RESUMEN
Even without the presence of the novel Coronavirus disease 2019 (COVID-19), acute kidney injury has been a serious problem in medicine for decades, with mortality rate up to 70% among those who eventually required renal replacement therapy, and the number has not changed significantly for the last 30 years despite major advances in technology and experience. On the other hand, even without acute kidney injury, COVID-19 was a major cause of death globally in the year 2020, but the occurrence of acute kidney injury among COVID-19 patients is an independent risk factor of increased mortality. Continuous renal replacement therapy has been recommended to treat acute kidney injury in COVID-19 patients instead of conventional intermittent hemodialysis. Moreover, its use might have another beneficial role in stopping the progression of severe COVID-19 by removing pro-inflammatory cytokines during cytokine storm syndrome, which is postulated as the pathophysiology behind severe and critically severe cases of COVID-19. This review will cover a brief history of continuous renal replacement therapy and its modalities, before digging up more into its use in COVID-19 patients, including the optimum filtration dose and timing, membrane filtration used, vascular access, anticoagulation therapy, and drug dosing adjustment during continuous renal replacement therapy.
RESUMEN
Myelopoiesis is invariably present and contributes to pathology in animal models of graft-versus-host disease (GVHD). In humans, a rich inflammatory infiltrate bearing macrophage markers has also been described in histological studies. In order to determine the origin, functional properties, and role in pathogenesis of these cells, we isolated single-cell suspensions from acute cutaneous GVHD and subjected them to genotype, transcriptome, and in vitro functional analysis. A donor-derived population of CD11c+CD14+ cells was the dominant population of all leukocytes in GVHD. Surface phenotype and NanoString gene expression profiling indicated the closest steady-state counterpart of these cells to be monocyte-derived macrophages. In GVHD, however, there was upregulation of monocyte antigens SIRPα and S100A8/9 transcripts associated with leukocyte trafficking, pattern recognition, antigen presentation, and costimulation. Isolated GVHD macrophages stimulated greater proliferation and activation of allogeneic T cells and secreted higher levels of inflammatory cytokines than their steady-state counterparts. In HLA-matched mixed leukocyte reactions, we also observed differentiation of activated macrophages with a similar phenotype. These exhibited cytopathicity to a keratinocyte cell line and mediated pathological damage to skin explants independently of T cells. Together, these results define the origin, functional properties, and potential pathogenic roles of human GVHD macrophages.