American Journal of Nephrology最新文献

{"title":"The \"Cardiovascular-Kidney-Metabolic\" Era in CKD Management: Integrated Risk Factor Control and Prognostic Benefits.","authors":"Zhiqiang Peng, Xiaowei Liang, Licong Su, Ziyang You, Liheng Zhu, Yaya Yang, Yu Wang, Dehui Liu, Min Liang","doi":"10.1159/000552163","DOIUrl":"10.1159/000552163","url":null,"abstract":"<p><strong>Introduction: </strong>The association between integrated management of metabolic risk factors, as proposed by the cardiovascular-kidney-metabolic syndrome concept, and cardiorenal outcomes in chronic kidney disease (CKD) patients is unclear; therefore, this study aimed to quantify this association, with a focus on specific risk factor combinations.</p><p><strong>Methods: </strong>This retrospective cohort study included 42,763 patients with CKD from the China Renal Data System (CRDS). The degree of joint risk factor management was assessed based on 4 metabolic risk factors, namely, blood pressure, glucose, low-density lipoprotein cholesterol, and body mass index (BMI). The association between cardiorenal outcomes and the degree of risk factor control or specific risk combinations was assessed using Cox proportional hazards models up to 64,699.25 person-years of follow-up.</p><p><strong>Results: </strong>In CKD patients, the degree of risk factor management demonstrated a dose-dependent association with lower risks of cardiovascular disease (CVD) events and CKD progression. Patients achieving management of all risk factors had significantly reduced HRs for CVD (0.69; 95% CI: 0.61-0.79) and CKD progression (0.79; 95% CI: 0.69-0.89) versus those with no management. The most protective combinations were blood pressure, glucose, and BMI management for CVD events (HR: 0.66; 95% CI: 0.57-0.77) and CKD progression (HR: 0.78; 95% CI: 0.69-0.89).</p><p><strong>Conclusions: </strong>In this large CKD cohort, achieving simultaneous control of blood pressure, glucose, and BMI was associated with the greatest reduction in both cardiovascular and kidney outcomes, supporting integrated multi-target management within the CKM syndrome framework.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-11"},"PeriodicalIF":3.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lower Risk of Acute Kidney Injury in Hospitalized Patients Treated with SGLT-2 Inhibitors: A Retrospective Matched Cohort Study.","authors":"Dion Gabriël Lodewijk de Martines, Kenan Hasan Ali Aydinoglu, Christina Gant, Ytzen Westra, Kim de Jong, Aaltje Ymkje Adema","doi":"10.1159/000551925","DOIUrl":"10.1159/000551925","url":null,"abstract":"<p><strong>Introduction: </strong>Recent studies have shown possible protective effects of sodium-glucose co-transporter-2 inhibitors (SGLT-2is) for acute kidney injury (AKI). As SGLT-2is have diuretic properties, uncertainty remains regarding their effect on the risk of AKI during hospital admission, where hypovolemia frequently occurs. Therefore, we assessed the association between (pre)hospital treatment with SGLT-2i and AKI risk in hospitalized patients.</p><p><strong>Methods: </strong>We performed a matched cohort study. We identified hospitalized patients with prehospital use of SGLT-2i in the Frisius Medical Centre Leeuwarden, between October 21, 2021, and February 12, 2024. These were matched 1:1 to hospitalized patients without prehospital use of SGLT-2i. AKI incidence was the main outcome. Second, SGLT-2i treatment during hospitalization was assessed.</p><p><strong>Results: </strong>Overall,1,054 hospital admissions were included, 527 with and 527 without prehospital SGLT-2i use. Overall, 34% of patients were women; the median age was 71 years (IQR 65-78). SGLT-2i was indicated for heart failure in 16%, chronic kidney disease 6%, type 2 diabetes 7%, and at least two indications in 72%. Hospital-acquired AKIs occurred in 17.5% admissions with prehospital SGLT-2i treatment and 25.8% among those without (RR = 0.68 [95% CI = 0.53-0.86]). AKI risk was similarly decreased in patients continuing SGLT-2i during hospital admission (RR 0.65 [0.49-0.85]). AKI was associated with increased length of hospital stay (median 7 days, IQR 4-11, versus 3 days, IQR 1-7 without AKI); SGLT-2i use was not. Overall, SGLT-2i treatment did not affect overall mortality. In patients with AKI, mortality was numerically lower in SGLT-2i patients (risk difference = 7.8%, 95% CI -0.9-15.7%), although the confidence interval includes zero.</p><p><strong>Conclusion: </strong>We observed a 32% lower risk of AKI in hospitalized patients using SGLT-2i at admission. This suggest a protective effect of SGLT-2i against AKI, which remained when SGLT-2i was continued during hospitalization.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-10"},"PeriodicalIF":3.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mineralocorticoid Receptor Antagonists in Dialysis.","authors":"Elias John Elenjickal, Thomas A Mavrakanas","doi":"10.1159/000551881","DOIUrl":"10.1159/000551881","url":null,"abstract":"<p><strong>Background: </strong>Aldosterone regulates genes controlling fluid and electrolyte balance through mineralocorticoid receptor (MR) activation. Sustained MR activation promotes inflammation, fibrosis, sodium retention, and myocardial remodeling. MR antagonists (MRAs) block aldosterone binding in the kidney, heart, and vasculature and are classified as steroidal or nonsteroidal. Although large, randomized trials have confirmed the benefits of steroidal MRAs in heart failure and of finerenone in diabetic kidney disease, these pivotal studies systematically excluded patients with kidney failure receiving dialysis. Over the past decade, several phase 2 and 3 trials have evaluated MRAs in dialysis, yielding heterogeneous and sometimes conflicting results. This review summarizes the biological rationale, evolving clinical evidence, and future directions for MR blockade in dialysis.</p><p><strong>Summary: </strong>Pharmacokinetic studies indicate that spironolactone and eplerenone are highly protein-bound, hepatically metabolized, and not dialyzable, supporting cautious use in dialysis with potassium monitoring. Early randomized trials from East Asia suggested potential cardiovascular benefit with spironolactone 25 mg daily; however, these studies were underpowered and reported relatively few outcome events. More definitive evidence is now available from two large multicenter randomized controlled trials. In ALCHEMIST (n = 644), spironolactone 25 mg daily did not reduce major adverse cardiovascular events compared with placebo over a median follow-up of 2.7 years [hazard ratio (HR) 1.00, 95% confidence interval (CI) 0.73-1.36]. Similarly, in ACHIEVE (n = 2,538), spironolactone failed to reduce the composite of cardiovascular death or hospitalization for heart failure (HR 0.92, 95% CI: 0.78-1.09) over 1.8 years and was associated with higher rates of hyperkalemia. A contemporary meta-analysis incorporating these trials confirmed neutral efficacy but higher rates of asymptomatic hyperkalemia and gynecomastia.</p><p><strong>Key messages: </strong>Current evidence indicates that steroidal MRAs confer no cardiovascular or survival benefit in maintenance dialysis and modestly increase the risk of hyperkalemia and endocrine adverse effects.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-19"},"PeriodicalIF":3.8,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potentially Modifiable Factors Associated with Longitudinal Health-Related Quality of Life in the National Unified Renal Translational Research Enterprise Chronic Kidney Disease (NURTuRE-CKD) Cohort.","authors":"Thomas Phillips, Scott Harris, Olalekan Lee Aiyegbusi, Melissa Benavente, Paul Cockwell, Philip A Kalra, Paul J Roderick, David C Wheeler, Maarten W Taal, Simon D S Fraser","doi":"10.1159/000551177","DOIUrl":"10.1159/000551177","url":null,"abstract":"<p><strong>Introduction: </strong>People with non-dialysis-dependent chronic kidney disease (NDD-CKD) experience worse health-related quality of life (HRQoL) than those without. This study hypothesised that potentially modifiable factors affecting longitudinal HRQoL in an NDD-CKD cohort could be identified as potential therapeutic targets for improving HRQoL outcomes.</p><p><strong>Methods: </strong>The NURTuRE-CKD cohort study recruited 2,996 participants with NDD-CKD from UK nephrology centres from 2017. Sociodemographic, medical history, medication, anthropometric, biomarker, and patient-reported outcome measure data were collected at baseline and first follow-up. HRQoL was measured at the second follow-up. The primary outcome was HRQoL measured by EuroQoL 5-dimension 5 level (EQ-5D-5L), mapped to EQ-5D-3L index value, and visual analogue score (VAS). Multivariable mixed effects linear regression models were adjusted and fit to examine the effect of potentially modifiable factors at baseline on the longitudinal EQ-5D-3L index value. Similar models were also fit to assess the effects of change in these factors across follow-up on the index value and VAS.</p><p><strong>Results: </strong>In total, 2,062 participants (68.8%) attended the first follow-up, and 1,019 (34.0%) the second follow-up. EQ-5D-5L responses worsened over time for the index value, VAS and in each dimension. Baseline factors independently associated with worse longitudinal HRQoL were obesity, smoking, sarcopenia, pain, breathlessness, weakness, anxiety, depression, and raised parathyroid hormone, whereas renin-angiotensin system inhibitor use at baseline was associated with improved HRQoL. The status of factors across follow-up, such as persistent obesity, new sarcopenia, increasing phosphate, new and persistent anxiety and depression, and worsening pain, were associated with worse HRQoL, whereas improved acidosis, improved pain and weakness were associated with improved HRQoL.</p><p><strong>Conclusion: </strong>Several potentially modifiable factors are independently associated with HRQoL, and NDD-CKD interventions should consider these as therapeutic targets, as well as part of holistic CKD care.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-18"},"PeriodicalIF":3.2,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Finerenone Treatment Discontinuation on Kidney and Cardiovascular Outcomes: A Fidelity Analysis.","authors":"Ajay K Singh, Stefan D Anker, Bertram Pitt, Peter Rossing, Luis M Ruilope, Christiane Ahlers, Youssef M K Farag, Marc Lambelet, Meike Brinker, Katja Rohwedder, Zihe Zheng, Gerasimos Filippatos","doi":"10.1159/000549873","DOIUrl":"10.1159/000549873","url":null,"abstract":"<p><strong>Introduction: </strong>Finerenone reduced the risk of heart and kidney events in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in FIDELITY, a prespecified pooled analysis combining data from the phase III FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049) trials. This FIDELITY analysis aimed to identify and assess key predictors of finerenone discontinuation and evaluate the impact of discontinuation on its efficacy in people with CKD and T2D.</p><p><strong>Methods: </strong>Adults with CKD (urine albumin-to-creatinine ratio 30-≤5,000 mg/g, estimated glomerular filtration rate [eGFR] ≥25 mL/min/1.73 m2) and T2D on optimized renin-angiotensin system inhibition were randomized 1:1 to finerenone or placebo. Baseline characteristics were identified and assessed as predictors of treatment discontinuation using a multivariate Cox proportional hazards model. Stratified Cox models with treatment discontinuation as a time-varying covariate were used to assess the effect of treatment discontinuation on composite kidney and cardiovascular (CV) outcomes (kidney: kidney failure, sustained ≥57% eGFR decrease from baseline over at least 4 weeks, or kidney-related death; CV: CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure).</p><p><strong>Results: </strong>Among 12,990 participants included in the analysis, 22.8% and 21.6% prematurely discontinued treatment in the finerenone and placebo arms, respectively. Advanced age, White/Black race, lower eGFR, higher urine albumin-to-creatinine ratio, and higher serum potassium at baseline were identified as predictors of finerenone discontinuation. Crude event rates per 100 patient-years for the composite kidney and CV outcomes were lower with finerenone versus placebo under treatment (kidney: 1.09 vs. 1.71; CV: 2.98 vs. 3.78) as well as after discontinuation (kidney: 11.95 vs. 13.67; CV: 14.07 vs. 14.73). The effect of finerenone on composite kidney and CV outcomes appeared to be reduced after discontinuation (hazard ratio [HR] = 0.82; 95% confidence interval [CI] 0.66-1.02; HR = 0.93; 95% CI: 0.79-1.09, respectively) versus the time on-treatment (HR = 0.65; 95% CI: 0.54-0.78; p_interaction = 0.0959; HR = 0.79; 95% CI: 0.70-0.88; p_interaction = 0.0960, respectively).</p><p><strong>Conclusion: </strong>In FIDELITY, treatment discontinuation rates were similar in the finerenone and placebo arms. Finerenone demonstrated numerically higher kidney and CV benefits during treatment versus after discontinuation.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-12"},"PeriodicalIF":3.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When KDIGO Meets Frailty: Rethinking Chronic Kidney Disease Targets in Adults Aged 80 Years and Older.","authors":"Carmine Zoccali, Mehmet Kanbay, Andrzej Wiecek, Francesca Mallamaci","doi":"10.1159/000551636","DOIUrl":"10.1159/000551636","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) is highly prevalent in very old adults and frequently coexists with frailty, multimorbidity, and limited life expectancy. In this population, the risk-benefit balance of standard KDIGO-style treatment targets for blood pressure, glycemic control, albuminuria, lipid management, anemia, and CKD-mineral and bone disorder is fundamentally altered. The clinical trials underpinning these recommendations enrolled few very old patients and virtually no frail octogenarians or nonagenarians, so the evidence base is poorly aligned with the realities of advanced age.</p><p><strong>Summary: </strong>This narrative review examines CKD progression in frail very old adults, with particular attention to frailty, geriatric syndromes, and competing risks of end-stage kidney disease and death. It then proposes a pragmatic framework to adapt KDIGO-style targets by incorporating frailty assessment, life expectancy, and patient goals of care into therapeutic decisions. For each major treatment domain, the discussion moves from abstract targets to clinically meaningful, individualized ranges, emphasizing treatment simplification, systematic deprescribing, and preservation of physical and cognitive function as primary outcomes.</p><p><strong>Key messages: </strong>The review identifies urgent research priorities, including trials that intentionally enroll frail older adults, evaluations of deprescribing strategies, and studies comparing conservative kidney management with dialysis in this highly vulnerable and rapidly growing patient group.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proenkephalin for Cardiovascular and All-Cause Mortality: The REasons for Geographic and Racial Differences in Stroke Study (REGARDS) Study.","authors":"Ryan N Pavlovich, Mary Cushman, Suzanne E Judd, Virginia J Howard, Monika M Safford, Alexander L Bullen, Nicholas Wettersten","doi":"10.1159/000549907","DOIUrl":"10.1159/000549907","url":null,"abstract":"<p><strong>Introduction: </strong>Individuals with kidney dysfunction have greater risk of mortality, especially cardiovascular mortality, but current markers of kidney function, including estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), may not adequately capture this risk. Proenkephalin (PENK) is an emerging biomarker reflecting kidney glomerular function. We evaluated the association of PENK with all-cause and cardiovascular mortality in The REasons for Geographic and Racial Disparities in Stroke (REGARDS) cohort study and whether associations varied by sex and race.</p><p><strong>Methods: </strong>PENK was measured in 1,021 Black and White participants randomly sampled from REGARDS. We evaluated the association of PENK with all-cause and cardiovascular mortality in nested multivariable Cox proportional hazard models adjusting for confounders including UACR and eGFR calculated using the 2021 CKD-EPI combined creatinine-cystatin C race-free equation. Effect modification by sex and race was tested.</p><p><strong>Results: </strong>Mean age was 67 years, 50% were women, 50% were Black, mean eGFR was 82 mL/min/1.73 m2 and median UACR was 7.7 mg/g. There were 471 deaths and 142 cardiovascular deaths over a median follow-up of 11.6 years. When adjusting for comorbidities and UACR, each doubling of PENK was associated with higher risk of death (HR 1.22, 95% confidence interval [CI] 1.00-1.48, p = 0.05) but this association was not significant after adjusting for eGFR (HR 0.85, 95% CI: 0.65-1.10, p = 0.85). There was a significant interaction by sex (p-interaction = 0.004) with higher PENK levels associated with lower mortality in women. PENK was associated with cardiovascular mortality after adjusting for comorbidities and UACR (HR 1.70, 95% CI: 1.20-2.42, p = 0.004), but this was not significant when adjusting for eGFR (HR 1.36, 95% CI: 0.84-2.21, p = 0.20). There was no significant interaction by sex or race.</p><p><strong>Conclusion: </strong>PENK does not provide additional risk stratification for all-cause and cardiovascular mortality beyond current biomarker measures of eGFR.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-15"},"PeriodicalIF":3.8,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13068383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-Inducible Factor-1α Drives Cellular Senescence via Autophagy Activation to Promote Acute Kidney Injury-to-CKD Transition.","authors":"Manzhu Zhang, Lingxu Li, Xinyue Mao, Xiaoying Yun, Meiting Wu, Chang Wang, Bing Li","doi":"10.1159/000551542","DOIUrl":"10.1159/000551542","url":null,"abstract":"<p><strong>Introduction: </strong>Ischemia and hypoxia are central drivers of acute kidney injury (AKI), and hypoxia-inducible factor (HIF) is a key regulator of cellular oxygen homeostasis. Our previous study showed that HIF-1α is protective during the early stage of AKI; however, its role in the transition from AKI to chronic kidney disease (CKD) remains unclear. Cellular senescence has been implicated in CKD progression and can be accelerated by hypoxia. Nevertheless, whether HIF-1α signaling mediates cellular senescence and promotes the AKI-to-CKD transition is poorly understood.</p><p><strong>Methods: </strong>Ischemia-reperfusion injury models of AKI with adaptive repair (AR) or maladaptive repair (MAR) were used to examine the dynamics of HIF-1α, cellular senescence, and autophagy. In human renal proximal tubular epithelial cells (HK-2), a hypoxia/reoxygenation (H/R) injury model was used to evaluate the relationships among HIF-1α, autophagy, and senescence. Finally, the association between HIF-1α levels and cellular senescence was assessed in renal biopsies from CKD patients.</p><p><strong>Results: </strong>The AR group exhibited rapid and sufficient HIF-1α expression, accompanied by acute senescence, with HIF-1α levels returning to baseline upon the completion of repair. In contrast, the MAR group showed delayed and sustained HIF-1α activation, driving chronic senescence and progressive fibrosis. The activation of autophagy was closely associated with the expression of HIF-1α in the AR and MAR groups. In vitro, silencing HIF-1α expression attenuated autophagy activity, senescence, and fibrosis in HK-2 cells under H/R. However, HIF-1α overexpression had the opposite effect. The autophagy activator rapamycin reversed the inhibitory effects of HIF-1α knockdown, whereas the autophagy inhibitor bafilomycin A1 diminished the pro-senescent and pro-fibrotic effects of HIF-1α overexpression. Analysis of CKD patient biopsies confirmed elevated HIF-1α expression, which correlated with reduced eGFR, increased fibrosis, and enhanced cellular senescence.</p><p><strong>Conclusion: </strong>Adequate HIF-1α activation during early AKI is associated with acute senescence and renal repair, whereas sustained HIF-1α drives chronic senescence via persistent autophagy activation and may contribute to the AKI-to-CKD transition.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-25"},"PeriodicalIF":3.8,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13167096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Efficacy and Safety of Enarodustat for the Treatment of Anemia in Hemodialysis-Dependent Chronic Kidney Disease Patients: A Phase 3, Multicenter, Randomized, Active-Comparator (Recombinant Human Erythropoietin), Open-Label Study - The ENARODIAL Study.","authors":"Haishan Wu, Zhen Ai, Aiying Liu, Hong Ye, Changyou Sun, Aicheng Yang, Wenli Chen, Zhihua Zheng, Caili Wang, Yuehong Li, Ning Cao, Cheng Wang, Yuou Xia, Hong Cheng, Ping Luo, Qiongqiong Yang, Yuehong Yan, Hua Zhou, Nan Mao, Zibo Xiong, Bicheng Liu, Daqing Hong, Qingping Chen, Bo Liang, Qun Luo, Yu Wang, Yongjun Shi, Xiaonong Chen, Li Zhou, Tiekun Yan, Bin Zhu, Jianwen Wang, Menghua Chen, Yongjun Zhu, Tianjun Guan, Song Wang, Shengmei Mu, Yuanyuan Chen, Xiaojuan Lian, Zichen Liu, Yuanwen Xu, Wei Chen","doi":"10.1159/000550548","DOIUrl":"10.1159/000550548","url":null,"abstract":"<p><strong>Introduction: </strong>Enarodustat is an oral HIF-PHI for the treatment of chronic kidney disease anemia.</p><p><strong>Methods: </strong>This phase 3, multicenter, randomized 24-week study assessed enarodustat's noninferiority to rHuEPO for treating hemodialysis-dependent CKD (HD-CKD) anemia. Overall, 100 ESAs-treated patients were randomized 1:1 to enarodustat or rHuEPO for a 24-week treatment with dose adjustment every 4 weeks to maintain hemoglobin (Hb) within target range 100-120 g/L. The primary efficacy endpoint was the between-group difference in mean Hb over weeks 20-24 (evaluation period [noninferiority margin: -10 g/L]). Safety was assessed by treatment-emergent adverse events (TEAEs).</p><p><strong>Results: </strong>Of the 100 patients treated (enarodustat: 50; rHuEPO: 50), 93 completed the study. Demographic and baseline characteristics were comparable. During the evaluation period, the mean Hb level was 106.81 g/L in the enarodustat group and 99.68 g/L in the rHuEPO group. Enarodustat was noninferior to rHuEPO (least squares mean difference: 7.47 g/L [95% confidence interval: 4.17, 10.78]; p < 0.001). The mean Hb level in the enarodustat group remained within the target range throughout the treatment period, with a maintenance rate of 79.6% during weeks 20-24 versus 51.0% for rHuEPO. After switching from ESAs, the enarodustat group showed increased total iron-binding capacity, transferrin, and serum iron, decreased hepcidin by week 4, and increased RET% by week 2. TEAEs incidences were comparable (enarodustat: 90.0%, rHuEPO: 90.0%), with no additional safety concerns for enarodustat.</p><p><strong>Conclusions: </strong>Enarodustat was noninferior to rHuEPO for the treatment of anemia in HD-CKD patients, with good safety and tolerability over 24 weeks.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-12"},"PeriodicalIF":3.8,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13082764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Calciprotein Particle Maturation Time with Echocardiographic Measures in the CRIC Study.","authors":"Ashwin Sunderraj, Xuan Cai, Andreas Pasch, Matthew Feinstein, Rupal Mehta, Anand Srivastava, Ana C Ricardo, Debbie L Cohen, Tamara Isakova","doi":"10.1159/000550442","DOIUrl":"10.1159/000550442","url":null,"abstract":"<p><strong>Introduction: </strong>Vascular calcification is common in chronic kidney disease (CKD) and is associated with adverse cardiac outcomes. We investigated the relationship of T50, a measure of mineral stress that is associated with vascular calcification, with left ventricular (LV) echocardiographic abnormalities among patients with CKD in the Chronic Renal Insufficiency Cohort (CRIC).</p><p><strong>Methods: </strong>Linear regression models were used to examine the cross-sectional associations of T50 with LV mass index, and multinomial logistic regression models were used to analyze the cross-sectional associations of T50 with echocardiographic evidence of LV concentric remodeling, LV concentric hypertrophy, and LV eccentric hypertrophy. Multivariable models are adjusted for age, sex, race/ethnicity, clinical site, systolic blood pressure, body mass index, diabetes, smoking, history of cardiovascular disease, estimated glomerular filtration rate, and 24-h urinary protein.</p><p><strong>Results: </strong>Among 2,280 participants, mean age was 59 years and 47.0% were female; 28.5% showed evidence of LV concentric remodeling, 15.0% showed evidence of LV eccentric hypertrophy, and 36.3% showed evidence of LV concentric hypertrophy. In unadjusted model, each 1 standard deviation (1-SD) lower of T50 was associated with greater odds for eccentric hypertrophy and concentric hypertrophy. After sequential adjustment for demographics, clinical factors, and kidney function measures, these associations were lost for eccentric hypertrophy (OR per 1-SD lower: 1.09; 95% CI: 0.92-1.29) and concentric hypertrophy (OR per 1-SD lower: 1.05; 95% CI: 0.91-1.21). In the unadjusted model, each 1-SD lower of T50 was associated with increased LV mass index; this association was lost in the multivariable-adjusted model (β = 0.33; 95% CI: -0.63 to 1.28). Similar findings were observed when T50 was examined in quartiles.</p><p><strong>Conclusion: </strong>Among the CRIC cohort, T50 was not associated with LV concentric remodeling, LV eccentric hypertrophy, or LV concentric hypertrophy after multivariable adjustment that included measures of kidney function.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-10"},"PeriodicalIF":3.8,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}