Arteriovenous fistula (AVF) is the preferred vascular access for patients with end-stage renal disease; however, its failure is primarily due to neointimal hyperplasia. Five patients who underwent initial AVF surgery served as the control group, and another five patients with failed AVF surgery served as the experimental group. Herein, we employed mass spectrometry (MS)-based quantitative proteomics coupled with tandem mass tag labeling to screen differentially expressed proteins (DEPs) in the anastomotic cephalic vein, followed by bioinformatics analyses and verification experiments. A total of 121 DEPs were identified in the failed AVF group. GO analysis was primarily enriched in protein binding, nucleic acid binding, enzyme binding, mRNA binding, cadherin binding, catalytic activity, and cell adhesion molecule binding. KEGG pathways were mainly enriched in cell aggregation and adhesion, actin cytoskeleton, extracellular matrix-receptor interaction, PI3K-Akt signaling pathway, complement and coagulation cascades, and cholesterol metabolism. Protein-protein interaction network consisted of 86 (71.07%) DEPs, including complement VII (C7), factor IX (F9), SERPINC1, microfibril-associated glycoprotein 4 (MFAP4), complement C1s subcomponent, complement C1q subcomponent subunit A, complement C1q subcomponent subunit B, tissue factor, and von Willebrand factor, which interacting with numerous other proteins. In the expanded validation for different patients, C7, F9, SERPINC1, and MFAP4, were verified by immunohistochemical staining and Western blotting, which were consistent with the proteomics results. Collectively, this study identifies a series of potential diagnostic biomarkers, and explores the underlying mechanisms associated with AVF dysfunction.
Acute kidney injury (AKI) is common among hospitalized patients, but laboratory-defined AKI may not be documented. We aimed to determine the frequency of undocumented AKI in internal medicine wards, compare clinical characteristics and in-hospital outcomes by documentation status, and explore associated factors. We conducted a retrospective single-center study of adult hospitalizations with AKI defined by serum creatinine criteria; urine-output criteria were unavailable. Because reliable pre-admission creatinine values were not consistently available, the lower of admission and discharge creatinine was used as reference and compared with maximal creatinine. Among 161 hospitalizations in 161 unique patients, 39 (24.2%) were undocumented. Undocumented cases had lower admission creatinine (2.1 vs 2.9 mg/dL; p < 0.001), lower maximal creatinine (2.2 vs 3.3 mg/dL; p < 0.001), and more frequent malignancy (23.1% vs 7.4%; p = 0.016). Length of stay and in-hospital mortality did not differ significantly. In 149 hospitalizations with a demonstrable creatinine change, 33 (22.1%) were undocumented. Higher maximal creatinine remained associated with lower odds of underdocumentation (adjusted OR 0.67 per 1 mg/dL, 95% CI 0.50-0.89; p = 0.006). Approximately one quarter of serum creatinine-defined AKI cases were undocumented, particularly those with lower maximal creatinine. Prospective studies should assess whether structured AKI detection and documentation improve kidney-related care and outcomes.
BACKGROUND:Chronic kidney disease (CKD) is driven by inflammation, fibrosis, and metabolic dysfunction. While circadian rhythm dysregulation is well documented in chronic disorders, its specific impact on CKD pathogenesis remains elusive. METHODS:We performed four-hour interval time-series RNA sequencing on renal tissues from control and CKD mice. We used the JTK_CYCLE algorithm to identify rhythmic genes and categorize them as lost, acquired, or sustained in CKD; we subsequently performed focused bioinformatic analyses. RESULTS:The renal circadian profile was substantially altered; acquired rhythmicity emerged as the dominant pattern, and core clock gene expression was disrupted. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that upregulated acquired-rhythmic genes in CKD were enriched in immune-inflammatory pathways; the expression of these genes peaked at Zeitgeber time (ZT) 12-16, consistent with a higher level of renal macrophage infiltration at ZT16 than at ZT0. Conversely, genes associated with nutrient and energy metabolism pathways were downregulated but acquired rhythmicity in CKD. Dapagliflozin improved renal function and restored the circadian expression rhythms of NR1D1 and p-BMAL1. CONCLUSIONS:CKD profoundly remodels the renal circadian transcriptome, driving immune-inflammatory and metabolic pathways into maladaptive rhythmicity. Furthermore, dapagliflozin can partially restore the expression of renal core clock genes.
Serum potassium fluctuations are common but understudied in maintenance hemodialysis (MHD) patients. This retrospective cohort study investigated the association between serum potassium variability, measured by the coefficient of variation (K-CV), and all-cause mortality in 201 MHD patients. Patients were divided into low and high K-CV groups according to the median K-CV cutoff and followed for a median of 72 months. Multivariate Cox regression, adjusted for confounders, revealed that patients in the high K-CV group had a significantly increased mortality risk compared to the low K-CV group (adjusted HR = 1.537, 95% CI: 1.026-2.302, p = 0.037). When analyzed continuously, log(K-CV) showed a strong dose-response relationship with mortality (HR = 7.627, p = 0.010). Subgroup analyses indicated this association was particularly pronounced in patients with lower inflammation and better nutritional status. These findings demonstrate that K-CV, a marker of serum potassium variability, serves as an independent predictor of all-cause mortality in MHD patients. Its prognostic value supports the use of K-CV for risk stratification to identify high-risk patients requiring intensive monitoring and tailored potassium management strategies in dialysis care.
BACKGROUND:Reduced estimated glomerular filtration rate (eGFR) is a suspected risk factor for bleeding after percutaneous renal biopsy, but its association with hemorrhage requiring embolization is unclear. We evaluated this association using a matched case‑control study. METHODS:This single‑center, retrospective, matched case‑control study included patients who underwent ultrasound‑guided native renal biopsy between 2012 and 2025 at a Chinese tertiary hospital. Cases (n = 16) were patients with severe bleeding requiring selective renal artery embolization; controls (n = 64) had no post‑biopsy bleeding, matched 1:4 by sex and age. eGFR was calculated using the CKD‑EPI equation, analyzed as a continuous variable and categorized according to KDIGO criteria (<30, 30-60, ≥60 mL/min/1.73 m2). Multivariable logistic regression, restricted cubic spline analysis, subgroup analyses, LASSO regression, and sensitivity analyses (ROC curve, dichotomized eGFR, complete‑case analysis) were performed. RESULTS:In fully adjusted models, each 1 mL/min/1.73m2 increase in eGFR was associated with 4% lower bleeding risk (OR 0.96, 95% CI 0.93-0.98, p = 0.007). eGFR ≥60 versus <30 mL/min/1.73 m2 gave OR 0.09 (95% CI 0.01-0.75, p = 0.03), with a significant dose‑response trend (P for trend = 0.02). Restricted cubic spline analysis revealed a linear inverse association. Results were consistent across subgroups and sensitivity analyses. CONCLUSIONS:Lower eGFR may be independently associated with increased risk of embolization-requiring bleeding after renal biopsy in a linear dose-response manner. Given the limited sample size, these exploratory findings require validation in larger, prospective cohorts. eGFR may aid in preoperative risk stratification.
Background: Acute kidney injury (AKI) is associated with high mortality and adverse outcomes. Fibroblast growth factor 23 (FGF23) has emerged as a potential biomarker for AKI; however, its diagnostic and prognostic utility remains inconsistent.Methods: We conducted a systematic review and meta-analysis of studies evaluating circulating intact FGF23 (iFGF23) or C-terminal FGF23 (cFGF23) (PROSPERO: CRD42022302659). PubMed, EMBASE, CNKI, and Wanfang databases were searched through June 9, 2026. QUADAS-2 was used for quality assessment. A random-effects bivariate model pooled sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (SROC AUC).Results: Twenty-three studies were included: 17 diagnostic, 6 prognostic (one addressing both). For AKI diagnosis, the pooled sensitivity was 0.79 (95% CI 0.73-0.86), specificity 0.82 (95% CI 0.75-0.89), PLR 4.40 (95% CI 2.59-6.21), NLR 0.25 (95% CI 0.16-0.34), DOR 17.49 (95% CI 8.67-35.16), and SROC AUC 0.87 (95% CI 0.81-0.92). Substantial heterogeneity was observed (I2 = 67%), with iFGF23 demonstrating higher accuracy than cFGF23 (AUC 0.91 vs 0.81). For AKI mortality, pooled sensitivity was 0.77 (95% CI 0.69-0.84), specificity 0.76 (95% CI 0.70-0.82), DOR 10.89 (95% CI 6.86-17.30), and SROC AUC 0.77 (95% CI 0.70-0.83). Significant heterogeneity was noted (I2 = 86.2% for sensitivity, 80.4% for specificity). No significant publication bias was detected.Conclusions: Circulating FGF23 exhibits moderate-to-high diagnostic and moderate prognostic performance in AKI, though interpretation is limited by substantial heterogeneity. It may serve as a complementary biomarker for risk stratification, pending further validation with standardized protocols.
BACKGROUND:Reduced renal size has traditionally been considered a relative contraindication to kidney biopsy because of the perception that advanced chronic damage provides limited diagnostic or therapeutic benefit. However, the actual clinical value of renal biopsy in patients with small kidneys remains insufficiently investigated. METHODS:We conducted a retrospective single-center study including patients with chronic kidney disease who underwent renal biopsy between June 2020 and December 2025. Patients with renal length ≤9 cm were defined as having small kidneys. Baseline clinical data, pathological diagnoses, treatment modifications following biopsy, and follow-up clinical outcomes were analyzed. Subgroup analyses were performed according to pathological categories. RESULTS:Among 1,084 biopsied patients, 76 (7.0%) had small kidneys. Renal biopsy revealed heterogeneous etiologies, with IgA nephropathy (IgAN) accounting for 46.1% of cases. Treatment strategies were modified in 67.1% of patients after renal biopsy. During follow-up, biopsy-guided management was associated with reduced proteinuria and stable renal function. CONCLUSIONS:In selected patients with small kidneys, renal biopsy was associated with high diagnostic yield and frequent treatment modifications.
Arterial remodeling is common in end-stage renal disease (ESRD). This prospective cohort study explored the potential prognostic value of carotid intima-media thickness (CIMT) and ultrafast pulse wave velocity (ufPWV) - including pulse wave velocity at the beginning (PWV-BS) and end of systole (PWV-ES) for cardiovascular (CV) events and all-cause mortality in 115 maintenance hemodialysis (MHD) patients followed for 39 months. Compared with non-ESRD controls, MHD patients exhibited significantly higher CIMT (1.60 vs 0.80 mm, p = 0.004), while ufPWV parameters appeared comparable. During follow-up, 21 CV events and 17 deaths were recorded. In univariable analysis, CIMT was associated with CV events and positively correlated with diabetes (r = 0.271, p = 0.003). However, after adjusting for diabetes, this association was no longer statistically significant (HR 1.350, 95% CI 0.865-2.106, p = 0.186). Neither PWV-BS nor PWV-ES was associated with outcomes in the overall cohort. Preliminary subgroup analysis of patients with diabetes (n = 36, 15 CV events) observed an inverse association between left PWV-ES and CV events. In conclusion, CIMT was no longer significantly associated with CV events after adjustment for diabetes in the limited model, whereas local ufPWV parameters were not significantly associated with CV events or all-cause mortality in the analyses performed within the overall MHD population. Given the issue of multiple comparisons and small sample size, the isolated finding between left PWV-ES and CV events in the diabetic subgroup must be treated strictly as hypothesis-generating, requiring independent validation in a larger cohort.
BACKGROUND:This study aimed to evaluate the efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis (MHD). METHODS:In this phase III, multicenter, randomized, open-label, non-inferiority trial, patients with hyperphosphatemia on maintenance hemodialysis were randomly assigned to receive either ferric citrate or sevelamer carbonate tablets for 12 weeks. The primary endpoint was the change in serum phosphorus levels from baseline to week 12, with a non-inferiority margin of 0.32 mmol/L. Secondary endpoints included changes in serum calcium, intact parathyroid hormone, and safety assessments. RESULTS:A total of 239 patients were randomized to the ferric citrate group (n = 119) or the sevelamer carbonate group (n = 120). The mean change in serum phosphorus levels was -0.70 ± 0.50 mmol/L in the ferric citrate group and -0.61 ± 0.59 mmol/L in the sevelamer carbonate group (least squares mean difference, -0.09 mmol/L; 95% CI, -0.24 to 0.05 mmol/L; non-inferiority margin, 0.32 mmol/L). No significant inter-group differences were found in the percentage of patients achieving target phosphorus levels (49.09% vs. 48.28%, p = 0.902). Ferric citrate significantly improved iron-related parameters and hemoglobin levels. Most treatment-emergent adverse events were mild, with gastrointestinal disorders being the most common. CONCLUSIONS:Ferric citrate tablets were non-inferior to sevelamer carbonate in reducing serum phosphorus levels in hyperphosphatemia patients on maintenance hemodialysis, with the added benefit of improving iron-related anemia and a favorable safety profile.
This study aimed to investigate the association between the Naples Prognostic Score (NPS) and the Charlson Comorbidity Index (CCI) and to evaluate the relationship of NPS with inflammatory and nutritional status in patients undergoing peritoneal dialysis (PD). A total of 59 PD patients (mean age 41.8 ± 18.1 years, 30 females) who received PD between 2020 and 2025 were retrospectively analyzed. NPS was calculated using serum albumin, total cholesterol, neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR), and patients were classified into NPS groups. Comorbidity burden was assessed using CCI. Group comparisons and correlation analyses were performed to determine associations between NPS, clinical variables, laboratory parameters, and CCI. The mean NPS and CCI were 2.80 ± 1.21 and 3.71 ± 2.21, respectively. Patients with higher NPS had significantly longer dialysis duration and elevated markers of systemic inflammation, including C-reactive protein, neutrophils, and monocytes, whereas they showed lower lymphocyte counts, lymphocyte-to-monocyte ratio, LDL cholesterol, and total cholesterol (all p < 0.05). NPS correlated positively with CRP and NLR and negatively with albumin, total protein, lymphocyte count, total cholesterol, and LMR (all p < 0.05). No significant association was found between NPS and CCI in group comparisons or correlation analyses. While NPS is significantly associated with systemic inflammation and impaired nutritional status in PD patients, it does not reflect comorbidity burden as measured by CCI. These findings suggest that despite its retrospective design, NPS may serve as a practical, laboratory-based marker of inflammatory and nutritional derangements in PD, distinct from chronic comorbidity indices.
This study evaluated the association of Chuanhuang Patent Formula (CHPF) with short-term renal function parameters and long-term prognosis in patients with acute kidney injury (AKI) on chronic kidney disease (CKD) (A on C) and explored potential subgroups that might derive greater benefit. This retrospective cohort included 205 patients with A on C admitted between January 2016 and October 2025. After 1:1 propensity score matching, 81 patients were included in each group. The primary composite outcome was progression to CKD stage 5, maintenance renal replacement therapy initiation, or all-cause mortality, while secondary outcomes evaluated renal function parameters at 2 and 4 weeks. Renal function parameters were more favorable in the CHPF group at 2 and 4 weeks after treatment initiation. Long-term survival analysis showed that CHPF treatment was associated with a lower risk of the primary outcome (hazard ratio [HR] = 0.56; 95% confidence interval [CI]: 0.32-0.98; p = 0.041). Notably, hypertension-stratified subgroup analysis showed that the association between CHPF treatment and outcome-free survival appeared more evident in patients with comorbid hypertension (p = 0.045), whereas no significant difference was observed in patients without hypertension (p = 0.26). In conclusion, CHPF could be a promising adjunctive therapeutic strategy for patients with A on C and was associated with more favorable 2- and 4-week renal function parameters and long-term outcome-free survival. Patients with comorbid hypertension might represent a potential subgroup that could derive greater benefit from CHPF treatment; however, this exploratory finding should be interpreted cautiously and validated in prospective studies.
Fabry disease is an X-linked hereditary lysosomal storage disease caused by variants in the GLA gene. These variants result in reduced or absent α-galactosidase A (α-Gal A) enzyme activity, leading to the progressive accumulation of enzyme metabolism substrates in multiple organs. This accumulation ultimately causes systemic clinical manifestations involving multiple organ systems. Renal involvement is a common clinical manifestation in Fabry disease and an important determinant of morbidity and disease progression. Early identification and active intervention of renal involvement in Fabry disease can effectively slow the progression of renal function deterioration and may significantly reduce the incidence of secondary cerebrovascular and cardiovascular events in advanced stages of Fabry disease nephropathy. This review summarizes the latest research advances on renal involvement in Fabry disease, covering its epidemiology, pathogenesis, clinical manifestations, diagnostic indicators, differential diagnosis and treatment strategies, in order to deepen the understanding of renal involvement in Fabry disease and reduce missed diagnosis and misdiagnosis.
INTRODUCTION:Chronic kidney disease-associated pruritus (CKD-aP) affects 55% of hemodialysis patients and substantially impairs quality of life (QoL) and treatment adherence. Difelikefalin, a selective kappa-opioid receptor agonist, received regulatory approval following the KALM trials. However, the applicability of these findings to routine practice remains unclear. We systematically evaluated real-world evidence (RWE) on the effectiveness and safety of difelikefalin in patients with CKD-aP. METHODS:Comprehensive searches of PubMed, Embase, CENTRAL, Scopus, Web of Science, and CINAHL were conducted on 15 December 2025. Inclusion criteria were RWE studies, including observational studies and trial extension analyses reporting the efficacy (WI-NRS and 5-D Itch scores), QoL (Skindex-10), or safety in patients with CKD-aP using difelikefalin. Exclusion criteria included RCTs without open-label extensions and pruritus due to alternative causes. Two reviewers independently screened studies and extracted data. The study was prospectively registered as CRD420251266218. RESULTS:Twelve studies (n = 3,524) met eligibility criteria. Across real-world settings, 35-92.9% of patients achieved a ≥ 3-point WI-NRS reduction, compared with 51% in pooled KALM-1/KALM-2 data. All studies assessing sleep-related QoL reported significant benefit. Overall AE incidence ranged from 0% to 64.4%, with 6.3-16% considered treatment-related. Common AEs included dizziness, diarrhea, nausea, hyperkalaemia, somnolence, and altered mental status. No treatment-related deaths or fatal serious adverse events were reported. CONCLUSIONS:RWE supports the effectiveness of difelikefalin in hemodialysis patients with CKD-aP. However, included studies are heterogeneous and at high risk of bias. Future research should investigate difelikefalin in peritoneal dialysis and earlier-stage CKD cohorts, alongside health economic evaluations and implementation studies.
Acute kidney injury (AKI) is a severe clinical syndrome, with ischemia/reperfusion (I/R) being one of its most common causes. Although D‑pinitol (DP), an inositol‑like bioactive molecule, is known to confer renal protection, its efficacy against I/R‑induced AKI remains unknown. A mouse kidney I/R model was employed to evaluate the renoprotective effect of DP. Relevant targets associated with DP and AKI were retrieved from publicly available databases. Subsequently, network pharmacology analysis was conducted to identify the potential targets and signaling pathways. Molecular docking was then performed to predict the binding affinity of DP to core targets identified. Furthermore, in vivo and in vitro experiments were performed to validate these findings. Systemic toxicity was assessed by serological and histopathological examinations. The results show that DP significantly attenuated I/R-induced kidney dysfunction and apoptosis. Network pharmacology analysis identified 108 overlapping targets, with AKT1, HSP90AA1, SRC, CASP3, and MMP9 identified as core targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed PI3K/AKT signaling pathway as the primary mechanism. Consistent with these predictions, DP enhanced PI3K and AKT phosphorylation in kidney tissue. Molecular docking indicated that DP exhibited the strongest binding affinity to SRC, suggesting it as a potential target. In a hypoxia/reoxygenation (H/R)-induced human renal proximal tubular epithelial (HK-2) cell model, DP significantly increased the phosphorylation of SRC, PI3K, and AKT, and these effects were abrogated by the SRC specific inhibitor PP2. Collectively, DP alleviated I/R‑induced injury and apoptosis, potentially through activation of the SRC/PI3K/AKT signaling pathway.
INTRODUCTION:Hemodialysis (HD), peritoneal dialysis (PD), and continuous kidney replacement therapy (CKRT) are major modalities of kidney replacement therapy (KRT) in pediatric acute kidney injury (AKI). This study uses TriNetX data to identify clinical characteristics of pediatric AKI patients receiving HD, PD, and CKRT and compare outcomes across 30-, 90-, 180-, and 365-day follow-ups. METHODS:Pediatric patients aged 0-18 years with AKI (August 2004-August 2024) were identified using ICD-10 and CPT codes within the TriNetX U.S. Network. Three cohorts (HD, PD, CKRT) were analyzed for outcomes and comorbidities. Kidney transplant recipients were excluded. Cohorts were not propensity matched to reflect real-world disease burden. A total of 7,476 pediatric patients (mean age ∼9 years) initiated KRT [HD 39.1% (n = 2,929), PD 41.9% (n = 3,139), CKRT 18.8% (n = 1,408)]. RESULTS:CKRT patients had higher BUN (19.7 mg/dL) and glucose (136 mg/dL). Intestinal diseases were frequent comorbidities. Hypertension was most common in CKRT (12.1%). Diuretics (12.1%) and epinephrine (11.3%) were the most used medications. At 30 days, mortality was lowest in HD (13.7%) vs PD (14.9%) and CKRT (19.9%). This persisted at 365 days (CKRT 24.2%). Ventilation rates were 22.0% (HD), 23.1% (PD), 25.6% (CKRT). ICU admission was highest in CKRT (71.1%). CONCLUSIONS:CKRT had the greatest ten-year incidence (3.6%) and prevalence (3.8%). HD and PD had lower observed mortality and ICU admission than CKRT, a pattern likely reflecting confounding by indication rather than a causal effect of modality. CKRT patients showed higher comorbidity burden and mortality, emphasizing the need for individualized management in pediatric AKI.
Calcific uremic arteriolopathy (CUA) is a rare, severe condition affecting patients with chronic kidney disease (CKD). The etiology of CUA is unclear. Here, we aimed to identify factors associated with its development. We reviewed the existing evidence on its pathomechanisms and risk factors. We searched EMBASE and PubMed up to February 2026, reviewing all studies that would facilitate a comparison of CKD patients with and without CUA. Of 2374 screened publications, 35 met our inclusion criteria. The factors that consistently emerged related to CUA were decreased albumin, higher alkaline phosphatase, diabetes, increased body mass index, female sex, vitamin K antagonist (VKA) use, increased calcium phosphate product, and calcification and thrombosis in subcutaneous small arteries. Factors that appeared to be likely associated with CUA were anemia, suboptimal dialysis efficiency, peritoneal dialysis, inflammation, arterial hypertension, smoking, and hepatobiliary disease. Findings on matrix Gla protein alterations implicated in mediating VKA effects, parathyroid hormone, and hypercoagulability were ambiguous in our literature analyses. In addition, we found that a standardized system for CUA skin biopsy evaluation is lacking. In summary, our review delineates the major risk factors and pathogenic parameters associated with CUA development. Furthermore, it underscores areas in which robust data on CUA pathomechanisms are lacking.
BACKGROUND AND HYPOTHESIS:Patients receiving maintenance dialysis experience substantial pill burden from complex comorbidities and intensive treatment regimens. Although higher pill burden is linked to treatment burden and poorer health-related quality of life (HRQoL), optimized pharmacologic management may improve overall well-being. We evaluated the association between pill burden and HRQoL across dialysis modalities. METHODS:We conducted a cross-sectional study of adult patients receiving maintenance hemodialysis (HD), hemodiafiltration (HDF), or peritoneal dialysis (PD) at a tertiary care center. Pill burden was defined as the total number of oral tablets taken daily and categorized as <10, 10-15, or >15 tablets/day. HRQoL was assessed using validated Thai versions of the Kidney Disease Quality of Life-36 (KDQOL-36) and EQ-5D-5L questionnaires. Univariable and multivariable linear regression analyses evaluated associations between pill burden and HRQoL outcomes after adjustment for confounders. RESULTS:A total of 156 patients were included: 64 HD, 64 HDF, and 28 PD patients. Median pill burden was 11.5, 10, and 7.5 tablets/day in the HD, HDF, and PD groups, respectively. Antihypertensive and CKD-mineral and bone disorder medications were the main contributors. After adjustment, pill burden was not significantly associated with PCS-12, MCS-12, SPKD, EKD, or EQ-5D-5L-VAS scores. However, patients receiving >15 tablets/day had significantly lower BKD scores, while higher pill burden was independently associated with higher EQ-5D-5L index scores. HDF and PD were consistently associated with better HRQoL than HD. CONCLUSIONS:Pill burden demonstrated a complex relationship with HRQoL. Dialysis modality appeared to exert a stronger influence on HRQoL than pill burden itself.
Diabetic kidney disease (DKD) involves complex inflammatory and microvascular injury, but cell-specific molecular signatures linked to neutrophil extracellular traps (NETs) remain unclear. We aimed to identify NET-associated biomarkers of glomerular injury in DKD. Bulk glomerular transcriptomic datasets were analyzed using differential expression, weighted gene co-expression network analysis, and machine learning (LASSO and random forest). Single-cell RNA sequencing (scRNA-seq) defined cell-specific expression and intercellular communication. Candidates were evaluated in independent cohorts, in vitro high-glucose co-culture datasets, and db/db mice. Exploratory in silico drug-screening was also performed. VCAN and ESM1 emerged as core candidate genes. In bulk cohorts, VCAN was upregulated and ESM1 downregulated, yielding strong combined diagnostic performance. scRNA-seq revealed ESM1 decreases predominantly in glomerular endothelial cells, while VCAN increases in mesangial cells. NET-related activity enriched primarily in the endothelium, whereas VCAN-expressing cells associated with matrix remodeling. In vitro, ESM1 showed early endothelial-predominant decreases under injury. In db/db mice, renal VCAN and NET markers were elevated, while ESM1 levels were reduced and correlated with albuminuria severity. Molecular docking identified potential targeting compounds. In conclusion, VCAN and ESM1 are promising biomarkers reflecting distinct, cell-type-enriched patterns of NET-related glomerular injury in DKD, supporting a dual-track model of endothelial dysfunction and paracrine matrix remodeling.
