AIMS:Kidney transplantation (KT) improves survival in end-stage renal disease (ESRD); however, the post-transplant fracture risk remains uncertain. This study aimed to compare the fracture incidence between kidney transplant recipients (KTRs) and waitlisted dialysis patients and to examine the association between fracture events and all-cause mortality in each group. MATERIALS AND METHODS:This study included a single-center cohort of 504 KTRs and 423 waitlisted dialysis patients treated at a tertiary hospital in South Korea from 1998 to 2019. Fractures were identified through radiological report review, and mortality data were retrieved from medical records. Multivariate Cox regression models were used to evaluate mortality predictors, including fracture events, as covariates. RESULTS:The fracture incidence did not differ significantly between KTRs (9.1%) and dialysis patients (12.5%). Moreover, fractures were not significantly associated with increased mortality in either group (KTRs: hazard ratio (HR), 2.03; 95% confidence interval (CI), 0.62 - 6.67; p = 0.24; dialysis: HR, 0.97; 95% CI, 0.12 - 8.08; p = 0.98). Age was the strongest mortality predictor. Among KTRs, tacrolimus use was associated with lower mortality compared with cyclosporine (HR, 0.18; 95% CI, 0.05 - 0.66; p = 0.009). CONCLUSION:KTRs have a fracture risk comparable to that of dialysis patients, and fractures were not significantly associated with mortality. The survival benefits of KT are driven by factors other than fracture-related complications. Ongoing, proactive bone health management remains essential in KTRs because transplantation does not eliminate the elevated fracture risk.
OBJECTIVE:This study aimed to investigate the potential of the platelet-to-lymphocyte ratio (PLR) as a predictive biomarker for augmented renal clearance (ARC) in patients undergoing intracerebral hemorrhage (ICH) surgery. MATERIALS AND METHODS:A single-center retrospective cohort study was conducted on 174 patients who underwent ICH surgery. Pearson or Spearman correlation analyses were used to examine the relationship between PLR and baseline characteristics. Restricted cubic spline curves were employed to assess the association between PLR and ARC occurrence. Logistic regression models were applied to identify risk factors for ARC, while the predictive performance of PLR was evaluated using receiver operating characteristic curves. All statistical analyses were performed using IBM SPSS Statistics v.24.0 and R v.4.0.2. RESULTS:Among the 174 patients, 99 (56.9%) developed ARC. The optimal cutoff value for PLR was determined to be 201.31. The AUC of PLR for predicting ARC was 0.69 (95% CI: 0.61 - 0.77), with a sensitivity of 65.3% and specificity of 73.7%. Subgroup analyses revealed that this association was particularly pronounced in patients aged over 55 years, those with a body mass index ≤ 25 kg/m2, an APACHE II score of 10 - 20, and a hemorrhage volume ≤ 30 mL. Integrating PLR into a composite model (APACHE II, SOFA, and GCS) increased the AUC from 0.70 (95% CI: 0.62 - 0.78) to 0.73 (95% CI: 0.65 - 0.81). The addition of PLR to the composite scoring system yielded a category net reclassification improvement of 0.12 (95% CI: 0.00 - 0.25). CONCLUSION:Preoperative low PLR is significantly associated with the early occurrence of ARC and serves as an independent predictor for ARC.
BACKGROUND:Residual kidney function influences outcomes and quality of life in peritoneal dialysis (PD), but the optimal initiation strategy remains uncertain. MATERIALS AND METHODS:We retrospectively studied 120 incident PD patients treated at a tertiary nephrology center in China from February to December 2023. Patients were categorized by initial prescription as low-dose continuous ambulatory PD (CAPD-L), full-dose CAPD (CAPD-F), daytime ambulatory PD (DAPD), or automated full-dose PD (APD-F). Twelve-month outcomes included 24-hour residual urine volume, weekly total Kt/V, nutritional and mineral markers, and documented uremia-related symptoms. Baseline imbalance was assessed using standardized mean differences, and longitudinal changes were analyzed using repeated-measures models with group-by-time interactions. Urine volume was considered a surrogate measure of residual kidney function. RESULTS:Baseline imbalance was notable, particularly for age and urine volume. At 12 months, mean 24-hour urine volumes were 962.7 ± 198.6, 790.5 ± 210.4, 960.1 ± 180.3, and 945.7 ± 190.2 mL/day in the CAPD-L, CAPD-F, DAPD, and APD-F groups, respectively. The between-group difference was significant (p = 0.006), as was the unadjusted group-by-time interaction (p = 0.003). Weekly total Kt/V remained above 1.7 in all groups. No significant between-group differences were observed in serum albumin or documented uremia-related symptoms at 12 months. CONCLUSION:Initial low-dose CAPD and daytime PD were associated with different residual urine-volume trajectories while dialysis adequacy was maintained. No symptom-burden benefit was demonstrated. Given the non-randomized design, baseline imbalance, limited adjustment for treatment selection, and use of urine volume as a surrogate, these findings are exploratory and require prospective confirmation.
OBJECTIVE:To assess the associations of life's crucial 9 (LC9) and its components with all-cause and cardiovascular disease (CVD)-related mortality in patients with diabetic kidney disease (DKD). MATERIALS AND METHODS:Records of DKD patients were extracted from the National Health and Nutrition Examination Survey database. The relationships of LC9 scores with all-cause and CVD-related mortality were investigated by weighted univariate and multivariable COX proportional hazard models, with hazard ratios (HRs) and 95% confidence intervals (CIs). The associations were further explored based on different characteristics of DKD patients, including age, sex, CVD, cancer, diabetic retinopathy, and anemia. Random forest models were used to evaluate the importance of LC9 components for all-cause and CVD-related mortality. RESULTS:Among 1,877 DKD patients, 586 died from any cause, and 193 were CVD-related. DKD patients with elevated LC9 scores (≥ 47.778) had lower odds of all-cause and CVD-related mortality, compared to those with LC9 score < 47.778. For per 10-point increase in LC9 score, the risk of all-cause and CVD-related mortality decreased by 0.26 and 0.37 times in DKD patients, respectively. Similar results were found in different characteristics of DKD patients. Physical activity, sleep duration, and BMI were the most important factors for all-cause mortality in DKD patients, followed by depression. For CVD-related mortality risk, sleep duration and depression were of significant importance, followed by dietary quality. CONCLUSION:High LC9 scores were associated with lower odds of all-cause and CVD-related mortality, suggesting that incremental improvements in modifiable factors may be beneficial to the prognosis of DKD patients.
BACKGROUND:Sodium-glucose cotransporter 2 (SGLT2) inhibitors are now recommended as first-line therapies for chronic kidney disease. However, real-world evidence on henagliflozin, China's first-developed SGLT2 inhibitor, for treating IgA nephropathy (IgAN) is lacking. This study explored the real-world efficacy and safety of henagliflozin in Chinese IgAN patients. MATERIALS AND METHODS:This study retrospectively reviewed 48 IgAN patients on henagliflozin for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio (UACR). Secondary outcomes included estimated glomerular filtration rate (eGFR), serum creatinine (Scr), uric acid (UA), and albumin (Alb). Adverse events (AEs) were also recorded. RESULTS:Henagliflozin induced a significant reduction in UACR between baseline and week 12 (227.26; IQR, 90.13 - 677.85 vs. 153.06; IQR, 24.68 - 401.76 mg/g; p < 0.001), with a median decrease of 47.9%. Clinical response, defined as a ≥ 30% decrease in UACR, was achieved in 64.6% of patients by week 12. The UA levels also decreased markedly (p < 0.001). The eGFR declined until week 8 (p ≤ 0.015) but returned to near-baseline level by week 12 (p = 0.055). Scr increased over time (p = 0.005), and Alb improved until week 8 (p ≤ 0.007) and then plateaued at week 12 (p = 0.45). AEs included urinary tract infections in 5 patients, Scr increase of ≥ 50% in 1, and hyperkalemia in 1. CONCLUSION:Henagliflozin demonstrated significant albuminuria- and UA-lowering effects over 12 weeks in Chinese IgAN patients. With renal-metabolic benefits and favorable safety, henagliflozin is emerging as an encouraging therapeutic option for IgAN.
AIM:C3 glomerulopathy (C3G) is a rare, complement-mediated kidney disease with significant diagnostic and therapeutic challenges. Despite a growing number of publications, no study has comprehensively mapped the global research landscape. This bibliometric analysis aimed to evaluate publication trends, influential contributors, thematic evolution, and collaboration networks in C3G research from 1980 to 2025. MATERIALS AND METHODS:A systematic bibliometric analysis was conducted using PubMed-indexed publications from 1980 - 2025 retrieved with predefined Boolean queries. Eligible articles included original research and reviews addressing the pathophysiology, diagnosis, and management of C3G. Bibliometric parameters were analyzed using the Bibliometrix package in R (v4.3) and VOSviewer (v1.6.20). Citation data were verified via Google Scholar. RESULTS:A total of 967 publications across 273 journals were identified. Research output increased exponentially after 2013, coinciding with the C3G Consensus Report and the rise of complement-targeted therapies. Pediatric Nephrology, Kidney International, and JASN were the leading publication venues. The United States, United Kingdom, and Italy were the most productive countries, with emerging contributions from China, India, and Türkiye. S. Sethi was the most prolific author (24 papers). Keyword co-occurrence and citation network analyses demonstrated a thematic shift from morphologic classification ("dense deposit disease") toward molecular and therapeutic paradigms ("complement inhibition," "iptacopan," "pegcetacoplan"). Collaboration networks remained modest and regionally clustered. CONCLUSION:Global research on C3G has evolved from descriptive pathology toward precision complement therapeutics. However, significant geographical disparities persist, emphasizing the need for stronger international collaboration and equitable access to emerging complement inhibitors.
INTRODUCTION:IgA nephropathy (IgAN) is a leading cause of glomerulonephritis worldwide with variability by race and ethnicity. This study aimed to provide insights on the treatment journey and clinical outcomes in Asian-American patients with IgAN treated with delayed-release budesonide (Nefecon) in a real-world setting. MATERIALS AND METHODS:In this observational cohort study, a total of 45 consecutive patients with IgAN treated with Nefecon at Chinatown Kidney Care (CKC) (New York, NY, USA) were included. Study outcomes included treatment patterns and clinical outcomes (time to kidney failure, estimated glomerular filtration rate (eGFR), and urine protein-to-creatinine ratio (UPCR)). All variables were summarized descriptively. Subgroup analyses were performed among patients who were treated for ≥ 9 months vs. those treated for < 9 months. RESULTS:Overall, after 9 months of treatment, eGFR remained stable and UPCR decreased by an average of 19%. Improved clinical outcomes were reported among those who were treated for ≥ 9 months (preservation of eGFR and 26% reduction in UPCR) compared with those treated for < 9 months (decline in eGFR and ~ 3% reduction in UPCR). Nefecon was well tolerated with no severe or unexpected adverse events reported. CONCLUSION:Real-world IgA nephropathy treatment-associated outcomes with Nefecon in Asian-American patients for proteinuria and kidney function were consistent with those observed in the NefIgArd clinical trial. The reduction in proteinuria and improvement in kidney function was greater in patients who completed the 9-month course of therapy. These findings reveal an opportunity for further education among nephrologists regarding the recommended duration of treatment with Nefecon.
BACKGROUND:IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with ~ 30% of patients progressing to end-stage kidney disease (ESKD) within 20 years of diagnosis, imposing a significant disease burden. OBJECTIVE:To systematically review the progression of IgAN from its pathogenesis to ESKD and explore modern management strategies based on precise risk stratification. MATERIALS AND METHODS:A systematic review of existing literature was conducted to integrate key evidence in the fields of IgAN pathogenesis, risk assessment, and treatment. RESULTS:The progression of IgAN is driven by the "four-hit" theory, with abnormal activation of the complement system being a key amplifier of injury. Persistent proteinuria, hypertension, and tubular atrophy/interstitial fibrosis (T lesion) on renal biopsy are the strongest predictors of disease progression. Modern management emphasizes precise risk stratification integrating clinical and pathological indicators. In terms of treatment, renin-angiotensin system inhibitors (RASi) and SGLT2 inhibitors are the cornerstone of supportive therapy for all patients with proteinuria. For those with rapid progression and remaining at high risk despite optimized supportive treatment, glucocorticoids or novel targeted drugs may be considered as appropriate. CONCLUSION:The management of IgAN has entered the era of precision medicine, with the integration of mechanism research, risk prediction, and diversified treatment strategies being the core for delaying disease progression.
BACKGROUND:Dickkopf-3 (DKK3) is a stress-induced glycoprotein involved in Wnt/β-catenin signaling and has emerged as a marker of renal tubular injury and fibrosis. Although urinary DKK3 has been associated with kidney disease progression independent of albuminuria, its relationship with vascular dysfunction in diabetic kidney disease (DKD) remains unclear. This study aimed to investigate the association between urinary DKK3, albuminuria, and arterial stiffness in patients with DKD. MATERIALS AND METHODS:In this cross-sectional study, 45 patients with DKD and 30 age- and sex-matched healthy controls were enrolled. Urinary DKK3 levels were measured using enzyme-linked immunosorbent assay and normalized to urinary creatinine. Arterial stiffness was assessed by pulse wave velocity (PWV) using an oscillometric device. Correlation and multivariable linear regression analyses were performed to evaluate independent associations among urinary DKK3, albuminuria, and PWV. RESULTS:Urinary DKK3/creatinine ratios were significantly higher in patients with DKD compared to controls (p < 0.001). In DKD patients, urinary DKK3 showed strong positive correlations with albuminuria (r = 0.785, p < 0.001) and PWV (r = 0.454, p = 0.023). Albuminuria was also significantly correlated with PWV (r = 0.543, p = 0.005). In multivariable regression analysis, urinary DKK3 independently predicted albuminuria (β = 0.546, p = 0.004), whereas albuminuria was the only independent predictor of PWV (β = 0.443, p = 0.026). CONCLUSION:Urinary DKK3 is significantly associated with albuminuria and arterial stiffness in DKD. While DKK3 primarily reflects renal tubular stress and fibrotic activation, albuminuria represents systemic endothelial dysfunction and vascular damage. These findings suggest that urinary DKK3 provides complementary information by capturing tubular injury within the cardiorenal axis. If validated in prospective studies, DKK3 may serve as a noninvasive biomarker for early risk stratification of cardiorenal progression.
BACKGROUND:Podocyte injury is a pivotal driver of chronic kidney disease (CKD) progression in focal segmental glomerulosclerosis (FSGS). Although hederagenin (HDG) has shown promise in the treatment of CKD, its specific protective effects against podocyte injury in FSGS, along with its underlying pharmacological mechanisms, remain to be fully elucidated. MATERIALS AND METHODS:Potential protein targets of HDG and FSGS-related genes were retrieved from the Genecards database. Molecular docking was performed to validate binding interactions between HDG and key targets. Building on findings from adriamycin (ADR)-induced FSGS mouse and MPC5 cell line studies, HDG's inhibitory effect on podocyte injury in FSGS was further confirmed. RESULTS:A total of 103 potential HDG targets and 2378 FSGS-related targets were identified. Integrated drug-disease network and protein-protein interaction (PPI) analyses suggested potential mechanisms for HDG in FSGS treatment. Molecular docking pinpointed IL-6 and NOS2 as therapeutic targets, indicating their involvement in HDG's inhibitory effects. In vivo and in vitro experiments demonstrated that HDG alleviated renal injury in ADR-induced FSGS in mice and attenuated TGF-β1-induced damage in MPC5 cells. Furthermore, HDG significantly reduced both mRNA and protein expression levels of IL-6 and NOS2. CONCLUSION:HDG protects podocytes from injury by inhibiting IL-6 and NOS2 in FSGS, which is consistent with the results predicted by network pharmacological analysis. These findings support HDG as a promising therapeutic candidate for FSGS treatment.
BACKGROUND:Acute kidney injury (AKI) is a common sequela of ventilator-associated pneumonia (VAP), further complicating patient care and outcomes. The red cell distribution width-to-platelet ratio (RPR), an established marker of inflammation, may be linked to the development of AKI in VAP patients. PURPOSE:The study aimed to examine the connection between RPR and the incidence of AKI in VAP patients. MATERIALS AND METHODS:This study utilized data from the Medical Intensive Care Database. Logistic regression was applied to investigate the connection between RPR and AKI prevalence in VAP patients. Restricted cubic splines were used to determine if the relationship was non-linear, and subgroup analyses were conducted. The predictive performance of the scoring tool, with RPR included, was evaluated using integrated discrimination improvement and net reclassification index calculations. RESULTS:Our study included 1,547 VAP patients, of whom 1,070 had AKI. Logistic regression analysis demonstrated that higher log (RPR × 1,000) values were significantly associated with increased AKI prevalence in VAP patients (OR = 1.741, 95% CI: 1.124 - 2.738, p = 0.014). The highest tertile group had a significantly higher AKI prevalence compared to the lowest tertile group (OR = 2.333, 95% CI: 1.259 - 4.447, p = 0.008). Our analysis found no evidence of non-linear associations or significant interactions among subgroups. The predictive performance of the scoring tool was enhanced when RPR was incorporated. CONCLUSION:Our analysis revealed that RPR is associated with higher AKI incidence in VAP patients. This discovery provides a new tool for early detection of patients at high risk for VAP-related AKI.
OBJECTIVE:The complex pathophysiological mechanism of end-stage renal disease (ESRD) has not been fully understood. Cuproptosis is a newly discovered type of programmed cell death. Therefore, this study attempts to clarify the relationship between cuproptosis-related genes (CRGs) and the phenotype of ESRD. MATERIALS AND METHODS:The National Center for Biological Information Gene Expression Omnibus database was applied to obtain the GSE37171 dataset comprising whole-genome microarray analysis of peripheral blood samples. A 3 : 1 case-control design was employed with 75 ESRD patients and 20 healthy controls who were frequency-matched for age, sex, and ethnicity. Based on differentially expressed genes (DEGs) and genes related to cuproptosis, CRGs were identified. Thereafter, we explored two different subpopulations based on the cuproptosis gene and analyzed their expression and immune infiltration. Genes specific to the CRG cluster were identified through the weighted gene co-expression network analysis algorithm, and the best prediction model was determined and verified by four machine learning methods. RESULTS:The study identified 14 differentially expressed CRGs, among which ATP7B, SLC31A1, LIAS, LIPT1, DLD, MTF1, CDKN2A, DBT, and DLST had relatively high expression levels in the ESRD samples. Compared with the control group, expression levels of FDX1, DLAT, PDHA1, PDHB, and GLS were significantly lower in the ESRD group, and CRGs played a key role in the regulation of immune infiltration in ESRD. Two cuproptosis-related molecular clusters were identified in the ESRD samples. Cluster2 was more correlated with the immune infiltration of ESRD. By analyzing the intersection points between CRG cluster and key genes of ESRD, a total of 888 specific DEGs were identified. Functional differences related to specific DEGs were further explored using gene set variation analysis. Five significant genes (SMC5, USP47, USP53, AGA, and DMXL1) were identified by the support vector machine model as key predictors for ESRD disease risk, achieving an area under the curve (AUC) of 1.00 in internal validation. However, external validation in independent cohorts is required prior to clinical application. Individual gene analysis showed an AUC > 0.81 in discriminating ESRD patients from healthy controls, and the expression of all 5 genes in ESRD patients was significantly lower than in the control group. CONCLUSION:This study clarified the relationship between CRGs and the phenotype of ESRD, analyzed their specific roles in the immune microenvironment, and obtained a predictive model, providing new insights for the study of its potential therapeutic targets.
Minimal change disease (MCD) is a common cause of nephrotic syndrome in adults, with limited evidence available on its treatment and prognosis. In this study, we retrospectively included the clinical characteristics and treatment results of adult MCD patients in our center and explored and analyzed potential risk factors for relapse in MCD patients. We included 51 adult MCD patients with a median age of 29 years, and 30 were men. Among them, 16 patients (31.37%) had acute kidney injury (AKI) at presentation. The average urinary protein excretion was 6.39 ± 5.54 g. Notably, 29 (59%) patients had hematuria; 16 (31.37%) patients developed AKI; and 25 patients (49.02%) experienced at least 1 relapse. 13 patients (25.49%) experienced 2 relapses, and 9 patients (17.65%) experienced 3 or more relapses during the observation period. Compared with non-relapse patients, relapse patients were younger (mean age, 18 years (18 - 32 years)), and fewer patients (n = 8, 32%) had positive urinary red blood cells. The time from treatment to remission and baseline albumin, renal function, urine protein quantification, and other laboratory indicators did not significantly differ between the two groups (all, p > 0.05). Single and multivariate logistic regression analysis revealed age of onset, drug-related adverse effects during treatment, and AKI as the risk factors for relapse. This study identified young age at onset, treatment-related adverse effects, and AKI as independent risk factors for relapse in adult-onset MCD patients. Rituximab may be an effective treatment for relapsed MCD patients.
This case report presents the clinical course and treatment outcomes of a 61-year-old male renal transplant patient who developed recurrent bladder cancer while receiving long-term immunosuppressive therapy. Computed tomography (CT) revealed two tumors in the bladder trigone (largest diameter 8.4 mm). After initial treatment with transurethral resection of the bladder tumor (TURBT), the patient underwent regular bladder instillations of epirubicin. However, a follow-up examination 1 month later revealed disease recurrence, leading to a second TURBT. Due to the patient's renal impairment (baseline creatinine 107.8 µmol/L, glomerular filtration rate (GFR) 79.19 mL/min/1.73m2) and human epidermal growth factor receptor 2 (HER2) overexpression (2+), the decision was made to employ an antibody-drug conjugate (ADC) targeting HER2 (disitamab vedotin, 120 mg intravenously). The report outlines the patient's background, the progression of his disease, the decision-making process behind the use of ADC therapy, and the subsequent response to treatment. The successful control of the disease with ADC therapy in this complex patient population highlights its potential as an effective and less toxic alternative to conventional chemotherapy, particularly in patients with recurrent bladder cancer after renal transplantation.
BACKGROUND:Autosomal dominant polycystic kidney disease (ADPKD) is increasingly recognized as a systemic disorder with early vascular involvement, even before significant kidney function decline. Arterial stiffness and ocular microvascular alterations may reflect subclinical vascular changes in this population. However, data regarding the relationship between systemic arterial stiffness and choroidal microvascular structure in early ADPKD are limited. MATERIALS AND METHODS:A total of 41 patients with ADPKD and 40 controls were included. In this single-center, cross-sectional study, patients with ADPKD and preserved kidney function (estimated glomerular filtration rate > 60 mL/min/1.73m2) and age- and sex-matched healthy controls were evaluated. Arterial stiffness was assessed using the cardio-ankle vascular index (CAVI). Ocular structural and microvascular parameters were measured using spectral-domain optical coherence tomography, including the choroidal vascularity index (CVI). Group comparisons, correlation analyses, and multivariable linear regression models were performed to identify independent determinants of CAVI and CVI. RESULTS:CAVI was significantly higher in the ADPKD group compared with controls (p < 0.01). CVI was also significantly increased in patients with ADPKD, whereas subfoveal choroidal thickness did not differ between groups. No significant correlation was observed between CAVI and CVI. In multivariable analyses, ADPKD status remained independently associated with both higher CAVI and higher CVI after adjustment for relevant covariates. CONCLUSION:Patients with early-stage ADPKD exhibit increased systemic arterial stiffness and choroidal microvascular remodeling despite preserved kidney function. The coexistence of elevated CAVI and CVI suggests early, multi-level vascular involvement in ADPKD. Combined assessment of systemic and ocular vascular parameters may provide complementary insights into subclinical vascular alterations in this patient population.
Introduction: As the number of elderly patients with end-stage kidney disease (ESKD) increases, the importance of understanding how age affects post-transplant success grows. We sought to quantify the association of age with key outcomes in recipients. Materials and methods: We did a single-center retrospective cohort analysis of all DDKT recipients who received kidneys between January 2001 and June 2021, stratified by age into 4 groups (18 - 49, 50 - 59, 60 - 69, >= 70). Outcomes of interest included sored graft failure (DCGF), and death with a functioning graft (DWFG) within 5 years of transplant and acute rejection (AR) within 1 year of transplant. Results: Of 3,119 recipients, 1,192 (38.2%) were 18 - 49 years old (reference group), 947 (30.4%) were 50 - 59, 795 (25.5%) were 60 - 69, and 185 (5.9%) were >= 70. The adjusted hazard ratio (aHR) for UCGF was 1.22 (95% CI: 1.01 - 1.48) for 50 - 59 years; 1.78 (95% CI: 1.47 - 2.17) for 60 - 69; and 2.83 (95% CI: 2.13 - 3.76) for >= 70. The aHR for DCGF was only statistically significant for the >= 70 age group at 1.73 (95% CI: 1.16 - 2.96). The aHR for DWFG was 2.00 (95% CI: 1.47 - 2.73) for 50 - 59 and 5.45 (95% CI: 3.95 - 8.26) for >= 70. The aHR for AR was 0.73 (95% CI: 0.61 - 0.88) for >= 70. Conclusion: DDKT recipients over the
AIM:Chronic kidney disease and biological aging share overlapping mechanisms, but conventional risk models may not adequately capture their combined impact on mortality. This study aimed to determine whether integrating DNA methylation-based biological age (epigenetic age) with renal function estimates could enhance mortality risk prediction. MATERIALS AND METHODS:A mortality risk model incorporating estimated glomerular filtration rate was developed in the UK Biobank and externally validated in the National Health and Nutrition Examination Survey (1999 - 2002). Four epigenetic age measures (Horvath, Hannum, PhenoAge, and GrimAge) were evaluated for their added value in predicting mortality. Model performance was assessed using discrimination metrics and survival analyses. RESULTS:Among the epigenetic age measures, GrimAge showed the most substantial improvement in model performance when combined with creatinine-based kidney function estimates. Adding GrimAge improved discrimination for mortality prediction (change in C-statistic: 0.16; p < 0.001). In the external cohort, individuals classified as low risk by chronological age but as high risk by GrimAge had significantly higher mortality. Chronological age-adjusted kidney function showed no predictive value, while GrimAge-based models identified at-risk individuals with preserved kidney function. Models using creatinine outperformed those using cystatin C across all measures of biological age. CONCLUSION:Integrating epigenetic age measures with renal function indicators improves mortality prediction. GrimAge is particularly effective in identifying individuals at high risk who may not be detected using standard approaches. Incorporating biological aging markers into kidney health assessments may allow more precise and personalized risk stratification.
Perinephric myxoid pseudotumor of fat (PMPF) is a very rare, benign perirenal mass that has been described in patients with advanced and inflammatory kidney disease. On imaging, PMPF can mimic benign and malignant lesions ranging from simple cysts to poorly differentiated malignant liposarcoma. Histologically, it consists of adipose cells, myxoid stroma, spindle cells and inflammatory cells, mainly lymphocytes. Herein, we report on our center's experience with PMPF in kidney transplant recipients with allograft loss presenting for re-transplant evaluation and provide a review of the existing literature. PMPF often presents as an incidental radiologic finding in end-stage kidney disease patients undergoing evaluation for re-transplantation. It may represent a localized reaction to renal parenchymal inflammation often caused by recurrent rejection, or chronic immunologic intolerance of previous allografts. PMPF is benign but should be differentiated from malignant entities such as well-differentiated liposarcoma.
BACKGROUND:Persistent rejection despite aggressive management is common among kidney transplant recipients (KTRs). One approach is to treat the rejection and also intensify the maintenance immunosuppression by adding belatacept to the standard triple immunosuppressive regimen. To the best of our knowledge, the safety of this approach has not been previously reported. MATERIALS AND METHODS:In this study, we included all patients who had persistent microvascular inflammation (MVI) on two or more sequential biopsies and were treated according to the standard of care for rejection. Cases were selected based on the maintenance of quadruple immunosuppression after persistent rejection management. Controls were selected by matching some of the baseline characteristics for patients who were maintained on a standard triple immunosuppressive regimen only. RESULTS:15 KTR cases were compared with 21 KTR controls. The median number of rejection episodes before adding belatacept was 3 (IQR 2 - 4), with a mean interval from transplant to the initiation of quadruple immunosuppression of 43.6 months. By the end of the analysis, 10 (67%) cases and 15 (71%) controls (p = 0.76) had infectious complications. The most common infectious complications in the cases were urinary tract infection and pyelonephritis, while BKV was more common in controls. All but 1 case had a follow-up biopsy after quadruple immunosuppression. Of the cases and controls, all but control had persistent rejection. CONCLUSION:While many infectious complications were observed in this high-risk population with resistant MVI, the safety profile of quadruple immunosuppression seems comparable to that of triple immunosuppression. Although initial efficacy experience was not encouraging in this series, larger controlled studies are needed to better define the benefits and risks of this approach.
BACKGROUND:Anemia is common in maintenance hemodialysis (MHD). Therapy with erythropoiesis-stimulating agents (ESAs) may be limited by inflammation-related hyporesponsiveness and safety concerns. Real-world evidence on roxadustat across baseline anemia severities is limited. MATERIALS AND METHODS:In this single-center retrospective cohort, 300 MHD patients who switched from ESAs to roxadustat monotherapy were grouped by baseline hemoglobin (Hb): severe < 80 g/L (n = 82), moderate 80 - 99 g/L (n = 137), and mild 100 - 110 g/L (n = 81). The primary outcome was sustained Hb target achievement (100 - 120 g/L for ≥ 2 consecutive visits within 12 weeks without rescue therapy). Hb trajectories were assessed using linear mixed-effects models, and predictors of target achievement were identified by multivariable logistic regression with false discovery rate adjustment. RESULTS:At 12 weeks, sustained Hb achievement increased with baseline Hb: 46.3% (severe), 64.2% (moderate), and 76.5% (mild) (q = 0.0012). Hb variability decreased across groups (time-weighted coefficients of variation 7.5, 6.1, and 5.2%; q = 0.008). Early Hb rise was fastest in severe anemia (+1.85 vs. +1.24 vs. +0.74 g/L/week over weeks 0 - 4; q = 0.028). Adverse events occurred in 47.7%, mostly grade 1 - 2, without between-group differences in serious events or discontinuation. Higher C-reactive protein (per 10 mg/L, OR 0.42; q = 0.012) and poor prior ESA response (OR 0.60; q = 0.013) predicted lower target attainment, whereas higher prealbumin (per 10 mg/L, OR 1.35; q = 0.004), IV iron (OR 1.52; q = 0.021), and ≥ 50% dose titration (OR 1.59; q = 0.019) predicted higher attainment. CONCLUSION:Roxadustat improved and stabilized Hb across anemia severities in MHD, with best control in milder anemia; inflammation, nutrition, prior ESA response, iron use, and dose titration influenced success.
