American Journal of Nephrology最新文献

{"title":"Anti-PLA2R IgG4-to-IgG Ratio Helps Predict Remission of PLA2R-Associated Primary Membranous Nephropathy.","authors":"Yuting Liu, Zhenling Deng, Zihan Wang, Shang Gao, Tianyu Zheng, Danxia Zheng, Song Wang, Biao Huang, Yue Wang","doi":"10.1159/000547713","DOIUrl":"10.1159/000547713","url":null,"abstract":"<p><strong>Introduction: </strong>PLA2R-associated primary membranous nephropathy (PMN) was classified as IgG4-associated autoimmune disease, in which anti-PLA2R antibody is predominantly IgG4 subclass. Our objective was to explore the capability of anti-PLA2R IgG4-to-IgG ratio for predicting remission in PLA2R-associated PMN patients.</p><p><strong>Methods: </strong>A total of 143 patients with anti-PLA2R IgG ≥14 RU/mL were biopsy-confirmed as PLA2R-associated PMN. Serum samples collected at the time of renal biopsy were tested for anti-PLA2R IgG and anti-PLA2R IgG4 using time-resolved fluoroimmunoassay. The anti-PLA2R IgG4-to-IgG ratio was calculated as anti-PLA2R IgG4 (ng/mL) divided by anti-PLA2R IgG (RU/mL). Patients were divided into high-ratio and low-ratio groups by cutoff value of 31.5 ng/RU determined by the maximally selected log-rank statistic. The relationship between anti-PLA2R IgG4-to-IgG ratio and remission was analyzed using Cox proportional hazard regression.</p><p><strong>Results: </strong>Compared to the low-ratio group, patients in the high-ratio group were significantly younger (52 [40-60] vs. 58 [51-61] years, p = 0.035), had higher estimated glomerular filtration rate (102 [88-111] vs. 94 [72-100] mL/min/1.73 m2, p = 0.004), and obtained higher 6-month partial remission rates (64.6% vs. 30.0%, p = 0.001) and 1-year complete remission rates (38.3% vs. 7.7%, p = 0.003). The higher remission rates with high ratio remained in both moderate-low-risk and high-risk subgroups categorized according to KDIGO 2021 guidelines. The anti-PLA2R IgG4-to-IgG ratio had a significant positive relation with partial remission (hazard ratio [95% confidence interval] = 2.09 [1.27-3.46], p = 0.004), which also persisted across both risk subgroups. Kaplan-Meier survival curves confirmed the significantly higher possibility of partial remission in the high-ratio group.</p><p><strong>Conclusion: </strong>An elevated anti-PLA2R IgG4-to-IgG ratio may be a supplementary predictor for remission in PLA2R-associated PMN.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783211","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":"Vitamin D in Chronic Kidney Disease: Familiar Treatment, Unresolved Questions.","authors":"Alireza Zomorodian, Khashayar Sakhaee","doi":"10.1159/000547690","DOIUrl":"10.1159/000547690","url":null,"abstract":"","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-3"},"PeriodicalIF":3.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783212","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":"Longitudinal Impacts of Bariatric Surgery on eGFR in CKD Patients.","authors":"Siddharth S Madapoosi, Lindsey M Kornowske, Kenn B Daratha, Christina L Reynolds, Cami R Jones, Katherine R Tuttle, Laura H Mariani","doi":"10.1159/000547339","DOIUrl":"10.1159/000547339","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity is associated with chronic kidney disease (CKD) incidence and progression. We examined whether bariatric surgery is associated with change in eGFR trajectory among patients with and without CKD.</p><p><strong>Methods: </strong>Patients who underwent bariatric surgery at two health systems were identified using ICD-9/ICD-10 and CPT codes. Linear mixed models were fit on estimated glomerular filtration rate (eGFR) trajectory pre- and post-surgery among patients with or without CKD. Models were adjusted for age, sex, race, ethnicity, body mass index, hypertension, diabetes, follow-up duration, and type of bariatric surgery. Post-surgery, eGFR trajectory among patients with CKD was also compared following 1:2 propensity score matching to (1) patients without CKD who underwent surgery and (2) patients with CKD who did not undergo surgery.</p><p><strong>Results: </strong>Patients with CKD (n = 139) at Michigan Medicine had a slower annual rate of eGFR decline post-surgery compared to patients without CKD (n = 278) (1.54 [-2.26, -0.81] vs. 3.15 [-3.41, -2.87] mL/min/1.73 m2; p < 0.001), despite adjusting for degree of weight loss. Among patients with CKD, surgery was associated with a slower annual rate of eGFR decline (-0.20 [-0.83, 0.43] post-surgery vs. -1.11 [-1.37, -0.85] mL/min/1.73 m2 for non-surgery patients; p < 0.001). In an external validation study of patients with CKD in the Providence health system, bariatric surgery predicted an average increase in annualized eGFR slope by 1.19 [0.12, 2.25] mL/min/1.73 m2 (p = 0.03).</p><p><strong>Conclusion: </strong>Bariatric surgery is associated with less eGFR decline and may have weight-independent effects on preserving kidney function among persons living with obesity and CKD.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-11"},"PeriodicalIF":3.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706019","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":"Ertugliflozin Mitigates Renal Ischemia-Reperfusion Injury through the Downregulation of HIF-1α Expression.","authors":"Shan Li, Qimeng Wang, Mingming Wang, Rongyun Su, Yinghui Wang, Xiangchun Liu, Qingzhen Liu, Gang Liu","doi":"10.1159/000547539","DOIUrl":"10.1159/000547539","url":null,"abstract":"<p><strong>Introduction: </strong>Renal ischemia-reperfusion (I/R) injury can lead to acute kidney injury. SGLT-2 inhibitors, commonly used as hypoglycemic agents, have demonstrated the ability to mitigate cardiac I/R injury. Some studies have indicated that SGLT-2 inhibitors may safeguard renal tubular epithelial cells from damage caused by high glucose levels via mitochondrial mechanisms. SGLT-2 inhibitors alleviate renal hypoxia and cellular stress and enhance nutrient deprivation signaling. These combined effects may account for their inhibition of HIF-1α and activation of HIF-2α, which in turn leads to increased erythropoiesis, while also preventing organelle dysfunction, inflammation, and fibrosis. Our aim is to verify the efficacy of ertugliflozin in alleviating renal ischemia-reperfusion injury and to explore its potential protective mechanism.</p><p><strong>Methods: </strong>HK-2 cells were exposed to hypoxia for 16 h, followed by a 3 h re-oxygenation period (H16R3), with or without ertugliflozin treatment. The activity and phenotype of HK-2 cells were detected by using detection methods such as CCK-8 assay, mitochondrial membrane potential detection, flow cytometry, and protein electrophoresis. It was determined through cell immunofluorescence staining, RNA interference experiments, and gene overexpression transfection experiments that ertugliflozin alleviated H/R-induced HK-2 cell damage by inhibiting HIF-1α in the HIF-1α-iNOS-NO pathway. In in vivo experiments, the bilateral renal pedicles were occluded using a vascular clamp for 25 min to induce renal ischemia. After 24 h post-operation, the mouse was continuously administered ertugliflozin by gavage until the third day after the operation. The total duration of ertugliflozin administration was 8 days. Blood samples and kidney tissues of the mouse were collected. Qualitative and quantitative analyses of mouse histological specimens were conducted through experiments such as enzyme-linked immunosorbent assay, H&E staining, immunohistofluorescence staining, and immunohistochemical staining.</p><p><strong>Results: </strong>This study analyzed the effects of ertugliflozin on kidney I/R from both cellular and animal model perspectives. Transcriptome sequencing was used to screen the HIF-1 signaling pathway as the relevant signaling pathway through which ertugliflozin exerts its renal protective effect. RNA interference experiments and gene overexpression plasmid transfection experiments were conducted to clarify that ertugliflozin exerts corresponding renal protective effects in renal tubular epithelial cells and kidney I/R-induced renal injury through the HIF-1α site in the HIF-1α-Inos pathway.</p><p><strong>Conclusion: </strong>Our study provides compelling preliminary evidence that ertugliflozin may improve I/R-induced acute kidney injury by downregulating HIF-1α. This study provides some reference value for the treatment and management of renal I/R injury.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-22"},"PeriodicalIF":3.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706005","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":"Preeclampsia and Onset of Renal Disorders in the Long-Term Period following Pregnancy.","authors":"Sam Amar, Gilles Paradis, Aimina Ayoub, Antoine Lewin, Amanda Maniraho, Brian J Potter, Nathalie Auger","doi":"10.1159/000547538","DOIUrl":"10.1159/000547538","url":null,"abstract":"<p><strong>Introduction: </strong>Preeclampsia is associated with acute renal complications during pregnancy, but the risk of renal sequelae later in life is unclear. We determined if preeclampsia was associated with chronic renal complications in the long-term period following pregnancy.</p><p><strong>Methods: </strong>We conducted a longitudinal cohort study of 1,431,156 pregnant women in QC, Canada with 25,598,024 person-years of follow-up between 1989 and 2023. The main exposure measure was preeclampsia, and outcomes included hospitalization for vascular and nonvascular renal complications up to 34 years after pregnancy. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between preeclampsia and subsequent kidney complications using Cox regression models adjusted for patient characteristics.</p><p><strong>Results: </strong>Patients with preeclampsia had a higher hospitalization rate for renal complications than patients without preeclampsia (29.4 vs. 19.5 per 10,000 person-years). Preeclampsia was associated with 1.45 times the risk of hospitalization for renal disease during follow-up (95% CI 1.40-1.50). Risks were particularly elevated for renal vascular disease (HR 3.74, 95% CI 3.21-4.37), diabetic kidney disease (HR 3.71, 95% CI 3.18-4.32), and glomerulopathy (HR 3.44, 95% CI 2.92-4.05). Associations were also present with obstructive uropathy (HR 1.44, 95% CI 1.30-1.58). Severe forms of preeclampsia, including early onset preeclampsia (HR 1.90, 95% CI 1.72-2.10) and superimposed preeclampsia (HR 2.52, 95% CI 2.22-2.85), were strongly associated with subsequent renal morbidity.</p><p><strong>Conclusion: </strong>Preeclampsia, especially severe preeclampsia, is associated with the long-term risk of renal disease. Patients with preeclampsia may benefit from nephrological follow-up in the long-term period after pregnancy.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-9"},"PeriodicalIF":3.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681807","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":"The Role of Extracorporeal Therapy in Light Chain Cast Nephropathy.","authors":"Cihan Heybeli, Emanuele De Simone, Nelson Leung","doi":"10.1159/000547342","DOIUrl":"10.1159/000547342","url":null,"abstract":"<p><strong>Background: </strong>A comparison of the efficacy of different extracorporeal platforms in reducing free light chain levels in the setting of light chain cast nephropathy has not been discussed in detail.</p><p><strong>Summary: </strong>Recent advances in treating multiple myeloma have increased overall survival and brought a cure closer to reality. Kidney failure remains one of the most significant factors impacting survival, and the recovery of kidney function is crucial in this aspect. Light chain cast nephropathy is the most common subtype of kidney injury caused by toxic monoclonal proteins in myeloma patients and is closely related to the concentration of the involved serum-free light chain (sFLC). A fast decline in sFLC is associated with improved kidney recovery rates. Negative results in randomized controlled trials of extracorporeal therapies have not yet distracted clinicians from applying these options in light chain cast nephropathy due to the demonstrated efficiency of these modalities in sFLC removal compared to conventional dialytic therapies. This review summarizes the efficiency of sFLC reduction with available extracorporeal methods in patients with multiple myeloma and severe kidney failure when combined with anti-myeloma therapy.</p><p><strong>Key messages: </strong>Since achieving a hematologic response is crucial in light chain cast nephropathy, it appears tough to demonstrate the possible benefit of extracorporeal FLC removal in cast nephropathy in this setting. High-cutoff hemodialysis reduces serum FLC by about 90% after several sessions when combined with anti-myeloma therapy, albeit with albumin loss. Other options, such as medium cutoff hemodialysis and adsorptive methods, may provide a less efficient removal with lower loss of plasma proteins. The contribution of extracorporeal therapy to renal recovery is still unclear.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635976","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":"Efficacy and Safety of Tenapanor in Hemodialysis Patients with Hyperphosphatemia: A Systematic Review and Meta-Analysis of Short-Term Randomized Controlled Trials.","authors":"Laibah Arshad Khan, Bakhtawara Alam, Naresh Kumar Ladhwani, Hamna Abid, Zain Mazhar, Saim Umar Gondal, Jawria Tufail, Ahmed Zia, Syeda Zil E Zehra Naqvi, Muhammad Usama Saeed, Zain Ui Abideen, Vishaka Sahjwani, Om Kumar Lohana, Varoon Kumar, Saiyad Ali, Zainab Amjad","doi":"10.1159/000546265","DOIUrl":"10.1159/000546265","url":null,"abstract":"<p><strong>Introduction: </strong>Tenapanor is currently seen as a promising treatment for hyperphosphatemia in hemodialysis patients. Although previous meta-analysis has investigated its efficacy and safety, the potential impact of tenapanor remained a topic of further investigation. This meta-analysis aimed to provide an updated and thorough assessment of tenapanor efficacy in reducing serum phosphate levels and its safety in hemodialysis patients, integrating new evidence, and refining the analysis of treatment outcomes.</p><p><strong>Methods: </strong>In this systematic review and meta-analysis, we searched online databases up to August 2024 for studies evaluating the efficacy and safety of tenapanor in hemodialysis patients. Only short-term randomized controlled trials (4-8 weeks) comparing tenapanor with placebo were included. The primary outcome was the change in serum phosphate levels from baseline. Safety was assessed based on data regarding drug-related adverse effects (AEs), including diarrhea and other gastrointestinal AEs.</p><p><strong>Results: </strong>Among the selected 8 clinical trials with a total of 1,001 patients, tenapanor showed a significant reduction in serum phosphate levels from baseline compared to placebo (mean difference: -1.39 mg/dL; 95% confidence interval [CI]: -1.94, 0.84; p < 0.0001). A greater number of patients in the tenapanor group were able to achieve target serum phosphate levels of ≤5.5 mg/dL (relative risk: 2.80; 95% CI: 1.70, 4.61; p < 0.0001). Drug-related AEs, gastrointestinal AEs, and diarrhea were more severe in the tenapanor group compared to the placebo.</p><p><strong>Conclusion: </strong>In summary, the results indicate that tenapanor effectively lowers serum phosphate levels in hemodialysis patients and facilitates achievement of target levels, although drug-related side effects were common. However, these findings are based exclusively on short-term trials (4-8 weeks). Further long-term studies are needed to confirm the sustained efficacy and safety of tenapanor.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599101","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":"Circulating Proteins for Prediction of Kidney Disease Progression and Cardiovascular Outcomes: Individual Participant Data Meta-Analysis of Four Cohorts.","authors":"Carolina Lopez-Silva, Aditya Surapaneni, Josef Coresh, Teresa K Chen, Pascal Schlosser, Eugene P Rhee, Sushrut S Waikar, Insa M Schmidt, Rajat Deo, Peter Ganz, Ruth Dubin, Vasan S Ramachandran, Paul L Kimmel, Sarah J Schrauben, Chirag R Parikh, Joseph V Bonventre, Mirela Dobre, Panduranga S Rao, Ana C Ricardo, Matthew R Weir, Morgan E Grams","doi":"10.1159/000547138","DOIUrl":"10.1159/000547138","url":null,"abstract":"<p><strong>Introduction: </strong>KIM-1, TNFRSF1A, and TNFRSF1B have been accepted as early risk markers in diabetic kidney disease by the US Food and Drug Administration. Whether they may be useful in identifying high-risk patients for cardiovascular/kidney clinical trial enrollment in other important subgroups is uncertain.</p><p><strong>Methods: </strong>We evaluated the potential prognostic enrichment of KIM-1, TNFRSF1A, and TNFRSF1B in four cohorts: the Atherosclerosis Risk in Communities (ARIC) (N = 4,594, mean age 76 years, 55% women, mean eGFR 68 mL/min/1.73 m2), African American Study of Kidney Disease and Hypertension (AASK) (N = 705, mean age 55 years, 39% women, mean mGFR 46 mL/min/1.73 m2), Chronic Renal Insufficiency Cohort (CRIC) (N = 2,943, mean age 59 years, 45% women, mean eGFR 35 mL/min/1.73 m2), and Boston Kidney Biopsy Cohort (BKBC) (N = 434, mean age 54 years, 48% women, mean eGFR 51 mL/min/1.73 m2). We evaluated three outcomes: 40% glomerular filtration rate (GFR) decline, kidney failure, and incident cardiovascular disease (CVD) overall and in two subgroups historically underrepresented in clinical trials: participants with no diabetes, and those with albuminuria <200 mg/g.</p><p><strong>Results: </strong>Published models (40% decline tool, kidney failure risk equation, and PREVENT) using clinical variables had moderate to strong risk discrimination in each cohort: 40% GFR decline, AUROC range: 0.78-0.90; kidney failure, C-statistic range: 0.75-0.93; and CVD, C-statistic range: 0.59-0.79. After addition of biomarkers, there was a small but significant improvement in the meta-analyzed overall population: change in AUROC in 40% GFR decline: 0.02, p < 0.001; change in C-statistic for kidney failure: 0.01, p = 0.02; change in C-statistic for CVD: 0.01, p = 0.03. Among participants without diabetes, the change was statistically significant only for 40% decline; among patient with albuminuria <200 mg/g, the change was statistically significant only for the two kidney outcomes.</p><p><strong>Conclusion: </strong>KIM-1, TNFRSF1A, and TNFRSF1B may not be strong prognostic enrichment biomarkers over and above clinical risk estimates. Clinical trials should test whether they help with predictive enrichment.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526021","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":"Effects of Ferric Derisomaltose in Heart Failure with Iron Deficiency according to Renal Function in the IRONMAN Randomised Controlled Trial.","authors":"Fozia Z Ahmed, Paul R Kalra, John G F Cleland, Abdallah Al-Mohammad, Andrew L Clark, Victor K S Chong, Alan G Japp, Rebecca E Lane, Stephen J Leslie, Iain C Macdougall, Thuraia Nageh, Rajiv Sankaranarayanan, Jolanta Sobolewska, Aaron Wong, Elizabeth A Thomson, Mark C Petrie, Iain B Squire, Ian Ford, Philip A Kalra","doi":"10.1159/000547121","DOIUrl":"10.1159/000547121","url":null,"abstract":"<p><strong>Introduction: </strong>For heart failure (HF) with iron deficiency (ID), the benefits of intravenous iron might differ according to kidney function.</p><p><strong>Methods: </strong>IRONMAN was a randomised, open-label trial of intravenous ferric derisomaltose (FDI) versus usual care (UC) in patients with HF, left ventricular ejection fraction ≤45%, and ID (transferrin saturation <20% and/or ferritin <100 µg/L). The primary composite endpoint of recurrent hospitalisation for HF and cardiovascular (CV) death was lower in those assigned to FDI. Analysis according to baseline estimated glomerular filtration rate (eGFR) is now reported, with outcomes assessed in 3 categories of eGFR.</p><p><strong>Results: </strong>Of 1,137 patients randomised, eGFR was <45 mL/min/1.73 m2 for 435 (38%), 45-59 mL/min/1.73 m2 for 295 (26%), and ≥60 mL/min/1.73 m2 for 407 (36%). Patients with eGFR <45 mL/min/1.73 m2 were older and had more severe HF and more events. For the primary outcome, the primary endpoint rates per 100 patient-years for FDI versus UC across eGFR categories were 164 and 213 (rate ratio [RR]: 0.77 [95% CI: 0.57, 1.03]), 84 and 105 (RR: 0.79 [95% CI: 0.51, 1.22]), 88 and 93 (RR: 0.98 [95% CI: 0.62, 1.54]), respectively, but no statistically significant interaction between eGFR category and treatment effect was observed (p_interaction = 0.67). When eGFR was <45 mL/min/1.73 m2, FDI was associated with more favourable effects on Minnesota Living with Heart Failure score at 4 months (p < 0.001; p_interaction = 0.01 by eGFR class) and trends to greater reductions in first hospitalisation for HF or CV death (hazard ratio [HR]: 0.76 [95% CI: 0.58, 0.99]; p_interaction = 0.53) and first hospitalisation for myocardial infarction, stroke or HF, or CV death (HR: 0.71 [95% CI: 0.55, 0.92]; p_interaction = 0.29), although tests for interaction by eGFR class were not significant.</p><p><strong>Conclusion: </strong>For patients with HF and ID, those with eGFR <45 mL/min/1.73 m2 are more symptomatic, have worse outcomes, and might receive greater benefit from FDI. Analysis of other randomised trials, ideally an individual patient data meta-analysis, are required to confirm these findings.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526022","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":"Utility of Cardiac Biomarkers (N-Terminal Pro-B-Type Natriuretic Peptide and Hs-Troponin-T) in Predicting Mortality, Cardiovascular, and Renal Outcomes in Patients with Chronic Kidney Disease.","authors":"Senthil K Vasan, Rajkumar Chinnadurai, Sharmilee Rengarajan, Darren Green, Helen Alderson, Nicolas Vuilleumier, Philip A Kalra","doi":"10.1159/000546489","DOIUrl":"10.1159/000546489","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiac biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin-T (Hs-cTnT) are good prognostic indicators of long-term clinical cardiovascular outcomes in patients with chronic kidney disease (CKD). However, the clinical utility of combined biomarkers in predicting death and cardio-renal outcomes in patients with CKD remains unclear. This study examined the prognostic accuracy and incremental value of NT-proBNP and Hs-cTnT for all-cause mortality, major adverse cardiovascular event (MACE), and end-stage kidney disease (ESKD) in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients.</p><p><strong>Methods: </strong>Data from 1,946 individuals with NDD-CKD prospectively included in the Salford Kidney Study were used to investigate the associations between NT-proBNP and Hs-cTnT with study endpoints. Hazard ratio or sub-hazard ratio and 95% confidence intervals (95% CIs) were estimated using multivariate Cox-regression and competing risk models. The discriminatory power of NT-proBNP and Hs-cTnT along with kidney biomarkers (eGFR and uACR) and Framingham risk score (FRS) were calculated using Harrell's C-index. Endpoint-specific risk scores were generated using regression coefficients obtained in a training dataset and confirmed in a validation one.</p><p><strong>Results: </strong>During median follow-up of 71.5 months, 931 (47.8%) deaths, 553 (28.4%) MACE, and 554 (28.5%) ESKD events occurred. Baseline NT-proBNP and Hs-cTnT elevations were associated with significant increased risk of mortality, MACE, and ESKD independently of FRS. Combining NT-proBNP, Hs-cTnT, and FRS yielded the highest prognostic accuracy for all-cause mortality and MACE (respective C-statistics: 0.713; 95% CI: 0.695-0.731, and 0.697; 95% CI: 0.673-0.721), while combining NT-proBNP and Hs-cTnT with eGFR and uACR performed best at predicting ESKD (C-statistics: 0.821; 95% CI: 0.786-0.826).</p><p><strong>Conclusion: </strong>In NDD-CKD patients, NT-proBNP and Hs-cTnT are predictors of all-cause mortality, MACE, and ESKD, independently of eGFR and uACR. Combining NT-proBNP and Hs-cTnT with eGFR and uACR outperformed risk prediction for ESKD compared to kidney biomarkers used alone or in combination.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12324707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482841","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}