Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease globally, yet reliable biomarkers for its diagnosis and progression assessment are lacking. This study employed artificial intelligence techniques, including weighted gene co-expression network analysis (WGCNA) and machine learning, to identify crucial genes associated with DKD. Validation was conducted using online databases such as Nephroseq and KIT, alongside biological samples from human serum, urine, peripheral blood mononuclear cell (PBMC) mRNA, kidney tissues, DKD rat models, and high glucose-treated HK-2 cells. Statistical analyses evaluated the correlations. The study revealed that C-X-C motif chemokine ligand 3 (CXCL3) was markedly upregulated in the serum and urine of DKD patients compared to healthy controls and those with type 2 diabetes mellitus, primary glomerulonephritis (e.g., IgA nephropathy, membranous nephropathy, minimal change disease). Immunohistochemistry showed significantly higher CXCL3 in both the glomeruli and tubulointerstitium of DKD patient kidneys than in those from controls. Elevated CXCL3 mRNA levels were also noted in PBMCs from DKD patients, STZ-induced DKD rat kidneys, and high glucose-treated HK-2 cells. Furthermore, urinary CXCL3 protein levels positively correlated with the pathological grade, serum blood urea nitrogen (BUN), serum creatinine, and HbA1c percentage, while inversely correlating with estimated glomerular filtration rate (eGFR) in DKD patients. Mechanically, high glucose stimulation significantly upregulates the expression of inflammatory factors (including IL-6 and IL-1β) and fibrosis markers (α-SMA and CTGF) in HK-2 cells overexpressing CXCL3. Conversely, CXCL3 knockout in HK-2 cells led to substantial downregulation of these inflammatory and fibrotic markers in the same high glucose conditions. Elevated CXCL3 levels in the serum, urine, and kidney tissues, alongside increased mRNA in PBMCs, suggest its potential as a biomarker for diagnosing and monitoring DKD. Correlations of urinary CXCL3 with disease severity indicators further support its diagnostic and prognostic utility. Mechanically, CXCL3 promotes inflammation and fibrosis in DKD.

BACKGROUND:Venous thromboembolism (VTE) is a major cause of global morbidity and mortality, yet its underlying molecular mechanisms remain incompletely understood, limiting the development of novel targeted therapies. While neutrophil activation is implicated in VTE, its causal role and the key genetic drivers are poorly defined. This study aimed to bridge this knowledge gap using a multi-omics genetic approach. METHODS:We conducted a Summary-data-based Mendelian Randomization (SMR) study, integrating large-scale GWAS data for VTE with molecular QTL data (mQTL, eQTL, pQTL) for 996 neutrophil activation-related genes. Causal associations were identified using SMR and validated through colocalization analysis to distinguish robust causal links from linkage. RESULTS:Our analysis identified numerous causal associations at the methylation (223 sites), expression (41 genes), and protein (21 proteins) levels. Among these, PLAU, ALOX12, and LGALS3 emerged as key candidates due to evidence of epigenetic regulation of their gene expression. Specifically, increased PLAU expression showed a causal association with higher VTE risk (OR = 1.13, 95% CI = 1.04-1.24), a finding supported by strong colocalization evidence (PPH4 > 0.5). Similarly, elevated expression of ALOX12 (OR = 1.27, 95% CI = 1.07-1.51) and LGALS3 (OR = 1.44, 95% CI = 1.04-2.01) were causally linked to increased VTE susceptibility, although these expression-level associations did not meet our stringent threshold for colocalization. CONCLUSION:This study identifies PLAU, ALOX12, and LGALS3 as genetically prioritized, causal-candidate genes for VTE, enhancing our understanding of immunothrombosis and providing promising targets for future therapeutic development.

Peritoneal dialysis (PD)-related peritonitis is a common complication with high morbidity and mortality, and empirical antibiotic regimens vary across countries. Despite some research, inconsistent results and design limitations highlight the need to reassess the association between these regimens and outcomes. This study was affiliated with the PD Telemedicine-assisted Platform (PDTAP) study. The primary outcome was peritonitis-associated death, and the secondary outcomes were peritonitis-associated hemodialysis transfer and subsequent peritonitis within 6 months. Propensity score matching and logistic regression were used to access the relationship between empirical antibiotic administration and outcomes. Altogether, 1431 patients experienced a first episode of peritonitis from June 1, 2016, to April 30, 2019. Among them, 1203 patients were assigned to the cefazolin-based group (n = 637) or to the vancomycin-based group (n = 566) based on administration of empirical antibiotics against Gram-positive bacteria. Compared to the cefazolin-based group, patients in the vancomycin-based group were older, had a longer PD duration, and reported higher income, along with a greater prevalence of diabetes, cardiovascular disease, and peritonitis history (P < 0.05 for all). Both groups exhibited similar rates of peritonitis-associated death and subsequent peritonitis within 6 months (P > 0.05 for all), however, the vancomycin-based group was more prone to to hemodialysis transfer (11.00

Background:Telitacicept is a biologic that specifically targets B-lymphocyte stimulator and a proliferation-inducing ligand, demonstrating significant potential for therapeutic applications in B-cell-mediated autoimmune diseases. Currently, telitacicept is primarily utilized in the treatment of systemic lupus erythematosus. However, its therapeutic effect on immunoglobulin A nephropathy (IgAN) after hematopoietic stem cell transplantation (HSCT) has not been reported. This case report presents the clinical outcome of telitacicept administration in the treatment of IgAN following HSCT. Case report:A 36-year-old Asian man developed IgAN following allogeneic HSCT for acute myeloid leukemia (AML). The patient presented with features of high-risk nephrotic syndrome, including a urinary protein quantification of 8.28 g/24 h and serum albumin level of 29 g/L. The patient showed significant clinical improvement following treatment with moderate-dose glucocorticoids combined with telitacicept. After the treatment process, the urine albumin quantification decreased to 0.23 g/24 h, and serum albumin increased to 45.8 g/L. During the treatment, estimated glomerular filtration rate (eGFR) increased from 67.3 to 79.83 mL/min/1.73m2, and immune indicators immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) also demonstrated steady levels (IgA: 6.78-10.1 g/L, IgG: 0.5-1.41 g/L, IgM: 0.17-0.6 g/L). Notably, the patient's condition remained stable without any significant adverse effects throughout the rapid tapering of the glucocorticoid dose. Conclusion:This case suggests that telitacicept may be an effective treatment option for IgAN following HSCT, providing valuable insights into future therapeutic strategies for managing post-HSCT IgAN.

ABSTRACT Background To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. Methods The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). Results A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19–281], P = .006}, MACE [HR 1.99 (95% CI 1.16–3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15–2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. Conclusion This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.

Diabetic nephropathy (DN) is an important complication of diabetes and the leading cause of end‐stage renal disease globally. Renal tubular damage occurs to varying degrees in the early stages of DN prior to glomerular damage. Renalase (RNLS) is an amine oxidase, which is produced and secreted by the renal tubular epithelial cells. RNLS is reportedly closely related to renal tubular injury in acute and chronic kidney diseases. Herein, we aimed to evaluate the changes in tubular RNLS expression in DN and its correlation with DN‐associated renal tubular injury. Conditional permanent renal tubular epithelial rat‐cell line NRK‐52E was transfected with pcDNA3‐RNLS plasmid or administered recombinant rat RNLS protein and high glucose (HG) dose. A total of 22 adult Sprague‐Dawley rats were randomly divided into the control (CON, n = 10) or diabetic nephrology (DN, n = 12) group. Random blood glucose levels of the rats were measured by sampling of the caudal vein weekly. After 8 weeks, the rat's body weight, 24‐h urinary albumin concentration, and right kidney were evaluated. Our study suggested the decreased expression levels of RNLS in renal tissue and renal tubular epithelial cells in DN rats, accompanied by renal tubulointerstitial fibrosis, apoptosis of renal tubular epithelial cells, and activation of the p38MAPK signal pathway. Reversing the low RNLS expression can reduce the level of p38MAPK phosphorylation and delay renal tubular injury. Thus, the reduction of renal tubular RNLS expression in DN mediates tubulointerstitial fibrosis and cell apoptosis via the activation of the p38MAPK signal pathway. RNLS plays a key mediating role in DN‐associated tubular injury via p38MAPK, which provides new therapeutic targets and a theoretical basis for early prevention and treatment of DN.

The aim of this study was to elucidate the application of ultrasound examination of umbilical artery (UA) hemodynamics with urine microalbumin (UmA) determination in evaluating the outcomes of sPE patients. Altogether 80 sPE patients and 75 healthy pregnant women were recruited. UmA, RI (resistance index) and PI (pulsatility index) were separately measured by ELISA and the ultrasonic Doppler flow detector. The correlation between parameters was analysed using Pearson's coefficient method. The independent risk factors of sPE were identified using the Logistic regression model. sPE patients had increased UmA, RI and PI (all p < 0.05). UmA level was positively correlated with RI and PI in sPE patients. RI, PI and UmA were independent risk factors of sPE (all p < 0.05). sPE can predict adverse pregnancy outcomes. High UmA levels may increase the risk of poor prognosis. Overall, ultrasound examination of UA hemodynamics with UmA determination can predict the adverse pregnancy outcomes of sPE patients. IMPACT STATEMENT What is already known on this subject? Doppler ultrasound and urine microalbumin (UmA) measurement are important tools in assessing the clinical severity of severe preeclampsia (sPE). What do the results of this study add? This study aims to unravel the application of ultrasound examination of hemodynamics in the umbilical artery (UA) combined with the determination of UmA in evaluating the outcomes of sPE patients. What are the implications of these findings for clinical practice and/or further research? Ultrasound examination of hemodynamics in UA combined with the determination of UmA can predict the adverse pregnancy outcomes of sPE patients.

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.

Objectives: The primary objective of the Peritoneal Dialysis Telemedicine-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.

RATIONALE:Atypical hemolytic uremic syndrome (aHUS) is an uncommon and serious disease that manifests hemolytic anemia, thrombocytopenia, and acute kidney injury. Genetic complement abnormalities have been shown to be responsible. Compared with the aHUS caused by other mutated genes, aHUS secondary to CFB mutation in adults is extremely rare. We report an adult with CFB mutation developing aHUS. PATIENT CONCERNS:A 56-year-old man was admitted for 4-day history of nausea and fatigue, anuria for 2 days, and unconsciousness for 10 hours. DIAGNOSES:The patient presented with life-threatening anemia, thrombocytopenia, acute kidney injury, and nervous system abnormalities. The patient had schistocytes on the peripheral blood smear, increased lactate dehydrogenase (LDH), and plasma-free hemoglobin levels. The patient was later found to harbor a pathogenic variant in the CFB gene (C.1598A>G), and was diagnosed with aHUS and acute kidney injury. INTERVENTION:The patient was treated by plasmapheresis, continuous renal replacement therapy, blood transfusion, and anti-infective and antihypertensive treatment. OUTCOMES:After the treatment, the patient's consciousness returned to normal, and the hemoglobin, platelet, and serum creatinine recovered. The disease activity remained quiescent during the follow-up. LESSONS:A rare heterozygous variant c.1598A>G p.Lys 533Arg in the CFB gene, which was associated with adult-onset aHUS, was described and successfully treated. This case can help in understanding the early diagnosis and effective therapies of this rare disease.

Podocytes are the key cells involved in protein filtration in the glomerulus. Once proteins appear in the urine when podocytes fail, patients will end with renal failure due to the progression of glomerular damage if no proper treatment is applied. The injury and loss of podocytes can be attributed to diverse factors, such as genetic, immunologic, toxic, or metabolic disorders. Recently, autophagy has emerged as a key mechanism to eliminate the unwanted cytoplasmic materials and to prolong the lifespan of podocytes by alleviating cell damage and stress. Typically, the fundamental function of extracellular vesicles (EVs) is to mediate the intercellular communication. Recent studies have suggested that, EVs, especially exosomes, play a certain role in information transfer by communicating proteins, mRNAs, and microRNAs with recipient cells. Under physiological and pathological conditions, EVs assist in the bioinformation interchange between kidneys and other organs. It is suggested that EVs are related to the pathogenesis of acute kidney injury and chronic kidney disease, including glomerular disease, diabetic nephropathy, renal fibrosis and end-stage renal disease. However, the role of EVs in podocyte autophagy remains unclear so far. Here, this study integrated the existing information about the relevancy, diagnostic value and therapeutic potential of EVs in a variety of podocytes-related diseases. The accumulating evidence highlighted that autophagy played a critical role in the homeostasis of podocytes in glomerular disease.

A large number of coronavirus disease 2019 (COVID-19) patients have been cured and discharged due to timely and effective treatments. While some discharged patients have been found re-positive nucleic acid again in the recovery phase. Until now, there is still a great challenge to its infectivity and the specific potential mechanism which needs further discussion. However, more intensive attention should be paid to the prognosis of recovered patients. In this review, we mainly focus on the characteristics, potential reasons, infectivity, and outcomes of re-detectable positive patients, thereby providing some novel insights into the cognition of COVID-19.

A large number of coronavirus disease 2019 (COVID-19) patients have been cured and discharged due to timely and effective treatments. While some discharged patients have been found re-positive nucleic acid again in the recovery phase. Until now, there is still a great challenge to its infectivity and the specific potential mechanism which needs further discussion. However, more intensive attention should be paid to the prognosis of recovered patients. In this review, we mainly focus on the characteristics, potential reasons, infectivity, and outcomes of re-detectable positive patients, thereby providing some novel insights into the cognition of COVID-19.

Primary nephrotic syndrome (PNS) is the most common chronic kidney disease in childhood, where podocyte injury is a key factor in the occurrence of kidney disease. In the present study, the expression of IL-17 in renal tissues of patients with PNS and its relationship with podocyte injury were examined. Reverse transcription-quantitative PCR (RT-qPCR), western blot analysis and immunochemistry were used to measure the expression of IL-17 in renal biopsies of patients with ONS, including 9 patients with minimal change nephrotic syndrome (MCNS), 15 patients with mesangial proliferative glomerulonephritis (MsPGN) and 9 patients with focal segmental glomerulosclerosis (FSGS), in addition to 15 normal kidney tissues. IL-17 was found to be highly expressed in the renal tissues from patients with PNS, with the highest expression levels found in tissues from patients with FSGS and the lowest in those from MCNS. A negative correlation was observed between the levels of IL-17 mRNA and PCX mRNA in renal tissues, whereas a positive correlation between IL-17 mRNA levels and the number of urinary podocytes in patients with PNS was found. In vitro, IL-17 induced podocyte apoptosis and reduced the expression of markers associated with podocytes, including Wilm's tumor 1, nephrin, synaptopodin and podocalyxin, whilst increasing the levels of Fas, Fas ligand (FasL), active-caspase-8, active-caspase-3 and phosphorylated-p65. However, treatment with helenalin, a NF-κB inhibitor, decreased p65 phosphorylation, attenuated IL-17-induced podocyte apoptosis and suppressed the IL-17-activated Fas/FasL/caspase-8/caspase-3 apoptotic pathway. Taken together, these observations suggest that IL-17 was highly expressed in renal tissues from patients with PNS, where it induced podocyte apoptosis by activating the Fas/FasL/caspase-8/caspase-3 apoptotic pathway in a NF-κB-dependent manner.

Background: Convalescent plasma (CP) has been used successfully to treat many types of infectious disease, and has shown initial effects in the treatment of the emerging 2019 coronavirus disease (COVID19). However, its curative effects and feasibility have yet to be confirmed by formal evaluation and well designed clinical trials. To explore the effectiveness of treatment and predict the potential effects of CP with COVID-19, studies of different types of infectious disease treated with CP were included in this systematic review and meta-analysis. Methods: Related studies were obtained from databases and screened according to the inclusion criteria. The data quality was assessed, and the data were extracted and pooled for analysis. Results: 40 studies on CP treatment for infectious diseases were included. Our study found that CP treatment could reduce the risk of mortality, with a low incidence of adverse events, promote the production of antibodies, lead to a decline in viral load, and shorten the disease course. A meta-analysis of 15 controlled studies showed that there was a significantly lower mortality rate in the group treated with CP (pooled OR = 0.32; 95% CI = 0.19-0.52; p < 0.001, I-2 = 54%) compared with the control groups. Studies were mostly of low or very low quality, with a moderate or high risk of bias. The sources of clinical and methodological heterogeneity were identified. The exclusion of heterogeneity indicated that the results were stable. Conclusions: CP therapy has some curative effect and is well tolerated in treating infectious diseases. It is a potentially effective treatment for COVID-19. (c) 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).