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1.
Kidney360 ; 2(1): 33-41, 2021 01 28.
Article in English | MEDLINE | ID: covidwho-1776884

ABSTRACT

Background: AKI is a significant complication of coronavirus disease 2019 (COVID-19), with no effective therapy. Niacinamide, a vitamin B3 analogue, has some evidence of efficacy in non-COVID-19-related AKI. The objective of this study is to evaluate the association between niacinamide therapy and outcomes in patients with COVID-19-related AKI. Methods: We implemented a quasi-experimental design with nonrandom, prospective allocation of niacinamide in 201 hospitalized adult patients, excluding those with baseline eGFR <15 ml/min per 1.73 m2 on or off dialysis, with COVID-19-related AKI by Kidney Disease Improving Global Outcomes (KDIGO) criteria, in two hospitals with identical COVID-19 care algorithms, one of which additionally implemented treatment with niacinamide for COVID-19-related AKI. Patients on the niacinamide protocol (B3 patients) were compared against patients at the same institution before protocol commencement and contemporaneous patients at the non-niacinamide hospital (collectively, non-B3 patients). The primary outcome was a composite of death or RRT. Results: A total of 38 out of 90 B3 patients and 62 out of 111 non-B3 patients died or received RRT. Using multivariable Cox proportional hazard modeling, niacinamide was associated with a lower risk of RRT or death (HR, 0.64; 95% CI, 0.40 to 1.00; P=0.05), an association driven by patients with KDIGO stage-2/3 AKI (HR, 0.29; 95% CI, 0.13 to 0.65; P=0.03; P interaction with KDIGO stage=0.03). Total mortality also followed this pattern (HR, 0.17; 95% CI, 0.05 to 0.52; in patients with KDIGO stage-2/3 AKI, P=0.002). Serum creatinine after AKI increased by 0.20 (SEM, 0.08) mg/dl per day among non-B3 patients with KDIGO stage-2/3 AKI, but was stable among comparable B3 patients (+0.01 [SEM, 0.06] mg/dl per day; P interaction=0.03). Conclusions: Niacinamide was associated with lower risk of RRT/death and improved creatinine trajectory among patients with severe COVID-19-related AKI. Larger randomized studies are necessary to establish a causal relationship.


Subject(s)
Acute Kidney Injury , COVID-19 , Acute Kidney Injury/drug therapy , Adult , COVID-19/complications , Humans , Niacinamide/therapeutic use , Prospective Studies , Renal Dialysis/adverse effects , Retrospective Studies , Risk Factors
2.
Br J Pharmacol ; 179(14): 3831-3838, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1764897

ABSTRACT

Seriously ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hospitalized in intensive care units (ICUs) are commonly given a combination of drugs, a process known as multi-drug treatment. After extracting data on drug-drug interactions with clinical relevance from available online platforms, we hypothesize that an overall interaction map can be generated for all drugs administered. Furthermore, by combining this approach with simulations of cellular biochemical pathways, we may be able to explain the general clinical outcome. Finally, we postulate that by applying this strategy retrospectively to a cohort of patients hospitalized in ICU, a prediction of the timing of developing acute kidney injury (AKI) could be made. Whether or not this approach can be extended to other diseases is uncertain. Still, we believe it represents a valuable pharmacological insight to help improve clinical outcomes for severely ill patients.


Subject(s)
Acute Kidney Injury , COVID-19 , Acute Kidney Injury/drug therapy , COVID-19/drug therapy , Drug Interactions , Humans , Intensive Care Units , Retrospective Studies , SARS-CoV-2
3.
Signal Transduct Target Ther ; 7(1): 57, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1702971

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.


Subject(s)
Acute Kidney Injury/complications , COVID-19/complications , Cytokine Release Syndrome/complications , Disseminated Intravascular Coagulation/complications , Lymphopenia/complications , Myocarditis/complications , Pulmonary Embolism/complications , Acute Kidney Injury/drug therapy , Acute Kidney Injury/immunology , Acute Kidney Injury/virology , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Endothelial Cells/drug effects , Endothelial Cells/immunology , Endothelial Cells/virology , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/virology , Myocarditis/drug therapy , Myocarditis/immunology , Myocarditis/virology , Pulmonary Embolism/drug therapy , Pulmonary Embolism/immunology , Pulmonary Embolism/virology , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
4.
Int J Mol Sci ; 23(4)2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1700470

ABSTRACT

As of December 2021, SARS-CoV-2 had caused over 250 million infections and 5 million deaths worldwide. Furthermore, despite the development of highly effective vaccines, novel variants of SARS-CoV-2 continue to sustain the pandemic, and the search for effective therapies for COVID-19 remains as urgent as ever. Though the primary manifestation of COVID-19 is pneumonia, the disease can affect multiple organs, including the kidneys, with acute kidney injury (AKI) being among the most common extrapulmonary manifestations of severe COVID-19. In this article, we start by reflecting on the epidemiology of kidney disease in COVID-19, which overwhelmingly demonstrates that AKI is common in COVID-19 and is strongly associated with poor outcomes. We also present emerging data showing that COVID-19 may result in long-term renal impairment and delve into the ongoing debate about whether AKI in COVID-19 is mediated by direct viral injury. Next, we focus on the molecular pathogenesis of SARS-CoV-2 infection by both reviewing previously published data and presenting some novel data on the mechanisms of cellular viral entry. Finally, we relate these molecular mechanisms to a series of therapies currently under investigation and propose additional novel therapeutic targets for COVID-19.


Subject(s)
Acute Kidney Injury/drug therapy , Acute Kidney Injury/etiology , COVID-19/complications , Kidney/virology , Acute Kidney Injury/epidemiology , Acute Kidney Injury/mortality , Animals , Humans , Kidney/physiopathology , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/virology
5.
Acta Biochim Biophys Sin (Shanghai) ; 54(1): 1-11, 2022 01 25.
Article in English | MEDLINE | ID: covidwho-1674885

ABSTRACT

Since the first reported case in December of 2019, the coronavirus disease 2019 (COVID-19) has became an international public health emergency. So far, there are more than 228,206,384 confirmed cases including 4,687,066 deaths. Kidney with high expression of angiotensin-converting enzyme 2 (ACE2) is one of the extrapulmonary target organs affected in patients with COVID-19. Acute kidney injury (AKI) is one of the independent risk factors for the death of COVID-19 patients. The imbalance between ACE2-Ang(1-7)-MasR and ACE-Ang II-AT1R axis in the kidney may contribute to COVID-19-associated AKI. Although series of research have shown the inconsistent effects of multiple common RAS inhibitors on ACE2 expression and enzyme activity, most of the retrospective cohort studies indicated the safety and protective effects of ACEI/ARB in COVID-19 patients. This review article highlights the current knowledge on the possible involvement of intrarenal RAS in COVID-19-associated AKI with a primary focus on the opposing effects of ACE2-Ang(1-7)-MasR and ACE-Ang II-AT1R signaling in the kidney. Human recombinant soluble ACE2 or ACE2 variants with preserved ACE2-enzymatic activity may be the best options to improve COVID-19-associated AKI.


Subject(s)
Acute Kidney Injury/etiology , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/complications , Kidney/physiology , Renin-Angiotensin System/physiology , SARS-CoV-2/pathogenicity , Acute Kidney Injury/drug therapy , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Humans , Kidney/drug effects , Renin-Angiotensin System/drug effects , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism
6.
J Acquir Immune Defic Syndr ; 87(5): 1167-1172, 2021 08 15.
Article in English | MEDLINE | ID: covidwho-1662157

ABSTRACT

BACKGROUND: Data on clinical characteristics and outcomes of people living with HIV (PLWH) hospitalized with coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) are limited. SETTING: Large tertiary health care system in the Bronx, NY. METHODS: We performed a retrospective cohort study of 83 PLWH and 4151 patients without HIV hospitalized with COVID-19 from March 10, 2020, to May 11, 2020. We compared the clinical characteristics and outcomes associated with AKI by HIV serostatus and evaluated HIV-related factors for AKI among PLWH. AKI was defined and staged using Kidney Disease Improving Global Outcomes criteria. RESULTS: The incidence of AKI in hospitalized patients with COVID-19 did not differ significantly by HIV serostatus (54.2% in PLWH vs 49.5% in patients without HIV, P = 0.6). Despite a higher incidence of stage 3 AKI (28.9% vs 17.1% P = 0.05) in PLWH compared with those without HIV, there was no significant difference in the need for renal replacement therapy (22.2% vs 13.4% P = 0.12), renal recovery (76.9% vs 82.5% P = 0.61), or dependence on renal replacement therapy (7.7% vs 3.8% P = 0.27). CD4 T-cell count, HIV-1 RNA viral suppression, and antiretroviral therapy use were not associated with AKI. AKI was associated with increased need for invasive ventilation and in-hospital death, but HIV was not an independent risk factor of in-hospital death after AKI [adjusted hazard ratio 1.01 (95% CI: 0.59 to 1.72), P = 0.98]. CONCLUSIONS: HIV-related factors were not associated with increased risk of AKI in PLWH hospitalized with COVID-19. PLWH hospitalized with COVID-19 had more stage 3 AKI, but outcomes after AKI were similar to those without HIV.


Subject(s)
Acute Kidney Injury/drug therapy , COVID-19/complications , HIV Infections/drug therapy , Acute Kidney Injury/complications , Acute Kidney Injury/epidemiology , Aged , Antirheumatic Agents/therapeutic use , COVID-19/epidemiology , Female , HIV Infections/complications , HIV Infections/epidemiology , Hospital Mortality , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2
7.
J Med Virol ; 93(12): 6760-6764, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1544331

ABSTRACT

The coronavirus disease 2019 (COVID-19) has affected more than a hundred million individuals and caused more than three million deaths worldwide. Specific risk groups were defined for increased risk of mortality and morbidity in COVID-19, and renal transplant recipients are at a significantly increased risk regarding outcomes due to their immunosuppressed conditions. This study evaluated the general characteristics of kidney transplant recipients with COVID-19 infection. Among 1257 transplant cases, 56 had COVID-19 infection, and 23 (41%) were hospitalized during the 9-month study period. Among all COVID-19 cases, 58% were male with a mean age of 45.5 (±13.2, 19-71) years, and the most frequent comorbidities were hypertension (70.9%) and diabetes (23.6%). Hospitalized patients were older (p = 0.03) and had higher rates of hypertension (p = 0.008), diabetes (p = 0.002), and ischemic heart disease (p = 0.03). Therapeutic management included antimetabolite withdrawal and prednisolone increase in 71%, calcineurin inhibitor withdrawal in 8% and decrease in 58%, hydroxychloroquine in 17%, tocilizumab in 3%, and antivirals in 67% of patients. Acute kidney injury and respiratory failure developed in 34% and 85%, respectively. The mortality rate was 23%. These results emphasized that the COVID-19 infection in renal transplant recipients significantly increases the risk of morbidity and mortality. Therefore, these patients should be intervened earlier and monitored closely to prevent poor outcomes.


Subject(s)
COVID-19/physiopathology , Immunocompromised Host/drug effects , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/adverse effects , Acute Kidney Injury/drug therapy , Adult , Aged , Comorbidity , Female , Humans , Hydroxychloroquine/therapeutic use , Kidney/drug effects , Male , Middle Aged , Retrospective Studies , Transplant Recipients , Young Adult
8.
J Infect Dev Ctries ; 15(9): 1273-1276, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1478140

ABSTRACT

INTRODUCTION: An outbreak of coronavirus disease-19 (COVID-19) has occurred in different parts of the world. Although a large piece of information regarding the epidemiology, clinical features, and management of COVID-19 has been reported in the general population, there is very limited data regarding organ transplant recipients, particularly regarding the management of maintenance immunosuppressive agents during infection. METHODOLOGY: We described a case of kidney transplant recipient from Thailand who had COVID-19 pneumonia and severe acute kidney injury. RESULTS: The patient's serum creatinine peaked at 7.0 mg/dL on day 15 of illness and returned to baseline value of 2.0 mg/dL on day 26 of illness. We have shown how we modified tacrolimus, mycophenolate, and steroids in the patient who had received favipiravir and lopinavir/ritonavir for COVID-19 pneumonia. CONCLUSIONS: In this case, successful modification of this immunosuppressive regimen was accomplished to reduce drug interaction complications, aiming to avoid calcineurin inhibitor nephrotoxicity while maintaining appropriate levels of immunosuppression to prevent organ rejection and to promote the patient's recovery from infection.


Subject(s)
Acute Kidney Injury/virology , COVID-19/drug therapy , Immunosuppressive Agents/administration & dosage , Acute Kidney Injury/drug therapy , Adult , Amides/therapeutic use , Drug Combinations , Drug Interactions , Humans , Kidney Transplantation , Lopinavir/therapeutic use , Male , Mycophenolic Acid/administration & dosage , Pyrazines/therapeutic use , Ritonavir/therapeutic use , Steroids/administration & dosage , Tacrolimus/administration & dosage , Thailand , Transplant Recipients
9.
Molecules ; 26(19)2021 Sep 30.
Article in English | MEDLINE | ID: covidwho-1444276

ABSTRACT

Data obtained from several intensive care units around the world have provided substantial evidence of the strong association between impairment of the renal function and in-hospital deaths of critically ill COVID-19 patients, especially those with comorbidities and requiring renal replacement therapy (RRT). Acute kidney injury (AKI) is a common renal disorder of various etiologies characterized by a sudden and sustained decrease of renal function. Studies have shown that 5-46% of COVID-19 patients develop AKI during hospital stay, and the mortality of those patients may reach up to 100% depending on various factors, such as organ failures and RRT requirement. Catechins are natural products that have multiple pharmacological activities, including anti-coronavirus and reno-protective activities against kidney injury induced by nephrotoxic agents, obstructive nephropathies and AKI accompanying metabolic and cardiovascular disorders. Therefore, in this review, we discuss the anti-SARS-CoV-2 and reno-protective effects of catechins from a mechanistic perspective. We believe that catechins may serve as promising therapeutics in COVID-19-associated AKI due to their well-recognized anti-SARS-CoV-2, and antioxidant and anti-inflammatory properties that mediate their reno-protective activities.


Subject(s)
Acute Kidney Injury/etiology , Antiviral Agents/pharmacology , COVID-19/complications , Catechin/pharmacology , Protective Agents/pharmacology , Acute Kidney Injury/drug therapy , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Catechin/chemistry , Catechin/therapeutic use , Humans , Protective Agents/chemistry , Protective Agents/therapeutic use , SARS-CoV-2/drug effects
10.
Crit Care ; 25(1): 299, 2021 08 19.
Article in English | MEDLINE | ID: covidwho-1367680

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk. METHODS: This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV + AKI and COV - AKI, respectively), who were submitted to CRRT. Filter clotting risks were compared among groups. RESULTS: Between January 2019 and July 2020, 238 patients were evaluated: 188 in the COV + AKI group and 50 in the COV - AKI group. Filter clotting during the first filter use occurred in 111 patients (46.6%). Heparin use conferred protection against filter clotting (HR = 0.37, 95% CI 0.25-0.55), resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV + AKI patients than among the COV - AKI patients, although it was similar between the COV + AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (5990 ng/ml). In the multivariate analysis, heparin was associated with a lower risk of filter clotting (HR = 0.28, 95% CI 0.18-0.43), whereas an elevated D-dimer level and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was marginally associated with an increased risk of circuit clotting (HR = 2.15, 95% CI 0.99-4.68). CONCLUSIONS: In COV + AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with a low risk of complications.


Subject(s)
Acute Kidney Injury/drug therapy , Citric Acid/pharmacology , Continuous Renal Replacement Therapy/instrumentation , Heparin/pharmacology , Micropore Filters/standards , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Adult , COVID-19/complications , COVID-19/epidemiology , Citric Acid/adverse effects , Citric Acid/therapeutic use , Cohort Studies , Continuous Renal Replacement Therapy/methods , Continuous Renal Replacement Therapy/statistics & numerical data , Female , Heparin/adverse effects , Heparin/therapeutic use , Humans , Kaplan-Meier Estimate , Male , Micropore Filters/statistics & numerical data , Middle Aged , Proportional Hazards Models , Retrospective Studies
11.
Adv Sci (Weinh) ; 8(18): e2101498, 2021 09.
Article in English | MEDLINE | ID: covidwho-1316192

ABSTRACT

Acute kidney injury (AKI), as a common oxidative stress-related renal disease, causes high mortality in clinics annually, and many other clinical diseases, including the pandemic COVID-19, have a high potential to cause AKI, yet only rehydration, renal dialysis, and other supportive therapies are available for AKI in the clinics. Nanotechnology-mediated antioxidant therapy represents a promising therapeutic strategy for AKI treatment. However, current enzyme-mimicking nanoantioxidants show poor biocompatibility and biodegradability, as well as non-specific ROS level regulation, further potentially causing deleterious adverse effects. Herein, the authors report a novel non-enzymatic antioxidant strategy based on ultrathin Ti3 C2 -PVP nanosheets (TPNS) with excellent biocompatibility and great chemical reactivity toward multiple ROS for AKI treatment. These TPNS nanosheets exhibit enzyme/ROS-triggered biodegradability and broad-spectrum ROS scavenging ability through the readily occurring redox reaction between Ti3 C2 and various ROS, as verified by theoretical calculations. Furthermore, both in vivo and in vitro experiments demonstrate that TPNS can serve as efficient antioxidant platforms to scavenge the overexpressed ROS and subsequently suppress oxidative stress-induced inflammatory response through inhibition of NF-κB signal pathway for AKI treatment. This study highlights a new type of therapeutic agent, that is, the redox-mediated non-enzymatic antioxidant MXene nanoplatforms in treatment of AKI and other ROS-associated diseases.


Subject(s)
Acute Kidney Injury/drug therapy , Antioxidants/pharmacology , Oxidation-Reduction/drug effects , Polyvinyls/pharmacology , Pyrrolidines/pharmacology , Titanium/pharmacology , Acute Kidney Injury/metabolism , Apoptosis/drug effects , Humans , Kidney/drug effects , Kidney/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects
12.
J Med Virol ; 93(7): 4411-4419, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1263106

ABSTRACT

In late December 2019, an outbreak of a novel coronavirus which caused coronavirus disease 2019 (COVID-19) was initiated. Acute kidney injury (AKI) was associated with higher severity and mortality of COVID-19. We aimed to evaluate the effects of comorbidities and medications in addition to determining the association between AKI, antibiotics against coinfections (AAC) and outcomes of patients. We conducted a retrospective study on adult patients hospitalized with COVID-19 in a tertiary center. Our primary outcomes were the incidence rate of AKI based on comorbidities and medications. The secondary outcome was to determine mortality, intensive care unit (ICU) admission, and prolonged hospitalization by AKI and AAC. Univariable and multivariable logistic regression method was used to explore predictive effects of AKI and AAC on outcomes. Out of 854 included participants, 118 patients developed AKI in whom, 57 used AAC and 61 did not. Hypertension and diabetes were the most common comorbidities in patients developed AKI. AAC, lopinavir/ritonavir, ribavirin, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and corticosteroids had significant higher rate of administration in patients developed AKI. AAC were associated with higher deaths (odds ratio [OR] = 5.13; 95% confidence interval (CI): 3-8.78) and ICU admission (OR = 5.87; 95%CI: 2.81-12.27), while AKI had higher OR for prolonged hospitalization (3.37; 95%CI: 1.76-6.45). Both AKI and AAC are associated with poor prognosis of COVID-19. Defining strict criteria regarding indications and types of antibiotics would help overcoming concomitant infections and minimizing related adverse events.


Subject(s)
Acute Kidney Injury/epidemiology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/pathology , SARS-CoV-2/drug effects , Acute Kidney Injury/drug therapy , Acute Kidney Injury/virology , Adult , Angiotensin-Converting Enzyme Inhibitors , Azithromycin/therapeutic use , Coinfection/drug therapy , Coinfection/prevention & control , Critical Care/statistics & numerical data , Drug Combinations , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Iran/epidemiology , Linezolid/therapeutic use , Lopinavir/therapeutic use , Male , Middle Aged , Retrospective Studies , Ribavirin/therapeutic use , Ritonavir/therapeutic use , Treatment Outcome , Vancomycin/therapeutic use
13.
Pediatr Nephrol ; 36(11): 3771-3776, 2021 11.
Article in English | MEDLINE | ID: covidwho-1237500

ABSTRACT

BACKGROUND: The rising number of infections due to Severe Acute Respiratory Syndrome Coronavirus-2 (popularly known as COVID-19) has brought to the fore new antiviral drugs as possible treatments, including favipiravir. However, there is currently no data regarding the safety of this drug in patients with kidney impairment. The aim of this paper, therefore, is to share our experience of the use of favipiravir in pediatric patients affected by COVID-19 with any degree of kidney impairment. METHODS: The study enrolled pediatric patients aged under 18 years and confirmed as suffering from COVID-19 and multisystem inflammatory syndrome in children (MIS-C) with any degree of kidney injury, who were treated with favipiravir at the time of admission. RESULTS: Out of a total of 11 patients, 7 were diagnosed with MIS-C and 4 with severe COVID-19. The median age of the cases was 15.45 (9-17.8) years and the male/female ratio was 7/4. At the time of admission, the median serum creatinine level was 1.1 mg/dl. Nine patients were treated with favipiravir for 5 days, and 2 patients for 5 days followed by remdesivir for 5-10 days despite kidney injury at the time of admission. Seven patients underwent plasma exchange for MIS-C while 2 severely affected cases underwent continuous kidney replacement therapy (CKRT) as well. One severe COVID-19 patient received plasma exchange as well as CKRT. Serum creatinine values returned to normal in mean 3.07 days. CONCLUSIONS: Favipiravir seems a suitable therapeutic option in patients affected by COVID-19 with kidney injury without a need for dose adjustment.


Subject(s)
Acute Kidney Injury/physiopathology , Amides/administration & dosage , COVID-19/complications , COVID-19/drug therapy , Pyrazines/administration & dosage , Renal Elimination , Systemic Inflammatory Response Syndrome/drug therapy , Acute Kidney Injury/drug therapy , Acute Kidney Injury/immunology , Acute Kidney Injury/virology , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacokinetics , Adolescent , Alanine/administration & dosage , Alanine/analogs & derivatives , Alanine/pharmacokinetics , Amides/pharmacokinetics , COVID-19/immunology , COVID-19/virology , Child , Creatinine/blood , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Glomerular Filtration Rate , Humans , Male , Pyrazines/pharmacokinetics , SARS-CoV-2/isolation & purification , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/virology , Treatment Outcome
14.
Nano Lett ; 21(10): 4394-4402, 2021 05 26.
Article in English | MEDLINE | ID: covidwho-1230861

ABSTRACT

The high demand for acute kidney injury (AKI) therapy calls the development of multifunctional nanomedicine for renal management with programmable pharmacokinetics. Here, we developed a renal-accumulating DNA nanodevice with exclusive kidney retention for longitudinal protection of AKI in different stages in a renal ischemia-reperfusion (I/R) model. Due to the prolonged kidney retention time (>12 h), the ROS-sensitive nucleic acids of the nanodevice could effectively alleviate oxidative stress by scavenging ROS in stage I, and then the anticomplement component 5a (aC5a) aptamer loaded nanodevice could sequentially suppress the inflammatory responses by blocking C5a in stage II, which is directly related to the cytokine storm. This sequential therapy provides durable and pathogenic treatment of kidney dysfunction based on successive pathophysiological events induced by I/R, which holds great promise for renal management and the suppression of the cytokine storm in more broad settings including COVID-19.


Subject(s)
Acute Kidney Injury , COVID-19 , Reperfusion Injury , Acute Kidney Injury/drug therapy , Acute Kidney Injury/metabolism , Humans , Kidney/metabolism , Oxidative Stress , Reperfusion Injury/drug therapy , SARS-CoV-2
15.
Am J Health Syst Pharm ; 78(15): 1382-1384, 2021 07 22.
Article in English | MEDLINE | ID: covidwho-1199471

ABSTRACT

PURPOSE: This case report describes utilization of thromboelastography (TEG) in the setting of an acute major bleed in a patient on dabigatran who had concomitant acute kidney injury. SUMMARY: An 80-year-old female presented to the emergency department after a fall with complaints of pain in her knee, shoulder, and hip. Her medical history was significant for coronary artery disease, for which she took clopidogrel 75 mg daily, and atrial fibrillation, for which she took dabigatran 150 mg twice daily. The physical exam was remarkable for pain within the shoulder, hip, and knee, which had swelling and ecchymosis that extended into the right thigh. Given the possibility of compartment syndrome with multiple possible etiologies of coagulopathy, TEG and computed tomography angiography (CTa) of the right lower extremity were performed. The initial TEG showed prolonged R time and activated clotting time, indicating clotting factor dysfunction with no additional coagulopathy noted, including antiplatelet effects. On the basis of the TEG and CTa findings, it was decided to reverse dabigatran with 5 grams of idarucizumab. Approximately 1 hour after administration of idarucizumab, the patient was taken to interventional radiology where a limited angiogram of the right lower extremity showed no active extravasation. Because of the patient's renal dysfunction and the possibility of rebound hypercoaguability, repeat TEG tests were ordered at 4 and 8 hours after the initial reversal to ensure clearance of idarucizumab-dabigatran complexes. The repeat TEG values showed complete reversal of the initial coagulopathy noted. During the admission, the patient required no blood transfusions or surgical interventions and all her initial laboratory results improved. CONCLUSION: Serial TEG testing was successful at managing multiple coagulopathies in a patient at risk for trauma-induced compartment syndrome.


Subject(s)
Acute Kidney Injury , Atrial Fibrillation , Acute Kidney Injury/diagnosis , Acute Kidney Injury/drug therapy , Aged, 80 and over , Dabigatran/adverse effects , Female , Hemorrhage , Humans , Thrombelastography
17.
Ren Fail ; 43(1): 335-339, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1078673

ABSTRACT

The introduction of Bruton's tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies. Due to the reduction of cytokine release, it is effective in chronic graft-versus-host disease, and its use has also been suggested in autoimmune diseases and in prevention of COVID-19-associated lung damage. Despite this effect on the immune response, we report a severe hypersensitivity reaction in a 76-year-old male patient diagnosed with prolymphocytic leukemia. Four weeks after the ibrutinib start, non-oliguric acute kidney injury with proteinuria and microscopic hematuria developed and that was accompanied by lower limb purpuras and paresthesia. Renal biopsy revealed acute interstitial nephritis. Employing 1 mg/kg methylprednisolone administration, serum creatinine decreased from 365 µmol/L to 125 µmol/L at 11 days and the proteinuria-hematuria as well as the purpura, paresthesia resolved. Three months later at stabile eGFR of 56 ml/min/1.73 m2 methylprednisolone was withdrawn and a rituximab-venetoclax treatment was initiated without side effects. We conclude that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib can cause acute interstitial nephritis. Early detection, discontinuation of ibrutinib, glucocorticoid administration may help to better preserve renal function, thereby lowering the risk of potential subsequent kidney injury.


Subject(s)
Acute Kidney Injury/chemically induced , Adenine/analogs & derivatives , Nephritis, Interstitial/chemically induced , Piperidines/adverse effects , Proteinuria/chemically induced , Acute Kidney Injury/drug therapy , Adenine/adverse effects , Aged , Cytokines/drug effects , Glucocorticoids/therapeutic use , Humans , Kidney/pathology , Leukemia, Prolymphocytic/drug therapy , Male , Nephritis, Interstitial/drug therapy , Protein Kinase Inhibitors , Proteinuria/drug therapy
18.
PLoS One ; 16(1): e0245209, 2021.
Article in English | MEDLINE | ID: covidwho-1067409

ABSTRACT

Kidneys are one of the targets for SARS-CoV-2, it is reported that up to 36% of patients with SARS-CoV-2 infection would develop into acute kidney injury (AKI). AKI is associated with high mortality in the clinical setting and contributes to the transition of AKI to chronic kidney disease (CKD). Up to date, the underlying mechanisms are obscure and there is no effective and specific treatment for COVID-19-induced AKI. In the present study, we investigated the mechanisms and interactions between Quercetin and SARS-CoV-2 targets proteins by using network pharmacology and molecular docking. The renal protective effects of Quercetin on COVID-19-induced AKI may be associated with the blockade of the activation of inflammatory, cell apoptosis-related signaling pathways. Quercetin may also serve as SARS-CoV-2 inhibitor by binding with the active sites of SARS-CoV-2 main protease 3CL and ACE2, therefore suppressing the functions of the proteins to cut the viral life cycle. In conclusion, Quercetin may be a novel therapeutic agent for COVID-19-induced AKI. Inhibition of inflammatory, cell apoptosis-related signaling pathways may be the critical mechanisms by which Quercetin protects kidney from SARS-CoV-2 injury.


Subject(s)
Acute Kidney Injury/drug therapy , Acute Kidney Injury/virology , COVID-19/drug therapy , COVID-19/physiopathology , Quercetin/pharmacology , Databases, Factual , Databases, Genetic , Humans , Molecular Docking Simulation , Protein Interaction Mapping/methods , Protein Interaction Maps , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification
19.
Molecules ; 25(23)2020 Dec 07.
Article in English | MEDLINE | ID: covidwho-966360

ABSTRACT

The inflammatory mediator and oxidant agent storm caused by the SARS-CoV-2 infection has been strongly associated with the failure of vital organs observed in critically ill patients with coronavirus disease 2019 (COVID-19) and the death of thousands of infected people around the world. Acute kidney injury (AKI) is a common renal disorder characterized by a sudden and sustained decrease in renal function with a critical influence on poor prognosis and lethal clinical outcomes of various etiologies, including some viral infection diseases. It is known that oxidative stress and inflammation play key roles in the pathogenesis and development of AKI. Quercetin is a natural substance that has multiple pharmacological properties, such as anti-inflammatory action, and is used as a dietary supplement. There is evidence of the anti-coronavirus activities of this compound, including against the target SARS-CoV-2 3CLpro. The ability to inhibit coronavirus and its inflammatory processes is strongly desired in a new drug for the treatment of COVID-19. Therefore, in this review, the dual effect of quercetin is discussed from a mechanistic perspective in relation to AKI kidney injury and its nephroprotective potential to SARS-CoV-2 patients.


Subject(s)
Acute Kidney Injury/drug therapy , COVID-19/complications , Quercetin/pharmacology , Acute Kidney Injury/etiology , Animals , COVID-19/drug therapy , COVID-19/epidemiology , Humans , Morbidity , Protective Agents/pharmacology , Protective Agents/therapeutic use , Quercetin/therapeutic use
20.
Biomed Res Int ; 2020: 1594726, 2020.
Article in English | MEDLINE | ID: covidwho-633800

ABSTRACT

Acute kidney injury (AKI) is a common complication of sepsis and has also been observed in some patients suffering from the new coronavirus pneumonia COVID-19, which is currently a major global concern. Thymoquinone (TQ) is one of the most active ingredients in Nigella sativa seeds. It has a variety of beneficial properties including anti-inflammatory and antioxidative activities. Here, we investigated the possible protective effects of TQ against kidney damage in septic BALB/c mice. Eight-week-old male BALB/c mice were divided into four groups: control, TQ, cecal ligation and puncture (CLP), and TQ+CLP. CLP was performed after 2 weeks of TQ gavage. After 48 h, we measured the histopathological alterations in the kidney tissue and the serum levels of creatinine (CRE) and blood urea nitrogen (BUN). We also evaluated pyroptosis (NLRP3, caspase-1), apoptosis (caspase-3, caspase-8), proinflammatory (TNF-α, IL-1ß, and IL-6)-related protein and gene expression levels. Our results demonstrated that TQ inhibited CLP-induced increased serum CRE and BUN levels. It also significantly inhibited the high levels of NLRP3, caspase-1, caspase-3, caspase-8, TNF-α, IL-1ß, and IL-6 induced by CLP. Furthermore, NF-κB protein level was significantly decreased in the TQ+CLP group than in the CLP group. Together, our results indicate that TQ may be a potential therapeutic agent for sepsis-induced AKI.


Subject(s)
Acute Kidney Injury/drug therapy , Acute Kidney Injury/etiology , Benzoquinones/therapeutic use , Sepsis/complications , Sepsis/drug therapy , Acute Kidney Injury/pathology , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/therapeutic use , Apoptosis/drug effects , Betacoronavirus , Blood Urea Nitrogen , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Creatinine/blood , Cytokines/metabolism , Disease Models, Animal , Humans , Inflammation Mediators/metabolism , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Male , Mice , Mice, Inbred BALB C , NF-kappa B/metabolism , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , SARS-CoV-2
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