Yu-Mei Wang

Kidney transplantation is an important treatment for end-stage renal disease, but lifelong immunosuppression is needed to prevent immune rejection, but the immunosuppressive therapy increases the risk of post-transplant complications. Therefore, how to improve the long-term survival of transplanted kidneys and reduce rejection has become a hot spot in current research. Recently, the 'gut-kidney axis' has received widespread attention as an important pathway for immune regulation. It refers to the fact that changes in either side of the gastrointestinal tract and kidney will affect the other side through energy metabolism, immuno-inflammation, intestinal mucosa, intestinal flora, among others, up and including to adverse consequences, which can be mutually causative. With the theory of 'gut-kidney axis', more and more studies have found that intestinal immune cells and microbiota play an important role in maintaining immune homeostasis and regulating the immune microenvironment of renal transplant recipients. Some studies have found that intestinal immune cells and microbiota not only influence the systemic immune status, but also may regulate the immune response of transplanted kidneys through metabolites and inflammatory mediators. In this review, we summarize the potential mechanisms of intestinal immune cells and microbiota in immune tolerance and rejection after renal transplantation based on the theory of 'gut-kidney axis'. In addition, we highlight microbiome modulation strategies, particularly dietary interventions and fecal microbiota transplantation, as emerging approaches with potential to improve transplant outcomes. A deeper understanding of the mechanism of action of the gut-kidney axis will provide new ideas and therapeutic targets for immunomodulation after renal transplantation.

Kidney transplantation is an effective method to improve the condition of patients with end-stage renal disease. The gut microbiota significantly affects the immune system and can be used as an influencing factor to change the prognoses of patients who have undergone kidney transplantation. Recipients after kidney transplantation showed a lower abundance of Firmicutes and Faecalibacterium prausnitzii and a higher proportion of Bacteroidetes and Proteobacteria. After using prebiotics, synbiotics, and fecal microbiota transplantation to regulate the microbial community, the prognoses of patients who underwent kidney transplantation evidently improved. We aimed to determine the relationship between gut microbiota and various postoperative complications inpatients who have undergone kidney transplantation in recent years and to explore how gut microecology affects post-transplant complications. An in-depth understanding of the specific functions of gut microbiota and identification of the actual pathogenic flora during complications in patients undergoing kidney transplantation can help physicians develop strategies to restore the normal intestinal microbiome of transplant patients to maximize their survival and improve their quality of life.

Background: Microlbuminuria is the earliest clinical evidence of diabetic kidney disease (DKD) and contributes to the induction and/or progression of DKD. Previous studies have shown that increased expression of angiopoietin2 (ANGPT2) is correlated with an increase in albuminuria. However, the critical role of ANGPT2 in albuminuria development remains unclear. Some studies have shown the significance of transcytosis in the occurrence of albuminuria, but it is unknown whether it takes place in albumin recycling in renal tubular cells of patients with DKD. Furthermore, the potential mechanism of this association also remains unclear. Methods: In this study, human renal tubular epithelial cells (HK-2) were cultured with high glucose in a Transwell plate to establish a transcytosis model, while C57BL/6 mice were intraperitoneally injected with streptozotocin to establish a DKD model. The expression of ANGPT2 and caveolin1 (CAV1) phosphorylation was dectected through immunohistochemistry and western blot analysis. Results: Transcytosis of albumin in renal tubular epithelial cells was downregulated after high glucose exposure, and increased expression of ANGPT2 and CAV1 phosphorylation both in vivo and in vitro was observed. Inhibition of ANGPT2 and CAV1 independently promoted transcytosis. Furthermore, ANGPT2 downregulation inhibited CAV1 phosphorylation, whereas CAV1 phosphorylation had no effect on the expression of ANGPT2. Conclusions: ANGPT2 reduces albumin transcytosis across renal tubular epithelial cells under high glucose conditions by activating CAV1 phosphorylation, thus increasing albuminuria in DKD. These findings suggested that ANGPT2 and CAV1 may be promising therapeutic targets for albuminuria in DKD.

Background: Acute kidney injury (AKI) is one of the postoperative complications following orthotopic liver transplantation (OLT), and is related to the high morbidity and mortality. Although there were numerous propensity factors for AKI, their cumulative influence remains unclear. Our aims were to develop a score model to predict postoperative AKI and to evaluate the impact of AKI on the recipients’ long-term survival. Methods: We retrospectively analyzed 99 adult patients underwent OLT in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between October 2014 and July 2020. The patients were dichotomized into the non-AKI and the AKI groups according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. We defined stage-1 AKI as mild AKI, stage-2 AKI and stage-3 AKI as severe AKI. Results: Overall, 29 (29.29%) patients developed AKI after OLT, of these, stage-1, stage-2, stage-3 account for 20.20% (20 of 99 patients), 2.02% (2 of 99 patients), 7.07% (7 of 99 patients), respectively; and 13.79% of postoperative AKI patients (4 of 29 patients) accepted renal replacement therapy (RRT). Operative time and MELD-Na score predicted the postoperative AKI, with odds ratio of 1.006, 1.061, respectively. The generated AKI prediction model is as follows: -5.594+0.007×operative time+0.060×MELD-Na. The area under the receiver operating characteristic curve (AUC) for the AKI prediction model was 0.762, and the sensitivity and specificity were 79.3%, 61.4%, respectively. There was no difference in long-term survival among the mild AKI group and the non-AKI group (P=0.751). However, the impact of severe AKI on long-term survival of patients was statistically significant when comparing the non-AKI group and the mild AKI group (P=0.001, P=0.011). Conclusions: AKI occurs frequently in adult patients after OLT, and it poses a threat to patients’ long-term survival. The severe AKI has negative impact on long-term survival, while the mild AKI has limited impact on long-term survival, compared with non-AKI group. The novel AKI prediction model has prognostic value in identifying patients at high risk for postoperative AKI.

Acute kidney injury (AKI) is one of the most prevalent complications among hospitalized coronavirus disease 2019 (COVID-19) patients. Here, we aim to investigate the causes, risk factors, and outcomes of AKI in COVID-19 patients. We found that angiotensin-converting enzyme II (ACE2) and transmembrane protease serine 2 (TMPRSS2) were mainly expressed by different cell types in the human kidney. However, in autopsy kidney samples, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein was detected in ACE2⁺ or TMPRSS2⁺ renal tubular cells, whereas the RNAscope^® Assay targeting the SARS-CoV-2 Spike gene was positive mainly in the distal tubular cells and seldom in the proximal tubular cells. In addition, the TMPRSS2 and kidney injury marker protein levels were significantly higher in the SARS-CoV-2-infected renal distal tubular cells, indicating that SARS-CoV-2-mediated AKI mainly occurred in the renal distal tubular cells. Subsequently, a cohort analysis of 722 patients with COVID-19 demonstrated that AKI was significantly related to more serious disease stages and poor prognosis of COVID-19 patients. The progressive increase of blood urea nitrogen (BUN) level during the course of COVID-19 suggests that the patient’s condition is aggravated. These results will greatly increase the current understanding of SARS-CoV-2 infection.

Introduction This retrospective, single-center study was performed to systemically describe the characteristics and outcomes of patients with severe and critical coronavirus disease 2019 (COVID-19) in Wuhan, analyze the risk factors, and propose suggestions for clinical diagnosis and treatment to guide the subsequent clinical practice. Methods A total of 753 consecutive patients with COVID-19 admitted to the West Campus of Wuhan Union Hospital from January 22, 2020 to May 7, 2020 were enrolled in this study. Demographic, clinical, laboratory, and outcome data were extracted from the electronic medical records of Wuhan Union Hospital and were exhaustively analyzed using R (version 3.6.1). Results A total of 493 severe and 228 critical cases out of 753 COVID-19 cases were considered in this study. Among the critical cases, the death rate was 79.4%, and age was a risk factor for death. Compared to the severe disease group, the critical disease group had higher white blood cell (WBC) and neutrophil counts and a decreased lymphocyte count at admission. Compared to early death cases (death within 1 week after admission), a more prolonged course of the disease was associated with a higher risk of hypoproteinemia, liver injury, thrombocytopenia, anemia, disseminated intravascular coagulation (DIC), coagulation disorders, acute kidney injury (AKI), and infection. Higher creatine kinase (CK) and lactate dehydrogenase (LDH) levels were related to early death events, but univariate and multivariate analyses confirmed only LDH as an independent predictor of early death. Notably, anticoagulation therapy was associated with an improved prognosis of critical cases in this cohort. Conclusion Our results showed large differences between patients with severe and critical COVID-19. During the course of COVID-19 in the critical disease group, the incidence of hypoproteinemia, anemia, thrombocytopenia, and coagulation disorders increased significantly, which highlighted the importance of medical care in the first week after admission. LDH could act as an independent predictor of early death in critical cases, and anticoagulation therapy was correlated with an improved prognosis of patients with critical COVID-19.

Angiopoietins (Angs) are a family of vascular growth factors that share multiple cellular functions related to cell survival, proliferation, and migration. Angs play physiological and pathological roles through the Tie tyrosine kinase receptors. The Ang‐Tie signaling pathway participates in the developmental and tumor‐induced angiogenesis and is also involved in many disease settings, such as vascular diseases, systemic inflammation, and cancers. Since Angs are widely expressed in the kidney, an enormous amount of research focuses on their roles in the kidney. In this review, we describe the biological functions of the Ang‐Tie signaling pathway and summarize their roles in kidney development and maturation, acute and chronic kidney diseases, diabetic nephropathy, lupus nephropathy, hemolytic uremic syndrome, end‐stage renal diseases, and renal cell carcinoma. Understanding the molecular mechanisms of Ang‐Tie signaling may reveal potential therapeutic targets for preventing or alleviating kidney diseases.