American Journal of Nephrology最新文献

{"title":"Adjunctive active vitamin D (AVD) decreases kidney function during treatment of secondary hyperparathyroidism (SHPT) with extended-release calcifediol (ERC) in non-dialysis chronic kidney disease (ND-CKD).","authors":"Akhtar Ashfaq, John Choe, Stephen A Strugnell, Nilay Patel, Stuart M Sprague, Keith C Norris, Edgar Lerma, P Martin Petkovich, Charles W Bishop","doi":"10.1159/000544086","DOIUrl":"https://doi.org/10.1159/000544086","url":null,"abstract":"<p><strong>Introduction: </strong>Sustained 30% reductions of intact parathyroid hormone (iPTH) with ERC are associated with slower decline in estimated glomerular filtration rate (eGFR) in ND-CKD patients with SHPT. Such iPTH reductions usually require elevation of serum total 25-hydroxyvitamin D (25D) to ≥50 ng/mL, but achieving these reductions can be limited by the ERC dose ceiling (60 μg/day), raising the question of whether adjunctive (adj) AVD might be appropriate to further reduce iPTH.</p><p><strong>Methods: </strong>This randomized controlled trial (RCT) examined whether adj AVD could safely increase iPTH reductions achieved with ERC and further reduce the rate of eGFR decline in 78 ND-CKD adults treated with ERC for 38 weeks. Participants had mean age of 66 years, body mass index of 35 kg/m2, 41% were female, 63% White, 36% Black, 19% Hispanic. At ERC initiation, participants had plasma iPTH 85-<500 pg/mL, eGFR 15-<60 mL/min/1.73 m2, serum 25D 10-<30 ng/mL, corrected serum calcium (Ca) 8.4-<9.8 mg/dL, serum phosphorus (P) 2.0-<5.0 mg/dL, and absence of macroalbuminuria (>300 mg/g creatinine). At baseline (BL; week 38), participants had plasma iPTH >70 pg/mL and serum Ca <9.8 mg/dL and were randomized 3:1:1:1 to daily ERC (60 μg) for 14 additional weeks with (n=40) or without (n=38) adj daily oral calcitriol (0.25 μg), doxercalciferol (0.5 μg) or paricalcitol (1.0 μg). Measurements of eGFR, iPTH, 25D, Ca, P and fibroblast growth factor 23 (FGF23) were obtained at BL and through end of treatment (EOT).</p><p><strong>Results: </strong>No significant intergroup differences were observed at BL. Mean 25D at BL was 65 ng/mL and rose 14 ng/mL by EOT in both groups (p<0.001). Mean BL iPTH was 137 pg/mL and fell by a further 35.4% (p<0.001) with adj AVD therapy versus 2.2% without. Mean Ca, P and FGF23 increased with adj AVD by 0.40 mg/dL (p<0.001), 0.27 mg/dL (p<0.01) and 49.1 pg/mL (155%; p<0.001), respectively, but remained unchanged with ERC alone. Mean BL eGFR was 25.4 mL/min/1.73m2 and fell by 11.8% (p<0.05) with adj AVD versus 3.0% without.</p><p><strong>Conclusion: </strong>Adj AVD at these doses enabled 35% more iPTH reduction in ND-CKD patients with mild to moderate SHPT on long-term ERC treatment but increased mean serum Ca and P by 0.40 and 0.27 mg/dL, respectively, FGF23 by more than 2-fold and eGFR decline by 4-fold, suggesting that adding AVD to ERC has untoward effects that override the nephrosparing impact of iPTH reductions with ERC treatment alone. Corroboration is warranted with a larger, longer RCT.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-21"},"PeriodicalIF":4.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482074","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":"Fibroblast Growth Factor 23, Endogenous Erythropoietin, Erythropoiesis-Stimulating Agents, and Erythropoietin Resistance in Hemodialysis Patients.","authors":"Naoto Hamano, Hirotaka Komaba, Hisae Tanaka, Hiroo Takahashi, Yuichiro Takahashi, Toru Hyodo, Miho Hida, Takao Suga, Takehiko Wada, Takatoshi Kakuta, Masafumi Fukagawa","doi":"10.1159/000543506","DOIUrl":"https://doi.org/10.1159/000543506","url":null,"abstract":"<p><strong>Introduction: </strong>Recent experimental studies have reported that fibroblast growth factor 23 (FGF23) inhibits erythropoiesis by suppressing erythropoietin (EPO) production and downregulating the EPO receptor. Conversely, either endogenous or exogenous EPO has been shown to stimulate FGF23 production. However, little is known about the relationships between FGF23, erythropoiesis-stimulating agent (ESA) treatment, ESA resistance, and endogenous EPO in hemodialysis patients.</p><p><strong>Methods: </strong>We analyzed cross-sectional data from a cohort of 654 maintenance hemodialysis patients. We examined the associations of intact or C-terminal FGF23 with ESA treatment, ESA resistance index (ERI), hemoglobin, C-reactive protein, and endogenous EPO levels using linear regression models. EPO was measured only in patients not receiving ESAs.</p><p><strong>Results: </strong>A total of 458 patients (70%) were treated with ESAs. The median EPO concentration in non-ESA users was 7.8 (interquartile range, 5.3-14.4) mIU/mL. The median levels of intact and C-terminal FGF23 were 1,598 (interquartile range, 548-4,586) pg/mL and 38.7 (interquartile range, 14.0-127.6) pmol/L, respectively, in non-ESA users and 1,955 (interquartile range, 573-5,264) pg/mL and 41.4 (interquartile range, 13.9-116.8) pmol/L, respectively, in ESA users. After adjustment for potential confounders, higher ESA dose was associated with higher FGF23 levels measured by both intact and C-terminal assays. Higher C-terminal FGF23 was also associated with higher ERI, lower hemoglobin, and higher endogenous EPO, but no such associations were observed for intact FGF23 levels.</p><p><strong>Conclusions: </strong>Both intact and C-terminal FGF23 showed similar associations with ESA dose, but they showed different patterns of association with other parameters related to anemia. Further research is needed to elucidate the mechanisms underlying these different associations.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-9"},"PeriodicalIF":4.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466494","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":"Immunotherapy and cellular therapies for cancers in kidney transplant patients.","authors":"Massini Merzkani, Rose Mary Attieh, Kenar D Jhaveri, Naoka Murakami","doi":"10.1159/000544826","DOIUrl":"https://doi.org/10.1159/000544826","url":null,"abstract":"<p><p>Background Kidney transplant is a treatment of choice for end-stage kidney disease, with longer survival and better quality of life post-transplant. However, long-term immunosuppression comes with an increased risk of cancer and infection. Cancer is one of the leading causes of death after kidney transplant. While novel cancer therapies become available, transplant recipients are usually excluded from clinical trials Summary In this review, we summarize the updated knowledge on immunosuppression management in kidney transplant recipients treated with immune checkpoint inhibitors, bispecific T cell engager (BiTE) therapy, and chimeric antigen receptor (CAR) T cell therapies. Key Messages Transplant nephrologists should be empowered to participate in the decision making of cancer treatment together with patients, care partners and oncologist, by managing immunosuppression.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-23"},"PeriodicalIF":4.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466542","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":"Supplement-induced acute kidney injury reproduced in kidney organoids.","authors":"Hiroyuki Nakanoh, Kenji Tsuji, Kazuhiko Fukushima, Soichiro Haraguchi, Shinji Kitamura, Jun Wada","doi":"10.1159/000544795","DOIUrl":"https://doi.org/10.1159/000544795","url":null,"abstract":"<p><strong>Introduction: </strong>Acute kidney injury (AKI) associated with the consumption of Beni-koji CholesteHelp supplements, which contain red yeast rice (Beni-Koji), has become a significant public health concern in Japan. While renal biopsy findings from several case reports have suggested tubular damage, no definitive causal relationship has been established, and the underlying mechanisms of kidney injury remain poorly understood. The complexity of identifying toxic substances in supplements containing various bioactive compounds makes conventional investigative approaches both time-consuming and challenging. This highlights an urgent need to establish a reliable platform for assessing organ-specific toxicity in such supplements. In this study, we utilized a kidney organoid model derived from adult rat kidney stem cells (KS cells) to assess the potential tubular toxicity of these supplements.</p><p><strong>Methods: </strong>KS cell clusters were cultured in three-dimensional system supplemented with growth factors to promote kidney organoids. The organoids were subsequently exposed to Beni-koji CholesteHelp supplements or cisplatin, followed by histological and molecular analyses to evaluate structural and molecular impacts.</p><p><strong>Results: </strong>Established organoids had the kidney-like structures including tubular-like structures and glomerulus-like structures at the tips of multiple tubules. Treatment with Beni-koji CholesteHelp supplements induced significant tubular damage in the organoids, characterized by epithelial cell thinning, structural disruption, and increase in cleaved caspase-3-positive apoptotic tubular cells, similar to the organoids treated with cisplatin.</p><p><strong>Conclusions: </strong>These findings provide the first evidence suggesting that certain toxicants in specific batches of Beni-koji CholesteHelp supplements cause direct renal tubular injury. This KS cell-based organoid system represents a cost-effective, reproducible, and technically simple platform for nephrotoxicity screening.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-15"},"PeriodicalIF":4.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466508","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":"Erratum.","authors":"","doi":"10.1159/000543485","DOIUrl":"https://doi.org/10.1159/000543485","url":null,"abstract":"","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1"},"PeriodicalIF":4.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412847","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":"DOT1L regulates cellular senescence during the progression from acute kidney injury to chronic kidney disease via the micro-222-5p/WNT9B signaling pathway.","authors":"Congcong Yao, Wei Wei, Guoyu Wu, Yan Zhang, Keke Sun, Zhiyuan Liu, Yushanjiang Abudureheman, Heng Wu, Qi Lv, Ayinuer Paredong, Songtao Shou, Heng Jin","doi":"10.1159/000544694","DOIUrl":"https://doi.org/10.1159/000544694","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) is a common clinical condition where cellular senescence plays a crucial role in its progression. Previous studies have suggested that DOT1L plays a pivotal role in cellular senescence, yet its specific mechanisms in regulating AKI cellular senescence remain unclear.</p><p><strong>Methods: </strong>This study utilized a glycerol-induced in vivo AKI model and employed the DOT1L-specific inhibitor EPZ004777 (EPZ) to suppress DOT1L function. Aging staining, PAS staining, and Masson staining were employed to assess renal aging, injury, and interstitial fibrosis. In vitro experiments utilized doxorubicin-treated human kidney tubular epithelial (HK-2) cells to establish an AKI cellular senescence model. EPZ was used to inhibit DOT1L, evaluating its impact on cellular senescence. High-throughput miRNA sequencing was performed to analyze differential expression of miRNAs downstream of DOT1L, and DOT1L overexpression and dual luciferase reporter gene experiments were conducted to explore interactions among DOT1L, miR-222-5p, and WNT9B.</p><p><strong>Results: </strong>The results demonstrated that in vivo inhibition of DOT1L significantly reduced cellular senescence and improved renal tubular injury and interstitial fibrosis. In the doxorubicin -induced HK-2 cell model, DOT1L inhibition markedly decreased cellular senescence and lowered mRNA and protein levels of senescence markers, while alleviating cell cycle arrest. DOT1L inhibition notably upregulated miR-222-5p expression and suppressed WNT9B expression, with opposite effects observed with DOT1L overexpression.</p><p><strong>Conclusion: </strong>DOT1L regulates cellular senescence through the miR-222-5p/WNT9B pathway in AKI. These findings suggest that DOT1L may serve as a potential therapeutic target to mitigate the progression of AKI to chronic kidney disease.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-20"},"PeriodicalIF":4.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405051","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 value of diffusion kurtosis imaging to assess liver and kidney recovery after mesenchymal stem cell intervention in CCl4-induced cirrhotic rats.","authors":"Jiaming Qin, Shuangshuang Xie, Yongquan Yu, Cheng Zhang, Yumeng Zhao, Dan Tong, Zhandong Hu, Jinxia Zhu, Wen Shen","doi":"10.1159/000544056","DOIUrl":"https://doi.org/10.1159/000544056","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the potential of diffusion kurtosis imaging (DKI) in monitoring the improvement of liver and kidney injury in cirrhotic rats after bone marrow derived mesenchymal stem cells (BMSCs) treatment.</p><p><strong>Methods: </strong>Thirty rats were induced with liver cirrhosis via subcutaneous injection of carbon tetrachloride. Six rats were randomly selected for DKI scanning and subsequently euthanized for biochemical and histological analysis. The remaining 24 rats were randomly divided into a BMSC group (n=12) and control group (n=12). In the BMSC group, six rats underwent dynamic DKI scans and were sacrificed after 13, 14, 15, and 16 weeks, while the other 6 rats were sacrificed after being scanned in the 14th week. The control group followed the same protocol as the BMSC group. Additionally, six normal rats were euthanized after undergoing DKI scanning to provide baseline data. Liver and kidney DKI parameters, biochemical markers, liver fibers, kidney hematoxylin-eosin (HE) score, and alpha smooth muscle actin (α-SMA) were analyzed.</p><p><strong>Results: </strong>Compared to baseline, there was a significant increase in liver fibers and kidney HE scores by week 12. At weeks 13, 14, 15,and 16, the mean kurtosis (MK) of the liver in the BMSC group was significantly lower than that at week 12 and in the control group. At week 16, the mean diffusion (MD) in the BMSC group was significantly higher than that at week 12 and in the control group. The apparent diffusivity coefficient (ADC) values in the BMSC group were higher than those at week 12 and in the control group at weeks 13, 14, and 16. All regions of kidney showed decreased MK values from weeks 14 to 16 compared to week 12 and the control group. Liver fiber was moderately or highly correlated with all DKI parameters. MK and ADC of the renal cortex (CO) and outer stripe of the outer medulla (OSOM) showed moderate correlation with HE scores and α-SMA.</p><p><strong>Conclusion: </strong>DKI can serve as a non-invasive means to effectively monitor the process of liver and kidney injury improvement in cirrhotic rats treated with BMSCs.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-21"},"PeriodicalIF":4.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397762","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":"Gender Differences in Kidney Failure incidence in Australia: a Registry study.","authors":"Belinda C Stallard, Stephen P McDonald","doi":"10.1159/000543663","DOIUrl":"https://doi.org/10.1159/000543663","url":null,"abstract":"<p><p>Introduction Previous studies have shown that there is a higher incidence of men initiating kidney replacement therapy (KRT) in comparison to women. However, the contribution of gender disparity may well differ among the different types of kidney disease, and over time. Utilising a nationwide Registry, we examined disease- and gender-specific trends in incident kidney failure required KRT. Methods Registry-based analysis of all incident patients commencing KRT in Australia using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. All patients who initiated dialysis in Australia from January 1971 to 31 December 2021 were included. Confidence intervals around rates were calculated and compared using Poisson distributions. Results During the study period a total of 31834 women and 47718 men were recorded in ANZDATA to have commenced KRT in Australia, a male to female ratio of 1.51 [1.49-1.53]. The male to female ratio increased over time from 1.05 [0.83-1.34] in 1971 to 1.78 [1.66-1.92] in 2021. There was a progressive increase in the male:female ratio with age; for those starting in 2017-21 this rose from 1.37 [95% CI 1.26-1.50] among 25-44 years olds to 4.38 [2.47-5.53] among those ≥85 years at KRT start. Conclusions Men had a significantly higher rate of starting KRT in Australia compared with women, and this difference is increasing over time. This disparity also varied between types of primary kidney disease but was higher among older age groups. It is still seen for causes (such as polycystic kidney disease) that have equal gender disease distribution, suggesting differences in propensity to commence KRT as well as differences in underlying disease processes.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-20"},"PeriodicalIF":4.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121861","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":"Early-Onset Peritonitis and Outcomes of Peritoneal Dialysis: A Cohort Study with Data from the RDPLF.","authors":"Lucas Poulain, Clémence Bechade, Antoine Lanot, Maxence Ficheux, Sonia Guillouet, Thierry Lobbedez, Annabel Boyer","doi":"10.1159/000542835","DOIUrl":"10.1159/000542835","url":null,"abstract":"<p><strong>Introduction: </strong>Peritonitis occurring within the first months on peritoneal dialysis (PD) has been associated with poorer PD outcomes. Whether early peritonitis is a risk factor for transfer to haemodialysis in the long term is a matter of investigation.</p><p><strong>Methods: </strong>This retrospective study was conducted using data from the French Language PD Registry of incident PD patients between 2002 and 2018. Early-onset peritonitis (EOP) was defined as peritonitis occurring during the first 3 months on PD. Our hypothesis was that EOP was associated with an increased risk of transfer to haemodialysis during the first months on PD but that it was no longer associated with an increased risk of transfer to haemodialysis several months after the start of PD. The associations between EOP and the different outcomes were explored via time-dependent coefficient Cox regression and Fine and Gray regression.</p><p><strong>Results: </strong>EOP was associated with an increased risk of PD cessation by transfer to haemodialysis within the first 12 months of PD and beyond (<12 months cs-HR 1.50, 95% CI: 1.36-1.66 and >12 months cs-HR 1.17, 95% CI: 1.06-1.28, respectively).</p><p><strong>Conclusion: </strong>EOP is associated with a greater risk of PD cessation due to transfer to haemodialysis, especially within the first year after peritonitis occurrence, and with a persistent effect in the long term. Reducing or delaying EOP, notably through its systematic reporting and monitoring as a KPI to help in the implementation of QIPs, could have a favourable impact on patient-level outcomes.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-12"},"PeriodicalIF":4.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121860","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":"Association between serum iron store biomarkers and all-cause mortality in Japanese patients undergoing hemodialysis: a nationwide cohort study.","authors":"Hiroki Nishiwaki, Takahiro Imaizumi, Takeshi Hasegawa, Takaaki Kosugi, Yukio Maruyama, Kazuhiko Tsuruya, Yasuhiko Ito, Hirokazu Honda, Masanori Abe, Norio Hanafusa, Takahiro Kuragano","doi":"10.1159/000543888","DOIUrl":"https://doi.org/10.1159/000543888","url":null,"abstract":"<p><p>Introduction We evaluated the association between iron-related biomarkers-key indicators of iron metabolism and inflammation, and crucial in the management of anemia in patients undergoing hemodialysis-and all-cause mortality. This study aimed to clarify the nuanced relationship between these biomarkers and mortality outcomes, addressing the limitations of traditional cutoff-based analyses. Methods We conducted a prospective cohort analysis of patients undergoing dialysis across Japan using data from the Japan Renal Database collected between 2019 and 2020. Patients who had been on dialysis for at least 3 months by the end of 2019 were considered eligible. The associations between iron-related biomarkers and all-cause within 1 year were analyzed using Cox proportional hazards models. The relationship between each biomarker and outcome was illustrated using restricted cubic spline curves, while the combined association of serum ferritin and TSAT with mortality was shown using contour plots. Results A total of 215,927 patients were included in the analysis. During the follow-up period, 17,803 (8.24%) deaths were recorded. Contour plots demonstrated increased mortality risk in areas with low ferritin and TSAT levels. Additionally, even in regions with high TSAT levels, there was a trend toward increased mortality risk with increasing ferritin levels. Conversely, in areas with low ferritin levels, there was a trend toward a decreased risk of death. Conclusions Our findings highlight the complex interplay between serum ferritin and TSAT levels, emphasizing the limitations of relying on single cutoff values for clinical decision-making. The study underscores the need for individualized approaches to iron management in patients undergoing hemodialysis.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-23"},"PeriodicalIF":4.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078432","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}