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ObjectiveThe aberrant mobilization and activation of various T lymphocyte subpopulations play a pivotal role in the pathogenesis of diabetic kidney disease (DKD), yet the regulatory mechanisms underlying these processes remain poorly understood. Our study is premised on the hypothesis that the dysregulation of immune checkpoint molecules on T lymphocytes disrupts kidney homeostasis, instigates pathological inflammation, and promotes DKD progression.MethodsA total of 360 adult patients with DKD were recruited for this study. The expression of immune checkpoint molecules on T lymphocytes was assessed by flow cytometry for peripheral blood and immunofluorescence staining for kidney tissue. Single-cell sequencing (scRNA-seq) data from the kidneys of DKD mouse model were analyzed.ResultsPatients with DKD exhibited a reduction in the proportion of CD3+TIM-3+ T cells in circulation concurrent with the emergence of significant albuminuria and hematuria (p=0.008 and 0.02, respectively). Conversely, the incidence of infection during DKD progression correlated with an elevation of peripheral CD3+TIM-3+ T cells (p=0.01). Both univariate and multivariate logistic regression analysis revealed a significant inverse relationship between the proportion of peripheral CD3+TIM-3+ T cells and severe interstitial mononuclear infiltration (OR: 0.193, 95%CI: 0.040,0.926, p=0.04). Immunofluorescence assays demonstrated an increase of CD3+, TIM-3+ and CD3+TIM-3+ interstitial mononuclear cells in the kidneys of DKD patients as compared to patients diagnosed with minimal change disease (p=0.03, 0.02 and 0.002, respectively). ScRNA-seq analysis revealed decreased gene expression of TIM3 on T lymphocytes in DKD compared to control. And one of TIM-3's main ligands, Galectin-9 on immune cells showed a decreasing trend in gene expression as kidney damage worsened.ConclusionOur study underscores the potential protective role of TIM-3 on T lymphocytes in attenuating the progression of DKD and suggests that monitoring circulating CD3+TIM3+ T cells may serve as a viable strategy for identifying DKD patients at heightened risk of disease progression.

Objective Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is a prevalent problem affecting hemodialysis (HD) patients. Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. We explored the ability of roxadustat to increase the hemoglobin (Hb) concentration in ESA-hyporesponsive patients undergoing HD and assessed its effect on iron metabolism and inflammation. Methods This prospective study included 30 patients with ESA-hyporesponsive anemia who had been undergoing stable dialysis. All patients received roxadustat three times per week for 24 weeks. The primary endpoint was the mean change in Hb from baseline to the average level over weeks 20 to 24. Iron metabolism markers, C-reactive protein, interleukin (IL)-6, and safety were also assessed. Results At week 24, roxadustat treatment resulted in a 2.5 ± 1.3 g/dL increase in the Hb level. In total, 28 of 30 patients (93.3%) had an Hb level increase of more than 1.0 g/dL from baseline. Seventeen patients (56.7%) met the endpoint, with a mean Hb level of at least 10.0 g/dL. Iron metabolism and IL-6 levels were also improved. Conclusions Oral roxadustat is effective for ESA-hyporesponsive anemia in maintenance HD patients and may also improve iron metabolism and IL-6 levels.

Endotoxins and cytokines play an important role in multiple organ failure pathogenesis in patients with severe Gram-negative bacterial infection. We present a clinical case where an oXiris hemofilter was used for continuous renal replacement therapy (CRRT) treatment in a patient with septic shock after liver transplantation. A 35-year-old man with a 20-year history of hepatitis B presented with jaundice, loss of appetite, and decreased urine output. He was diagnosed with decompensated cirrhosis with acute-on-chronic liver failure, and liver transplantation was indicated. The day after surgery, he developed hyperthermia, hypotension, anuria, and a progressive increase in blood inflammatory markers and creatinine. Combined with the donor source and blood culture results, septic shock after transplantation was considered. The patient was immediately treated with endotoxin and cytokine adsorption CRRT (oXiris hemofilter) with tigecycline, caspofungin, and ganciclovir as anti-infectives. After 48 hours on CRRT, his blood pressure gradually stabilized, the CLIF Consortium Acute-on-Chronic Liver Failure score decreased from 63 to 43. Procalcitonin, endotoxin, and the inflammatory factors interleukin (IL)-6 and IL-10 also decreased gradually. The patient’s liver and kidney functions were completely restored. Our experience suggests that oXiris CRRT combined with antibacterial therapy is an effective treatment for septic shock after liver transplantation.