Kidney Diseases最新文献

Introduction: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease and is increasingly recognized to involve early and progressive tubulointerstitial injury. However, the key molecular drivers of this process and their therapeutic potential remain poorly defined.

Methods: We conducted an integrative analysis of three DKD transcriptomic datasets using weighted gene correlation network analysis and differential expression analysis, followed by single-cell RNA sequencing to localize candidate genes to specific renal cell types. Functional validation was performed using in vitro assays in HK-2 and THP-1 cells, in vivo DKD mouse models, and patient kidney tissue. A virtual screening approach was applied to identify candidate inhibitors.

Results: We identified CXCL6, a C-X-C motif chemokine, as a central hub gene selectively upregulated in tubular epithelial cells of DKD kidneys. Urinary CXCL6 levels strongly correlated with markers of renal dysfunction. Mechanistically, high-glucose-induced CXCL6 expression in tubular cells, promoting macrophage recruitment, polarization toward a pro-inflammatory phenotype, and increased cytokine release. Through virtual screening, we identified salvianolic acid B (Sal-B) as a putative CXCL6 inhibitor. Sal-B treatment suppressed CXCL6 secretion, macrophage infiltration, and inflammatory cytokine production in vitro.

Conclusion: Our study uncovers CXCL6 as a key mediator of tubulointerstitial inflammation in DKD, linking tubular injury to immune cell recruitment and cytokine-driven damage. Furthermore, we identify Sal-B as a promising therapeutic candidate targeting this newly characterized pathway, offering potential for diagnostic and therapeutic advancement in DKD.

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.

Introduction: Weight gain and central obesity are common in peritoneal dialysis (PD) patients. In the general population, body roundness index (BRI) has been found to be a convenient anthropometric measurement for the assessment of central obesity and visceral adiposity. However, the role of BRI in PD patients has not been explored.

Methods: We recruited 145 new PD patients. BRI, body composition by bioimpedance spectroscopy, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were measured at baseline and then after 1 year of PD. Patients were stratified into four groups based on their changes in BRI after 1 year of PD, using the traditional BRI cutoff of 5. Outcome measures include patient survival and hospitalization rate.

Results: The change in BRI after 1 year of PD had a modest but significant correlation with the change in HOMA-IR (r = 0.497, p = 0.041). For the group with baseline BRI <5, patients who had their BRI raised to ≥5 (low-high group, n = 20) had significantly lower patient and technique survival rates than those whose BRI remained <5 (low-low group, n = 55), and the result remained significant after adjusting for clinical confounders by multi-variable Cox regression (adjusted hazard ratio 2.885, 95% CI: 1.278-6.509, p = 0.011). The low-high group also had significantly higher hospitalization rates (2.51 [1.63-3.93] vs. 0.98 [0.26-1.91] per year, p = 0.0008) and longer hospitalization stay (17.3 [12.2-35.5] vs. 5.0 [1.0-13.3] days per year, p = 0.015) than the low-low group.

Conclusion: An increase in BRI after 1 year of PD was associated with worsening of insulin resistance, worse patient survival, and more hospitalization.