Association of severity and mortality of Covid-19 cases among acute kidney injury and sexual dimorphism.
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ABSTRACT: Introduction
The outbreak of coronavirus disease 2019 (Covid-19) severely impacted global health and economic status. The native receptor-ligand interaction of Angiotensin-converting enzyme 2 (ACE2) and S protein induces host cell pathogenesis via immunosuppression.Material and methods
The emerging evidence reports the sex disparity in Covid-19 induced mortality rate which affects abundantly men population. Although the biological interaction of Covid-19 with receptor upregulates the viral genome protein interactions and initiates the predictive multiorgan failure followed by acute kidney injury (AKI) in Covid-19 infected male population.Conclusion
Besides, the knowledge and lessons learned from the study depict that cellular and molecular links may explain the risk and severity of Covid-19 and AKI in the male population and lead to management of Covid-19 induced AKI. Therefore, this review explored the pathways associated with the pathogenesis of two diseased conditions with sex disparity.
SUBMITTER: Singh MK
PROVIDER: S-EPMC8898193 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
Publications
Association of severity and mortality of Covid-19 cases among acute kidney injury and sexual dimorphism.
Singh Mukul Kumar MK Jain Mayank M Shyam Hari H Sahu Dinesh Kumar DK Mishra Archana A Shankar Pratap P Kumar Shailendra S Singh Vishwajeet V
Molecular biology reports 20220306 7
<h4>Introduction</h4>The outbreak of coronavirus disease 2019 (Covid-19) severely impacted global health and economic status. The native receptor-ligand interaction of Angiotensin-converting enzyme 2 (ACE2) and S protein induces host cell pathogenesis via immunosuppression.<h4>Material and methods</h4>The emerging evidence reports the sex disparity in Covid-19 induced mortality rate which affects abundantly men population. Although the biological interaction of Covid-19 with receptor upregulates ...[more]
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Project description:Acute kidney injury (AKI) is a common complication of cardiovascular diseases (CVDs) in both males and females, increasing mortality rate substantially. Premenopausal females appear to be more protected, suggesting a potential protective role of female sex hormones. Here, we tested the hypothesis that ovariectomy (OVX) eliminates the beneficial effect of female sex on renal protection following acute myocardial infarction (MI). Seven days post-MI, both sexes exhibited worsened kidney function and a substantial decrease in total kidney NAD levels. Unlike MI female mice, MI males showed exacerbated morphological alterations with increased proinflammatory, proapoptotic, and profibrotic biomarkers. The expression of NAD+ biosynthetic enzymes NAMPT and NMRK-1 was increased in MI females only, while males showed a substantial increase in NAD+ consuming enzyme PARP-1. OVX did not eliminate the female-sex protection of glomerular morphology but was associated with swelling of proximal convoluted tubules with MI as in males. With OVX, MI females had enhanced proinflammatory cytokine release, and a further decrease in creatinine clearance and urine output was observed. Our findings suggest that MI induced AKI in both sexes with pre-menopausal female mice being more protected. Ovariectomy worsens aspects of AKI in females after MI, which may portend increased risk for development of chronic kidney disease.
| S-EPMC9816372 | biostudies-literature
Project description:ImportanceThe current definition and staging of acute kidney injury (AKI) considers alterations in serum creatinine (sCr) level and urinary output (UO). However, the relevance of oliguria-based criteria is disputed.ObjectiveTo determine the contribution of oliguria, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, to AKI diagnosis, severity assessment, and short- and long-term outcomes.Design, setting, and participantsThis cohort study included adult patients admitted to a multidisciplinary intensive care unit from January 1, 2010, to June 15, 2020. Patients receiving long-term dialysis and those who declined consent were excluded. Daily sCr level and hourly UO measurements along with sociodemographic characteristics and severity scores were extracted from electronic medical records. Long-term mortality was assessed by cross-referencing the database with the Swiss national death registry. The onset and severity of AKI according to the KDIGO classification was determined using UO and sCr criteria separately, and their agreement was assessed.Main outcomes and measuresUsing a multivariable model accounting for baseline characteristics, severity scores, and sCr stages, the association of UO criteria with 90-day mortality was evaluated. Sensitivity analyses were conducted to assess how missing sCr, body weight, and UO values, as well as different sCr baseline definitions and imputations methods, would affect the main results.ResultsAmong the 15 620 patients included in the study (10 330 men [66.1%] with a median age of 65 [IQR, 53-75] years, a median Simplified Acute Physiology Score II score of 40.0 [IQR, 30.0-53.0], and a median follow-up of 67.0 [IQR, 34.0-100.0] months), 12 143 (77.7%) fulfilled AKI criteria. Serum creatinine and UO criteria had poor agreement on AKI diagnosis and staging (Cohen weighted κ, 0.36; 95% CI, 0.35-0.37; P < .001). Compared with the isolated use of sCr criteria, consideration of UO criteria enabled identification of AKI in 5630 patients (36.0%). Those patients had a higher 90-day mortality than patients without AKI (724 of 5608 [12.9%] vs 288 of 3462 [8.3%]; P < .001). On multivariable analysis accounting for sCr stage, comorbidities, and illness severity, UO stages 2 and 3 were associated with a higher 90-day mortality (odds ratios, 2.4 [95% CI, 1.6-3.8; P < .001] and 6.2 [95% CI, 3.7-10.5; P < .001], respectively). These results remained significant in all sensitivity analyses.Conclusions and relevanceThe findings of this cohort study suggest that oliguria lasting more than 12 hours (KDIGO stage 2 or 3) has major AKI diagnostic implications and is associated with outcomes irrespective of sCr elevations.
| S-EPMC8569487 | biostudies-literature
Project description:Rationale & objectiveAlthough 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 designMulticenter, observational, cohort study.Setting & participantsPatients 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.ExposurePositive test for SARS-CoV-2.OutcomeAKI by KDIGO (Kidney Disease: Improving Global Outcomes) criteria.Analytical approachEvaluated 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.ResultsOf 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]).LimitationsPossibility of residual confounding.ConclusionsCOVID-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.
| S-EPMC7791318 | biostudies-literature
Project description:BackgroundAcute liver injury (ALI), a complication often seen in COVID-19 patients, can lead to severe liver damage, multi-organ failure, acute vascular events, and can potentially escalate to patient mortality. Given this, we initiated a meta-analysis to investigate the correlation between ALI and adverse outcomes in COVID-19 patients.MethodsWe conducted an exhaustive search of databases, including Medline, Embase, PubMed Central, ScienceDirect, Google Scholar, and the Cochrane Library, from the November 2019 until January 2022. The quality of the included studies was evaluated using the Newcastle Ottawa (NO) scale. Our meta-analysis was carried out using a random-effects model and results were presented as pooled odds ratios (ORs) with their corresponding 95% confidence intervals (CIs).ResultsOur analysis incorporated 20 studies involving a total of 13,850 participants, predominantly from China and the United States. According to the NO scale, the majority of these studies were categorized as low-quality. Patients with ALI faced approximately 7 times higher odds of severe COVID-19 symptoms (pooled OR = 7.09; 95%CI: 4.97 to 10.12) and over 5 times higher odds of mortality (pooled OR = 5.50; 95%CI: 3.37 to 8.99) when compared to those without ALI.ConclusionOur findings affirm that ALI is a potent predictor of adverse outcomes, including severity and mortality, among COVID-19 patients. Recognizing and promptly addressing ALI in COVID-19 patients could be pivotal in improving prognosis and tailoring individualized patient management strategies. This underscores the need for clinicians to be vigilant about liver complications in the COVID-19 patients and integrate appropriate interventions in the treatment paradigm.
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Project description:In both humans and mice, repair of acute kidney injury is worse in males than in females. Here, we provide evidence that this sexual dimorphism results from sex differences in ferroptosis, an iron-dependent, lipid-peroxidation-driven regulated cell death. Using genetic and single-cell transcriptomic approaches in mice, we report that female sex confers striking protection against ferroptosis, which was experimentally induced in proximal tubular (PT) cells by deleting glutathione peroxidase 4 (Gpx4). Single-cell transcriptomic analyses further identify the NFE2-related factor 2 (NRF2) antioxidant protective pathway as a female resilience mechanism against ferroptosis. Genetic inhibition and pharmacological activation studies show that NRF2 controls PT cell fate and plasticity by regulating ferroptosis. Importantly, pharmacological NRF2 activation protects male PT cells from ferroptosis and improves cellular plasticity as in females. Our data highlight NRF2 as a potential therapeutic target to prevent failed renal repair after acute kidney injury in both sexes by modulating cellular plasticity.
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Project description:Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Department of Veterans Affairs Healthcare System hospitalized with a primary diagnosis indicating AKI (ICD9 codes 584.xx). In the exploratory phase, three multivariate prediction models for progression to stage 4 CKD were developed. In the confirmatory phase, the models were validated in 11,589 patients admitted for myocardial infarction or pneumonia during the same time frame that had RIFLE codes R, I, or F and complete data for all predictor variables. Of the 5351 patients in the AKI group, 728 entered stage 4 CKD after hospitalization. Models 1, 2, and 3 were all significant with 'c' statistics of 0.82, 0.81, and 0.77, respectively. In model validation, all three were highly significant when tested in the confirmatory patients, with moderate to large effect sizes and good predictive accuracy ('c' 0.81-0.82). Patients with AKI who required dialysis and then recovered were at especially high risk for progression to CKD. Hence, the severity of AKI is a robust predictor of progression to CKD.
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Project description:Introduction: Acute kidney injury (AKI) among the pediatric population is considered a risk factor for mortality and morbidities during pediatric intensive care unit (PICU) admission. The association between AKI and increased mortality risk and length of stay (LOS) is still inconclusive. This retrospective cohort study aimed to evaluate the impact of AKI severity upon critical management and clinical parameters with an evaluation of severity progression among AKI patients admitted to the PICU at a tertiary care hospital. Methods: AKI, defined with the Kidney Disease Improving Global Outcomes (KDIGO) classification, was determined based on serum creatinine and urine output with respect to the patient's baseline value. The following outcomes were examined: mortality, mechanical ventilation use, use of non-invasive ventilation, recovery at discharge, and LOS in the hospital and PICU stratified by type of AKI upon admission. Medical records of the 165 included patients were reviewed for clinical data and study outcomes. Results: The median age of the patients was 7 years (IQR 1.5-10 years), and 58% were boys; 78 (47.2%) had stage 1 AKI, 49 (29.71%) had stage 2 AKI, and 38 (23%) had stage 3 AKI at admission. The mortality rate was 26%. The median LOS in the PICU was statistically significant between AKI stages, with a higher median LOS among patients with AKI stage 3 at admission. Using the maximum KDIGO stage, there was no association between AKI and mortality (adjusted OR 1.91, 95% CI 0.05), whereas for the mechanical ventilation outcome, the adjusted OR was 1.84 (95% CI 0.42-8.1). Conclusions: The severity of AKI is not associated solely with mortality and clinical outcomes as the numbers of comorbidities and organ failures contribute to mortality. However, improving awareness of AKI and understanding the disease progression course would reduce acute and long-term morbidity and mortality.
| S-EPMC11818388 | biostudies-literature
Project description:BackgroundResearch regarding COVID-19 and acute kidney injury (AKI) in older adults is scarce. We evaluated risk factors and outcomes of AKI in hospitalized older adults with and without COVID-19.MethodsObservational study of patients admitted to two geriatric clinics in Stockholm from March 1st to June 15th, 2020. The difference in incidence, risk factors and adverse outcomes for AKI between patients with or without COVID-19 were examined. Odds ratios (OR) for the risk of AKI and in-hospital death were obtained from logistic regression.ResultsThree hundred-sixteen older patients were hospitalized for COVID-19 and 876 patients for non-COVID-19 diagnoses. AKI occurred in 92 (29%) patients with COVID-19 vs. 159 (18%) without COVID-19. The odds for developing AKI were higher in patients with COVID-19 (adjusted OR, 1.70; 95% confidence interval [CI] 1.04-2.76), low baseline kidney function as depicted by estimated glomerular filtration rate (eGFR) [4.19 (2.48-7.05), for eGFR 30 to < 60 mL/min, and 20.3 (9.95-41.3) for eGFR < 30 mL/min], and higher C reactive protein (CRP) (OR 1.81 (1.11-2.95) in patients with initial CRP > 10 mg/L). Compared to patients without COVID-19 and without AKI, the risk of in-hospital death was highest in patients with COVID-19 and AKI [OR 80.3, 95% CI (27.3-235.6)], followed by COVID-19 without AKI [16.3 (6.28-42.4)], and by patients without COVID-19 and with AKI [10.2 (3.66-28.2)].ConclusionsGeriatric patients hospitalized with COVID-19 had a higher incidence of AKI compared to patients hospitalized for other diagnoses. COVID-19 and reduced baseline kidney function were risk factors for developing AKI. AKI and COVID-19 were associated with in-hospital death.
| S-EPMC7982881 | biostudies-literature
Project description:BackgroundCreatinine is widely used to estimate renal function, but this is not practical in critical illness. Low creatinine has been associated with mortality in many clinical settings. However, the associations between predialysis creatinine level, Sepsis-related Organ Failure Assessment (SOFA) score, fluid overload, and mortality in acute kidney injury patients receiving dialysis therapy (AKI-D) has not been fully addressed.MethodsWe extracted data for AKI-D patients in the eICU and MIMIC databases. We conducted a retrospective observational cohort study using the eICU dataset. The study cohort was divided into the high-creatine group and the low-creatinine group by the median value (4 mg/dL). The baseline patient information included demographic data, laboratory tests, medications, and comorbid conditions. The independent association of creatinine level with 30-day mortality was examined using multivariate logistic regression analysis. In sensitivity analyses, the associations between creatinine, SOFA score, and mortality were analyzed in patients with or without fluid overload. We also carried out an external validity using the MIMIC dataset.ResultsIn all 1,600 eICU participants, the 30-day mortality rate was 34.2%. The crude overall mortality rate in the low-creatinine group (44.9%) was significantly higher than that in the high-creatinine group (21.9%; P < 0.001). In the fully adjusted models, the low-creatinine group was associated with a higher risk of 30-day mortality (odds ratio, 1.77; 95% confidence interval, 1.29-2.42; P < 0.001) compared with the high-creatinine group. The low-creatinine group had higher SOFA and nonrenal SOFA scores. In sensitivity analyses, the low-creatinine group had a higher 30-day mortality rate with regard to the BMI or albumin level. Fluid overloaded patients were associated with a significantly worse survival in the low-creatinine group. The results were consistent when assessing the external validity using the MIMIC dataset.ConclusionsIn patients with AKI-D, lower predialysis creatinine was associated with increased mortality risk. Moreover, the mortality rate was substantially higher in patients with lower predialysis creatinine with concomitant elevation of fluid overload status.
| S-EPMC9512211 | biostudies-literature
Project description:ImportanceNeonatal acute kidney injury (AKI) is common and associated with morbidity and mortality. The temporal relationship between AKI and critical illness, as well as the frequency of AKI definition components (urine output and serum creatinine [sCr] concentration change), are unknown in extremely low-birth-weight (ELBW) (<1000 g), extremely preterm (<29 weeks' completed gestational age [GA]) infants.ObjectiveTo measure the frequency of AKI from birth to death or discharge with attention to the definition components as well as the temporal relationship of AKI to critical illness and death.Design, setting, and participantsA single-center, multiyear, retrospective cohort study was conducted at an academic level IV neonatal intensive care unit between January 1, 2012, and January 1, 2020. Participants included inborn ELBW and infants at 22 to 28 weeks' completed GA with confirmed congenital anomalies who survived 12 hours or more.ExposuresExtremely preterm birth and ELBW.Main outcomes and measuresThe primary outcome was AKI frequency. The timing, severity, and criteria for AKI were measured. The temporal relationship between AKI, organ dysfunction, and outcomes were quantified using odds ratios (ORs), logistic regression, and Shapley Additive Explanations. Acute kidney injury recognition, imaging, pediatric nephrology consultation, and follow-up were determined.ResultsA total of 436 infants (52% male; 44% Black) met the inclusion criteria (median BW, 725 g; median GA, 25.7 wk). Acute kidney injury was common in the first week of life (44%), primarily based on the change in the sCr concentration criterion (88%), and negatively associated with GA (OR, 0.69; 95% CI, 0.60-0.78), but positively associated with antecedent critical illness (OR, 1.17; 95% CI, 1.12-1.23), severe intraventricular hemorrhage (OR, 1.86; 95% CI, 1.12-3.08), late-onset sepsis (OR, 1.03; 95% CI, 1.02-1.03), and mortality (OR, 2.77; 95% CI, 1.63-4.72). Acute kidney injury had negligible clinical contribution to death within the model (Shapley Additive Explanation, <0.5% change to outcome) relative to antecedent patient-concentration organ dysfunction (6%-15% change). Among infants with severe AKI, recognition (32%), nephrology inpatient consultation (16%), and outpatient follow-up (9%) were not common.Conclusions and relevanceIn this cohort study of ELBW infants, AKI was common in the first week of life, inversely associated with GA, and followed organ (primarily cardiovascular) dysfunction. Acute kidney injury considered as the primary pathway to mortality was rare, and amelioration of AKI to modify death was not well supported.
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