiological, and drug concentration data can be used for model-based dosage individualization of cefepime in intensive care unit patients.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cefepime/pharmacokinetics , Critical Illness/therapy , Drug Dosage Calculations , Precision Medicine/methods , Acute Kidney Injury/blood , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Cefepime/administration & dosage , Cefepime/adverse effects , Humans , Male , Middle Aged
4.
BMC Nephrol ; 22(1): 297, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1381255

ABSTRACT

BACKGROUND: Kidney disease and renal failure are associated with hospital deaths in patients with COVID - 19. We aimed to test if contrast enhancement affects short-term renal function in hospitalized COVID - 19 patients. METHODS: Plasma creatinine (P-creatinine) was measured on the day of computed tomography (CT) and 24 h, 48 h, and 4-10 days after CT. Contrast-enhanced (n = 142) and unenhanced (n = 24) groups were subdivided, based on estimated glomerular filtration rates (eGFR), > 60 and ≤ 60 ml/min/1.73 m2. Contrast-induced acute renal failure (CI-AKI) was defined as ≥27 µmol/L increase or a > 50% rise in P-creatinine from CT or initiation of renal replacement therapy during follow-up. Patients with renal replacement therapy were studied separately. We evaluated factors associated with a > 50% rise in P-creatinine at 48 h and at 4-10 days after contrast-enhanced CT. RESULTS: Median P-creatinine at 24-48 h and days 4-10 post-CT in patients with eGFR> 60 and eGFR≥30-60 in contrast-enhanced and unenhanced groups did not differ from basal values. CI-AKI was observed at 48 h and at 4-10 days post contrast administration in 24 and 36% (n = 5/14) of patients with eGFR≥30-60. Corresponding figures in the eGFR> 60 contrast-enhanced CT group were 5 and 5% respectively, (p < 0.037 and p < 0.001, Pearson χ2 test). In the former group, four of the five patients died within 30 days. Odds ratio analysis showed that an eGFR≥30-60 and 30-day mortality were associated with CK-AKI both at 48 h and 4-10 days after contrast-enhanced CT. CONCLUSION: Patients with COVID - 19 and eGFR≥30-60 had a high frequency of CK-AKI at 48 h and at 4-10 days after contrast administration, which was associated with increased 30-day mortality. For patients with eGFR≥30-60, we recommend strict indications are practiced for contrast-enhanced CT. Contrast-enhanced CT had a modest effect in patients with eGFR> 60.


Subject(s)
Acute Kidney Injury/chemically induced , COVID-19/complications , Contrast Media/adverse effects , Creatinine/blood , Iodine/adverse effects , Kidney/drug effects , Acute Kidney Injury/blood , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , Aged , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , Female , Glomerular Filtration Rate , Humans , Kidney/diagnostic imaging , Kidney/physiopathology , Male , Middle Aged , Odds Ratio , Regression Analysis , Renal Replacement Therapy , Retrospective Studies , Time Factors , Tomography, X-Ray Computed
5.
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
6.
Sci Rep ; 11(1): 12606, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1270673

ABSTRACT

Increasing evidence has shown that Coronavirus disease 19 (COVID-19) severity is driven by a dysregulated immunologic response. We aimed to assess the differences in inflammatory cytokines in COVID-19 patients compared to contemporaneously hospitalized controls and then analyze the relationship between these cytokines and the development of Acute Respiratory Distress Syndrome (ARDS), Acute Kidney Injury (AKI) and mortality. In this cohort study of hospitalized patients, done between March third, 2020 and April first, 2020 at a quaternary referral center in New York City we included adult hospitalized patients with COVID-19 and negative controls. Serum specimens were obtained on the first, second, and third hospital day and cytokines were measured by Luminex. Autopsies of nine cohort patients were examined. We identified 90 COVID-19 patients and 51 controls. Analysis of 48 inflammatory cytokines revealed upregulation of macrophage induced chemokines, T-cell related interleukines and stromal cell producing cytokines in COVID-19 patients compared to the controls. Moreover, distinctive cytokine signatures predicted the development of ARDS, AKI and mortality in COVID-19 patients. Specifically, macrophage-associated cytokines predicted ARDS, T cell immunity related cytokines predicted AKI and mortality was associated with cytokines of activated immune pathways, of which IL-13 was universally correlated with ARDS, AKI and mortality. Histopathological examination of the autopsies showed diffuse alveolar damage with significant mononuclear inflammatory cell infiltration. Additionally, the kidneys demonstrated glomerular sclerosis, tubulointerstitial lymphocyte infiltration and cortical and medullary atrophy. These patterns of cytokine expression offer insight into the pathogenesis of COVID-19 disease, its severity, and subsequent lung and kidney injury suggesting more targeted treatment strategies.


Subject(s)
COVID-19/mortality , COVID-19/physiopathology , Cytokines/blood , Acute Kidney Injury/blood , Acute Kidney Injury/pathology , Acute Kidney Injury/virology , Aged , COVID-19/blood , COVID-19/therapy , Case-Control Studies , Cytokine Release Syndrome/virology , Female , Hospitals , Humans , Lung/pathology , Lung/virology , Male , Middle Aged , New York City , Respiration, Artificial , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/virology , Treatment Outcome
7.
J Clin Lab Anal ; 35(6): e23805, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1241507

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) has been reported developing commonly in coronavirus disease 2019 (COVID-19) patients and could increase the risk of poor outcomes in these patients. We design this study to explore the value of serum procalcitonin (PCT) on predicting AKI and construct risk score for predicting AKI in COVID-19 patients. METHODS: Patients diagnosed with COVID-19 and hospitalized in Renmin Hospital of Wuhan University between January 30 and February 24, 2020, were included. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the strongest predictors of AKI. Multivariate logistic regression analysis was conducted to find independent risk factors for AKI and construct risk score using odds ratio (OR) value of those risk factors. Receiver operating characteristics (ROC) curves were plotted, and area under the ROC curve (AUC) value was calculated to evaluate the predictive value of single PCT level and the constructed risk score. RESULTS: Among 389 included COVID-19 patients, 28 (7.2%) patients developed AKI. LASSO regression showed hypertension, saturation of arterial oxygen (SaO2 ), PCT, and blood urea nitrogen (BUN) were the strongest predictors for AKI. After multivariate logistic regression analysis, only SaO2 (<0.001), PCT (p = 0.004), and BUN (p = 0.005) were independently associated with development of AKI in COVID-19 patients. The AUC of single PCT and constructed risk score was 0. 881 and 0.928, respectively. CONCLUSION: PCT level is correlated with AKI in COVID-19 patients. The efficient risk score consisted of SaO2 , PCT, and BUN is readily accessible for physicians to evaluate the possibility of AKI in COVID-19 patients.


Subject(s)
Acute Kidney Injury , COVID-19 , Procalcitonin/blood , Acute Kidney Injury/blood , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/virology , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/complications , COVID-19/epidemiology , China , Female , Humans , Male , Middle Aged , Risk Assessment , Risk Factors , SARS-CoV-2
8.
Ther Drug Monit ; 43(4): 451-454, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1197045

ABSTRACT

OBJECTIVE: The authors report on a case of a 59-year-old man hospitalized in the intensive care unit because of severe SARS-COV-2 infection (COVID-19). BACKGROUND: The patient had several comorbidities, including liver cirrhosis. He developed ventilation-associated bacterial pneumonia for which he was administered cefepime at an initial dose of 2 g/8 hours. Therapeutic drug monitoring was performed, showing overexposure with an initial trough concentration of >60 mg/L. METHODS: Analysis of pharmacokinetic data and model-based dose adjustment was performed using BestDose software. RESULTS: The patient had unexpected pharmacokinetic parameter values. Serum creatinine was only moderately increased, whereas measured creatinine clearance based on urine collection showed impaired renal function. Bacterial minimum inhibitory concentration was also considered in the dosing decisions. After dose reduction to 0.5 g/8 hours, the cefepime trough concentration progressively declined and reached the target values by the end of the therapy. A post-hoc analysis provided a different interpretation of drug overexposure. CONCLUSION: This case report illustrates how physiological, microbiological, and drug concentration data can be used for model-based dosage individualization of cefepime in intensive care unit patients.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cefepime/pharmacokinetics , Critical Illness/therapy , Drug Dosage Calculations , Precision Medicine/methods , Acute Kidney Injury/blood , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Cefepime/administration & dosage , Cefepime/adverse effects , Humans , Male , Middle Aged
9.
Medicina (Kaunas) ; 57(3)2021 Mar 11.
Article in English | MEDLINE | ID: covidwho-1167651

ABSTRACT

Renal biopsy is useful to better understand the histological pattern of a lesion (glomerular, tubulointerstitial, and vascular) and the pathogenesis that leads to kidney failure. The potential impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the kidneys is still undetermined, and a variety of lesions are seen in the kidney tissue of coronavirus disease patients. This review is based on the morphological findings of patients described in case reports and a series of published cases. A search was conducted on MEDLINE and PubMed of case reports and case series of lesions in the presence of non-critical infection by SARS-CoV-2 published until 15/09/2020. We highlight the potential of the virus directly influencing the damage or the innate and adaptive immune response activating cytokine and procoagulant cascades, in addition to the genetic component triggering glomerular diseases, mainly collapsing focal segmental glomerulosclerosis, tubulointerstitial, and even vascular diseases. Kidney lesions caused by SARS-CoV-2 are frequent and have an impact on morbidity and mortality; thus, studies are needed to assess the morphological kidney changes and their mechanisms and may help define their spectrum and immediate or long-term impact.


Subject(s)
Acute Kidney Injury/pathology , COVID-19/pathology , Glomerulonephritis/pathology , Kidney/pathology , Thrombotic Microangiopathies/pathology , Acute Kidney Injury/blood , Acute Kidney Injury/immunology , Adaptive Immunity/immunology , Arteriosclerosis/immunology , Arteriosclerosis/pathology , COVID-19/blood , COVID-19/immunology , Cytokines/immunology , Glomerulonephritis/immunology , Glomerulonephritis, IGA/immunology , Glomerulonephritis, IGA/pathology , Glomerulosclerosis, Focal Segmental/immunology , Glomerulosclerosis, Focal Segmental/pathology , Humans , Immunity, Innate/immunology , Infarction/immunology , Infarction/pathology , Kidney/blood supply , Kidney/immunology , Kidney Cortex Necrosis/immunology , Kidney Cortex Necrosis/pathology , Nephritis, Interstitial/immunology , Nephritis, Interstitial/pathology , Nephrosis, Lipoid/immunology , Nephrosis, Lipoid/pathology , Rhabdomyolysis , SARS-CoV-2 , Thrombophilia/blood , Thrombotic Microangiopathies/immunology
11.
Clin Chem Lab Med ; 59(3): 599-607, 2021 02 23.
Article in English | MEDLINE | ID: covidwho-1067439

ABSTRACT

OBJECTIVES: Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes. METHODS: Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was maximum COVID-19 severity within 30 days of index ED visit. RESULTS: A total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease (p<0.05), as well as in those who developed severe acute kidney injury (AKI) and new positive bacterial cultures (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 and IL-10/lymphocyte count were associated with 42% (p=0.031) and 32% (p=0.013) increased odds, respectively, of severe COVID-19. When standardized to a one-unit standard deviations scale, an increase in the IL-10 was a stronger predictor of maximum 30-day severity and severe AKI than increases in IL-6 or IL-8. CONCLUSIONS: The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of new positive bacterial cultures. IL-10 and IL-10/lymphocyte count at ED presentation were independent predictors of COVID-19 severity. Moreover, elevated IL-10 was more strongly associated with outcomes than pro-inflammatory IL-6 or IL-8. The anti-inflammatory response in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.


Subject(s)
COVID-19/diagnosis , Interleukin-10/metabolism , Acute Kidney Injury/blood , Acute Kidney Injury/complications , Acute Kidney Injury/diagnosis , Adult , Aged , Bacterial Infections/blood , Bacterial Infections/complications , Bacterial Infections/diagnosis , COVID-19/blood , COVID-19/complications , Cohort Studies , Emergency Service, Hospital , Female , Hospitalization , Humans , Interleukin-10/blood , Lymphocyte Count , Male , Middle Aged , Prognosis
13.
Platelets ; 32(1): 130-137, 2021 Jan 02.
Article in English | MEDLINE | ID: covidwho-1066099

ABSTRACT

The coronavirus disease 19 (COVID-19) is a highly transmittable viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 utilizes metallocarboxyl peptidase angiotensin receptor (ACE) 2 to gain entry into human cells. Activation of several proteases facilitates the interaction of viral spike proteins (S1) and ACE2 receptor. This leads to cleavage of host ACE2 receptors. ACE2 activity counterbalances the angiotensin II effect, its loss may lead to elevated angiotensin II levels with modulation of platelet function, size and activity. COVID-19 disease encompasses a spectrum of systemic involvement far beyond respiratory failure alone. Several features of this disease, including the etiology of acute kidney injury (AKI) and the hypercoagulable state, remain poorly understood. Here, we show that there is a high incidence of AKI (81%) in the critically ill adults with COVID-19 in the setting of elevated D-dimer, elevated ferritin, C reactive protein (CRP) and lactate dehydrogenase (LDH) levels. Strikingly, there were unique features of platelets in these patients, including larger, more granular platelets and a higher mean platelet volume (MPV). There was a significant correlation between measured D-dimer levels and MVP; but a negative correlation between MPV and glomerular filtration rates (GFR) in critically ill cohort. Our data suggest that activated platelets may play a role in renal failure and possibly hypercoagulability status in COVID19 patients.


Subject(s)
Acute Kidney Injury/etiology , Angiotensin II/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Blood Platelets/pathology , COVID-19/complications , Pandemics , Receptors, Virus/metabolism , SARS-CoV-2 , Thrombocytopenia/etiology , Thrombophilia/etiology , Acute Kidney Injury/blood , Acute Kidney Injury/physiopathology , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/epidemiology , Comorbidity , Diabetes Mellitus/epidemiology , Female , Fibrin Fibrinogen Degradation Products/analysis , Glomerular Filtration Rate , Humans , Hypertension/epidemiology , Male , Mean Platelet Volume , Middle Aged , Renin-Angiotensin System/physiology , Thrombophilia/blood , Young Adult
14.
Swiss Med Wkly ; 151: w20420, 2021 01 18.
Article in English | MEDLINE | ID: covidwho-1055196

ABSTRACT

The authors present the case of a 58-year-old man with the unique combination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and, later on, haemophagocytic lymphohistiocytosis admitted to the intensive care unit. During his ICU stay the patient developed a variety of complications including acute respiratory distress syndrome, pulmonary embolism, right heart failure and suspected HLH leading to multiorgan failure and death. Despite the proven diagnosis of haemophagocytic lymphohistiocytosis, the excessively high ferritin levels of the patient did not seem fully explained by this diagnosis. Therefore, the authors want to highlight different causes of hyperferritinaemia in critically ill patients and underline the importance of differential diagnoses when interpreting continuously rising ferritin levels.


Subject(s)
Acute Kidney Injury/physiopathology , COVID-19/physiopathology , Heart Failure/physiopathology , Hyperferritinemia/blood , Liver Failure/physiopathology , Lymphohistiocytosis, Hemophagocytic/physiopathology , Pulmonary Embolism/physiopathology , Acute Kidney Injury/blood , Acute Kidney Injury/etiology , Alanine Transaminase/blood , COVID-19/blood , COVID-19/complications , COVID-19/therapy , Creatinine/blood , Disease Progression , Fatal Outcome , Heart Failure/etiology , Humans , Hyperferritinemia/etiology , Liver Failure/blood , Liver Failure/etiology , Lymphohistiocytosis, Hemophagocytic/etiology , Male , Middle Aged , Multiple Organ Failure/etiology , Multiple Organ Failure/physiopathology , Pulmonary Embolism/etiology , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , SARS-CoV-2
15.
Nephrology (Carlton) ; 26(6): 513-521, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1050365

ABSTRACT

AIM: This study aims to determine the frequency of COVID-19 related AKI and to identify the early predictors of AKI. METHODS: This study is a single-center, retrospective, observational study. Hospitalized COVID-19 patients between 24/03/2020 and 31/05/2020 were included in the study. All patients were evaluated for renal dysfunctions with urine dipstick, protein/creatinine ratio, albumin/creatinine ratio in spot urine, serum cystatin C, serum creatinine level on hospital admission, and 28th day of hospital admission. To assess the utility of these parameters to predict AKI, a receiver-operating characteristic curve was generated and the area under the curve (AUC) was calculated. RESULTS: 348 patients were included. The average incidence of AKI was 4.9% (n = 17). The incidence of AKI in mild, moderate and severe COVID-19 cases was 1.3% (n = 4), 9.0% (n = 3) and 76.9% (n = 10), respectively. Proteinuria was detected in 7.8% (n = 27) of patients with a urine dipstick test. In spot urine analysis, proteinuria was found in 20.1% (n = 70) of patients. The frequency of persistent proteinuria was 5.2% (n = 18). The AUC alue of serum cystatin C, D-dimer and albumin/creatinine ratio to predict COVID-19 related AKI were 0.96 (0.90 to 1.0), 0.94 (0.89-0.98), and 0.95 (0.91-0.98). CONCLUSION: In COVID-19 patients with normal serum creatinine levels on hospital admission, albuminuria, serum cystatin C and D-dimer levels may be an early predictor of COVID-19 related AKI and these patients should be monitored closely for AKI. Since the sample size in the AKI group was small, our study results should be confirmed with larger cohort studies.


Subject(s)
Acute Kidney Injury/etiology , COVID-19/complications , SARS-CoV-2 , Acute Kidney Injury/blood , Acute Kidney Injury/epidemiology , Adult , Aged , Creatinine/blood , Cystatin C/blood , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Male , Middle Aged , Retrospective Studies
16.
Am J Kidney Dis ; 77(4): 490-499.e1, 2021 04.
Article in English | MEDLINE | ID: covidwho-1012701

ABSTRACT

RATIONALE & OBJECTIVE: Although coronavirus disease 2019 (COVID-19) has been associated with acute kidney injury (AKI), it is unclear whether this association is independent of traditional risk factors such as hypotension, nephrotoxin exposure, and inflammation. We tested the independent association of COVID-19 with AKI. STUDY DESIGN: Multicenter, observational, cohort study. SETTING & PARTICIPANTS: Patients admitted to 1 of 6 hospitals within the Yale New Haven Health System between March 10, 2020, and August 31, 2020, with results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing via polymerase chain reaction of a nasopharyngeal sample. EXPOSURE: Positive test for SARS-CoV-2. OUTCOME: AKI by KDIGO (Kidney Disease: Improving Global Outcomes) criteria. ANALYTICAL APPROACH: Evaluated the association of COVID-19 with AKI after controlling for time-invariant factors at admission (eg, demographic characteristics, comorbidities) and time-varying factors updated continuously during hospitalization (eg, vital signs, medications, laboratory results, respiratory failure) using time-updated Cox proportional hazard models. RESULTS: Of the 22,122 patients hospitalized, 2,600 tested positive and 19,522 tested negative for SARS-CoV-2. Compared with patients who tested negative, patients with COVID-19 had more AKI (30.6% vs 18.2%; absolute risk difference, 12.5% [95% CI, 10.6%-14.3%]) and dialysis-requiring AKI (8.5% vs 3.6%) and lower rates of recovery from AKI (58% vs 69.8%). Compared with patients without COVID-19, patients with COVID-19 had higher inflammatory marker levels (C-reactive protein, ferritin) and greater use of vasopressors and diuretic agents. Compared with patients without COVID-19, patients with COVID-19 had a higher rate of AKI in univariable analysis (hazard ratio, 1.84 [95% CI, 1.73-1.95]). In a fully adjusted model controlling for demographic variables, comorbidities, vital signs, medications, and laboratory results, COVID-19 remained associated with a high rate of AKI (adjusted hazard ratio, 1.40 [95% CI, 1.29-1.53]). LIMITATIONS: Possibility of residual confounding. CONCLUSIONS: COVID-19 is associated with high rates of AKI not fully explained by adjustment for known risk factors. This suggests the presence of mechanisms of AKI not accounted for in this analysis, which may include a direct effect of COVID-19 on the kidney or other unmeasured mediators. Future studies should evaluate the possible unique pathways by which COVID-19 may cause AKI.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/epidemiology , Acute Kidney Injury/blood , Acute Kidney Injury/therapy , Aged , C-Reactive Protein/metabolism , COVID-19/metabolism , COVID-19/therapy , Cohort Studies , Creatinine/blood , Diuretics/therapeutic use , Female , Hospital Mortality , Humans , Intensive Care Units , Length of Stay , Male , Middle Aged , Proportional Hazards Models , Renal Dialysis , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/epidemiology , Respiration, Artificial , Risk Factors , SARS-CoV-2 , Severity of Illness Index , United States/epidemiology , Vasoconstrictor Agents/therapeutic use
17.
PLoS One ; 16(1): e0244779, 2021.
Article in English | MEDLINE | ID: covidwho-1007116

ABSTRACT

BACKGROUND: Currently, the SARS-CoV-2 promptly spread across China and around the world. However, there are controversies about whether preexisting chronic kidney disease (CKD) and acute kidney injury complication (AKI) are involved in the COVID-19 pandemic. MEASUREMENTS: Studies reported the kidney outcomes in different severity of COVID-19 were included in this study. Standardized mean differences or odds ratios were calculated by employing Review Manager meta-analysis software. RESULTS: Thirty-six trials were included in this systematic review with a total of 6395 COVID-19 patients. The overall effects indicated that preexisting CKD (OR = 3.28), complication of AKI (OR = 11.02), serum creatinine (SMD = 0.68), abnormal serum creatinine (OR = 4.86), blood urea nitrogen (SMD = 1.95), abnormal blood urea nitrogen (OR = 6.53), received continuous renal replacement therapy (CRRT) (OR = 23.63) were significantly increased in severe group than that in nonsevere group. Additionally, the complication of AKI (OR = 13.92) and blood urea nitrogen (SMD = 1.18) were remarkably elevated in the critical group than that in the severe group. CONCLUSIONS: CKD and AKI are susceptible to occur in patients with severe COVID-19. CRRT is applied frequently in severe COVID-19 patients than that in nonsevere COVID-19 patients. The risk of AKI is higher in the critical group than that in the severe group.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/epidemiology , Renal Insufficiency, Chronic/epidemiology , Acute Kidney Injury/blood , Blood Urea Nitrogen , COVID-19/blood , China/epidemiology , Creatinine/blood , Humans , Odds Ratio , Pandemics , Renal Insufficiency, Chronic/blood , SARS-CoV-2/isolation & purification , Treatment Outcome
18.
Int J Lab Hematol ; 43 Suppl 1: 129-136, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-998961

ABSTRACT

INTRODUCTION: Severe COVID-19 is often compounded by a prothrombotic state that is associated with poor outcomes. In this investigation, we aimed to evaluate ADAMTS13 activity, von Willebrand factor level (VWF:Ag), and the corresponding ADAMTS13 activity/VWF:Ag ratio, in patients with COVID-19 and for associations with disease progression and acute kidney injury (AKI). METHODS: Patients presenting to the emergency department (ED) with COVID-19 were enrolled in this prospective, observational study. ADAMTS13 activity and VWF:Ag were measured at index ED visit. The primary endpoint was severe AKI defined by KDIGO stage 2 + 3 criteria, while the secondary endpoint was peak 30-day COVID-19 severity. RESULTS: A total of 52 adult COVID-19 patients were enrolled. Overall, we observed that 23.1% of the cohort had a relative deficiency in ADAMTS13 activity, while 80.8% had elevated VWF:Ag. The ADAMTS13 activity/VWF:Ag ratio was significantly lower in patients with severe AKI (P = .002) and those who developed the severe form of COVID-19 (P = .020). The ADAMTS13 activity/VWF:Ag ratio was negatively correlated with age (P < .001) and LDH (P < .001), while positively correlated with hemoglobin (P = .041). After controlling for confounders, a one-unit increase in ADAMTS13/VWF:Ag ratio was associated with 20% decreased odds of severe AKI. CONCLUSION: A low ADAMTS13 activity:VWF:Ag ratio at ED presentation is associated with progression to severe COVID-19 disease and severe AKI, with a pattern suggestive of a secondary microangiopathy. Further interventional studies should be conducted to assess the restoration of ADAMTS13:VWF:Ag ratio in hospitalized patients with COVID-19.


Subject(s)
ADAMTS13 Protein/blood , Acute Kidney Injury/blood , COVID-19/blood , SARS-CoV-2 , Thrombotic Microangiopathies/etiology , von Willebrand Factor/analysis , ADAMTS13 Protein/deficiency , Acute Kidney Injury/etiology , Adult , Aged , COVID-19/complications , Comorbidity , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Severity of Illness Index , Thrombophilia/etiology
19.
Blood Purif ; 50(4-5): 520-530, 2021.
Article in English | MEDLINE | ID: covidwho-992129

ABSTRACT

BACKGROUND: Critically ill patients with COVID-19 may develop multiple organ dysfunction syndrome, including acute kidney injury (AKI). We report the incidence, risk factors, associations, and outcomes of AKI and renal replacement therapy (RRT) in critically ill COVID-19 patients. METHODS: We performed a retrospective cohort study of adult patients with COVID-19 diagnosis admitted to the intensive care unit (ICU) between March 2020 and May 2020. Multivariable logistic regression analysis was applied to identify risk factors for the development of AKI and use of RRT. The primary outcome was 60-day mortality after ICU admission. RESULTS: 101 (50.2%) patients developed AKI (72% on the first day of invasive mechanical ventilation [IMV]), and thirty-four (17%) required RRT. Risk factors for AKI included higher baseline Cr (OR 2.50 [1.33-4.69], p = 0.005), diuretic use (OR 4.14 [1.27-13.49], p = 0.019), and IMV (OR 7.60 [1.37-42.05], p = 0.020). A higher C-reactive protein level was an additional risk factor for RRT (OR 2.12 [1.16-4.33], p = 0.023). Overall 60-day mortality was 14.4% {23.8% (n = 24) in the AKI group versus 5% (n = 5) in the non-AKI group (HR 2.79 [1.04-7.49], p = 0.040); and 35.3% (n = 12) in the RRT group versus 10.2% (n = 17) in the non-RRT group, respectively (HR 2.21 [1.01-4.85], p = 0.047)}. CONCLUSIONS: AKI was common among critically ill COVID-19 patients and occurred early in association with IMV. One in 6 AKI patients received RRT and 1 in 3 patients treated with RRT died in hospital. These findings provide important prognostic information for clinicians caring for these patients.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/complications , Critical Illness/epidemiology , Hospital Mortality , Renal Replacement Therapy , Respiratory Distress Syndrome/etiology , SARS-CoV-2 , Acute Kidney Injury/blood , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Aged , Aged, 80 and over , Brazil/epidemiology , C-Reactive Protein/analysis , Comorbidity , Creatinine/blood , Female , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Multiple Organ Failure/etiology , Multiple Organ Failure/mortality , Renal Insufficiency, Chronic/complications , Renal Replacement Therapy/statistics & numerical data , Respiration, Artificial/adverse effects , Respiration, Artificial/statistics & numerical data , Respiratory Distress Syndrome/therapy , Retrospective Studies , Risk Factors , Treatment Outcome
20.
PLoS One ; 15(12): e0243528, 2020.
Article in English | MEDLINE | ID: covidwho-968571

ABSTRACT

Although the lungs are major targets for COVID-19 invasion, other organs-such as the kidneys-are also affected. However, the renal complications of COVID-19 are not yet well explored. This study aimed to identify the incidence of acute kidney injury (AKI) in patients with COVID-19 and to evaluate its impact on patient outcomes. This retrospective study included 704 patients with COVID-19 who were hospitalized at two hospitals in Daegu, Korea from February 19 to March 31, 2020. AKI was defined according to the serum creatinine criteria in the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The final date of follow-up was May 1, 2020. Of the 704 patients, 28 (4.0%) developed AKI. Of the 28 patients with AKI, 15 (53.6%) were found to have AKI stage 1, 3 (10.7%) had AKI stage 2, and 10 (35.7%) had AKI stage 3. Among these patients, 12 (42.9%) recovered from AKI. In the patients with AKI, the rates of admission to intensive care unit (ICU), administration of mechanical ventilator (MV), and in-hospital mortality were significantly higher than in patients without AKI. Multivariable analysis revealed that old age (Hazard ratio [HR] = 4.668, 95% confidence interval [CI] = 1.250-17.430, p = 0.022), high neutrophil-to-lymphocyte ratio (HR = 1.167, 95% CI = 1.078-1.264, p < 0.001), elevated creatinine kinase (HR = 1.002, 95% CI = 1.001-1.004, p = 0.007), and severe AKI (HR = 12.199, 95% CI = 4.235-35.141, p < 0.001) were independent risk factors for in-hospital mortality. The Kaplan-Meier curves showed that the cumulative survival rate was lowest in the AKI stage 3 group (p < 0.001). In conclusion, the incidence of AKI in patients with COVID-19 was 4.0%. Severe AKI was associated with in-hospital death.


Subject(s)
Acute Kidney Injury , COVID-19 , Critical Care , Hospital Mortality , Patient Admission , SARS-CoV-2 , Acute Kidney Injury/blood , Acute Kidney Injury/etiology , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Middle Aged , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Severity of Illness Index , Survival Rate
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