Immunoglobulin A nephropathy (IgAN) is a major cause of kidney failure. This study aimed to investigate the treatment patterns, clinical outcomes, and economic burden of IgAN in China. This was a retrospective multicenter cohort study. Adult patients had biopsy-proven primary IgAN diagnosed between 01/01/2015, and 06/30/2023 in China. The index date was the date of the renal biopsy. Time-to-event analysis was performed for event-free from composite renal events (occurrence of end-stage kidney disease, a 40

Introduction The discordance between cystatin C- and creatinine-based eGFR (eGFRdiff) predicts mortality in CKD, but what this index actually reflects remains unclear. We examined the relative contributions of several biomarkers, representing muscle mass, middle-molecule retention, cardiac injury, inflammation, and physical function, to the eGFRdiff-mortality association in a nationally representative US population. Materials and Methods We analyzed 1503 adults with CKD stages 1-4 from NHANES 1999-2004 with mortality follow-up through 2019. The exposure was percentage eGFRdiff. Survey-weighted Cox models estimated HRs for mortality. Attenuation analyses quantified the contribution of each candidate biomarker. Residualization analyses decomposed the B2M signal by adjusting for creatinine-based, cystatin C-based, and combined eGFR estimates separately. Results 911 all-cause and 313 cardiovascular deaths occurred. Each 1-SD more negative eGFRdiff was associated with higher all-cause (HR 1.29; 95%CI 1.15-1.46) and cardiovascular mortality (HR 1.46; 95%CI 1.23-1.72). DXA-derived muscle mass yielded negligible attenuation (1.3%), and physical limitation produced modest attenuation (11.2%). In contrast, B2M produced the largest attenuation (73.4%), followed by hs-cTnT (32.0%) and NT-proBNP (23.0%). Residualization on eGFRcr preserved the B2M attenuation (80.1%), whereas residualization on eGFRcys abolished it (-7.9%). B2M residualized on eGFRcr-cys retained 21.9% attenuation. Conclusions Middle-molecule retention (represented by B2M), not muscle mass, is the primary contributor to the prognostic value of eGFRdiff, with cardiac biomarkers contributing secondarily. Residualization patterns support a biological signal consistent with shrunken pore syndrome rather than a mathematical artifact of how eGFR is estimated. Calculable from routine assays, eGFRdiff may offer a practical indicator of middle-molecule burden and cardiac stress for CKD risk stratification.

BackgroundType I cryoglobulinemia consists of a single monoclonal immunoglobulin and can induce small-vessel vasculitis with renal involvement. Cryoglobulinemic glomerulonephritis is a rare manifestation, pathologically characterized by membranoproliferative glomerulonephritis (MPGN). In this report, we present a case of type I cryoglobulinemic renal injury characterized by crystalline cryoglobulinemic glomerulonephritis type I. Our objective is to provide a detailed insight into the presentation, underlying diseases, diagnosis, treatment, and outcomes of crystalline cryoglobulinemic glomerulonephritis type I.Case presentation: A 38-year-old man presented with acute kidney injury (AKI) without any other systemic symptoms. A kidney biopsy confirmed the presence of abundant pseudothrombi within the glomerular capillary lumens, with no significant proliferative lesions observed. Immunofluorescence microscopy (IF) demonstrated strong, diffuse, homogeneous staining for IgG1 and Lambda light chain. Electron microscopy revealed a microtubular substructure characteristic of nephropathy. Following the initial course of rituximab, plasma exchange (PE), and methylprednisolone, the treatment yielded successful results. However, renal dysfunction recurred 18 months later, prompting a second renal biopsy, which exhibited findings similar to the first. Additionally, bone marrow biopsy identified an aberrant monotypic plasma cell clone. Subsequently, daratumumab therapy was initiated, leading to a recovery in kidney function.ConclusionIn nephropathies associated with crystalline cryoglobulinemic glomerulonephritis type I, renal and bone marrow biopsies play a crucial role in establishing the diagnosis and determining the optimal therapeutic approach. It is essential to consider primary diseases prior to selecting the initial management strategy.

IntroductionThis real-world analysis aimed to evaluate the primary endpoint safety profile and the secondary effectiveness and treatment patterns of sodium zirconium cyclosilicate (SZC) for hyperkalemia management in China, addressing the current evidence gap on SZC use in clinical practice.MethodsThis multi-center, prospective, non-interventional cohort study enrolled patients (aged ≥18 years), including new and ongoing SZC users, from 34-sites. Treatment was categorized into correction-phase (FAS-P1) and maintenance phase (FAS-P2, new and ongoing users). The subgroup analysis was performed in patients undergoing hemodialysis (full analysis set-hemodialysis [FAS-H]). The primary objective included the safety of SZC whereas treatment patterns and effectiveness were the secondary objectives.ResultsOf the 1,000 enrolled patients, 442, 878, and 474 were included in FAS-P1, FAS-P2, and FAS-H subgroups, respectively. The most frequently used SZC dosage was 5 g once-daily in FAS-P (42.1%), and FAS-P2 (37.7%). In the FAS-P1 and FAS-P2 groups, 64% and 65.4% of patients reported AEs; 26.9% and 30.8% reported SAEs. The serum potassium (sK+) was reduced from 5.8 to 5.0 mmol/L in FAS-P1. The mean “with-in” sK+ levels over 6-month was 5.1 mmol/L in FAS-P2, of which the new-user group were slightly higher vs. ongoing group of FAS-P2 with a mean sK+ of 5.2 and 5.0 mmol/L, respectively. Furthermore, SZC showed good efficacy in patients with different chronic kidney disease stage subgroups of FAS-P2.ConclusionIn real-world clinical practice, no new safety issues of SZC were identified. SZC was effective in lowering sK+ levels in the correction-phase and remained stable during the maintenance-phase.

Despite advancements in dialysis technology, patients with kidney failure who are on maintenance haemodialysis (MHD) continue to experience high morbidity and mortality. Haemoadsorption combined with haemodialysis (HAHD) has emerged as a promising therapy to address these challenges. In light of the increasing adoption of HAHD in patients receiving MHD, there is a pressing need to demonstrate the safety and effectiveness of HAHD treatment. Consequently, a panel of Chinese experts developed a consensus on HAHD on the basis of the published literature and collective clinical experience. The consensus outlines six critical issues concerning HAHD treatment: patient population, contraindications, heparinization and priming procedures, prescription of HAHD, adjustment of medication dosages, and potential treatment-associated adverse events. After evaluation using a Delphi methodology, 19 statements achieved consensus (7 recommendations and 12 practice points). The overarching goal is to provide best-practice recommendations formulated by the HAHD consensus group to guide the use of haemoadsorption in MHD patients.

Introduction:WS016 is a highly selective cation exchanger which traps potassium in the intestinal tract, reducing serum potassium levels in patients with hyperkalemia. This study aimed to evaluate the efficacy and safety of WS016 in hyperkalemic patients. Methods:One hundred forty eligible patients were randomized to receive either WS016 (3 g, 6 g, or 12 g), thrice daily, or placebo for 48 hours. Among those who achieved normokalemia, patients were randomized to WS016 (3 g, 6 g, and 12 g), once daily for 12 days. The primary outcome was the exponential rate of change in serum potassium levels from baseline over the acute and maintenance treatment period, respectively. Results:During the acute treatment phase, the mean exponential rates of reduction from baseline were 0.19% (P = 0.27), 0.17% (P = 0.35), and 0.33% (P < 0.0001) per hour in the WS016 3 g, 6 g, and 12 g group, respectively, compared with a 0.13% with placebo. In contrast, during the maintenance phase, all WS016 groups showed a numerically slower mean daily increase in serum potassium compared with their corresponding placebo groups. The daily increase rate was 0.90% with WS016 12 g versus 1.24% with placebo, the difference was -0.34% (95% confidence interval [CI]: -1.30% to 0.63%; P = 0.49). The overall incidence of adverse events was comparable between WS016 and placebo groups as follows: 26.9% (WS016) versus 20.0% (placebo) during the acute phase and 27.0% versus 31.3% in the maintenance phase. Conclusion:WS016 reduced serum potassium levels rapidly and maintained more patients within the normokalemic range.

IntroductionCardiovascular disease represents the leading cause of mortality among patients with chronic kidney disease (CKD). CKD-associated cardiomyopathy is characterized by pathological left ventricular hypertrophy and myocardial fibrosis. Pegmolesatide, a novel pegylated continuous erythropoietin receptor activator, has demonstrated efficacy in treating renal anemia. However, the biological effects of Pegmolesatide beyond erythropoiesis remain poorly characterized.MethodsThis study established a 5/6 nephrectomy rat model of CKD. The animals were randomized into four groups: sham-operated (Sham), sham-operated plus Pegmolesatide (Sham + Pegmolesatide), CKD model (CKD), and CKD model plus Pegmolesatide (CKD + Pegmolesatide). Cardiac function was assessed by echocardiography, while histopathological examination evaluated cardiac and renal structural changes. Serum renal function parameters were measured using biochemical assays. Myocardial expression of proteins and mRNAs related to fibrosis, hypertrophy, and associated signaling pathways was analyzed by Western blot and quantitative PCR. Furthermore, transcriptomic sequencing of myocardial tissue was performed, and in vitro experiments were conducted using AC16 human cardiomyocytes stimulated with serum from stage 5 CKD patients.ResultsTranscriptomic sequencing suggested that the cardioprotective effects of Pegmolesatide might be associated with improved mitochondrial function and modulation of the STAT3 signaling pathway. Results demonstrated that Pegmolesatide significantly improved cardiac functional parameters and attenuated both myocardial fibrosis and cardiomyocyte hypertrophy. Mechanistic investigations revealed that these cardioprotective effects were mediated through inhibition of JAK2/STAT3 signaling pathway activation and concomitant improvement of mitochondrial function.DiscussionThese findings demonstrate that pegmolesatide exerts anti-anemic effect-independent cardioprotection, offering novel insights into treating CKD-associated cardiomyopathy.

Background:Chronic kidney disease-associated pruritus (CKD-aP) is a common and debilitating condition in patients receiving in-centre haemodialysis. This study evaluated the efficacy and safety of difelikefalin (a new, intravenous treatment for moderate-to-severe CKD-aP approved in >40 countries) in a Chinese population receiving haemodialysis. Methods:This Phase 3, multicentre, randomized placebo-controlled study included a 12-week double-blind treatment period, during which patients received either difelikefalin or placebo, followed by an optional 14-week open-label extension, in which all patients received difelikefalin. Endpoints included change from baseline in the Worst Itching Intensity Numerical Rating Scale (WI-NRS) at Week 4 (primary endpoint), the percentage of patients achieving a clinically relevant ≥3-point change in WI-NRS, patient-reported health-related quality-of-life measures, and incidence of adverse events. Results:Difelikefalin-treated patients showed significantly greater improvements in least squares mean change from baseline in WI-NRS at Week 4 of the double-blind period compared with placebo [difelikefalin minus placebo: -0.81 (95% confidence interval: -1.25, -0.37); P = .0003], and patients with ≥3-point improvement in WI-NRS at Week 12 (48.7% versus 33.8%, nominal P = .0235). Difelikefalin also improved health-related quality of life, with clinically relevant changes observed in 5-D itch and Skindex-10 in most patients at Week 4 of the open-label extension (estimated ≥62% and ≥56%, respectively). Adverse events were mostly mild or moderate in severity and generally consistent with the known safety profile of difelikefalin. Conclusion:Difelikefalin effectively reduced pruritus intensity and improved quality of life in Chinese patients with CKD-aP receiving haemodialysis, supporting its use in this population.

Bone remodeling relies on a balance between osteoclast-mediated resorption and osteoblast-mediated formation. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, promotes osteoblast differentiation but its effects on osteoclasts remain unclear. This study investigated roxadustat's impact on osteoclast differentiation and function in vitro using primary murine bone marrow-derived mononuclear cells differentiated with M-CSF and RANKL. Cell viability, TRAP staining, bone resorption assays, RNA-seq, flow cytometry, immunofluorescence, Western blot for p27, and rescue experiments with the cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor abemaciclib were performed. Roxadustat suppressed osteoclast differentiation and resorption without cytotoxicity in a concentration-dependent manner. RNA-seq revealed enrichment of cell cycle pathways; although differentiation was inhibited, roxadustat paradoxically promoted osteoclast precursor proliferation, evidenced by increased Ki67 and decreased p27 expression. The inhibitory effects on osteoclastogenesis and resorption were partially reversed by abemaciclib. Given that terminal differentiation typically requires cell cycle exit, these findings suggest that roxadustat may inhibit osteoclast differentiation at least in part by disrupting this process, promoting precursor proliferation, and downregulating p27. Together with its known anabolic effects on osteoblasts, roxadustat might have dual therapeutic potential for bone disorders with renal anemia, such as osteoporosis in chronic kidney disease.

INTRODUCTION:Patients with advanced stages of chronic kidney disease (CKD) and dialysis-dependent kidney failure are at a greater risk of cardiovascular events and mortality than those with early stages of CKD. There are no completed definitive randomized trials on the safety and efficacy of anticoagulant therapy in this patient population. METHODS:Treatment of cardiovascular disease with low-dose Rivaroxaban in Advanced Chronic Kidney disease (TRACK) is a multi-center, randomized, placebo-controlled trial (NCT03969953), designed to enrol 1886 adult participants with CKD stage 4 or 5 (estimated glomerular filtration rate 29 mL/min/1.73 m2) or dialysis-dependent kidney failure and high cardiovascular risk (defined as at least one of the following risk factors; coronary artery disease, non-hemorrhagic non-lacunar stroke, peripheral artery disease [PAD], diabetes mellitus, or age 65 years). Participants are randomized to rivaroxaban 2.5 mg twice daily or matching placebo. The primary efficacy outcome is a composite of cardiovascular death, myocardial infarction, stroke, or PAD event. The primary safety outcome is major bleeding, defined as a composite of fatal bleeding, bleeding leading to hospitalization, or symptomatic bleeding in a critical area or organ. From January 2021 through July 2025, 1458 eligible participants (mean age 63.2 years, 700 [48%] age 65 years, 432 [29.6%] women, 715 [49%] dialysis-dependent kidney failure and 743 [51%] CKD stage 4 or 5, 1125 [77.2%] diabetes mellitus, 674 [46.2%] treated with aspirin at baseline) underwent randomization. CONCLUSION:TRACK will evaluate the effect of low dose rivaroxaban on major adverse cardiovascular events in participants with CKD stages 4 and 5 and dialysis-dependent kidney failure, and elevated cardiovascular risk.

Recombinant human erythropoietin (rhEPO) fused with human immunoglobulin G (IgG) Fc fragment (rhEPO-Fc) is a novel erythropoiesis-stimulating agent designed to extend plasma half-life and enhance biological activity. However, data on the efficacy and safety of rhEPO-Fc in hemodialysis patients with chronic kidney disease (CKD)-related anemia remain limited. This phase 3 trial enrolled patients from 45 Chinese hospitals. Participants were randomized (2:1) to receive either rhEPO-Fc or rhEPO (Chinese hamster ovary cell-derived) for 28 weeks. The rhEPO-Fc responders were eligible for a 24-week extension period. The primary endpoint was the least square mean (LSM) change in hemoglobin (Hb) levels from baseline between weeks 21 and 28. Among 356 rhEPO-Fc and 178 rhEPO recipients, patients receiving rhEPO-Fc demonstrated non-inferiority Hb maintenance compared with rhEPO. The inter-group LSM differences in the full analysis set and per-protocol set were 3.96 g/L (95% CI: 3.02-4.89; p < 0.001) and 2.27 g/L (95% CI: 0.60-3.95; p = 0.008), respectively. Adverse drug reaction rates were comparable (rhEPO-Fc: 39.2% vs. rhEPO: 40.2%). Dose adjustments due to treatment-emergent adverse events were significantly lower with rhEPO-Fc (0.0% vs. 2.2%; p < 0.05). Deaths unrelated to the study drugs occurred in two rhEPO-Fc and four rhEPO patients. These findings indicated that rhEPO-Fc effectively maintained Hb levels in patients with CKD anemia undergoing hemodialysis, showing comparable efficacy to rhEPO with reduced dosing frequency and a similar safety profile.

Renal tubular injury contributes substantially to the progression of acute kidney injury (AKI) and chronic kidney disease (CKD). S-palmitoylation is a reversible lipid modification that regulates protein localization, stability, trafficking, and signaling. In renal tubular epithelial cells (TECs), it supports epithelial polarity, ciliary function, ion transport, and receptor activity. During renal tubular injury, dysregulated S-palmitoylation can disrupt tubular homeostasis by altering epithelial cell responses. It may aggravate cell damage, amplify inflammation, and promote failed repair and fibrosis. Changes in renal vascular cells and podocytes may also influence tubular injury through renal perfusion and the glomerular filtrate. However, the effects of S-palmitoylation are not the same. Some changes promote injury, whereas others preserve tubular function or limit injury signaling. The outcome depends on the modified protein, the enzyme involved, and the renal cell type. This mini-review summarizes the physiological roles of S-palmitoylation in renal tubules, its direct and indirect contributions to tubular injury, and therapeutic strategies targeting palmitoyltransferases, depalmitoylases, and specific substrates. Because global modulation may disrupt protective pathways, future interventions should prioritize pathogenic enzyme–substrate pairs and cell-specific delivery.

IgA-dominant infection-related glomerulonephritis (IgA-IRGN) and primary IgA nephropathy (IgAN) share similar clinicopathological features, making differentiation challenging despite distinct therapeutic strategies. This study compares the clinicopathological characteristics and short-term prognoses of the two conditions to identify diagnostic differentiators. This retrospective study included patients diagnosed with IgA-IRGN (n = 30) and IgAN (n = 120). We comparatively analyzed their clinical and pathological features, as well as the short-term prognostic differences. Univariate and multivariable logistic regression analyses were conducted to evaluate independent associations. Different pathological scoring systems were utilized to assess their diagnostic value. Short-term prognosis was evaluated at a 6-month follow-up, based on changes in the estimated glomerular filtration rate (eGFR) and the remission rate of proteinuria. Compared to IgAN, IgA-IRGN patients had higher mean arterial pressure, incidences of edema, acute kidney injury (AKI), and hypertension. Serum albumin, eGFR, and complement C3 were lower, while 24-hour proteinuria, neutrophil-to-albumin ratio (NAR), and neutrophil-to-C3 ratio (NC3r) were higher. Pathologically, IgA-IRGN showed diffuse endocapillary hypercellularity (100

Importance:Approximately 10% to 15% of patients with advanced chronic kidney disease (CKD) experience a fatal or nonfatal cardiovascular event annually. The effects of antithrombotic therapies on cardiovascular events in patients with advanced CKD are unknown. Objective:To determine whether low-dose rivaroxaban reduces rates of adverse cardiovascular events compared with placebo in patients with advanced CKD. Design, Setting, and Participants:Randomized, double-blind, placebo-controlled trial conducted at 90 centers in 12 countries. Eligible participants were adults with CKD stage 4 or 5 and patients with dialysis-dependent kidney failure. Participants had a history of either coronary artery disease; nonhemorrhagic, nonlacunar stroke; peripheral artery disease; diabetes; or were 65 years or older. Enrollment occurred between January 2021 and July 2025. The trial was stopped early on August 7, 2025, for lack of efficacy. Final follow-up occurred on October 30, 2025. Statistical analyses were conducted in February and March 2026. Interventions:Patients were randomized 1:1 to receive rivaroxaban 2.5 mg twice daily or placebo. Main Outcomes and Measures:The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or a peripheral artery disease event. The primary safety outcome was major bleeding. Results:Of 1458 randomized patients (mean [SD] age, 63.2 [11.6] years, 432 [29.6%] female), 1360 (93.3%) completed follow-up. During a median follow-up of 1.7 years, the primary outcome occurred in 164 patients (22.6%) in the low-dose rivaroxaban group and 151 (20.7%) in the placebo group (13.0 vs 11.8 events per 100 person-years; hazard ratio, 1.09 [95% CI, 0.87-1.36]; P = .46). Major bleeding occurred in 64 patients (8.8%) receiving low-dose rivaroxaban and 44 (6.0%) receiving placebo (5.1 vs 3.4 events per 100 person-years; hazard ratio, 1.51 [95% CI, 1.02-2.22]; P = .04). Conclusions and Relevance:In patients with advanced CKD at high cardiovascular risk, low-dose rivaroxaban did not reduce the risk of a composite cardiovascular outcome. Major bleeding rates were significantly higher in the low-dose rivaroxaban group compared with the placebo group. Trial Registration:ClinicalTrials.gov Identifier: NCT03969953.

Introduction: Despite advancements in hemodialysis (HD) technology, mortality remains unacceptably high in end-stage kidney disease (ESKD) patients, with cardiovascular disease (CVD) as the leading cause. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a critical contributor to CVD pathogenesis. However, longitudinal evidence on trends in CKD-MBD biomarker (calcium, phosphorus, parathyroid hormone [PTH]) target attainment and its association with clinical outcomes in Chinese HD patients remains limited. Methods: Utilizing data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS, 2009–2022), this multicenter cohort included 4,650 maintenance HD patients across 45 facilities in Beijing, Shanghai, and Guangzhou. Through multistage cluster sampling, we analyzed decade-long trends in CKD-MBD target achievement (per KDIGO and Chinese guidelines) and evaluated associations with all-cause and cardiovascular mortality using multivariable Cox models. Results: Over the decade, phosphorus target attainment (3.5–5.5 mg/dL) significantly improved (32.8%→43.2%, Δ + 31.7%), yet achievement of stricter targets (2.5–4.5 mg/dL) remained suboptimal (24.4%). Calcium target rates (8.4–10.2 mg/dL) increased from 66.3% to 70.5%, paralleled by rising hypercalcemia (>10.2 mg/dL: 9.5%→12.7%). Triple target attainment (calcium+phosphorus+PTH) improved from 10.8% to 22.5%. Survival analysis suggested that achieving phosphorus targets was independently associated with lower all-cause mortality (HR = 0.77, 95% CI 0.64–0.93) and cardiovascular mortality (HR = 0.73, 0.58–0.93), while stricter phosphorus targets did not show additional associations with improved outcomes. Concurrent triple target achievement was associated with a 39.6% reduction in cardiovascular mortality risk (HR = 0.60, 0.38–0.96). Conclusion: While single-parameter CKD-MBD management has progressed in Chinese HD patients, multiparameter synergistic control remains inadequate. Achieving phosphorus targets appears to be strongly associated with survival benefits. Further optimization of guideline implementation, particularly through integrated management of multiple parameters, may contribute to reducing cardiovascular events and mortality.

Recent advancements in membrane technology have significantly improved dialyzer permeability, enabling the enhanced clearance of molecules across a broad spectrum, from small water-soluble solutes to large middle-molecules (LMM). While current end-stage renal disease (ESRD) guidelines recognize three HD modalities (low-flux HD, high-flux HD, and expanded HD), existing dialyzer classification systems fail to adequately incorporate the clearance capacity for larger molecular weight toxins, limiting their clinical utility for optimal dialyzer selection. To address this gap, a working group of Chinese nephrology and blood purification experts convened. Using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology with Delphi surveys, the group developed a performance-based dialyzer classification system. The consensus achieved two key objectives: (1) establishing clinically relevant evaluation indicators for dialyzer performance, and (2) proposing an improved classification framework based on these parameters. This initiative aligns with the latest international standards for uremic toxin classification and ESRD treatment strategies while specifically focusing on user-centered performance metrics. Building upon existing dialyzer classifications and membrane categories, the consensus provides enhanced differentiation of LMM toxin clearance capabilities. The resulting recommendations aim to guide clinicians in selecting the most appropriate dialyzers for specific patient needs, thereby optimizing the treatment efficacy and patient outcomes. Although developed to address specific challenges in Chinese clinical practice, this consensus offers valuable insights into the global nephrological community. Its practical, performance-oriented approach to dialyzer classification has the potential to improve the standardization of dialysis care worldwide, ultimately benefiting patient safety and treatment quality.

Serum albumin is a key biomarker of nutrition in patients receiving peritoneal dialysis (PD). However, prior studies have largely relied on single or averaged measurements, which fail to capture long-term dynamic changes. This study aimed to identify five-year serum albumin trajectories in PD patients and evaluate their associations with mortality. We conducted a retrospective cohort study of adult PD patients in a tertiary hospital in Beijing, China, with at least one annual albumin measurement during the first five years of PD. Group-based trajectory modeling (GBTM) identified latent albumin trajectory patterns. Multinomial logistic regression was used to examine baseline factors associated with trajectory membership, and Cox proportional hazards models were used to assess associations with all-cause mortality. Among 153 patients, three distinct albumin trajectories were identified: high-stable (HS, n = 56; 36.6

Importance: Approximately 10% to 15% of patients with advanced chronic kidney disease (CKD) experience a fatal or nonfatal cardiovascular event annually. The effects of antithrombotic therapies on cardiovascular events in patients with advanced CKD are unknown. Objective: To determine whether low-dose rivaroxaban reduces rates of adverse cardiovascular events compared with placebo in patients with advanced CKD. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial conducted at 90 centers in 12 countries. Eligible participants were adults with CKD stage 4 or 5 and patients with dialysis-dependent kidney failure. Participants had a history of either coronary artery disease; nonhemorrhagic, nonlacunar stroke; peripheral artery disease; diabetes; or were 65 years or older. Enrollment occurred between January 2021 and July 2025. The trial was stopped early on August 7, 2025, for lack of efficacy. Final follow-up occurred on October 30, 2025. Statistical analyses were conducted in February and March 2026. Interventions: Patients were randomized 1:1 to receive rivaroxaban 2.5 mg twice daily or placebo. Main Outcomes and Measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or a peripheral artery disease event. The primary safety outcome was major bleeding. Results: Of 1458 randomized patients (mean [SD] age, 63.2 [11.6] years, 432 [29.6%] female), 1360 (93.3%) completed follow-up. During a median follow-up of 1.7 years, the primary outcome occurred in 164 patients (22.6%) in the low-dose rivaroxaban group and 151 (20.7%) in the placebo group (13.0 vs 11.8 events per 100 person-years; hazard ratio, 1.09 [95% CI, 0.87-1.36]; P = .46). Major bleeding occurred in 64 patients (8.8%) receiving low-dose rivaroxaban and 44 (6.0%) receiving placebo (5.1 vs 3.4 events per 100 person-years; hazard ratio, 1.51 [95% CI, 1.02-2.22]; P = .04). Conclusions and Relevance: In patients with advanced CKD at high cardiovascular risk, low-dose rivaroxaban did not reduce the risk of a composite cardiovascular outcome. Major bleeding rates were significantly higher in the low-dose rivaroxaban group compared with the placebo group. Trial Registration: ClinicalTrials.gov Identifier: NCT03969953.