Safety of Remdesivir in Patients With Acute Kidney Injury or CKD.
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ABSTRACT:
SUBMITTER: Thakare S
PROVIDER: S-EPMC7547837 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Safety of Remdesivir in Patients With Acute Kidney Injury or CKD.
Thakare Sayali S Gandhi Chintan C Modi Tulsi T Bose Sreyashi S Deb Satarupa S Saxena Nikhil N Katyal Abhinav A Patil Ankita A Patil Sunil S Pajai Atim A Bajpai Divya D Jamale Tukaram T
Kidney international reports 20201010 1
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Project description:IntroductionMetabolic acidosis in patients with chronic kidney disease (CKD) results from a loss of kidney function. It has been associated with CKD progression, all-cause mortality, and other adverse outcomes. We aimed to determine whether metabolic acidosis is associated with a higher risk of acute kidney injury (AKI).MethodsThis was a retrospective cohort study. Using electronic health records and administrative data, we enrolled 2 North American cohorts of patients with CKD Stages G3-G5 as follows: (i) 136,067 patients in the US electronic medical record (EMR) based cohort; and (ii) 34,957 patients in the Manitoba claims-based cohort. The primary exposure was metabolic acidosis (serum bicarbonate between 12 mEq/l and <22 mEq/l). The primary outcome was the development of AKI (defined using ICD-9 and 10 codes at hospital admission or a laboratory-based definition based on Kidney Disease: Improving Global Outcomes guidelines). We applied Cox proportional hazards regression models adjusting for relevant demographic and clinical characteristics.ResultsIn both cohorts, metabolic acidosis was associated with AKI: hazard ratio (HR) 1.57 (95% confidence interval [CI] 1.52-1.61) in the US EMR cohort, and HR 1.65 (95% CI 1.58-1.73) in the Manitoba claims cohort. The association was consistent when serum bicarbonate was treated as a continuous variable, and in multiple subgroups, and sensitivity analyses including those adjusting for albuminuria.ConclusionMetabolic acidosis is associated with a higher risk of AKI in patients with CKD. AKI should be considered as an outcome in studies of treatments for patients with metabolic acidosis.
| S-EPMC9546743 | biostudies-literature
Project description:BackgroundPrevious studies reported that compared with percutaneous coronary interventions (PCIs), coronary artery bypass grafting (CABG) is associated with a reduced risk of mortality and repeat revascularization in patients with mild to moderate chronic kidney disease (CKD) and end-stage renal disease (ESRD). Information about outcomes associated with CABG versus PCI in patients with advanced stages of CKD is limited. We evaluated the incidence and relative risk of acute kidney injury (AKI) associated with CABG versus PCI in patients with advanced CKD.MethodsWe examined 730 US veterans with incident ESRD who underwent a first CABG or PCI up to 5 years prior to dialysis initiation. The association of CABG versus PCI with AKI was examined in multivariable adjusted logistic regression analyses.ResultsA total of 466 patients underwent CABG and 264 patients underwent PCI. The mean age was 64 ± 8 years, 99% were male, 20% were African American and 84% were diabetic. The incidence of AKI in the CABG versus PCI group was 67% versus 31%, respectively (P < 0.001). The incidence of all stages of AKI were higher after CABG compared with PCI. CABG was associated with a 4.5-fold higher crude risk of AKI {odds ratio [OR] 4.53 [95% confidence interval (CI) 3.28-6.27]; P < 0.001}, which remained significant after multivariable adjustments [OR 3.50 (95% CI 2.03-6.02); P < 0.001].ConclusionCABG was associated with a 4.5-fold higher risk of AKI compared with PCI in patients with advanced CKD. Despite other benefits of CABG over PCI, the extremely high risk of AKI associated with CABG should be considered in this vulnerable population when deciding on the optimal revascularization strategy.
| S-EPMC7967886 | biostudies-literature
Project description:Acute kidney injury (AKI) is a frequent clinical complication in critically ill patients, and it rapidly develops into renal failure with high morbidity and mortality. However, other than dialysis, no effective therapeutic interventions can offer reliable treatment to limit renal injury and improve survival. Here, we firstly reported that remdesivir (RDV, GS-5734), a broad-spectrum antiviral nucleotide prodrug, alleviated AKI by specifically inhibiting NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages. Mechanically, RDV effectively suppressed the activities of nuclear transcription factor (NF)-κB, mitogen-activated protein kinase (MAPK), which further led to the reduction of the inflammasome genes of NLRP3 transcription, limiting the activation of NLRP3 inflammasome in vivo and in vitro. RDV also inhibited other pro-inflammatory genes including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-12, IL-1β, and interferon-β (IFN-β), leading to the reduction of inflammatory factors release. Thus, RDV can ameliorate AKI via modulating macrophage inflammasome activation and inflammatory immune responses and may have a therapeutic potential for patients with AKI in clinical application.
| S-EPMC8176923 | biostudies-literature
Project description:IntroductionChronic kidney disease (CKD) and acute kidney injury (AKI) are strongly associated with excess morbidity and mortality and frequently co-occur in critically ill septic patients, but how their interplay affects clinical outcomes is not well elucidated.MethodsWe conducted a single-center, retrospective cohort study of 2632 adult patients admitted to the intensive care unit (ICU) with severe sepsis or septic shock. Subjects were classified into 6 groups according to baseline CKD (no-CKD: estimated glomerular filtration rate [eGFR] ≥60; CKD: eGFR 15-59 ml/min per 1.73 m2) and incident AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (no-AKI, AKI stage 1, AKI stages ≥2) during ICU stay. Study outcomes were 90-day mortality (in hospital or within 90 days of discharge) and incident/progressive CKD.ResultsPrevalent CKD was 46% and incident AKI was 57%. Adjusted hazard ratios (95% confidence intervals) for 90-day mortality relative to the reference group of no-CKD/no-AKI were 1.5 (1.1-2.0) in no-CKD/AKI stage 1, 2.4 (1.9-3.1) in no-CKD/AKI stages≥2, 1.1 (0.8-1.4) in CKD/no-AKI, 1.2 (0.9-1.6) in CKD/AKI stage 1, and 2.2 (1.7-2.9) in CKD/AKI stages ≥2. A similar trend was observed for incident/progressive CKD during a median follow-up of 15.3 months.ConclusionStage 1 AKI on CKD was not associated with an independent increased risk of adverse outcomes in critically ill septic patients. AKI stages ≥2 on CKD and any level of AKI in no-CKD patients were strongly and independently associated with adverse outcomes. Sepsis-associated stage 1 AKI on CKD may represent distinct underlying pathophysiology, with more prerenal cases and less severe de novo intrinsic damage, which needs further investigation.
| S-EPMC6224792 | biostudies-literature
Project description: Not available
| S-EPMC9727512 | biostudies-literature
Project description:Background and aimTo investigate and quantify the risks of AKI and ALI associated with remdesivir use, given the underlying diseases of SARS-CoV-2 infection.MethodsThis self-controlled case series (SCCS) study was conducted using electronic hospital records between 23 January 2020 and 31 January 2021 as retrieved from the Hong Kong Hospital Authority which manages all laboratory-confirmed COVID-19 cases in Hong Kong. Outcomes of AKI and ALI were defined using the KDIGO Guideline and Asia Pacific Association of Study of Liver consensus guidelines. Incidence rate ratios (IRR) for AKI and ALI following the administration of remdesivir (exposure) in comparison to a non-exposure period were estimated using the conditional Poisson regression models.ResultsOf 860 COVID-19 patients administered remdesivir during hospitalisation, 334 (38.8%) and 137 (15.9%) had incident ALI and AKI, respectively. Compared with the baseline period, both ALI and AKI risks were increased significantly during the pre-exposure period (ALI: IRR = 6.169, 95% CI = 4.549-8.365; AKI: IRR = 7.074, 95% CI = 3.763-13.298) and remained elevated during remdesivir treatment. Compared to the pre-exposure period, risks of ALI and AKI were not significantly higher in the first 2 days of remdesivir initiation (ALI: IRR = 1.261, 95% CI = 0.915-1.737; AKI: IRR = 1.261, 95% CI = 0.889-1.789) and between days 2 and 5 of remdesivir treatment (ALI: IRR = 1.087, 95% CI = 0.793-1.489; AKI: IRR = 1.152, 95% CI = 0.821-1.616).ConclusionThe increased risks of AKI and ALI associated with intravenous remdesivir treatment for COVID-19 may be due to the underlying SARS-CoV-2 infection. The risks of AKI and ALI were elevated in the pre-exposure period, yet no such increased risks were observed following remdesivir initiation when compared to the pre-exposure period.
| S-EPMC9111503 | biostudies-literature
Project description:Background and hypothesisCardiovascular diseases are a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Acute kidney injury (AKI) has been increasingly recognized as a potential exacerbating factor for cardiovascular events in these patients. The CKD-REIN study aims to explore the relationship between AKI and the risk of major adverse cardiovascular events (MACE) in a cohort of CKD patients. We hypothesize that AKI is a significant and independent predictor of MACE in patients with CKD, and that the severity of AKI correlates with the risk of subsequent cardiovascular events.MethodsThis prospective cohort study included 3033 adult CKD patients from 40 outpatient nephrology clinics in France. Patients were followed for a median of 5.2 years. AKI episodes were identified and staged based on the KDIGO-AKI criteria. Cardiovascular events, including myocardial infarction, stroke, heart failure hospitalization, and cardiovascular death, were systematically recorded. The association between AKI and MACE was analyzed using a multivariable Cox model, adjusting for confounders such as demographic characteristics, medical history, and baseline kidney function.ResultsDuring the follow-up, 530 patients experienced at least one episode of AKI. The cumulative incidence of MACE at 1 year post-AKI was 8.1%. Patients with AKI had a significantly increased risk of MACE, with an adjusted hazard ratio (HR) of 5.78 (P < .001). The risk was consistent across different MACE components and was independent of age, sex, CKD stage, or comorbidities. The risk of MACE was higher for more severe AKI stages and for AKI events requiring hospitalization or associated with incomplete renal recovery.ConclusionThe findings of this study confirm that AKI is a significant independent predictor of MACE in CKD patients, demonstrating a strong severity-response relationship. These results underscore the importance of vigilant cardiovascular monitoring and preventive strategies in CKD patients following AKI episodes. Understanding the mechanisms linking AKI to cardiovascular outcomes is crucial for developing targeted interventions to mitigate these risks.
| S-EPMC11646099 | biostudies-literature
Project description:Macrophages are key immune cells in AKI and may determine the fate of AKI to CKD progression. Here, by taking advantages of single cell RNA-sequencing technology, we generated a mononuclear macrophage atlas from the initiation of AKI till the progression to CKD.
2024-12-31 | GSE239287 | GEO
Project description:ObjectivesRemdesivir is an antiviral agent with positive effects on the prognosis of Coronavirus Disease (COVID-19). However, there are concerns about the detrimental effects of remdesivir on kidney function which might consequently lead to Acute Kidney Injury (AKI). In this study, we aim to determine whether remdesivir use in COVID-19 patients increases the risk of AKI.MethodsPubMed, Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, medRxiv, and bioRxiv were systematically searched until July 2022, to find Randomized Clinical Trials (RCT) that evaluated remdesivir for its effect on COVID-19 and provided information on AKI events. A random-effects model meta-analysis was conducted and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. The primary outcomes were AKI as a Serious Adverse Event (SAE) and combined serious and non-serious Adverse Events (AE) due to AKI.ResultsThis study included 5 RCTs involving 3095 patients. Remdesivir treatment was not associated with a significant change in the risk of AKI classified as SAE (Risk Ratio [RR]: 0.71, 95% Confidence Interval [95% CI] 0.43‒1.18, p = 0.19, low-certainty evidence) and AKI classified as any grade AEs (RR = 0.83, 95% CI 0.52‒1.33, p = 0.44, low-certainty evidence), compared to the control group.ConclusionOur study suggested that remdesivir treatment probably has little or no effect on the risk of AKI in COVID-19 patients.
| S-EPMC10099148 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) and chronic kidney disease (CKD) have become worldwide public health problems, but little information is known about the epidemiology of acute kidney disease (AKD)-a state in between AKI and CKD. We aimed to explore the incidence and outcomes of hospitalized patients with AKD after AKI, and investigate the prognostic value of AKD in predicting 30-day and one-year adverse outcomes.MethodsA total of 2,556 hospitalized AKI patients were identified from three tertiary hospitals in China in 2015 and followed up for one year.AKD and AKD stage were defined according to the consensus report of the Acute Disease Quality Initiative 16 workgroup. Multivariable regression analyses adjusted for confounding variables were used to examine the association of AKD with adverse outcomes.ResultsAKD occurred in 45.4% (1161/2556) of all AKI patients, 14.5% (141/971) of AKI stage 1 patients, 44.6% (308/691) of AKI stage 2 patients and 79.6% (712/894) of AKI stage 3 patients. AKD stage 1 conferred a greater risk of Major Adverse Kidney Events within 30 days (MAKE30) (odds ratio [OR], 2.36; 95% confidence interval 95% CI [1.66-3.36]) than AKD stage 0 but the association only maintained in AKI stage 3 when patients were stratified by AKI stage. However, compared with AKD stage 0, AKD stage 2-3 was associated with higher risks of both MAKE30 and one-year chronic dialysis and mortality independent of the effects of AKI stage with OR being 31.35 (95% CI [23.42-41.98]) and 2.68 (95% CI [2.07-3.48]) respectively. The association between AKD stage and adverse outcomes in 30 days and one year was not significantly changed in critically ill and non-critically ill AKI patients. The results indicated that AKD is common among hospitalized AKI patients. AKD stage 2-3 provides additional information in predicting 30-day and one-year adverse outcomes over AKI stage. Enhanced follow-up of renal function of these patients may be warranted.
| S-EPMC8158174 | biostudies-literature