Hongyu Chen

Our previous work demonstrated a protective role of protein S in early diabetic kidney disease (DKD). Protein S exerts antiinflammatory and antiapoptotic effects through the activation of TYRO3, AXL, and MER (TAM) receptors. Among the 3 TAM receptors, we showed that the biological effects of protein S were mediated largely by TYRO3 in diabetic kidneys. Our data now show that TYRO3 mRNA expression is highly enriched in human glomeruli and that TYRO3 protein is expressed in podocytes. Interestingly, glomerular TYRO3 mRNA expression increased in mild DKD but was suppressed in progressive DKD, as well as in focal segmental glomerulosclerosis (FSGS). Functionally, morpholino-mediated knockdown of tyro3 altered glomerular filtration barrier development in zebrafish larvae, and genetic ablation of Tyro3 in murine models of DKD and Adriamycin-induced nephropathy (ADRN) worsened albuminuria and glomerular injury. Conversely, the induction of TYRO3 overexpression specifically in podocytes significantly attenuated albuminuria and kidney injury in mice with DKD, ADRN, and HIV-associated nephropathy (HIVAN). Mechanistically, TYRO3 expression was suppressed by activation of TNF-α/NF-κB pathway, which may contribute to decreased TYRO3 expression in progressive DKD and FSGS, and TYRO3 signaling conferred antiapoptotic effects through the activation of AKT in podocytes. In conclusion, TYRO3 plays a critical role in maintaining normal podocyte function and may be a potential new drug target to treat glomerular diseases.

OBJECTIVES: assisted Platform Cohort (PDTAP) Study is to explore potential predictors and their effects on patient survival, technique survival, and the occurrence of infectious and noninfectious complications. DESIGN: The PDTAP study is a national-level cohort study in China. A newly developed PD telemedicine application provided a unique and convenient way to collect multicenter, structured data across units. SETTING: The PDTAP study was underway in 27 hospitals from 14 provinces located at 7 geographical regions (northwest, northeast, north, central, southwest, southeast, and south) in China. PARTICIPANTS: Our study aims to enroll at least 7000 adult patients with end-stage renal disease receiving PD. METHODS: Approval has been obtained through the ethics committees of all hospitals. All participants signed the informed consent form after the center had received ethics board approval in accordance with the Declaration of Helsinki. MAIN OUTCOME MEASURES: Patient survival, technique survival, hospitalization, and the occurrence of infectious and noninfectious complications. CONCLUSIONS: The PDTAP study aims to explore potential predictors and their effects on patient survival, technique survival, and infectious and noninfectious complications using a newly developed PD telemedicine system to collect multicenter, structured data in real-world practice. Substantial and transformable findings in relation to PD practices were expected. This study also developed a national-level infrastructure for further collaboration and ancillary investigation.

INTRODUCTION: Telemedicine (TM) has shown to provide potential benefits on clinical outcomes in patients with chronic kidney disease but limited evidences published in the peritoneal dialysis (PD) population. This study aimed to explore the long-term effects of TM on the mortality and technique failure. METHODS: The Peritoneal Dialysis Telemedicine-assisted Platform Cohort Study (PDTAP Study) was conducted prospectively in 27 hospitals in China since 2016. Patient and practice data were collected through the doctor-end of the TM app (Manburs) for all participants. TM including self-monitoring records, on-line education materials, and real-time physician-patient contact was only performed for the patient-end users of the Manburs. The primary outcome was all-cause mortality. The secondary outcomes were cause-specific mortality and all-cause and cause-specific permanent transfer to hemodialysis. RESULTS: A total of 7,539 PD patients were enrolled between June 2016 and April 2019, with follow-up till December 2020. Patients were divided into two cohorts: TM group (39.1%) and non-TM group (60.9%). A propensity score was used to create 2,160 matched pairs in which the baseline covariates were well-balanced. There were significantly lower risks of all-cause mortality (HR 0.59 [0.51, 0.67], p < 0.001), CVD mortality (HR 0.59 [0.49, 0.70], p < 0.001), all-cause transfer to hemodialysis (0.57 [0.48, 0.67], p < 0.001), transfer to hemodialysis from PD-related infection (0.67 [0.51, 0.88], p = 0.003), severe fluid overload (0.40 [0.30, 0.55], p < 0.001), inadequate solute clearance (0.49 [0.26, 0.92], p = 0.026), and catheter-related noninfectious complications (0.41 [0.17, 0.97], p = 0.041) in the TM group compared with the non-TM group. CONCLUSION: This study indicated real-world associations between TM usage and reduction in patient survival and technique survival through a multicenter prospective cohort.