Kidney Diseases最新文献

Introduction: Oral anemia treatments are preferred by patients on home-based peritoneal dialysis (PD). We evaluated the effectiveness and safety of oral roxadustat in Chinese patients with chronic kidney disease (CKD)-associated anemia on PD.

Methods: In this phase 4 study, patients with CKD-anemia on PD received roxadustat thrice weekly for 24 weeks. We assessed the proportion with hemoglobin ≥100 g/L at Weeks 20 and 24 (overall and stratified by type 2 diabetes mellitus [T2DM] vs. non-diabetes mellitus [DM]), quality of life changes according to the Functional Assessment of Cancer Therapy-Anemia (FACT-An), and 36-Item Short Form Health Survey (SF-36), and safety.

Results: Overall, 195 patients (116 male [59.5%]; mean ± standard deviation age, 46.3 ± 12.3 years) were enrolled; 189 (96.9%) were erythropoiesis-stimulating agent-treated and 43 (22.1%) had T2DM. Baseline hemoglobin was 98.1 ± 10.7 g/L and was <80 g/L in 10 (5.1%). The mean (95% confidence interval) proportion who achieved a hemoglobin concentration ≥100 g/L was 85.1% (79.8%, 90.5%) (T2DM: 89.2% [78.5%, 99.9%]; non-DM: 84.0% [77.8%, 90.1%]). The change in Total FACT-An score (baseline to Week 24), but not SF-36 scores, was clinically significant (-6.2 [-9.0, -3.4]), with a greater decrease in the T2DM subgroup. Residual renal function declined slightly from baseline to Week 24 (-0.2 mL/min/1.73 m²). Treatment-emergent adverse events occurred in 158 patients (81.0%) and were roxadustat-related in 20 (10.3%).

Conclusion: Roxadustat corrected anemia in Chinese patients with CKD on PD, irrespective of baseline T2DM. Adverse events were consistent with roxadustat's known safety profile and with PD patients' characteristics.

Introduction: Persons with type 2 diabetes mellitus (T2DM) attending hospitals frequently experience major complications. We assessed the potential use of unstructured free-text data extracted from electronic health records (EHRs) using natural language processing (NLP) and machine learning (ML) to develop a predictive model for chronic kidney disease (CKD) in T2DM.

Methods: This multicenter retrospective study included data from eight Spanish hospitals (2013-2018), extracted using NLP and ML techniques (EHRead®) based on SNOMED CT terminology. From a cohort of individuals with T2DM, we identified those with and without CKD at inclusion. Among individuals without CKD, we trained and validated a 2-year predictive model for CKD development. The model showing the best balance between performance and clinical interpretability was selected for integration into a web-based tool to support early detection and risk stratification.

Results: Of 588,786 individuals with T2DM, 316,597 were included for model development (training: 291,429 [92.1%]; validation: 25,168 [7.9%]; CKD incidence: 15.4% and 18.4%, respectively). A high proportion of missing data was observed in key clinical variables. Among models evaluated, logistic regression achieved the best performance (receiver operating characteristic area under the curve 0.72) using 27 predictors. Both a reduced 10-predictor model and a clinically refined 8-predictor model showed comparable performance to the full model in training and validation cohorts. The clinically refined model was selected for implementation in the web-based tool.

Conclusion: Unstructured EHR data enabled the development of a predictive model for 2-year CKD risk in persons with T2DM. Improving EHR data completeness remains essential to enhance future predictive modeling.

Background: Kidney transplantation is the best modality of kidney replacement therapy for kidney failure, and yet global shortages of donor kidneys persist.

Summary: The 5th International Congress of Chinese Nephrologists (ICCN), held in Hong Kong from December 13-15, 2024, hosted a "Kidney Donation Roundtable Workshop" to address this critical issue. The incidence of kidney transplantation varies across countries and regions, and detailed evaluation is essential to guide stakeholders in developing strategies to enhance kidney donation and improve patient outcomes worldwide. This paper summarizes expert opinions from the congress, focusing on strategies to enhance kidney donation globally.

Key messages: Improving public education, addressing ethical and cultural barriers, optimizing organ allocation systems, and leveraging policy incentives to promote both living and deceased donation are cornerstones in combating donor kidney shortages.

Introduction: Endothelium-mediated regulation of vascular tone plays a crucial role in modulating vascular functions, especially in the kidney, a highly vascularized organ. Therapeutic interventions targeting this process, such as endothelin axis blockage, have demonstrated positive results across various kidney diseases. However, the long-term effects remain poorly explored. Mendelian randomization (MR) and Transcriptome-Wide Association Study (TWAS) provide an approach to investigate the lifelong effects of genetically determined variations in endothelial vasoactive pathways on renal outcomes, mimicking a naturally occurring randomized controlled trial.

Method: The primary outcome is the estimated glomerular filtration rate (eGFR), and secondary outcomes include urine albumin-to-creatinine ratio (UACR), rapid kidney function decline, chronic kidney disease (CKD), and various cardiovascular events. From published Genome-Wide Association Studies (GWASs), we extracted summary statistics, employed the inverse variance weighted method for the main MR analysis, complemented by various sensitivity analyses, and utilized the S-PrediXcan for Transcriptome-Wide Association Study (TWAS) analysis.

Result: Genetically predicted eNOS pathway activation correlated with higher eGFR (0.03, 95% CI: 0.01-0.05, p = 6.2e-4), reduced risk of CKD (odds ratio 0.47, 95% CI: 0.34-0.64), and rapid kidney function decline (odds ratio 0.47, 95% CI: 0.31-0.72). Transcriptome association studies further confirmed a positive association between gene expression in the eNOS pathway and eGFR. Additionally, the overall endothelial vasoactive effect, represented by the genetically predicted modulation of eNOS, EDNRA, and PDE5A pathways, was significantly associated with higher eGFR (0.03, 95% CI: 0.01-0.04, p = 5.4e-5).

Conclusion: Our results shed light on a significant effect of endothelial vasoactive pathways in kidney-related outcomes, which hold promise for alternative targeted therapies in CKDs.

Introduction: The progression evaluation of autosomal dominant polycystic kidney disease (ADPKD) is critical to the treatment strategy and prognosis prediction of the disease, but the current evaluation methods are time-consuming and costly.

Methods: ADPKD patients were recruited in Shanghai Changzheng Hospital from February 2023 to October 2023. Based on the Mayo imaging classification (MIC) model, patients with different disease progression rates were classified into slowly progressive (SP) group (MIC 1A, 1B) or rapidly progressive (RP) group (MIC 1C, 1D, and 1E). The Raman spectra of urine samples from ADPKD patients were obtained by Surface-enhanced Raman spectroscopy (SERS) protocol and the characteristics of urine Raman spectra from SP and RP groups were analyzed. The ADPKD progression prediction model was constructed based on principal component analysis (PCA) and support vector machine (SVM).

Results: After adjusting for age, gender, and renal function, there were differences in Raman intensity of the six major Raman peaks (758/794/1,184/1,288/1,346/1,385 cm^-1) between patients with SP and RP ADPKD (p < 0.05). The substances of the above Raman peaks include tryptophan, uracil, adenine, phosphodiester bond, glucose, lipids, etc. The accuracy, sensitivity, and specificity of the ADPKD progression prediction model were 82.93%, 77.55%, and 86.11%, and after leaving-one-out cross validation (LOOCV), the accuracy, sensitivity, and specificity of were 70.25%, 65.31%, and 73.61%, respectively.

Conclusions: Urinary SERS detection can distinguish RP ADPKD patients from SP ones noninvasively, conveniently and quickly, with reasonable accuracy, sensitivity, and specificity. SERS combined with machine learning omics techniques might be a novel method to evaluate the progression of ADPKD.

Introduction: Renal anemia, a common complication of chronic kidney disease (CKD), is traditionally managed with erythropoiesis-stimulating agents (ESAs), which carry cardiovascular risks. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, offers a novel mechanism by enhancing erythropoietin production and iron metabolism. While randomized controlled trials demonstrate its efficacy, real-world data on long-term safety and effectiveness remain limited.

Methods: This retrospective study analyzed 6,414 hemodialysis patients with renal anemia from a single center (December 2018-December 2023), comparing roxadustat (n = 3,184) and ESA (n = 3,230) groups. Propensity score matching was used to balance the baseline characteristics. Efficacy outcomes included hemoglobin (Hb) changes (baseline to months 6-12 and 18-30) and Hb response rates. Safety endpoints assessed major adverse cardiovascular events (MACE), heart failure hospitalization (HHF), thromboembolism, and all-cause mortality. Sensitivity analyses addressed treatment crossover and confounding.

Results: Roxadustat showed significantly greater Hb increases versus ESA at 6-12 months (least-squares mean difference: 0.46 g/dL, p = 0.04) and 18-30 months (0.26 g/dL, p = 0.01). Hb response rates were higher with roxadustat (84.0% vs. 76%, p < 0.01). No significant differences were observed in MACE (HR: 1.08, p = 0.12), HHF (HR: 0.88, p = 0.25), thromboembolism (HR: 1.05, p = 0.34), or mortality (HR: 0.94, p = 0.29). Subgroup analyses suggested that roxadustat elevated MACE risk in patients with baseline hypertension or cardiovascular history, but sensitivity analyses nullified this association.

Conclusion: Roxadustat demonstrated superior efficacy in elevating and sustaining Hb levels compared to ESA over a longer observation period, with comparable cardiovascular safety in hemodialysis-dependent CKD patients. Roxadustat represents a viable alternative to ESA for renal anemia management, though long-term multicenter studies are needed to validate safety and optimize clinical use.

Introduction: Rituximab (RTX) is a key therapeutic agent for maintaining remission in steroid-dependent nephrotic syndrome and frequently relapsing nephrotic syndrome, demonstrating both efficacy and safety. However, reliable biomarkers for predicting relapse remain under investigation.

Methods: This single-center, retrospective, observational study included 70 patients who received RTX between January 2015 and January 2023. Patients were classified into two groups: the non-relapse group and the relapse group. Cox proportional hazards regression was used to analyze the associations between baseline clinical parameters and relapse risk, while Kaplan-Meier survival analysis was performed to estimate the recurrence-free survival rates.

Results: This cohort of 70 pediatric patients (71.4% male; median age: 9.5 years, interquartile range: 8.5-12.6) exhibited a 24-month post-rituximab relapse rate of 32.9% (23/70). Multivariate analysis identified elevated baseline memory B-cell levels (adjusted hazard ratio [HR] = 1.103, 95% confidence interval [CI]: 1.045-1.164, p < 0.001), reduced baseline natural killer (NK) cell levels (adjusted HR = 0.866, 95% CI: 0.752-0.997, p = 0.045), and higher IgG levels at 3 months post-RTX (adjusted HR = 1.245, 95% CI: 1.080-1.435, p = 0.003) as independent predictors of relapse. Kaplan-Meier survival analysis revealed that patients with memory B-cell counts below 19.65% of baseline (n = 38) had significantly higher 24-month relapse-free survival compared to those with counts above this threshold (n = 32; 86.8% vs. 43.8%; χ² = 13.918, p < 0.001). In contrast, patients with NK-cell levels below 6.45% of lymphocytes (n = 25) exhibited poorer 24-month relapse-free survival than those with higher NK-cell proportions (n = 45; 52.0% vs. 77.8%; χ² = 6.395, p = 0.011). Similarly, patients with IgG levels below 5.74 g/L (n = 35) demonstrated significantly better relapse-free survival compared to those with higher levels (n = 35; 85.3% vs. 47.2%; χ² = 11.030, p = 0.001).

Conclusion: Baseline memory B-cell and NK-cell levels (pre-RTX), as well as IgG levels at 3 months post-RTX, were identified as predictive biomarkers for the 2-year relapse risk following RTX therapy. These findings may contribute to the development of personalized RTX treatment strategies.

Background: The frequent co-occurrence of kidney and heart diseases stems from complex, bidirectional pathophysiological interactions, which contribute to elevated morbidity and mortality and present significant challenges in clinical management.

Summary: This review examines the shared regulatory mechanisms underlying cardiorenal syndrome and synthesizes current evidence on emerging treatment options, including decongestion strategies, renin-angiotensin-aldosterone system inhibitors/ARNIs, sodium-glucose cotransporter-2 inhibitors, MRAs, and GLP-1 receptor agonists. Supported by large randomized trials, these novel adosing are redefining therapeutic approaches and heralding a new era in cardiorenal medicine. We also emphasize the necessity of incorporating both cardiac and renal endpoints in pivotal trials of new therapies and highlight the need for further research into the efficacy and safety of combination treatments.

Key messages: Future clinical trials should adopt dual cardiorenal endpoints to better evaluate treatment effects. Combination therapies require rigorous investigation to establish optimal efficacy and safety profiles. These advances hold promise for optimizing multidisciplinary care, reducing disease burden, improving patient outcomes, and enhancing global health.

Introduction: Peritoneal fibrosis (PF) from long-term peritoneal dialysis (PD) is one of the main reasons for the ultrafiltration failure and the abandonment of PD in patients, and there is no effective treatment available. The dynamic changes in the PD microenvironment and their relationship to PD-related fibrosis remain unclear.

Methods: We performed single-cell RNA sequencing (scRNA-seq) on overnight PD effluent collected from a continuous ambulatory PD (CAPD) patient at two critical time points: the initiation of dialysis and after 3 years of treatment, so as to reveal the dynamic changes of immune cells and peritoneal mesothelial cells (PMCs) during prolonged PD.

Results: The results showed that six distinct populations of cells were identified within the PD effluent. The fibrotic progression exhibited a temporal shift in cellular dynamics: early-stage pathology was characterized by a sustained inflammatory response mediated primarily by macrophages, T cells, and PMCs, while late-stage pathogenesis transitioned to extracellular matrix (ECM) remodeling dominated by PMCs and fibroblasts.

Conclusion: These findings demonstrate that different cell types and microenvironment contribute to initial injury responses and subsequent tissue remodeling of peritoneum, which provides a deeper comprehension for the mechanism in PF.