Renal Failure最新文献

Cardiovascular-kidney-metabolic (CKM) syndrome significantly impacts a large segment of the general population. The risk factors associated with progression of CKM syndrome as well as all-cause mortality warrant further investigations. In this study, we aimed to assess whether nephrolithiasis history would help to identify the high-risk populations among CKM patients. We conducted a multi-center study involving patients with CKM syndrome at stages 2-3 from 28 urban centers across China. We employed multivariable Cox proportional hazards regression analysis to estimate hazard ratios (HRs) along with their corresponding 95% confidence intervals (CIs) for the associations with a history of nephrolithiasis. Subgroup analyses and sensitivity analyses were performed to enhance the robustness of our findings. A total of 344,220 CKM patients at stages 2-3 were included in this study. Among the participants, 28,451 had a history of nephrolithiasis. When compared to individuals without nephrolithiasis history, those with the history demonstrated an increased risk of progression to CKM stage 4 (HR 1.52, 95% CI [1.48-1.56]) and all-cause mortality (HR 1.08, 95% CI [1.03-1.14]). Similar results were obtained in the participants with asymptomatic nephrolithiasis. Consistent findings were observed through subgroup analyses and sensitivity analyses as well. The history of nephrolithiasis is associated with an elevated risk of incident cardiovascular disease and increased all-cause mortality among CKM patients. These findings highlight the significant role of nephrolithiasis in identifying high-risk populations within CKM patients.

Aging imposes significant influence in alteration of organ structure, function, and susceptibility to disease. Long non-coding RNAs (lncRNAs) are frequently dysregulated in the aging kidney, however, the key lncRNAs and associated mechanism involved in regulating kidney aging remains poorly investigated. Herein, we performed unbiased whole transcriptome sequencing on the kidney tissue samples from young and aging mice. The results of differentially expressed lncRNAs among two groups revealed that Gm44981, a 1943 bp lncRNA, was down regulated in the aging kidney. Fluorescence in situ hybridization (FISH) assay showed that Gm44981 was mainly located in the nucleus of glomerular mesangial cells (MCs). Functional experiments showed that overexpression of Gm44981 in MC cells significantly promoted cell proliferation capacity. Specifically, overexpression of Gm44981 was associated with increased H3K27me3 level and enhanced enrichment of EZH2 at the Cdkn1a promoter region, which correlated with the suppression of Cdkn1a expression and attenuated MCs senescence. Together, our findings highlighted the crucial roles of lncRNA Gm44981 in regulation of glomerular MCs senescence and provided novel targets for aging therapy.

Optimal regional citrate anticoagulation (RCA) for hemodialysis (HD) in high-bleeding-risk patients remains undefined. This prospective observational cohort study included 195 high-bleeding-risk patients (481 HD sessions) allocated to three RCA groups: RCA-one (prefilter citrate only, 141 patients/337 sessions), RCA-two (pre- and post-filter citrate, 51 patients/133 sessions), and RCA+saline (prefilter citrate + post-filter saline, 3 patients/11 sessions). Primary outcome: circuit survival time; secondary outcomes: complete dialysis rate, clotting scores, and adverse events. RCA-two had the highest complete dialysis rate (99.7% vs. 97.0% [RCA-one], 97.7% [RCA+saline]; p = .037) and lowest venous expansion chamber serious clotting (score = 3: 5.4% vs. 16.9%, 30.0%; p < .001). Non-severe venous clotting (score < 3) was highest in RCA-two (94.6% vs. 83.1%, 70%; p < .001), with no intergroup differences in dialyzer clotting (score < 3: 96.1% vs. 95.3%, 90%; p = .83). RCA-two had the lowest adverse event rate (1.8% vs. 10.8%, 11.1%; p = .001), including less hypotension (0.9% vs. 7.6%, 2.0%; p = .023) and no muscle cramps. Venous pretreatment calcium in RCA-two decreased at 2 h (p = .03) without serious electrolyte/acid-base imbalances. Circuit survival time did not differ among groups (p > .05). RCA is safe and effective for high-bleeding-risk HD patients. RCA-two (pre- and post-filter citrate) offers advantages in venous anticoagulation and safety but requires confirmation in large randomized trials.

The presence of pretransplant anti-human leukocyte antigen (HLA) donor-specific antibodies (DSAs) is still a significant barrier to successful kidney transplantation, as it increases the risk of rejection and graft failure. Rituximab (anti-CD20 antibody) has been administered in hopes of suppressing DSA production and rejection in those with preformed DSAs. However, existing studies report conflicting outcomes, underscoring the need for more data to guide clinical practice. Thus, we evaluated the efficacy of early posttransplant rituximab administration in a cohort of kidney transplant recipients with pretransplant anti-HLA DSAs. In this retrospective study of 77 patients, we compared 1-year transplant outcomes between patients treated with and without rituximab for pretransplant anti-HLA DSAs. Infectious complications tended to occur more often in the rituximab group (BK polyomavirus DNAemia >10,000 copies/mL, 3 [19%] vs. 8 [13%]; quantifiable cytomegalovirus DNAemia, 8 [50%] vs. 19 [31%]; infection requiring hospitalization, 5 [31%] vs. 11 [18%]), but none of these differences reached statistical significance. The incidence of biopsy-proven rejection (2 [13%] vs. 12 [20%]) and high plasma donor-derived cell-free DNA (2 [18%] vs. 12 [27%]) tended to be more frequent in the no-rituximab group, but none of these reached statistical significance. Preexisting DSA persisted or recurred in 44% of the patients that received rituximab, and in 46% of patients who did not receive rituximab. Similarly, de novo DSA occurred in 31% of those who received rituximab versus in 25% of those who did not. Rituximab administration did not result difference in graft and patient survival or rejection rates or recurrence of preexisting DSA.

Acute kidney injury requiring continuous kidney replacement therapy (AKI-CKRT) in the setting of coronavirus disease 2019 (COVID-19) carries a high mortality. In this two-center retrospective cohort study, we analyzed whether a simplified Sequential Organ Failure Assessment (SOFA) score, the 4-organ SOFA score with renal and neurologic sub-scores removed, would perform as well as the full SOFA score in predicting mortality. In our primary cohort, we identified 63 patients with COVID-19 hospitalized in April 2020 to July 2021 with AKI-CKRT and determined their 4-organ and full SOFA scores at CKRT initiation. Thirty-day and in-hospital mortality were 73.0% and 82.5%, respectively. The median 4-organ SOFA score at CKRT initiation among 30-day survivors was 7 (interquartile range 5.5-8.5) versus 8 (7-10) among 30-day non-survivors (p = 0.017). Four-organ SOFA scores for those who survived versus died before discharge were similar (p = 0.071). The full SOFA scores in survivors versus non-survivors were similar (p > 0.05). When comparing receiver operating characteristic curves, the 4-organ SOFA score to predict 30-day mortality performed best (area under curve 0.67). For external validation, we repeated our analysis in 88 patients with COVID-19 and AKI-CKRT from the MIMIC-IV database, and again the 4-organ score performed as well as the full SOFA score to predict 30-day and in-hospital mortality. Though hypothesis-generating and requiring additional validation, these findings suggest that 4-organ SOFA score performs as well as full SOFA score in predicting mortality in patients with COVID-19 and AKI-CKRT. However, these results reinforce prior data that SOFA score has limited prognostic value in COVID-19.

With the increasing prevalence of diabetes, the incidence rate of diabetic kidney disease (DKD) has risen yearly in China. While traditional therapies like renin-angiotensin system blockers remain foundational, the treatment paradigm is rapidly evolving with the emergence of novel agents, including SGLT2 inhibitors, mineralocorticoid antagonists, endothelin receptor antagonists, and GLP-1 receptor agonists. This study aims to provide an overview of the changing landscape of drug clinical trials on DKD in mainland China from 2013 to 2023. Detailed information of drug trials for DKD registered on the National Medical Products Administration Registration and Information Disclosure Platform for Drug Clinical Studies was collected. A total of 50 trials for DKD were included. Bioequivalence trials accounted for the most significant proportion (48%), followed by phase II (22%), phase I (20%), and phase III (10%). Chemical drugs accounted for the largest proportion (92%), followed by traditional Chinese medicine/natural medicine (8%). There were 18 different drugs involved in the 50 trials with Irbesartan (n = 24, 48%) ranked first in the number of trials. The parallel-group design was primarily used (48%), followed by crossover design (46%). Randomization was used by almost all trials (92%). Of all trials, 44 (88%) were launched domestically, whereas only 6 (12%) were international multi-center trials. Drug trials showed an uneven geographical distribution. Despite the progress in DKD drug clinical trials in mainland China during recent years, innovative drug research and development still has a long way to go. These findings provide an evidence base for optimizing global-regional alignment in DKD innovation policy.

The Cardiometabolic Index (CMI) reflects visceral adiposity and lipid dysregulation, while sarcopenia indicates skeletal muscle depletion, both representing metabolic and functional decline in chronic kidney disease (CKD). This study aimed to investigate the impact of CMI and sarcopenia, as well as their integration into a metabolico-muscular composite risk model, on all-cause and cardiovascular mortality in CKD patients. Based on data from the National Health and Nutrition Examination Survey spanning 1999-2006 and 2011-2018, a total of 1,886 CKD patients were included. Kaplan-Meier survival analysis, multivariable Cox proportional hazards models, restricted cubic spline regression, and subgroup analyses were employed for assessment, while time-dependent receiver operating characteristic analysis was used to evaluate predictive performance. Results showed that patients with both high CMI and sarcopenia had the lowest survival rate. After multivariable adjustment, Cox regression demonstrated that patients in the highest CMI quartile had significantly increased risks of all-cause mortality (HR = 2.25, 95% CI: 1.35-3.73) and cardiovascular mortality (HR = 4.03, 95% CI: 1.52-10.70). Sarcopenia was also associated with increased risks of both mortality types (all-cause: HR = 1.27, 95% CI: 1.10-2.49; cardiovascular: HR = 1.12, 95% CI: 1.06-2.21). Further analysis identified nonlinear relationships between CMI and both all-cause and cardiovascular mortality, regardless of sarcopenia status. This longitudinal cohort study demonstrates that elevated CMI and sarcopenia are independently associated with increased mortality risk in CKD patients, with the highest risk observed when both conditions coexist. Therefore, this study positions CMI and sarcopenia as prognostic biomarkers for mortality risk stratification in CKD.

This observational cohort study aimed to identify factors influencing long-term renal outcomes in 170 patients with biopsy-proven malignant hypertension (MHT)-associated renal thrombotic microangiopathy (TMA) who were dialysis-independent at baseline, recruited between 2008 and 2023. Over a median follow-up of 23.5 months, 52 patients (30.6%) progressed to end-stage renal disease (ESRD). Those developing ESRD exhibited significantly higher total cholesterol levels, heavier proteinuria, a greater proportion of global glomerulosclerosis, more advanced interstitial fibrosis/tubular atrophy, and lower baseline eGFR, along with lower use of renin-angiotensin-aldosterone system (RAAS) inhibitors. In Cox regression analysis, elevated total cholesterol (HR = 1.48 per 1 mmol/L change; 95% CI: 1.24-1.77, p < 0.001) and a higher percentage of glomerulosclerosis (HR = 1.24, 95% CI: 1.15-1.33, p < 0.001; per 5% increase of glomerulosclerosis) were independent risk factors for ESRD, while RAAS inhibitor use was associated with a significantly reduced risk (HR = 0.45, 95% CI: 0.25-0.82, p = 0.009). These findings underscore the prognostic value of lipid profiles and histologic injury severity in MHT-associated TMA and support the protective role of RAAS blockade in preserving renal function, which may guide risk stratification and therapeutic decisions in this high-risk population.

Patients with end-stage renal disease often require arteriovenous fistula (AVF) creation for hemodialysis. However, nearly 40% of patients develop aneurysmal dilatation of AVF (AVFA) after surgery, which can lead to prolonged bleeding at puncture sites, increased infection risk, and even potential rupture. Despite its high incidence, research on AVFA remains remarkably limited. This study makes an innovative discovery by establishing a link between AVFA formation and alternative splicing of fibronectin (FN), a crucial extracellular matrix component. Specifically, we demonstrate that increased inclusion of the EDA exon in FN within vascular smooth muscle cells triggers phenotypic switching to a synthetic state and extracellular matrix remodeling through the ITGB1/FAK/Src/RUNX2 pathway. These changes ultimately reduce vascular mechanical strength and contribute to AVFA development. Furthermore, we identify the splicing factor SRSF5 as a key regulator of EDA inclusion and characterize its potential binding sites, providing potential therapeutic targets for AVFA prevention.

Peritoneal dialysis (PD) transforms the peritoneum into a dynamic therapeutic interface, with each exchange offering direct access to molecular and cellular signals from the peritoneal cavity. Among these, extracellular vesicles (EVs) have emerged as stable, information-rich messengers reflecting peritoneal health, inflammation, and fibrosis. The review explores the peritoneum as a living therapeutic interface, summarizing current evidence on EV biology, their molecular cargo, and potential roles in monitoring inflammation, fibrosis, and membrane function. It also discusses existing knowledge gaps, technological advances, and opportunities for translating EV research into clinical practice.