Activation of the α7nAChR by GTS-21 mitigates septic tubular cell injury and modulates macrophage infiltration.

The most common and serious complication among hospitalized and critically ill patients is sepsis-associated acute kidney damage (S-AKI), which raises the risk of comorbidities and is linked to a high mortality rate. Cholinergic anti-inflammatory pathway (CAP), an anti-inflammatory pathway mediated by the vagus nerve, acetylcholine, and α7 nicotinic acetylcholine receptors (α7nAChRs), offers new perspectives for the treatment of S-AKI. In this study, we investigated the role of CAP and α7nAChR in kidney injury by employing an LPS-induced septic kidney injury mouse model and GTS-21 intervention. C57BL/6 mice were injected with LPS, with or without GTS-21, in different subgroups. Kidney function was assessed by plasma creatinine, histology, and markers of kidney injury 24 h after intervention. The results demonstrated that GTS-21 could inhibit the systemic inflammatory response and directly protect the tubular cell injury from LPS. To explore the novel gene involved in this response, RNA sequencing of the renal proximal tubular epithelial cell (HK-2), pretreated with LPS and GTS-21, was conducted. The results indicate that GTS-21 administration reduces LPS-induced cytokines and chemokines secretion by HK-2, including CCL20, a potent chemokine attracting monocytes/macrophages. Furthermore, a macrophage transmigration assay revealed that GTS-21 inhibits macrophage transmigration by downregulating the expression of CCL20 in HK-2 cells. In conclusion, GTS-21, as an α7nAChR agonist, emerges as a noteworthy and versatile treatment for S-AKI. Its dual function of directly protecting renal tubular cells and regulating inflammatory responses represents a major advancement in the treatment of sepsis-induced AKI. This finding might pave the way for novel approaches to improving patient outcomes and reducing death rates in sepsis-related complications.

Association between COVID-19 vaccination and relapse of glomerulonephritis.

BACKGROUND: Vaccines for coronavirus disease 2019 (COVID-19) have been developed and are recommended for patients with chronic kidney disease; however, it has been reported that glomerulonephritis worsens after vaccination. We aimed to elucidate the incidence and association between COVID-19 vaccination and glomerulonephritis relapse. METHODS: We investigated the onset of renal events and adverse reactions after COVID-19 vaccination in 111 patients diagnosed with glomerulonephritis. Renal events were defined as worsening hematuria, increased proteinuria, and an increased creatine level over 1.5-fold from baseline. RESULTS: Patients were 57 ± 18 years old (55.9% female) and had an estimated glomerular filtration rate of 57.0 ± 25.0 ml/min/1.73 m2. A pathological diagnosis of IgA nephropathy was confirmed in 55.0%, minimal change disease in 22.5%, and membranous nephropathy in 10.8% of the patients. The BNT162b2 (Pfizer) and mRNA-1273 (Moderna) vaccines were administered in 88.2% and 11.7% of the cases, respectively. Renal events were observed in 22.5% of patients, 10.8% had increased proteinuria, 12.6% had worsening hematuria, and 1.8% received additional immunosuppressive treatment. Only 0.9% required temporary hemodialysis from exacerbation of renal dysfunction. Renal events were higher in younger patients (P = 0.02), being highest in those with IgA nephropathy, but there was no difference in the incidence between pathological diagnoses. There was a significantly higher incidence of renal events in patients with fever (P = 0.02). CONCLUSIONS: COVID-19 vaccination and glomerulonephritis relapse may be related, but further research is needed.