Jiachuan Xiong

Context: The triglyceride-glucose (TyG) index is a widely used surrogate marker of insulin resistance and associated with cardiometabolic outcomes. However, the comparative prognostic value of TyG-derived indices, particularly those incorporating anthropometric measures or long-term variability, for adverse outcomes after kidney transplantation remains unclear. Objective: To compare the prognostic performance of 15 TyG-derived indices for predicting new-onset diabetes after transplantation (NODAT), graft failure, and all-cause mortality in kidney transplant recipients (KTRs). Design: This prospective observational study was conducted within the TransplantLines Biobank and Cohort study and included 464 KTRs (median age, 56.9 years; 65.1% male) followed for a median of 71 months. Fifteen TyG-derived indices were classified into metabolic, anthropometry-adjusted, and variability-based domains. Their prognostic performance was assessed using an analytical framework integrating machine learning with conventional statistical methods. Results: Comparative analyses identified 4 indices, TyG-WWI, TyG-WHR, TyG mean, and TyG-BMI, as having superior predictive performance. Among them, anthropometry-adjusted indices (TyG-WHR and TyG-WWI) showed the most stable associations across 3 outcomes. In multivariable analyses, TyG-WHR independently predicted NODAT (HR 2.30, 95% CI 1.21-4.39), graft failure (HR 2.22, 95% CI 1.18-4.18), and mortality (HR 1.87, 95% CI 1.19-2.96), while TyG-WWI independently predicted mortality (HR 2.07, 95% CI 1.11-3.86). Cross-validation showed no consistent advantage of combined models over single well-performing indices. Conclusion: Among adult KTRs from the TransplantLines cohort with a functioning graft, TyG-WWI and TyG-WHR showed the most consistent associations with adverse post-transplant outcomes. Their potential role as complementary metabolic risk markers requires validation in larger and more diverse transplant cohorts.

Key Points: Platelet-activating factor receptor contributed to renal tubular epithelial cells G2/M arrest through suppressing mouse double minute 2–mediated p53 ubiquitin degradation in AKI-to-CKD transition. Phosphatidylethanolamine (18:0/18:1) served as a novel endogenous ligand of platelet-activating factor receptor, inducing the downstream signaling. WAY-639497, a small-molecule platelet-activating factor receptor antagonist identified by virtual screening, mitigated renal tubular epithelial cells G2/M arrest and AKI-to-CKD transition. Background: AKI represents a critical clinical complication with a high propensity of progression to CKD, yet effective therapies remain limited. G protein–coupled receptors mediate diverse pathophysiological processes and are promising therapeutic targets. Here, we investigated the role of platelet-activating factor receptor (PTAFR), a lipophilic G protein–coupled receptor, in AKI-to-CKD transition. Methods: A mouse model of ischemia-reperfusion injury (IRI)–induced AKI was built by bilateral renal artery clamping. The phenotypic role of PTAFR in renal tubular epithelial cells (RTECs) after AKI was investigated in tubule-specific PTAFR-deficiency mice. The functional and molecular mechanisms were determined by transcriptomic profiling, flow cytometry, coimmunoprecipitation, Western blotting, and immunofluorescence. Lipidomic analysis and biological experiments were used to identify the endogenous ligand of PTAFR. The translational potential of PTAFR was evaluated by structure-based high-throughput virtual screening of a small-molecule inhibitor in vivo and in vitro assays. Results: The expression of PTAFR was upregulated in RTECs after AKI in vivo and in vitro . Tubule-specific depletion of PTAFR alleviated IRI-induced RTEC injury and kidney fibrosis after AKI. Mechanistically, PTAFR promoted RTECs G2/M arrest by suppressing mouse double minute 2–mediated p53 ubiquitin degradation. Phosphatidylethanolamine (18:0/18:1) was identified as a novel PTAFR endogenous ligand inducing RTECs G2/M arrest. Urinary phosphatidylethanolamine (18:0/18:1) was correlated with kidney dysfunction and was able to effectively distinguish patients with AKI from healthy controls. High-throughput virtual screening identified WAY-639497, a small-molecule PTAFR antagonist, that was able to mitigate IRI-induced RTEC injury and kidney fibrosis after AKI. Conclusions: PTAFR promoted tubular epithelial cell G2/M arrest by inhibiting mouse double minute 2–mediated p53 ubiquitin degradation and further contributed AKI-to-CKD transition.

Background: Remnant cholesterol (RC) has been recognized as a critical risk factor for vascular diseases. However, its association with cardiovascular disease (CVD) and overall mortality in individuals with diabetic kidney disease (DKD) has not been thoroughly investigated. Methods: This retrospective single-center study enrolled 329 patients with biopsy-confirmed DKD from August 2009 to December 2018. The prognosis of patients with varying RC levels was compared. In addition, the association between RC levels and left ventricular structure and function was examined. Furthermore, the predictive capability of RC for clinical outcomes was assessed. Results: Over the follow-up period, 76 patients (23.1%) experienced CVD events, while 44 patients (13.4%) died. Kaplan-Meier analysis demonstrated that patients in the high RC group exhibited significantly elevated rates of CVD events ( p = 0.0047) and all-cause mortality ( p = 0.0213). Additionally, multivariate Cox regression analysis confirmed RC as an independent risk factor for CVD events (HR = 1.323, 95% CI 1.076-1.626, p = 0.008) and overall mortality (HR = 1.359, 95% CI 1.039-1.779, p = 0.025). Finally, the AUC analysis indicated that the inclusion of RC in traditional risk factors improved their predictive accuracy. Conclusion: RC independently contributes to the risk of CVD events and all-cause mortality in individuals with biopsy-confirmed DKD.

Focal segmental glomerulosclerosis (FSGS), a common cause of nephrotic syndrome, is diagnosed by renal biopsy showing focal segmental sclerosis with foot-process effacement. It has a poor prognosis and can rapidly progress to end-stage kidney disease (ESKD). While the etiology of FSGS is largely unknown, many genes have been linked to the familial form of the condition. One of its subtypes, FSGS8, is caused by a heterozygous mutation in the ANLN gene on chromosome 7p14. However, reports of disease-causing ANLN variants in the literature are scarce. Here, we report a novel variant of ANLN in a Chinese family with FSGS. The proband was in hospital for proteinuria and the laboratory tests elevated levels of serum creatinine and uric acid. Histopathology study of renal biopsy showed FSGS. Genetic testing based on whole-exome sequencing (WES) was performed to explore the molecular basis. A heterozygous pathogenic variant of the ANLN gene, NM_018685 c.2343G > C, was identified in the affected patients and further confirmed by Sanger sequencing. This variant leads to a missense mutation in the anillin protein, altering its structure. This novel pathogenic variant of the ANLN gene provides a molecular basis for FSGS8 and expands the known mutation spectrum for FSGS.

The myeloid-to-lymphoid ratio (MLR) has been associated with adverse outcomes in various clinical settings; however, its prognostic significance in chronic