Kidney Diseases最新文献

{"title":"Association between Restless Legs Syndrome and Sleep Disturbance and 3-Year Mortality in Hemodialysis Patients.","authors":"Lanbo Teng, Huanan Li, Yingying Han, Tao Yuan, Chuhan Xu, Tao Tan, Wenxiu Chang","doi":"10.1159/000545008","DOIUrl":"10.1159/000545008","url":null,"abstract":"<p><strong>Introduction: </strong>Whether restless legs syndrome (RLS) and sleep disturbance (SD) in hemodialysis (HD) patients influence all-cause and cardiovascular mortality remains controversial. The aim of this study was to evaluate the association between RLS or SD and 3-year mortality in HD patients.</p><p><strong>Methods: </strong>A total of 301 patients who underwent HD were examined in April 2021 and were followed up for 3 years. The median follow-up time was 36.0 [33.3, 36.0] months. Fifty-four patients fulfilled the diagnosis of RLS (17.9%), 126 patients complained of SD (41.9%). Demographic parameters, clinical features, laboratory indices, and two questionnaires to assess the diagnosis of RLS and sleep status were collected. All-cause mortality and cardiovascular mortality in this population were evaluated. Cox regression analyses and Kaplan-Meier curves were performed to determine the effect of RLS or SD on 3-year mortality.</p><p><strong>Results: </strong>The RLS group reported that 29 patients (53.8%) exhibited concurrent symptoms of SD. The presence of RLS or SD alone did not significantly elevate the risk of all-cause mortality (<i>p</i> = 0.053 and <i>p</i> = 0.193). However, the coexistence of RLS and SD was identified as an independent risk factor for all-cause mortality (<i>p</i> = 0.011). Furthermore, the various combinations associated with RLS or SD were found to be independently correlated with the risk of cardiovascular death (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>The combination of RLS and SD in HD patients is associated with an increased risk of cardiovascular and all-cause mortality, underscoring the clinical significance of this association.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"11 1","pages":"160-169"},"PeriodicalIF":3.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Treatment of IgA Nephropathy Based on a New Framework: Angiorenal Protection, Immunity Inhibition, B-Cell/Plasma-Cell Modulation, and Complement Inhibition.","authors":"Cheng Xue, Shengqiang Yu, Wei Gou, Yelei Xu, Li Yang, Bing Dai","doi":"10.1159/000544998","DOIUrl":"10.1159/000544998","url":null,"abstract":"","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"11 1","pages":"154-159"},"PeriodicalIF":3.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Value of Blood Pressure Rhythmicity for Estimated Glomerular Filtration Rate in Male Hypertensive Patients Aged 55 and Older.","authors":"Lulu Wang, Han Tian, Xinxin Xu, Xinyan Gu, Liu Li, Hui Zheng, Jie Xu, Chunsun Dai, Lei Jiang","doi":"10.1159/000544992","DOIUrl":"10.1159/000544992","url":null,"abstract":"<p><strong>Introduction: </strong>Blood pressure (BP) exhibits a circadian rhythm characterized by higher levels during wakefulness and lower levels during sleep; however, the functional and structural impact of the rhythms of BP remains uncertain.</p><p><strong>Methods: </strong>Two hundred hypertensive males aged 55 and older without overt cardiovascular or cerebrovascular diseases were enrolled in this longitudinal study. Of these, 188 were included in the analyses (12 lacked valid BP records for part of the 24-h period). Rhythmic profiling of BP was performed using ARSER, and rhythmicity was considered significant at <i>p</i> < 0.05. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology (CKD-EPI) formula. The primary outcome was the change in eGFR.</p><p><strong>Results: </strong>The average age was 64.9 ± 7.2 years. For systolic BP (SBP), 38 of the subjects exhibited a 12-h rhythm and 43 subjects a 24-h rhythm; for diastolic BP (DBP), 38 exhibited a 12-h rhythm, and 36 exhibited a 24-h rhythm. During the 3-year follow-up period, 16 of the subjects died, and 36 were lost to follow-up. The mean eGFR at baseline and follow-up were, respectively, 86.6 ± 14.0 and 81.0 ± 17.1 mL min^-1 1.73 m^-2 (<i>p</i> = 0.001). The urinary albumin:creatinine ratio did not vary significantly among the groups (<i>p</i> = 0.059). Subjects with 12-h rhythmic SBP exhibited a smaller reduction in eGFR than those with arrhythmic SBP (<i>p</i> = 0.014). However, the changes in eGFR were similar among the groups displaying 12-h or 24-h rhythmic DBP or arrhythmic DBP. We defined a decline in eGFR as a reduction of >1/2 SD between baseline and follow-up. Adjusting for confounding factors (including age, smoking, alcohol consumption, diabetes mellitus, BMI, albumin levels, administration time of antihypertensive drugs, and duration of hypertension), the risk of a decline in eGFR was 70% lower in subjects with 12-h rhythmic SBP than in those with arrhythmic SBP (heart rate = 0.307 [0.108-0.874], <i>p</i> = 0.027).</p><p><strong>Conclusion: </strong>SBP with a 12-h period is a protective predictor of the decline in eGFR in hypertensive males. It is, therefore, necessary to focus on the rhythmic profiling of BP.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"11 1","pages":"186-193"},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uric Acid and Atherosclerosis in Patients with Chronic Kidney Disease: Recent Progress, Mechanisms, and Prospect.","authors":"Yuchu Liu, Zeyu Li, Yuanwen Xu, Haiping Mao, Naya Huang","doi":"10.1159/000543781","DOIUrl":"10.1159/000543781","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) is a prevalent global health concern, significantly linked to increased cardiovascular morbidity and mortality. Among various risk factors, uric acid (UA) has emerged as a potentially modifiable contributor to cardiovascular complications in CKD patients.</p><p><strong>Summary: </strong>Elevated serum uric acid levels frequently occur in individuals with CKD and are associated with the development of atherosclerosis (AS). Uric acid has been demonstrated to exacerbate inflammatory processes, promote oxidative stress, and cause endothelial dysfunction, which are critical factors that drive the formation of atherosclerotic plaques. Furthermore, high uric acid levels can worsen renal function, establishing a detrimental cycle that amplifies cardiovascular risk.</p><p><strong>Key messages: </strong>This review investigates the complex interconnection between UA and AS in patients with CKD, highlighting the underlying mechanisms and therapeutic considerations. A more profound comprehension of this relationship is essential for enhancing cardiovascular health and outcomes in this vulnerable population.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"11 1","pages":"112-127"},"PeriodicalIF":3.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically Predicted Causal Relationship between Gut Microbiota and Various Kidney Diseases.","authors":"Zi-Jin Chen, Rui Wang, Meng-Ying Yao, Jing-Hong Zhao, Bo Liang","doi":"10.1159/000544915","DOIUrl":"10.1159/000544915","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Although recent research suggests that alterations in gut microbiota play a critical role in the pathophysiology of kidney diseases, the causal relationship between specific intestinal flora and the risk of kidney diseases remains unclear. Here, we investigated the causal relationship between gut microbiota and different kidney diseases through mendelian randomization analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Gut microbiota and three types of kidney diseases, including diabetic nephropathy, IgA nephropathy, and membranous nephropathy, were identified from large-scale genome-wide association studies summary data. Inverse variance weighted method was employed to estimate causal relationships. Cochran's &lt;i&gt;Q&lt;/i&gt; test was utilized to uncover any heterogeneity. The mendelian randomization-Egger intercept test was employed to detect horizontal pleiotropy, and the leave-one-out method was used for testing the stability. In addition, the reverse, multivariable, and two-step mendelian randomization analysis was conducted to assess the causation possibilities. Furthermore, the associations between three types of kidney diseases and immune infiltration were determined.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We identified 1,531 single-nucleotide polymorphisms. There were 6 positive and 9 negative causal effects between gut microbiota and three types of kidney diseases. Specifically, &lt;i&gt;Dialister&lt;/i&gt; was a protective factor for diabetic nephropathy while &lt;i&gt;Lachnospiraceae UCG-008&lt;/i&gt; was a risk factor. &lt;i&gt;Clostridium innocuum&lt;/i&gt; was a protective factor for IgA nephropathy, while &lt;i&gt;Christensenellaceae R.7&lt;/i&gt;, &lt;i&gt;Clostridium sensu stricto&lt;/i&gt;1, &lt;i&gt;Lachnospiraceae UCG-004&lt;/i&gt;, &lt;i&gt;Lachnospiraceae UCG-010&lt;/i&gt;, &lt;i&gt;Oscillospira&lt;/i&gt;, &lt;i&gt;Ruminococcaceae UCG-010&lt;/i&gt;, and &lt;i&gt;Terrisporobacter&lt;/i&gt; were risk factors for IgA nephropathy. &lt;i&gt;Butyricicoccus&lt;/i&gt;, &lt;i&gt;Catenibacterium&lt;/i&gt;, &lt;i&gt;Flavonifractor&lt;/i&gt;, and &lt;i&gt;Lachnospira&lt;/i&gt; were associated with an increased risk of membranous nephropathy, while &lt;i&gt;Ruminococcaceae UCG-011&lt;/i&gt; was associated with a decreased risk of membranous nephropathy. Sensitivity analysis indicated the results were robust. No significant pleiotropy or heterogeneity was identified. Notably, the reverse mendelian randomization analysis did not reveal any causal relationship. After adjusting for environmental confounders, including CO, PM 2.5, PM 10, and exposure to tobacco smoke at home, these causal relationships still exist. Additionally, immune infiltration analysis indicated unique immune cell distribution in each type of kidney disease, which are largely consistent with later two-step approach, emphasizing the significance of immunological processes in the diseases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study uncovered the causal relationship between gut microbiota and three types of kidney diseases. This discovery provides fresh perspectives on how microbes contribute to kidney diseases, paving the way for more i","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"11 1","pages":"170-185"},"PeriodicalIF":3.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Approach to Repositioning Peritoneal Dialysis Catheters.","authors":"Xiuling Chen, Nan Wang, Yurong Zou, Jin Chen, Hui Gao, Guisen Li, Junru Wang","doi":"10.1159/000543824","DOIUrl":"10.1159/000543824","url":null,"abstract":"<p><strong>Introduction: </strong>Peritoneal dialysis (PD) is a crucial kidney replacement therapy for patients with end-stage kidney disease. Despite its advantages over hemodialysis (HD), long-term success can be hindered by catheter dysfunction, which often necessitates revision. Currently, surgical treatment methods for PD catheter malfunction include fluoroscopy-guided procedures and laparoscopic or open surgery to salvage or replace the catheter. Here, we introduce the first novel, minimally invasive surgery for repositioning PD catheters.</p><p><strong>Methods: </strong>From November 2021 to May 2024, 8 patients with PD catheter dysfunction underwent this innovative procedure at the Department of Nephrology, Sichuan Provincial People's Hospital. Surgical Procedure: On the side of the original abdominal incision, blunt separation was used to find the PD catheter tunnel segment. The anterior rectus abdominal muscle sheath was incised, followed by separation of the deep polyester sleeve. The original catheter was exposed in the abdominal port or purse-string suture, and the intra-abdominal segment of the dialysis catheter was pulled out. Blunt cleaning around the periphery was performed to ensure that the PD catheter was smooth, and a rigid guidewire was placed through the intra-abdominal segment of the proximal end of the catheter of the first lateral hole. The intra-abdominal segment of the PD catheter was placed into the pelvis via the original catheter in the abdominal port. Clinical data were retrospectively collected, and patients were followed up for safety and efficacy assessment.</p><p><strong>Results: </strong>In a study involving 8 patients, no significant complications were observed, with an immediate imaging success rate of 100% and a clinical PD catheter reset success rate of 75%. The catheter remained patent until the end of the study, with a mean follow-up time of 17.25 ± 9.25 months.</p><p><strong>Conclusion: </strong>This new method for resetting dysfunctional PD catheters demonstrates technical feasibility, simplicity, cost-effectiveness, and safety. It has the potential to emerge as an alternative, particularly suitable for resource-limited settings.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"11 1","pages":"104-111"},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Prognostic Index for Deceased Donor Kidneys and Criteria for Identifying Suitable Candidates for Kidney Transplantation from Expanded Criteria Donors with Prolonged Waiting Times.","authors":"Tai Yeon Koo, Joongyub Lee, Omi Na, Yonggu Lee, Jong Cheol Jeong, Jaeseok Yang","doi":"10.1159/000544792","DOIUrl":"10.1159/000544792","url":null,"abstract":"<p><strong>Introduction: </strong>The kidney donor profile index (KDPI) is a valuable prognostic tool in deceased donor kidney transplantation (DDKT), while its optimization for each country using local data is essential. It remains unclear which patients derive survival benefits from expanded criteria donor (ECD) DDKT compared to waitlist or standard criteria donor (SCD) DDKT, particularly in the context of long waiting times. This study aimed to develop a prognostic index for donor kidneys and propose criteria to identify suitable candidates for ECD DDKT in Korea.</p><p><strong>Methods: </strong>Two prediction models were developed using data from two cohorts based on national databases (the Korean Network for Organ Sharing and the National Health Insurance Data Sharing Service): cohort for the prediction of graft prognosis (<i>n</i> = 6,272) and cohort for the prediction of suitable candidates for ECD DDKT (<i>n</i> = 30,183).</p><p><strong>Results: </strong>The Korean KDPI (K-KDPI) comprises five donor factors (age, height, diabetes mellitus, serum creatinine levels, and hepatitis C virus), associated with graft failure. The discriminatory ability of the K-KDPI for graft outcomes surpassed that of the US KDPI and dichotomous ECD criteria. ECD kidneys (K-KDPI ≥70%) showed worse allograft survival compared to SCD kidneys (K-KDPI <70%). Candidates aged ≥40 years, with negative panel reactive antibody, and without diabetes mellitus had a significantly lower mortality risk with ECD DDKT than with waitlist-or-SCD DDKT, making them suitable for ECD DDKT.</p><p><strong>Conclusion: </strong>The K-KDPI and criteria for identifying suitable ECD recipients are expected to improve the quality assessment and efficient utilization of ECD kidneys in Korea with long waiting times.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"11 1","pages":"143-153"},"PeriodicalIF":3.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Cohort Study of the Long-Term Influences of SARS-CoV-2 on Kidney Allograft Outcomes in Chinese Recipients: 1-Year Follow-Up Experience.","authors":"Yisheng Ji, Shuang Fei, Hongsheng Ji, Fan OuYang, Runmin Ding, Li Sun, Hao Chen, Xiaobing Ju, Jun Tao, Zhijian Han, Mulong Du, Zijie Wang, Ruoyun Tan, Min Gu","doi":"10.1159/000543935","DOIUrl":"10.1159/000543935","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the study was to investigate the long-term effects of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection and novel coronavirus disease (COVID-19) on prognosis of kidney transplant recipients.</p><p><strong>Methods: </strong>A 1-year retrospective study was carried out among 362 domestic kidney transplant recipients who were divided into observational (COVID-19) and control groups. Stratification analysis was then carried out to investigate whether repeated infections and infection severity could influence graft prognosis. Kaplan-Meier curves assessed 1-year graft survival, while one-way analysis of variance (ANOVA) compared graft function and laboratory parameters. Generalized estimating equations and repeated-measures ANOVA confirmed the magnitude of the impact of COVID-19 on kidney grafts. Generalized logistic regression and Cox regression established a model for analyzing COVID-19 risk factors. Meta-analysis and subgroup analysis were performed for validation.</p><p><strong>Results: </strong>Exposure of COVID-19 had a significant effect on graft function within 1 year (<i>p</i> < 0.001), and this kind of effect was mostly brought by severer infections in the stratification analysis regarding graft survival rate (<i>p</i> < 0.001), estimated glomerular filtration rate (eGFR) level (<i>p</i> < 0.001), and 1-year eGFR slope (<i>p</i> = 0.014). Diagnostic model showed tacrolimus patients are less likely to get severe COVID-19 than cyclosporine (<i>p</i> = 0.004). Hyperglycemia (<i>p</i> = 0.004) and low hemoglobin (<i>p</i> = 0.023) are adverse factors for severe pneumonia. Hemoptysis, hypo-lymphopenia, high procalcitonin and ferritin are linked to poor allograft outcomes with SARS-CoV-2 infection.</p><p><strong>Conclusions: </strong>COVID-19 severity is linked to poor kidney allograft prognosis. Hyperglycemia, low hemoglobin, and drug protocols including cyclosporine rather than tacrolimus are correlated with COVID-19 pneumonia. Hemoptysis, low lymphocytes, high procalcitonin or ferritin were concerned with kidney allograft prognosis post-COVID-19.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"11 1","pages":"128-142"},"PeriodicalIF":3.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Fatty Acid-Binding Protein 4 as a Potential Biomarker and Therapeutic Target for Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis.","authors":"Lu Cheng, Qian Ren, Jing Liu, Mei-Lian Yu, Rong-Shuang Huang, Fan Guo, Liang Ma, Shen-Ju Gou, Ping Fu","doi":"10.1159/000543940","DOIUrl":"10.1159/000543940","url":null,"abstract":"<p><strong>Introduction: </strong>Fatty acid-binding protein 4 (FABP4) is a novel adipokine that is critically involved in many inflammatory and immune diseases. However, the role of FABP4 in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) remains unclear. The current study aimed to investigate the role of FABP4 in patients with ANCA-GN.</p><p><strong>Methods: </strong>Plasma and urine samples from 37 patients with active ANCA-GN and kidney biopsy specimens from another group of 56 patients with ANCA-GN were collected. The plasma and urinary levels of FABP4 were measured by enzyme-linked immunosorbent assay and the kidney FABP4 expression was determined by immunohistochemistry and immunofluorescence staining. Associations between FABP4 levels with clinical and pathologic parameters were analyzed. To further elucidate the role of FABP4 in ANCA-GN, a novel FABP4 inhibitor, BMS309403, was employed in a recognized rat model of experimental autoimmune vasculitis (EAV).</p><p><strong>Results: </strong>Plasma and urinary levels of FABP4 in active ANCA-GN patients were significantly higher than those in normal controls {52.8 ± 23.6 ng/mL vs. 16.9 ± 8.8 ng/mL, <i>p</i> < 0.01; median 126.6 (interquartile range [IQR] 28.4-311.2) ng/g Cr vs. median 0.0 (IQR 0.0-0.0) ng/g Cr, <i>p</i> < 0.01, respectively}. Immunohistochemical analysis revealed higher glomerular and tubular expression of FABP4 in the kidneys of ANCA-GN patients than those in normal controls (0.015 ± 0.012 vs. 0.004 ± 0.003, <i>p</i> < 0.001; 0.053 ± 0.026 vs. 0.011 ± 0.010, <i>p</i> < 0.001, respectively). Moreover, for ANCA-GN patients, urinary FABP4 levels were significantly higher in active ANCA than those in remission (184.3 ± 187.0 ng/g Cr vs. 9.4 ± 23.9 ng/g Cr, <i>p</i> < 0.01). Correlation analysis showed that urinary levels of FABP4 correlated with serum creatinine (<i>r</i> = 0.596, <i>p</i> < 0.0001), urinary albumin/Cr (<i>r</i> = 0.523, <i>p</i> = 0.001), blood neutrophil ratio (<i>r</i> = 0.386, <i>p</i> = 0.018), PT (<i>r</i> = 0.583, <i>p</i> = 0.001), APTT (<i>r</i> = 0.364, <i>p</i> = 0.034), hemoglobin level (<i>r</i> = -0.398, <i>p</i> = 0.015), estimated glomerular filtration rate (<i>r</i> = -0.680, <i>p</i> < 0.0001), crescent proportion (<i>r</i> = 0.661, <i>p</i> = 0.032), and all-cause death of ANCA-GN patients (HR 2.93, 95% CI [1.05-8.19]). Furthermore, FABP4 inhibition by BMS309403 ameliorated renal injury in a rat mole of ANCA-GN.</p><p><strong>Conclusions: </strong>Urinary FABP4 levels might reflect the disease activity and renal involvement of ANCA-associated vasculitis, and FABP4 might act as a promising therapeutic target against ANCA-GN.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"11 1","pages":"75-89"},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular and Renal Outcomes with Ertugliflozin by Baseline Use of Renin-Angiotensin-Aldosterone System Inhibitors or Diuretics, Including Mineralocorticoid Receptor Antagonist: Analyses from the VERTIS CV Trial.","authors":"David Z I Cherney, Robert Frederich, Richard E Pratley, Francesco Cosentino, Samuel Dagogo-Jack, Annpey Pong, Ira Gantz, Nilo B Cater, James P Mancuso, Urszula Masiukiewicz, Christopher P Cannon","doi":"10.1159/000543162","DOIUrl":"https://doi.org/10.1159/000543162","url":null,"abstract":"<p><strong>Introduction: </strong>VERTIS CV was a placebo-controlled cardiovascular (CV) outcome trial evaluating the sodium-glucose cotransporter 2 inhibitor ertugliflozin in patients with type 2 diabetes and established atherosclerotic CV disease. The aim of the current analyses was to evaluate VERTIS CV cardiorenal outcomes according to baseline use of renin-angiotensin-aldosterone system (RAAS) inhibitors or diuretics, including mineralocorticoid receptor antagonists (MRAs).</p><p><strong>Methods: </strong>Participants received ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo once daily and were followed for a mean of 3.5 years. Prespecified CV and kidney outcomes were analyzed by Cox proportional hazard modeling in participant subgroups defined by baseline use of RAAS inhibitors (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) or diuretics (loop diuretics, non-loop diuretics, MRAs), with interaction testing to assess for treatment effect modification.</p><p><strong>Results: </strong>A total of 8,246 patients were randomized in VERTIS CV. At baseline, 6,686 (81%) participants were being treated with RAAS inhibitors, 3,542 (43%) with diuretics, 1,252 (15%) with loop diuretics, and 674 (8%) with MRAs. No significant interactions were observed for cardiorenal outcomes by baseline use of RAAS inhibitors or MRAs (<i>p</i> _interaction > 0.05 for all). Statistically significant interactions for a first event of hospitalization for heart failure (HHF) or CV death, and of HHF (alone), were observed with baseline use of diuretics, including loop diuretics, with an increased benefit of ertugliflozin treatment versus placebo.</p><p><strong>Conclusion: </strong>In VERTIS CV, baseline use of diuretics, particularly loop diuretics, identified a subgroup that demonstrated greater benefit with ertugliflozin on first HHF/CV death and HHF outcomes, with no modification of treatment effect observed with baseline use of RAAS inhibitors or MRAs. There was no evidence of treatment effect on the kidney composite outcomes by baseline use of RAAS inhibitors, diuretics, loop diuretics, or MRAs.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"11 1","pages":"63-74"},"PeriodicalIF":3.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}