No abstract

Background Emerging evidence has demonstrated that acute kidney injury (AKI) is an important risk factor associated with increased morbidity and mortality in diabetic ketoacidosis (DKA) patients. The current study aimed to investigate the incidence rate, risk factors, long-term renal outcomes, and mortality in DKA patients with AKI. Methods A total of 179 patients diagnosed with DKA at Sun Yat-sen Memorial Hospital from January 2012 to January 2018 were included in the analysis. AKI was diagnosed according to the 2012 KDIGO criteria. Risk factors, long-term renal outcomes, and mortality were analyzed by logistic regression and Cox proportional hazards models. Results Among 179 DKA patients, 98 patients (54.75%) were diagnosed as AKI. Aging; increased blood glucose, serum uric acid and white blood cells; decreased serum pH and albumin; coma; and preexisting chronic kidney disease (CKD) were risk factors of AKI in patients with DKA. During follow-up, DKA patients with AKI showed more than a two-fold decline in eGFR within 1 year after discharge from the hospital when compared with non-AKI DKA patients. Furthermore, AKI was also an independent risk factor for poor long-term renal outcomes and mortality in DKA patients. Conclusions Multiple risk factors contribute to the development of AKI in DKA patients. AKI and advanced AKI stage are associated with rapid progressive CKD and long-term mortality in patients with DKA.

Background Acute kidney injury (AKI) occurs among patients with coronavirus disease-19 (COVID-19) and has also been indicated to be associated with in-hospital mortality. Remdesivir has been authorized for the treatment of COVID-19. We conducted a systematic review to evaluate the incidence of AKI in hospitalized COVID-19 patients. The incidence of AKI in different subgroups was also investigated. Methods A thorough search was performed to find relevant studies in PubMed, Web of Science, medRxiv and EMBASE from 1 Jan 2020 until 1 June 2020. The systematic review was performed using the meta package in R (4.0.1). Results A total of 16,199 COVID-19 patients were included in our systematic review. The pooled estimated incidence of AKI in all hospitalized COVID-19 patients was 10.0% (95% CI: 7.0–12.0%). The pooled estimated proportion of COVID-19 patients who needed continuous renal replacement therapy (CRRT) was 4% (95% CI: 3–6%). According to our subgroup analysis, the incidence of AKI could be associated with age, disease severity and ethnicity. The incidence of AKI in hospitalized COVID-19 patients being treated with remdesivir was 7% (95% CI: 3–13%) in a total of 5 studies. Conclusion We found that AKI was not rare in hospitalized COVID-19 patients. The incidence of AKI could be associated with age, disease severity and ethnicity. Remdesivir probably did not induce AKI in COVID-19 patients. Our systematic review provides evidence that AKI might be closely associated with SARS-CoV-2 infection, which should be investigated in future studies.

Exosomes have been shown to effectively regulate the biological functions of target cells. Here, we investigated the protective effect and mechanism of hypoxia-induced renal tubular epithelial cells (TECs)-derived exosomes on acute tubular injury. We found that in vitro hypoxia-induced tubular exosomes (Hy-EXOs) were protective in acute tubular injury by promoting TECs proliferation and improving mitochondrial functions. By using exosome miRNA sequencing, we identified miR-20a-5p was abundant and was a key mechanism for the protective effect of Hy-EXOs on tubular injury as up-regulation of miR-20a-5p enhanced but down regulation of miR-20a-5p inhibited the protective effect of Hy-EXOs on tubular injury under hypoxia conditions. Further study in a mouse model of ischemia-reperfusion induced acute kidney injury (IRI-AKI) also confirmed this notion as pre-treating mice with the miR-20a-5p agomir 48 hours prior to AKI induction was capable of inhibiting IRI-AKI by lowering serum levels of creatinine and urea nitrogen, and attenuating the severity of tubular necrosis, F4/80(+) macrophages infiltration and vascular rarefaction. Mechanistically, the protective effect of miR-20a-5p on AKI was associated with inhibition of TECs mitochondrial injury and apoptosis in vitro and in vivo. In conclusion, miR-20a-5p is enriched in hypoxia-derived tubular exosomes and protects against acute tubular injury. Results from this study also reveal that miR-20a-5p may represent as a novel therapy for AKI.

Aims: The effect of the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear, and data on ARNI treatment in peritoneal dialysis (PD) patients are lacking. The present study was designed to assess the efficacy and safety of sacubitril-valsartan in patients with HFpEF undergoing peritoneal dialysis.Methods and Results: End-stage kidney disease (ESKD) patients undergoing PD for 3 months with New York Heart Association (NYHA) class II–IV heart failure, ejection fraction of 50% or higher, and elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP) were assigned to receive sacubitril-valsartan. Patients were followed up regularly after medication treatment. The alterations in clinical and biochemical parameters before and after taking sacubitril-valsartan (generally 50–100 mg b.i.d) were investigated, and safety was also assessed. Twenty-one patients were recruited in this study. Compared with baseline levels, NT-proBNP levels [9769.0 (3093.5–21941.0) vs. 3034.0 (1493.2–6503.0), P = 0.002], and heart rate [80.0 (74.5–90.5) vs. 75.0 (70.3–87.0), P = 0.031] were markedly decreased after treatment with sacubitril-valsartan. Signs and symptoms of heart failure (21/21 vs. 15/21, P = 0.021) were obviously alleviated, NYHA classification and E/e' ratio showed a notable trend of improvement after 3–12 months of follow-up. None of the patients showed adverse drug reactions.Conclusions: The present data suggested that sacubitril-valsartan treatment in patients with HFpEF undergoing PD was effective and safe.

Many patients with systemic lupus erythematosus (SLE) have lupus nephritis, one of the severe complications of SLE. We previously reported that CD8+CD103+ T regulatory cells induced ex vivo with transforming growth factor β (TGF-β) (iTregs) inhibited immune cells responses to ameliorate excessive autoimmune inflammation. However, the molecular mechanism(s) underlying the role of these CD8+ iTregs is still unclear. Here we identified that CD39, which is highly expressed on CD8+ iTregs, crucially contributes to the immunosuppressive role of the CD8+CD103+ iTregs. We showed that adoptive transfer of CD8+CD103+ iTregs significantly relieves the chronic graft-versus-host disease with lupus nephritis and CD39 inhibitor mostly abolished the functional activities of these CD8+ iTregs in vitro and in vivo . CD39+ cells sorted from CD8+CD103+ iTregs were more effective in treating lupus nephritis than CD39− partner cells in vivo . Furthermore, human CD8+ iTregs displayed increased CD103 and CD39 expressions, and CD39 was involved in the suppressive function of human CD8+ iTregs. Thus, our data implicated a crucial role of CD39 in CD8+CD103+ iTregs in treating lupus nephritis, and CD39 could be a new phenotypic biomarker for the identification of highly qualified CD8+ Tregs. This subpopulation may have therapeutic potential in patients with SLE nephritis and other autoimmune diseases.

No abstract

Some aporphine alkaloids, such as crebanine, were found to present arrhythmic activity and also higher toxicity. A series of derivatives were synthesized by using three kinds of aporphine alkaloids (crebanine, isocorydine, and stephanine) as lead compounds. Chemical methods, including ring-opening reaction, bromination, methylation, acetylation, quaternization, and dehydrogenation, were adopted. Nineteen target derivatives were evaluated for their antiarrhythmic potential in the mouse model of ventricular fibrillation (VF), induced by CHCl₃, and five of the derivatives were investigated further in the rat model of arrhythmia, induced by BaCl₂. Meanwhile, preliminary structure-activity/toxicity relationship analyses were carried out. Significantly, -acetamidesecocrebanine (), three bromo-substituted products of crebanine (, ,), -methylcrebanine (), and dehydrostephanine () displayed antiarrhythmic effects in the CHCl₃-induced model. Among them, 7.5 mg/kg of was able to significantly reduce the incidence of VF induced by CHCl₃ ( < 0.05), increase the number of rats that resumed sinus rhythm from arrhythmia, induced by BaCl₂ ( < 0.01), and the number of rats that maintained sinus rhythm for more than 20 min ( < 0.01). Therefore, showed remarkably higher antiarrhythmic activity and a lower toxicity (LD = 59.62 mg/kg, mice), simultaneously, indicating that could be considered as a promising candidate in the treatment of arrhythmia. Structural-activity analysis suggested that variationsin antiarrhythmic efficacy and toxicity of aporphines were related to the C-1,C-2-methylenedioxy group on ring A, restricted ring B structural conformation,-quaternization of ring B, levoduction of 6a in ring C, and the 8-, 9-, 10-methoxy groups on ring D on the skeleton.