Iron therapy mitigates chronic kidney disease progression by regulating intracellular iron status of kidney macrophages.

Systemic iron metabolism is disrupted in chronic kidney disease (CKD). However, little is known about local kidney iron homeostasis and its role in kidney fibrosis. Kidney-specific effects of iron therapy in CKD also remain elusive. Here, we elucidate the role of macrophage iron status in kidney fibrosis and demonstrate that it is a potential therapeutic target. In CKD, kidney macrophages exhibited depletion of labile iron pool (LIP) and induction of transferrin receptor 1, indicating intracellular iron deficiency. Low LIP in kidney macrophages was associated with their defective antioxidant response and proinflammatory polarization. Repletion of LIP in kidney macrophages through knockout of ferritin heavy chain (Fth1) reduced oxidative stress and mitigated fibrosis. Similar to Fth1 knockout, iron dextran therapy, through replenishing macrophage LIP, reduced oxidative stress, decreased the production of proinflammatory cytokines, and alleviated kidney fibrosis. Interestingly, iron markedly decreased TGF-ß expression and suppressed TGF-ß-driven fibrotic response of macrophages. Iron dextran therapy and FtH suppression had an additive protective effect against fibrosis. Adoptive transfer of iron-loaded macrophages alleviated kidney fibrosis, validating the protective effect of iron-replete macrophages in CKD. Thus, targeting intracellular iron deficiency of kidney macrophages in CKD can serve as a therapeutic opportunity to mitigate disease progression.

The efficacy and effectiveness of the COVID-19 vaccines in reducing infection, severity, hospitalization, and mortality: a systematic review.

With the relatively rapid development of the COVID-19 pandemic, vaccine development has become crucial for limiting disease transmission. The accelerated growth in the approved COVID-19 vaccines has sparked concerns about their efficacies which have been assessed by many studies. This systematic review compares the efficacy and effectiveness of seven COVID-19 vaccines. A comprehensive systematic literature search was performed using several databases to identify studies reporting the effectiveness or the efficacy of the vaccines. Only 42 studies met our inclusion criteria, which revealed that the COVID-19 vaccines have successfully reduced the rates of infections, severity, hospitalization, and mortality among the different populations. The full-dose regimen of the Pfizer/BioNTech vaccine is the most effective against infections with the B.1.1.7 and B.1.351 variants. Despite of the high effectiveness of some of the COVID-19 vaccines, more efforts are required to test their effectiveness against the other newly emerging variants.