Acute Kidney Injury Associated With Lopinavir/Ritonavir Combined Therapy in Patients With COVID-19

Binois, Yannick; Hachad, Hafsah; Salem, Joe‐Elie; Charpentier, Julien; Lebrun‐Vignes, Bénédicte; Pène, Frédéric; Cariou, Alain; Chiche, Jean‐Daniel; Mira, Jean‐Paul; Nguyen, Lee S.

doi:10.1016/j.ekir.2020.07.035

Cited by 29 publications

(23 citation statements)

References 9 publications

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“…An analysis of the international pharmacovigilance post-marketing databases of the World Health Organization revealed a statistically significant nephrotoxicity signal, demonstrating a 20-fold higher risk of AKI with remdesivir use than that associated with other drugs frequently used in COVD-19 (hydroxychloroquine, tocilizumab and lopinavir/ritonavir) 154 . Cases of AKI associated with lopinavir and low-dose ritonavir therapy in the course of COVID-19 management were also reported 155 . Finally, rhabdomyolysis represents a potential non-pharmacological mechanism of nephrotoxicity in COVID-19 AKI through the precipitation of myoglobin and the release of free radicals, as has been described for other forms of AKI associated with viral infections 156 , 157 .…”

Section: Pathophysiology Of Covid-19 Akimentioning

confidence: 99%

Pathophysiology of COVID-19-associated acute kidney injury

et al. 2021

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Although respiratory failure and hypoxaemia are the main manifestations of COVID-19, kidney involvement is also common. Available evidence supports a number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection. Histopathological findings have highlighted both similarities and differences between AKI in patients with COVID-19 and in those with AKI in non-COVID-related sepsis. Acute tubular injury is common, although it is often mild, despite markedly reduced kidney function. Systemic haemodynamic instability very likely contributes to tubular injury. Despite descriptions of COVID-19 as a cytokine storm syndrome, levels of circulating cytokines are often lower in patients with COVID-19 than in patients with acute respiratory distress syndrome with causes other than COVID-19. Tissue inflammation and local immune cell infiltration have been repeatedly observed and might have a critical role in kidney injury, as might endothelial injury and microvascular thrombi. Findings of high viral load in patients who have died with AKI suggest a contribution of viral invasion in the kidneys, although the issue of renal tropism remains controversial. An impaired type I interferon response has also been reported in patients with severe COVID-19. In light of these observations, the potential pathophysiological mechanisms of COVID-19-associated AKI may provide insights into therapeutic strategies.

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Section: Pathophysiology Of Covid-19 Akimentioning

confidence: 99%

Pathophysiology of COVID-19-associated acute kidney injury

et al. 2021

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“…A high incidence of AKI, especially in critically ill patients, along with a lack of efficacy on primary endpoints during preliminary data analysis has led the Discovery trial investigators to an early termination of inclusions in the lopinavir/ritonavir arm ( Inserm, 2020 ). While it was not confirmed by the lopinavir/ritonavir versus standard of care randomized trial by Cao et al (2020) , Binois et al (2020) found an association between AKI and this treatment regimen in patients admitted in their ICU unit, notwithstanding potential confounding factors, as this study involved critically ill patients with features of viral sepsis. Interestingly, Arrestier et al (2020) explored three critically ill patients with AKI while on lopinavir/ritonavir treatment and found neither urinary crystals nor evidence of drugs by infrared spectroscopy analysis of urinary sediment.…”

Section: Acute Kidney Injury and Covid-19mentioning

confidence: 63%

The Good Treatment, the Bad Virus, and the Ugly Inflammation: Pathophysiology of Kidney Involvement During COVID-19

et al. 2021

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Kidney involvement is a common complication during SARS-CoV-2 infection. Its association with poor outcomes, especially in critically ill patients, raises issues whether kidney involvement reflects multi-organ damage or if it is a specific feature of the infection. Based on observational studies, autopsy series, and on current understanding of the route of entry of the virus, this review will highlight the different types of kidney involvement during COVID-19 and put them in the perspective of the different pathophysiological hypotheses. Virus entry route through ACE2 ligation and TMPRSS2 coligation allows identifying potential viral targets in the kidney, including tubules, endothelial cells, and glomerulus. While reports have described damages of all these structures and virus kidney tropism has been identified in renal extracts in autopsy series, no direct viral infection has been found in the latter structures thus far on kidney biopsies. Notwithstanding the technical challenge of disclosing viral invasion within tissues and cells, viral direct cytopathogenic effect generally does not appear as the cause of the observed renal damage. Inflammation and altered hemodynamics, described as “viral sepsis,” might rather be responsible for organ dysfunction, including kidneys. We shall place these various mechanisms into an integrated vision where the synergy between direct viral pathogenicity and systemic inflammation enhances renal damage. As SARS-CoV-2 inexorably continues its rampant spread, understanding the sequence of events in the kidneys might thus help inform improved therapeutic strategies, including antiviral drugs and immunomodulators.

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“…ACE2 receptor is also expressed by kidney and post-mortem biopsies confirmed viral inclusions in tubular epithelial cells and podocytes. Lopinavir/Ritonavir treatment may enhance acute kidney injury in SARS-CoV-2 infected patients [16]. On July 6, 2020, WHO decided to discontinue the Lopinavir/Ritonavir arms of SOLIDARITY international trial.…”

Section: Viral Protease Inhibitorsmentioning

confidence: 99%

Covid-19 Therapy: What Have We Learned In 8 Months?

Adamczyk-Popławska

Kwiatek

2020

Postępy Mikrobiologii - Advancements of Microbiology

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Coronaviruses (CoVs) are a group of RNA viruses that infect mammals and birds. In humans, CoVs mainly cause mild diseases, including the common cold. However, in the 21 st century three pandemic strains of novel CoVs, highly pathogenic to humans, emerged. These three novel CoVs are zoonosis. In 2002-2003, we dealt with the Severe Acute Respiratory Syndrome coronavirus (currently, SARS-CoV) and in 2012, the Middle East Respiratory Syndrome coronavirus (MERS-CoV). The emergence of SARS-CoV-2 in December 2019 in Wuhan (Hubei province, China) marked the next introduction of a novel, highly pathogenic CoV into the human population [112]. In most cases, SARS-CoV-2 causes mild or moderate respiratory illness and the recovery does not require any special treatment. However, some infected individuals, with associated medical conditions, developed a severe disease called Coronavirus Disease 2019 (COVID-19) with such clinical manifestations as dyspnea, hypoxia, and lung lesions, being an indication for treatment in

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Acute Kidney Injury Associated With Lopinavir/Ritonavir Combined Therapy in Patients With COVID-19

Cited by 29 publications

References 9 publications

Pathophysiology of COVID-19-associated acute kidney injury

Pathophysiology of COVID-19-associated acute kidney injury

The Good Treatment, the Bad Virus, and the Ugly Inflammation: Pathophysiology of Kidney Involvement During COVID-19

Covid-19 Therapy: What Have We Learned In 8 Months?

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