RESUMO
Interleukin-6 (IL-6) plays a key role in the pathogenesis of COVID-19, which determines the indications for the therapeutic use of its antagonists. However, data on their effectiveness and optimal timing of appointment are contradictory. The question of the possibility of their use in patients with impaired kidney function has not been studied. The aim of the study is to evaluate the efficacy and safety of the use of monoclonal antibodies to IL-6 receptors in COVID-19 in patients with chronic kidney disease (CKD) of stages 2-5 (predialysis) who do not need renal replacement therapy. Material and methods. A clinical retrospective uncontrolled single-center study included 45 patients (60% of men) with CKD stages 2-5 aged 22-95 years (median - 58 years) hospitalized with predominantly severe uncritical COVID-19 infection. Treatment of COVID-19 was carried out in accordance with the Interim guidelines for the prevention and treatment of new coronavirus infection of the Ministry of Health of Russian Federation. Results. The majority of patients (n=36;73.3%) had CKD stage 3b-5, CKD stage 2 was in 7 (15.5%) and stage 3a - in 5 (11.1%) patients. The median serum creatinine level (Cr) was 164 [131;292] mumol/l, glomerular filtration rate (GFR) was 30 [13;49] ml/min/1.73 m2, CRP 67.5 [37.2;106.75] mg/l. The introduction of monoclonal antibody to IL-6 receptors led to a decrease in the activity of the infectious process (CRP 1.55 [0.33;4.15] mg/l, p<0.001), regression of pneumonia, which did not require mechanical ventilation and hospitalization in the intensive care unit. According to the decision of the medical commission, patients were injected with monoclonal antibodies to IL-6 receptors: tocilizumab (n=36;80%), levilimab (n=2;4.4%), combined therapy with two drugs (n=7;15.5%). Therapy with IL-6 antagonists did not have a negative effect on kidney function. The levels of Cr decreased on average from 224.3+/-145.2 mmol/l at admission to 160+/-92.55 mmol/l at discharge (p<0.001), GFR increased from 32.6+/-20.9 ml/min/1.73 m2 at admission to 53+/-31.7 ml/min/1.73 m2 at discharge (p<0.001). In the majority of patients (n=36, 80%) GFR has risen, and only in 9 (20%) cases it remained approximately at the same low level. No serious adverse events have been reported with the use of IL-6 antagonists, as well as concomitant infectious complications. No deaths have been reported. The median length of stay in bed was 14 [10;19] days. Conclusion. The results of the study allow us to state that in patients with CKD, monoclonal antibodies to IL-6 receptors have a good safety profile and can be successfully used in moderate and severe forms of COVID-19, regardless of the state of kidney function.Copyright © 2022 by the authors.
RESUMO
Cytokine release syndrome plays a key role in the pathogenesis of COVID-19. Therapeutic plasma exchange (TPE) by removing pathogenic cytokines, can favorably influence the course of severe forms of this disease. However, conclusive studies on this issue are still lacking. Only descriptions of individual clinical cases or small cohort studies have been published. There are no data on the use of TPE in patients with renal failure in the literature. The study aims to evaluate the effect of TPE in the severe forms of COVID-19 in patients with advanced renal failure. Material and Methods: a retrospective, uncontrolled, observational study enrolled 211 patients aged 60,4±13,2. 90.5% of them received renal replacement therapy: 66.8% – hemodialysis, 9.5% – peritoneal dialysis, 14.2% renal transplant recipients with moderate to severe dysfunction, and 9.5% had acute kidney injury on chronic kidney disease that did not require dialysis treatment. Results. All patients were divided into 2 groups: 124 (58.8%) patients (treated from 01.07. to 15.12.2020), who received TPE (TPE group), and 87 (41.2%) patients (observed from 01.04. to 30.06.2020), who did not treat with TPE (control group). The condition of patients in both groups at admission was approximately comparable. The clinical picture of the disease was dominated by severe pneumonia. There were no significant differences in inflammatory markers: both groups had no significant differences in levels of CRP, ferritin, lactate dehydrogenase, or D-dimer. The groups also did not differ significantly in lymphopenia, thrombocytopenia, and azotemia. The mortality rate in the group of patients who did not receive TPE was 73.5%, while in the TPE group it was 45.16% (p<0.001). Among patients on chronic dialysis, the mortality rate in the control subgroup was 74.6%, and in the TPE subgroup – 44.15% (p<0.001). Conclusion:therapeutic plasma exchange is an efficient approach to the treatment of severe forms of COVID-19 in patients with advanced renal failure. Its effect, however, may be limited by the risk of death due to uremia. © 2022 JSC Vidal Rus. All rights reserved.
RESUMO
Interleukin-6 (IL-6) plays a key role in the pathogenesis of COVID-19, which determines the indications for the therapeutic use of its antagonists. However, data on their effectiveness and optimal timing of appointment are contradictory. The question of the possibility of their use in patients with impaired kidney function has not been studied. The aim of the study is to evaluate the efficacy and safety of the use of monoclonal antibodies to IL-6 receptors in COVID-19 in patients with chronic kidney disease (CKD) of stages 2-5 (predialysis) who do not need renal replacement therapy. Material and methods. A clinical retrospective uncontrolled single-center study included 45 patients (60% of men) with CKD stages 2-5 aged 22-95 years (median - 58 years) hospitalized with predominantly severe uncritical COVID-19 infection. Treatment of COVID-19 was carried out in accordance with the Interim guidelines for the prevention and treatment of new coronavirus infection of the Ministry of Health of Russian Federation. Results. The majority of patients (n=36;73.3%) had CKD stage 3b-5, CKD stage 2 was in 7 (15.5%) and stage 3a - in 5 (11.1%) patients. The median serum creatinine level (Cr) was 164 [131;292] μmol/l, glomerular filtration rate (GFR) was 30 [13;49] ml/min/1.73 m2, CRP 67.5 [37.2;106.75] mg/l. The introduction of monoclonal antibody to IL-6 receptors led to a decrease in the activity of the infectious process (CRP 1.55 [0.33;4.15] mg/l, p<0.001), regression of pneumonia, which did not require mechanical ventilation and hospitalization in the intensive care unit. According to the decision of the medical commission, patients were injected with monoclonal antibodies to IL-6 receptors: tocilizumab (n=36;80%), levilimab (n=2;4.4%), combined therapy with two drugs (n=7;15.5%). Therapy with IL-6 antagonists did not have a negative effect on kidney function. The levels of Cr decreased on average from 224.3±145.2 mmol/l at admission to 160±92.55 mmol/l at discharge (p<0.001), GFR increased from 32.6±20.9 ml/min/1.73 m2 at admission to 53±31.7 ml/min/1.73 m2 at discharge (p<0.001). In the majority of patients (n=36, 80%) GFR has risen, and only in 9 (20%) cases it remained approximately at the same low level. No serious adverse events have been reported with the use of IL-6 antagonists, as well as concomitant infectious complications. No deaths have been reported. The median length of stay in bed was 14 [10;19] days. Conclusion. The results of the study allow us to state that in patients with CKD, monoclonal antibodies to IL-6 receptors have a good safety profile and can be successfully used in moderate and severe forms of COVID-19, regardless of the state of kidney function. © 2022 by the authors.
RESUMO
COVID-19 is a severe acute respiratory disease caused by the SARS-CoV-2 virus. Although COVID-19 is characterized mainly by diffuse alveolar damage and acute respiratory failure, in some cases COVID-19 may acquire extra-respiratory features, including renal dysfunction that has existed earlier or developed de novo. The reasons for the extra-respiratory manifestations are biological properties of SARS-CoV-2 based on its multiple organ tropism. It has been shown that at least 50% of patients hospitalized for COVID-19 have proteinuria, hematuria, and signs of renal dysfunction, which in some cases reaches the degree of acute kidney injury (AKI). Here we present a review that discusses the clinical aspects and possible pathophysiological mechanisms of kidney damage in COVID-19. It is believed that renal damage observed in this disease is the result of a complex mechanism induced directly or indirectly by SARS-CoV-2 with the development of acute kidney injury. Two main pathophysiological mechanisms of kidney damage in COVID-19 are discussed. The first of them is the direct cytopathic effect of SARS-CoV-2 on the renal epithelium with the development of acute tubulonecrosis. The second mechanism is the cytokine storm syndrome that results from hyperactivation of the immune system with the development of acute renal and multiorgan infl ammatory damage accompanied by hypoxia, persistent hypotension, rhabdomyolysis, hyperactivation of the coagulation cascade, and microcirculation disorders. From a clinical point of view, it should be noted that signs of kidney damage are associated with an increase in the severity of COVID-19 and a poor outcome of the disease, and the prognosis becomes the worst with the development of AKI (the risk of death may increase by 5.3 times). The incidence of COVID-19 in patients with ESRD is higher than in the general population. The most typical for these patients is a severe course of the disease, which determines the increased mortality in comparison with the general population, caused by a respiratory failure with hyperactive infl ammation, cytokine storm, hemodynamic, and multiple organ failures. © 2021 JSC Vidal Rus. All rights reserved.
RESUMO
Vasculitis associated with the antineutrophilic cytoplasmic antibodies (ANCA) is an autoimmune systemic severe, often life-threatening, disease characterized by necrotizing infl ammation of small vessels. In 75-90% of cases of ANCA-associated vasculitis (AAV), a rapidly progressive pauci-immune necrotizing crescentic glomerulonephritis develops. Despite current treatment with high-dose glucocorticoids and either cyclophosphamide or rituximab, patients have a nine-fold increased mortality risk during the fi rst year of disease compared with healthy subjects. This high mortality is attributed mainly to infections and vasculitis activity. Recent data suggest that the activation of the complement system, and in particular the alternative complement pathway, plays a signifi cant role in the pathogenesis of AAV. It has been suggested that neutrophils primed by infection or pro-infl ammatory cytokines release properdin, which activates an alternative complement cascade with cleavage of C5 into C5a and C5b. Anaphylatoxin C5a binds to receptors on the surface of neutrophils, enhancing their priming and activation and thus contributing to the infl ammation. The randomized clinical trial showed that the selective C5a-receptor inhibitor avakopan was effective in the treatment of AAV. However, avacopan is currently not available in the everyday clinical practice. On the other hand, reports showing successful usage of monoclonal antibody against C5 eculizumab in severe AAV had been published. Here we present four cases of AAV complicated by COVID-19, for which conventional therapy with cy?lophosphamide could not be applied due to the particularly high risk of serious infectious complications, and eculizumab was used off-label by decision of the medical council and special commission. Taking this decision, we took into account data demonstrating the role of complement activation and, in particular, C5a in the pathogenesis of acute lung disease, induced by pathogenic viruses. Moreover, the successful usage of eculizumab in severe COVID-19 was reported recently. Thus, we sought to apply an approach aimed simultaneously at the pathogenetic mechanisms of both AAV and viral lung damage. © 2020 JSC Vidal Rus. All rights reserved.