American Journal of Nephrology最新文献

{"title":"Intradialytic Exercise Interventions to Enhance Physical Activity Levels in Hemodialysis Patients: A Systematic Review and Meta-analysis.","authors":"Siran Zhao, Gaoting Zhong, Aili Lv, Yuxiu Tao, Hongbao Liu, Honghong Lv, Zhonghui Zhai, Yang Li, Yan Hua, Yanqing Kang, Ya Zhang, Mei Huang, Chunping Ni","doi":"10.1159/000548114","DOIUrl":"https://doi.org/10.1159/000548114","url":null,"abstract":"<p><strong>Introduction: </strong>Physical activity levels in hemodialysis patients are low and continue to decline, increasing mortality risk. Intradialytic exercise improves hemodialysis patients' quality of life and enhances their physical and psychological health. But, existing reviews fail to provide the best evidence for enhancing physical activity levels in this population. This study is to examine the efficacy and safety of intradialytic exercise for hemodialysis patients.</p><p><strong>Methods: </strong>MEDLINE, EMBASE, the Cochrane Library CINAHL, Web of Science, PubMed, Wan Fang data, and SinoMed were searched up to March 2025. The reference lists of eligible studies were systematically checked to ensure comprehensive coverage of the relevant literature. Two independent reviewers searched the databases, selected trials, conducted a bias assessment, and extracted the data. Meta-analysis was conducted using Review Manager Version 5.4.1.</p><p><strong>Results: </strong>Of the 3880 studies that were screened, 23 studies involving 1114 patients were identified. Three types of exercise, seven exercise durations, and four exercise intensity standards were compared, and physical activity level, VO2 peak, muscle strength, and muscle mass were reported. Statistically, in terms of exercise type, combined aerobic and resistance exercise improved physical activity levels (SMD=0.99, 95% CI: 0.44 to 1.55) and VO2 peak (SMD=1.01, 95% CI: 0.56 to 1.46). Meanwhile, resistance exercise significantly improved muscle strength (SMD=0.52, 95% CI: 0.24 to 0.81). In terms of exercise intensity, moderate exercise intensity significantly improved Physical activity levels (SMD=0.55, 95% CI: 0.22 to 0.88), VO2 peak (SMD=0.59, 95% CI: 0.12 to 1.07), and muscle strength (SMD=0.37, 95% CI: 0.11 to 0.63). Additionally, higher-intensity exercise also significantly improved muscle strength (SMD=1.02, 95% CI: 0.51 to 1.53). As for exercise duration, programs lasting up to 3 months positively impacted Physical activity levels (SMD = 0.65, 95% CI: 0.17 to 1.13) and VO2 peak (SMD = 0.70, 95% CI: 0.19 to 1.21). Furthermore, exercise extending up to 6 months significantly improved muscle strength in hemodialysis patients (SMD = 0.41, 95% CI: 0.18 to 0.64).</p><p><strong>Conclusion: </strong>Evidence shows that intradialytic exercise intervention improves physical activity levels, VO2 peak, and muscle strength in hemodialysis patients. Future clinical intervention studies could conduct direct comparisons of protocols with different exercise modalities, intensities, and durations.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-35"},"PeriodicalIF":3.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172198","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":"NEK10 Drives Lipid Disturbances that Induce G2/M Phase Arrest in Renal Tubular Cells Under Albumin Overload.","authors":"Pingan Wang, Ting Liu, Minna Liu, Yangjie Dang, Junming Zhang, Yukun Gan, Mengxue Zhu, Yue Zhang, Qi Wei, Limin Liu","doi":"10.1159/000547768","DOIUrl":"https://doi.org/10.1159/000547768","url":null,"abstract":"<p><p>Albuminuria is a recognized independent risk factor for renal interstitial fibrosis and may induce G2/M phase arrest in proximal tubular epithelial cells (PTECs). Although protein overload disrupts fatty acid metabolism, the mechanistic link to cell cycle arrest remains unclear. This study investigates the role of NIMA-related kinase 10 (NEK10), a serine/threonine kinase implicated in cell cycle regulation, in mediating albumin-induced lipid dysregulation and G2/M arrest, which exacerbate tubulointerstitial fibrosis (TIF). Human renal tubular cells (HK-2) exposed to 10 mg/mL bovine serum albumin (BSA) for 24 - 48 hours exhibited lipid droplet accumulation, reduced ATP levels, impaired fatty acid oxidation, and increased G2/M phase arrest. These effects coincided with upregulated NEK10 expression and ERK1/2 phosphorylation. In vivo, NEK10 knockdown via recombinant adenovirus (rAAV-shNEK10) in unilateral ureteral obstruction (UUO) mice attenuated BSA-induced renal fibrosis, lipid accumulation, and tubular injury. Clinically, immunohistochemical analysis of kidney biopsies from chronic kidney disease (CKD) patients revealed elevated NEK10 expression, correlating with urinary protein levels (>3.5 g/24 h) and interstitial fibrosis. Our findings identify NEK10 as a critical regulator of albumin-induced metabolic dysfunction and cell cycle arrest, suggesting therapeutic targeting of NEK10 may mitigate fibrosis in proteinuric kidney diseases.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-29"},"PeriodicalIF":3.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038910","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":"Impact of Preexisting Intracranial Aneurysm on Incidence and Risk of De Novo Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease -Observational Study.","authors":"Satoshi Miyamoto, Shuhei Egashira, Jun Isozaki, Daiichiro Ishigami, Akinari Sekine, Naoki Sawa, Tatsuya Suwabe, Yoshifumi Ubara, Takehiko Wada, Wataro Tsuruta","doi":"10.1159/000548190","DOIUrl":"https://doi.org/10.1159/000548190","url":null,"abstract":"<p><p>Introduction Autosomal dominant polycystic kidney disease (ADPKD) has an elevated prevalence of intracranial aneurysms compared to the general population. However, the risk of de novo aneurysm formation in these patients remains unclear, leading to a lack of consensus regarding whom and when to follow. Although the data from general population tend to be referred, this assumption needs caution because patients with ADPKD have different characteristics such as location tendency, aneurysm size at rupture, and gene mutation. Here, we investigate the incidence of de novo aneurysm in ADPKD patients to examine whether patients without intracranial aneurysms on initial imaging needs frequent follow-up. Methods This is a retrospective cohort study conducted in two ADPKD referral centers in Japan. Consecutive samples of 2,117 adult patients with ADPKD from April 2003 to October 2024 were eligible. Of these, 850 patients without baseline brain imaging and 555 patients without follow-up brain imaging were excluded, leaving 712 patients included in this study. Patients were divided into two groups according to the presence of intracranial aneurysm on the initial image. The primary outcome was the incidence of de novo aneurysm formation during follow-up. Kaplan-Meier analysis and Cox proportional hazards models were used to estimate risk, adjusting for age, sex, hypertension, smoking history, and family history of subarachnoid hemorrhage or aneurysm. Results Of 712 patients, 181 had intracranial aneurysms on initial imaging (screening-positive) and 531 had none (screening-negative). The median age was 54 years (IQR, 45-62 years), and 398 (55.8%) were women. Over 4,580 person-years of follow-up, the overall incidence of de novo aneurysm formation was higher in the screening-positive group (1.2 per 100 person-years), than in the screening-negative group (0.26 per 100 person-years) (HR, 3.81; 95%CI, 1.50-9.67, p = 0.005). Conclusion ADPKD patients without preexisting aneurysms on initial imaging are at relatively low risk of developing de novo aneurysms. Our findings help to determine the adequate follow-up timing and its target in patients with ADPKD. However, caution is warranted in generalizing these results because the study population had a higher median age and more advanced kidney disease.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038920","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":"Plasma IL-22 predicts progression of early diabetic kidney disease.","authors":"Beatriz Fernandez-Fernandez, Takehiro Hasegawa, Yuko Saruta, Yun Li Guan, Ana Belen Sanz, Maria Dolores Sanchez-Niño, Adrian M Ramos, Jinny Sanchez-Rodriguez, Juan Francisco Navarro-Gonzalez, Alberto Ortiz","doi":"10.1159/000547738","DOIUrl":"https://doi.org/10.1159/000547738","url":null,"abstract":"<p><strong>Introduction: </strong>The residual risk of chronic kidney disease (CKD) progression remains high in clinical trials of kidney protective drugs in patients with diabetic kidney disease (DKD).</p><p><strong>Methods: </strong>In a prospective study, we assessed whether 16 plasma and 10 urine cytokine levels can inform the residual risk of CKD progression in 93 incident patients with DKD treated by Nephrology according to clinical guidelines.</p><p><strong>Results: </strong>Plasma and urine levels of 12 plasma and 7 urinary cytokines differed between patients with DKD and from healthy controls. Participants were categorized into CKD G1-G2 (preserved GFR) and CKD G3-G5 (GFR <60 ml/min/1.73 m2). After a median of 7.27 years (IQR; 5.34-9.56), 13/40 (32.5%) patients with CKD G1-G2 at baseline had progressed to CKD G3-G5. Progressors had higher plasma IL-22 and TNF-α levels than non-progressors. Plasma IL-22 and TNF-α levels in progressors were similar to those in patients already in CKD G3-G5 at baseline, suggesting that cytokine dysregulation precedes CKD progression. In patients with CKD G1-G2, cut-off points for plasma IL-22 and TNF-α predicted progression with an AUC of 0.76 and 0.77, respectively. Additionally, patients with CKD G1-G2 and plasma TNF-α or IL-22 levels equal to or above the cut-off value had significantly lower eGFR values at the end of follow-up and had more frequently progressed to a very high risk KDIGO category. In cluster analysis, clusters displaying the highest urinary or plasma cytokine levels were associated with worse GFR outcomes.</p><p><strong>Conclusion: </strong>Plasma IL-22 and TNF-α may help to identify patients with early DKD with a high residual risk of CKD progression despite treatment.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-21"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022700","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":"Inflammation-Driven Differential Response to Intravenous versus Oral Iron Supplementation in Hemodialysis Patients: A Post Hoc Analysis of the IHOPE Trial.","authors":"Haijiao Jin, Renhua Lu, Juan Cao, Hua Li, Xiaoxia Wang, Yinghui Qi, Qiu Li, Xudong Cai, Bin Song, Na Li, Lianglan Shen, Li Wang, Xiaoping Wang, Zhaohui Ni","doi":"10.1159/000548166","DOIUrl":"https://doi.org/10.1159/000548166","url":null,"abstract":"<p><strong>Background: </strong>Anemia is common in hemodialysis patients, and iron supplementation is essential for its management. However, the impact of baseline inflammation on the efficacy of oral versus intravenous iron remains unclear.</p><p><strong>Methods: </strong>This post hoc analysis of the IHOPE trial included 193 maintenance hemodialysis patients stratified by median baseline high-sensitivity C-reactive protein (hsCRP). Patients were randomized to receive intravenous iron sucrose (100 mg every 2 weeks) or oral polysaccharide-iron complex (150 mg twice daily) for 24 weeks. The primary outcome was hemoglobin level at 24 weeks. Secondary outcomes included hsCRP, oxidative stress markers, and iron parameters.</p><p><strong>Results: </strong>At 24 weeks, patients with high baseline hsCRP had lower hemoglobin levels than those with low hsCRP (113.8±12.0 vs 118.0±13.5 g/L, P=0.038), despite similar baseline values. Among patients receiving intravenous iron, those with high hsCRP had significantly lower hemoglobin (112.9 vs 121.3 g/L; P=0.005) and higher hsCRP and superoxide dismutase levels, suggesting persistent inflammation and oxidative stress. In contrast, hemoglobin levels were similar between high and low hsCRP subgroups in the oral iron group (P=0.913). Iron parameters and adverse events were comparable across groups.</p><p><strong>Conclusion: </strong>Baseline inflammation significantly modifies the response to iron supplementation in hemodialysis patients. Intravenous iron is less effective in patients with elevated hsCRP, while oral iron maintains consistent efficacy regardless of inflammatory status. These findings support an individualized iron therapy approach based on inflammatory profiling to optimize anemia management in dialysis patients.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-21"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022653","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":"Artificial Intelligence-Driven Nephrology: The Role of Large Language Models in Kidney Care.","authors":"Carmine Zoccali, Lauren Floyd, Orsolya Cseprekal, Michele F Eisenga, Safak Mirioglu, Fernando Caravaca-Fontàn, Francesca Mallamaci","doi":"10.1159/000548208","DOIUrl":"10.1159/000548208","url":null,"abstract":"<p><strong>Background: </strong>Artificial intelligence (AI) increasingly impacts medicine and medical specialties, including nephrology. Technologies such as large language models (LLMs), decision-support AI, and machine learning-powered predictive analytics enhance clinical care. These AI-driven tools show great potential in areas such as predicting the risk of chronic kidney disease (CKD), managing dialysis, supporting kidney transplantation, and treating CKD and diabetes-related kidney issues.</p><p><strong>Summary: </strong>General AI platforms like ChatGPT, Bard, and Google Gemini are useful for education and synthesizing knowledge. In contrast, specialized medical AI systems such as KidneyIntelX and DreaMed Advisor provide clinically validated decision support systems that aid physicians in patient care. Retrieval-augmented generation (RAG) enhances LLMs by accessing real-time medical data and research insights, reducing misinformation risks, and ensuring accurate, verified medical responses. However, LLMs still face challenges in adapting to complex patient cases. The effectiveness of RAG depends on the quality of the data retrieved and adherence to ethical and confidentiality standards, with human oversight often necessary.</p><p><strong>Key messages: </strong>(i) Improving AI accuracy, increasing model transparency, and ensuring seamless integration into clinical settings maximize AI benefits in nephrology. (ii) Regulatory approvals and validation are essential to build trust among patients, physicians, and healthcare institutions. (iii) When integrated correctly into clinical workflows, AI can transform nephrology practice by providing efficient, data-driven insights, improving patient outcomes, and reducing administrative burdens. (iv) Ethical, responsible adoption with stringent oversight is crucial for successfully implementing AI in nephrology.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938998","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":"Plasma and Urinary KIM-1 in Chronic Kidney Disease: Prognostic Value, Associations with Albuminuria, and Implications for Kidney Failure and Mortality.","authors":"Thomas McDonnell, Magnus Söderberg, Maarten W Taal, Nicolas Vuilleumier, Philip A Kalra","doi":"10.1159/000547867","DOIUrl":"10.1159/000547867","url":null,"abstract":"<p><strong>Introduction: </strong>Kidney injury molecule-1 (KIM-1) expression reflects proximal renal tubular damage, but plasma and urine KIM-1 have not been jointly studied in a CKD cohort.</p><p><strong>Methods: </strong>Plasma and urine KIM-1 were measured in 2,581 adults from the NURTuRE-CKD cohort, a multicentre, non-dialysis-dependent CKD cohort. Survival analyses, C-statistics, and net reclassification improvement were used to assess associations and predictive performance of plasma and urine KIM-1 for kidney failure (KF), all-cause mortality, and a secondary endpoint of combined CKD progression endpoint (CKE) (KF or >40% decline in eGFR) in the total cohort and in KDIGO albuminuria categories, early CKD (eGFR >45 mL/min/1.73 m2), and four plasma/urine KIM-1 groups, dichotomised above and below the median value.</p><p><strong>Results: </strong>Median age was 65 years, baseline eGFR 34.8 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (uACR) 22.3 mg/mmol. During median follow-up of 48.8 months, 616 (23.9%) participants developed KF, 817 (32%) experienced CKE, and 344 (13.3%) died. Plasma and urine KIM-1 levels increased with lower eGFR, higher uACR, and diabetes. Plasma KIM-1 was independently associated with KF, while urine KIM-1 was associated with pre-KF death. The combination of high plasma and high urine KIM-1 conferred the greatest hazards of KF and all-cause mortality. Combining plasma and urine KIM-1 led to a 24.1% improvement in net reclassification index for KF. In earlier stages of CKD, both biomarkers were associated with CKD progression and there were large improvements in risk prediction for plasma KIM-1 alone. Increased albuminuria amplified the relationship between plasma and urine KIM-1 and KF risk.</p><p><strong>Conclusion: </strong>This study highlights distinct prognostic associations of plasma and urine KIM-1 in CKD. Measuring both may be useful in improving risk stratification in people with CKD. For early-stage CKD, the need to use a combined CKE, including decline in eGFR, is emphasised as few of these people developed KF.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820289","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":"Intensive versus Less-Intensive Blood Pressure Control in Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Clinical Trials.","authors":"Parisa Fallahtafti, Davood Semirani-Nezhad, Saba Maleki, Sahar Zafarmandi, Parham Dastjerdi, Soheil Rahmati, Khatere Roozbehi, Farhad Shaker, Mehra Fekri, Michael Nanna, Jishanth Mattumpuram, Kaveh Hosseini, Hamidreza Soleimani","doi":"10.1159/000547812","DOIUrl":"10.1159/000547812","url":null,"abstract":"<p><strong>Introduction: </strong>High blood pressure accelerates chronic kidney disease (CKD) progression, but the optimal intensity of blood pressure control in this population remains unclear. We aimed to determine whether intensive blood pressure control, compared to less-intensive control, improves clinical outcomes in individuals with CKD.</p><p><strong>Methods: </strong>A comprehensive search of PubMed, Embase, Scopus, and the Cochrane Library was conducted through December 2024. Randomized controlled trials comparing intensive versus standard blood pressure targets in patients with CKD stage 3 or higher were included. Eligible studies reported all-cause mortality and at least one cardiovascular or renal outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool. A random-effects model was used to pool risk ratios (RRs) with 95% confidence intervals (CIs). Subgroup analyses were performed based on the baseline systolic blood pressure, inclusion of diabetic patients versus exclusion, and baseline glomerular filtration rate (GFR).</p><p><strong>Results: </strong>Eleven randomized controlled trials with 8,740 participants were included. Intensive blood pressure control did not significantly reduce all-cause mortality (6.4% vs. 6.9%; RR, 0.91 [95% CI 0.73-1.13]; p = 0.32), cardiovascular mortality (RR, 0.89 [95% CI 0.69-1.15]; p = 0.3), major adverse cardiovascular events (RR, 0.91 [95% CI 0.69-1.20]; p = 0.27), decline in kidney function (RR, 0.86 [95% CI 0.59-1.25]; p = 0.34), or progression to end-stage kidney disease (RR, 1.00 [95% CI 0.81-1.23]; p = 0.99).</p><p><strong>Conclusions: </strong>Intensive BP control did not improve overall mortality or renal outcomes in CKD patients. Further large, long-term studies are warranted.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793267","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 Association of Proteinuria Target Achievement Timing and Stability with Adverse Kidney Outcomes among Patients with IgA Nephropathy: A Cohort Study.","authors":"Run Li, Miao Hui, Pei Chen, Duoduo Zhang, Chen Tang, Xujie Zhou, Li Zhu, Sufang Shi, Lijun Liu, Jicheng Lv, Hong Zhang","doi":"10.1159/000547868","DOIUrl":"10.1159/000547868","url":null,"abstract":"<p><strong>Introduction: </strong>Current KDIGO guidelines for IgA nephropathy (IgAN) recommend proteinuria should be maintained at <0.5 g/day. In this study, we aimed to evaluate the association of proteinuria target achievement timing and stability with adverse kidney outcomes.</p><p><strong>Methods: </strong>A cohort study was conducted with IgAN patients at Peking University First Hospital. We introduced three metrics: the timing of proteinuria first to target (TTT) in part A, time in target range (TTR), and area out of target (AOT) of proteinuria in part B to describe target achievement timing and stability, respectively. The target of proteinuria was less than 0.5 g/day. We analyzed the association between those three metrics and the composite kidney outcome, which was defined as the first occurrence of either end-stage kidney disease or a >50% decrease in estimated glomerular filtration rate from baseline.</p><p><strong>Results: </strong>In part A, the primary outcome occurred in 166 (18.65%) patients. The 10-year kidney survival probability was 73% in TTT <6 months of group and 64% in TTT ≥6 months of group (p = 0.006). We identified a significant association between the rate of initial target achievement and clinical outcomes. In part B, the primary outcome occurred in 385 (23.21%) patients. The 10-year kidney survival probability was 45% in T1 (TTR = 0%), 60% in T2 (0%< TTR ≤50%), and 86% in T3 (50%< TTR ≤100%) groups (p < 0.001). The corresponding hazard ratios (95% CI) for the respective proteinuria-TTR categories were 0.54 (0.43-0.68) and 0.21 (0.15-0.31), respectively. Our results demonstrate that maintaining stable target-range duration strongly correlated with improved prognosis. Our further analysis using a restricted cubic spline model indicated that the association of TTR and primary outcome generally showed a linear relationship. The analysis of AOT showed consistent results.</p><p><strong>Conclusion: </strong>Our study supports the importance of rapidly reaching proteinuria remission (<6 months) and maintaining proteinuria within this target range for an extended period.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-17"},"PeriodicalIF":3.2,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793268","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":"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}