Rajiv Agarwal,Jennifer B Green,Hiddo J L Heerspink,Johannes F E Mann,Janet B McGill,Amy Mottl,Takeshi Osonoi,Atanu Pal,Peter Rossing,Julio Rosenstock,Muthiah Vaduganathan,Li Li,Na Li,Charlie Scott,Pravin Manjrekar,Satoshi Yamashita,Masaomi Nangaku
{"title":"Impact of Simultaneous Initiation of Finerenone and Empagliflozin on Urinary Albumin-to-Creatinine Ratio in Asia: Pre-Specified Analysis of CONFIDENCE.","authors":"Rajiv Agarwal,Jennifer B Green,Hiddo J L Heerspink,Johannes F E Mann,Janet B McGill,Amy Mottl,Takeshi Osonoi,Atanu Pal,Peter Rossing,Julio Rosenstock,Muthiah Vaduganathan,Li Li,Na Li,Charlie Scott,Pravin Manjrekar,Satoshi Yamashita,Masaomi Nangaku","doi":"10.2215/cjn.0000000865","DOIUrl":"https://doi.org/10.2215/cjn.0000000865","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"71 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hee Byung Koh,Hyo Jeong Kim,Hyung Woo Kim,Young Su Joo,Seung Hyeok Han,Tae-Hyun Yoo,Shin-Wook Kang,Jung Tak Park
BACKGROUNDWhile the association between diet-induced inflammation and the risk of cardiovascular disease or cancer has been previously reported, its contribution to chronic kidney disease (CKD) and the underlying biological mechanisms remain unclear. This study aimed to elucidate the mechanistic role of the Dietary Inflammatory Index (DII) in CKD through multi-omics-based mediation analyses and to provide clinically relevant insight.METHODSThis study included 158,722 United Kingdom (UK) Biobank participants without underlying CKD (median age 57 years; 53% female). The DII was assessed via a 24-hour dietary recall and categorized into quartiles. Incident CKD was identified using International Classification of Diseases (ICD)-10 and Office of Population Censuses and Surveys Classification of Interventions and Procedures (OPCS)-4 codes. In a sub-cohort with creatinine follow-up, CKD was also defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Mediation analyses using proteomics and metabolomics data were conducted to explore potential mechanisms linking diet-induced inflammation to CKD. Individual food item analyses were performed to identify their association with CKD via diet-induced inflammation.RESULTSDuring a median of 11.2 years of follow-up, CKD occurred in 4,382 patients. Cox regression revealed that the adjusted hazard ratios for incident CKD were higher in a stepwise fashion across higher DII quartiles (adjusted hazard ratio [aHR] and 95% confidence interval [CI]: Q2, 1.08 [0.99-1.18]; Q3, 1.15 [1.05-1.26]; Q4, 1.17 [1.06-1.29]) relative to Q1 (P-for-trend <0.001). Similar results were observed with eGFR-defined CKD. Proteomics-based mediation analysis identified death receptor and tumor necrosis factor (TNF) receptor-related proteins as mediators linking diet-induced inflammation to CKD. Metabolomics analysis highlighted omega-3 fatty acids, especially docosahexaenoic acid, as protective mediators. Oily fish intake was inversely associated with CKD risk, while sugar-rich and high-fat dairy consumption showed positive associations, partly through inflammatory pathways.CONCLUSIONSThe association between the DII and incident CKD risk may be partly mediated by alterations in circulating protein profiles involving TNF receptor superfamily-related pathways and plasma omega-3 fatty acids. Dietary counseling aimed at lowering the consumption of sugar-rich and high-fat dairy products may be beneficial.
{"title":"Dietary Inflammatory Potential and Chronic Kidney Disease Risk: Exploring the Mediation Effects of Circulating Proteins.","authors":"Hee Byung Koh,Hyo Jeong Kim,Hyung Woo Kim,Young Su Joo,Seung Hyeok Han,Tae-Hyun Yoo,Shin-Wook Kang,Jung Tak Park","doi":"10.2215/cjn.0000000847","DOIUrl":"https://doi.org/10.2215/cjn.0000000847","url":null,"abstract":"BACKGROUNDWhile the association between diet-induced inflammation and the risk of cardiovascular disease or cancer has been previously reported, its contribution to chronic kidney disease (CKD) and the underlying biological mechanisms remain unclear. This study aimed to elucidate the mechanistic role of the Dietary Inflammatory Index (DII) in CKD through multi-omics-based mediation analyses and to provide clinically relevant insight.METHODSThis study included 158,722 United Kingdom (UK) Biobank participants without underlying CKD (median age 57 years; 53% female). The DII was assessed via a 24-hour dietary recall and categorized into quartiles. Incident CKD was identified using International Classification of Diseases (ICD)-10 and Office of Population Censuses and Surveys Classification of Interventions and Procedures (OPCS)-4 codes. In a sub-cohort with creatinine follow-up, CKD was also defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Mediation analyses using proteomics and metabolomics data were conducted to explore potential mechanisms linking diet-induced inflammation to CKD. Individual food item analyses were performed to identify their association with CKD via diet-induced inflammation.RESULTSDuring a median of 11.2 years of follow-up, CKD occurred in 4,382 patients. Cox regression revealed that the adjusted hazard ratios for incident CKD were higher in a stepwise fashion across higher DII quartiles (adjusted hazard ratio [aHR] and 95% confidence interval [CI]: Q2, 1.08 [0.99-1.18]; Q3, 1.15 [1.05-1.26]; Q4, 1.17 [1.06-1.29]) relative to Q1 (P-for-trend <0.001). Similar results were observed with eGFR-defined CKD. Proteomics-based mediation analysis identified death receptor and tumor necrosis factor (TNF) receptor-related proteins as mediators linking diet-induced inflammation to CKD. Metabolomics analysis highlighted omega-3 fatty acids, especially docosahexaenoic acid, as protective mediators. Oily fish intake was inversely associated with CKD risk, while sugar-rich and high-fat dairy consumption showed positive associations, partly through inflammatory pathways.CONCLUSIONSThe association between the DII and incident CKD risk may be partly mediated by alterations in circulating protein profiles involving TNF receptor superfamily-related pathways and plasma omega-3 fatty acids. Dietary counseling aimed at lowering the consumption of sugar-rich and high-fat dairy products may be beneficial.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"79 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaqi Yang,Lauren Bernard,Jingsha Chen,Valerie K Sullivan,Bing Yu,Eugene P Rhee,Paul A Welling,Casey M Rebholz
BACKGROUNDThere is a need for objective biomarkers of dietary potassium. The mechanisms through which dietary potassium influences kidney health are incompletely understood.METHODSAtherosclerosis Risk in Communities study participants at visit 3 (1993-1995) with dietary and proteomics data were randomly divided into discovery (N=6,814) and replication (N=3,380) sets. We examined associations between dietary potassium and 4,955 aptamers using multivariable linear regression, adjusting for sociodemographic factors, health behaviors, and estimated glomerular filtration rate, with a false discovery rate of 0.05. Then, we tested the prospective associations between potassium-related proteins and incident chronic kidney disease (CKD).RESULTSDietary potassium was significantly associated with 147 proteins in discovery, of which 85 (33 positive, 52 negative) replicated. Of 85 replicated proteins, 30 were selected by elastic net and improved prediction of high dietary potassium individually and collectively. Over a median follow-up of 21 years, 1,698 CKD cases developed. A score derived from 30 elastic net-selected dietary potassium-related proteins was associated with 7% lower risk of CKD (95% CI, 0.88-0.98, P=0.01). Of 85 potassium-related proteins from replication, 10 were associated with incident CKD. Specifically, pigment epithelium-derived factor and follistatin-related protein 3 were inversely associated with potassium and linked to 57% and 55% higher risk of CKD, respectively. Positively associated with potassium, TOM1-like protein 1 and serine/threonine-protein kinase pim-1 were associated with 28% and 26% lower risk of CKD, respectively. A score of 6 proteins mediated the association between potassium and CKD risk was associated with 13% lower risk of CKD (95% CI, 0.83-0.92, P=8.09×10-7).CONCLUSIONProteins associated with dietary potassium and incident CKD represented biological pathways including iron metabolism, mitochondrial function, fibrosis, and immune-inflammatory responses, which help explain the impact of potassium intake on CKD.
{"title":"Plasma Proteomic Profile of Dietary Potassium and Incident Chronic Kidney Disease.","authors":"Jiaqi Yang,Lauren Bernard,Jingsha Chen,Valerie K Sullivan,Bing Yu,Eugene P Rhee,Paul A Welling,Casey M Rebholz","doi":"10.2215/cjn.0000000864","DOIUrl":"https://doi.org/10.2215/cjn.0000000864","url":null,"abstract":"BACKGROUNDThere is a need for objective biomarkers of dietary potassium. The mechanisms through which dietary potassium influences kidney health are incompletely understood.METHODSAtherosclerosis Risk in Communities study participants at visit 3 (1993-1995) with dietary and proteomics data were randomly divided into discovery (N=6,814) and replication (N=3,380) sets. We examined associations between dietary potassium and 4,955 aptamers using multivariable linear regression, adjusting for sociodemographic factors, health behaviors, and estimated glomerular filtration rate, with a false discovery rate of 0.05. Then, we tested the prospective associations between potassium-related proteins and incident chronic kidney disease (CKD).RESULTSDietary potassium was significantly associated with 147 proteins in discovery, of which 85 (33 positive, 52 negative) replicated. Of 85 replicated proteins, 30 were selected by elastic net and improved prediction of high dietary potassium individually and collectively. Over a median follow-up of 21 years, 1,698 CKD cases developed. A score derived from 30 elastic net-selected dietary potassium-related proteins was associated with 7% lower risk of CKD (95% CI, 0.88-0.98, P=0.01). Of 85 potassium-related proteins from replication, 10 were associated with incident CKD. Specifically, pigment epithelium-derived factor and follistatin-related protein 3 were inversely associated with potassium and linked to 57% and 55% higher risk of CKD, respectively. Positively associated with potassium, TOM1-like protein 1 and serine/threonine-protein kinase pim-1 were associated with 28% and 26% lower risk of CKD, respectively. A score of 6 proteins mediated the association between potassium and CKD risk was associated with 13% lower risk of CKD (95% CI, 0.83-0.92, P=8.09×10-7).CONCLUSIONProteins associated with dietary potassium and incident CKD represented biological pathways including iron metabolism, mitochondrial function, fibrosis, and immune-inflammatory responses, which help explain the impact of potassium intake on CKD.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"56 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jasmine M Akhtar,Carolyn N Sidoti,Kadiatou Diallo,Max C Downey,Samantha B Klitenic,Darren E Stewart,Karen B Vanterpool,Tamar Schiff,Jon J Snyder,Nicole M Ali,Allan B Massie,Dorry L Segev,Macey L Levan
{"title":"Advancing Genetic Risk Assessment in Living Kidney Donation: A Comprehensive Approach to Patient Education and Counseling.","authors":"Jasmine M Akhtar,Carolyn N Sidoti,Kadiatou Diallo,Max C Downey,Samantha B Klitenic,Darren E Stewart,Karen B Vanterpool,Tamar Schiff,Jon J Snyder,Nicole M Ali,Allan B Massie,Dorry L Segev,Macey L Levan","doi":"10.2215/cjn.0000000901","DOIUrl":"https://doi.org/10.2215/cjn.0000000901","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"3 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sylvia T Nguyen,Kiara L T Arakawa-Taum,Christie Izutsu,Bryan Brown
Historical events including United States (US) neocolonial administration and thermonuclear weapon testing within their homelands left many Compacts of Free Association (COFA) citizens, including those of Chuukese, Marshallese, Pohnpeian, Yapese, and Kosraean descent with poor health and educational outcomes that led to their migration to Hawai'i. A case-control study was conducted to quantify relative prevalence and severity of chronic diseases among COFA-affiliated patients compared to age- and sex-matched controls. Inclusion was based on a "Preferred Language" labeled as a COFA-affiliated language in the electronic health record. Cases and controls had received primary care at The Queen Emma Clinics, a hospital-embedded, mission-based clinic in Honolulu between January 1, 2018 through August 10, 2023. In comparison to the age- and sex-matched control group (N=1076), patients with COFA-affiliated preferred languages (N=353) had prevalence rates of diabetes mellitus two-fold higher (54% vs. 28%), chronic kidney disease 1.8-fold greater (24% vs. 14%), and history of stroke two-fold greater (13% vs. 7%) (all p<0.001). Prevalence of uncontrolled diabetes in the studied population was more than three-fold higher (16% vs 5%), and kidney failure 3.9-fold higher than that of the control group (10% vs. 3%). COFA-affiliated clinic patients had lower engagement with medical services on various indicators. COFA migrants in the US present to primary care with uniquely prevalent and advanced chronic diseases, especially type 2 diabetes mellitus and chronic kidney disease.
历史事件，包括美国的新殖民主义管理和在其本土进行的热核武器试验，使许多自由联合契约（COFA）公民，包括楚克人、马绍尔人、波纳佩人、雅浦人和Kosraean人的后裔，健康和教育状况不佳，导致他们移民到夏威夷。进行了一项病例对照研究，与年龄和性别匹配的对照组相比，量化cofa附属患者中慢性病的相对患病率和严重程度。纳入基于电子健康记录中标记为cofa附属语言的“首选语言”。2018年1月1日至2023年8月10日期间，病例和对照组在檀香山的艾玛女王诊所（Queen Emma Clinics）接受了初级护理。与年龄和性别匹配的对照组（N=1076）相比，cofa相关首选语言患者（N=353）的糖尿病患病率高2倍（54%对28%），慢性肾病患病率高1.8倍（24%对14%），卒中史患病率高2倍（13%对7%）（均p<0.001）。研究人群中未控制的糖尿病患病率比对照组高出3倍多（16%对5%），肾衰竭患病率比对照组高出3.9倍（10%对3%）。cofa附属诊所的患者在各种指标上对医疗服务的参与程度较低。在美国的COFA移民有独特的流行和晚期慢性疾病，特别是2型糖尿病和慢性肾脏疾病。
{"title":"Uncovering Chronic Disease Disparities Within Compacts of Free Association Migrant Populations in Hawaii.","authors":"Sylvia T Nguyen,Kiara L T Arakawa-Taum,Christie Izutsu,Bryan Brown","doi":"10.2215/cjn.0000000840","DOIUrl":"https://doi.org/10.2215/cjn.0000000840","url":null,"abstract":"Historical events including United States (US) neocolonial administration and thermonuclear weapon testing within their homelands left many Compacts of Free Association (COFA) citizens, including those of Chuukese, Marshallese, Pohnpeian, Yapese, and Kosraean descent with poor health and educational outcomes that led to their migration to Hawai'i. A case-control study was conducted to quantify relative prevalence and severity of chronic diseases among COFA-affiliated patients compared to age- and sex-matched controls. Inclusion was based on a \"Preferred Language\" labeled as a COFA-affiliated language in the electronic health record. Cases and controls had received primary care at The Queen Emma Clinics, a hospital-embedded, mission-based clinic in Honolulu between January 1, 2018 through August 10, 2023. In comparison to the age- and sex-matched control group (N=1076), patients with COFA-affiliated preferred languages (N=353) had prevalence rates of diabetes mellitus two-fold higher (54% vs. 28%), chronic kidney disease 1.8-fold greater (24% vs. 14%), and history of stroke two-fold greater (13% vs. 7%) (all p<0.001). Prevalence of uncontrolled diabetes in the studied population was more than three-fold higher (16% vs 5%), and kidney failure 3.9-fold higher than that of the control group (10% vs. 3%). COFA-affiliated clinic patients had lower engagement with medical services on various indicators. COFA migrants in the US present to primary care with uniquely prevalent and advanced chronic diseases, especially type 2 diabetes mellitus and chronic kidney disease.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"50 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDThe effectiveness of therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) trough levels in children with steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS) treated with mycophenolate mofetil (MMF) has not been adequately assessed.METHODSWe performed an international, retrospective study including children with SDNS/FRNS, treated with MMF as the first-line steroid-sparing agent, and a follow-up of more than six months. Patients were categorized into two groups: TDM, if MPA trough levels were monitored, and No-TDM, if not. In the TDM group, MMF doses were adjusted to maintain MPA trough levels of more than 3 µg/ml, unless toxicity occurred. The primary outcome was relapse-free survival.RESULTSA total of 167 patients were observed, 90 in the TDM and 77 in the No-TDM group. Relapse-free survival over the total follow-up was significantly longer in the TDM group (p=0.001, log-rank test) with an estimated relapse-free survival at six months of 73% for the TDM and 55% for the No-TDM group. After correcting for potential confounders, the association remained statistically significant (p<0.001). TDM patients also received lower doses of prednisone after MMF introduction. In the TDM group, children were more likely to modify their initial dose (90% vs 9%; p<0.001). While MMF dose was not associated with relapse (median 1186 vs 1298 mg/m2; p=0.14), MPA trough levels were significantly higher in children who did not relapse (4.0 vs 2.7 µg/ml, p=0.001). Among children maintaining mean MPA levels more than 2.9 µg/ml, relapse-free survival at 6 months was 86%. Reported side effects were similar in both groups.CONCLUSIONSMonitoring MPA trough levels was associated with an approximately 20% higher MMF effectiveness in maintaining remission at six months in children with SDNS/FRNS. Personalized MMF dosing, adjusted to maintain MPA levels more than 2.9 µg/ml, was both safe and effective. We recommend including MPA trough level monitoring in future studies comparing MMF with other steroid-sparing agents in SDNS/FRNS children.
背景：在接受霉酚酸酯（MMF）治疗的类固醇依赖或频繁复发肾病综合征（SDNS/FRNS）患儿中，治疗性药物监测（TDM）霉酚酸（MPA）谷底水平的有效性尚未得到充分评估。方法：我们进行了一项国际回顾性研究，包括SDNS/FRNS患儿，接受MMF作为一线类固醇保留剂治疗，随访超过6个月。患者分为两组：TDM组（如果监测MPA低谷水平）和non -TDM组（如果没有监测）。在TDM组中，调整MMF剂量以维持大于3µg/ml的MPA谷水平，除非发生毒性。主要终点为无复发生存期。结果共观察167例患者，其中TDM组90例，非TDM组77例。TDM组的无复发生存期比总随访期明显更长（p=0.001， log-rank检验），TDM组6个月无复发生存期估计为73%，无TDM组为55%。在校正了潜在的混杂因素后，相关性仍然具有统计学意义（p<0.001）。TDM患者在引入MMF后也接受了较低剂量的强的松治疗。在TDM组中，儿童更有可能修改初始剂量（90% vs 9%; p<0.001）。虽然MMF剂量与复发无关（中位1186 vs 1298 mg/m2， p=0.14），但未复发儿童的MPA低谷水平显著较高（4.0 vs 2.7µg/ml, p=0.001）。在平均MPA水平高于2.9 μ g/ml的儿童中，6个月无复发生存率为86%。两组报告的副作用相似。结论：监测MPA谷底水平与MMF维持SDNS/FRNS患儿6个月缓解的有效性提高约20%相关。调整个体化MMF剂量以维持大于2.9 μ g/ml的MPA水平，既安全又有效。我们建议在未来的研究中，比较MMF与其他类固醇保留剂对SDNS/FRNS儿童的影响时，纳入MPA槽水平监测。
{"title":"Effectiveness of Mycophenolate Mofetil Trough Level Monitoring in Children with Relapsing Nephrotic Syndrome.","authors":"William Morello,Silvia Bernardi,Giuseppe Puccio,Anita Bellotti,Evgenia Preka,Mathilde Grapin,Maud Prévot,Marina Charbit,Teresa Nittoli,Maurizio Gallieni,Luciana Ghio,Alberto Edefonti,Olivia Boyer,Giovanni Montini","doi":"10.2215/cjn.0000000824","DOIUrl":"https://doi.org/10.2215/cjn.0000000824","url":null,"abstract":"BACKGROUNDThe effectiveness of therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) trough levels in children with steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS) treated with mycophenolate mofetil (MMF) has not been adequately assessed.METHODSWe performed an international, retrospective study including children with SDNS/FRNS, treated with MMF as the first-line steroid-sparing agent, and a follow-up of more than six months. Patients were categorized into two groups: TDM, if MPA trough levels were monitored, and No-TDM, if not. In the TDM group, MMF doses were adjusted to maintain MPA trough levels of more than 3 µg/ml, unless toxicity occurred. The primary outcome was relapse-free survival.RESULTSA total of 167 patients were observed, 90 in the TDM and 77 in the No-TDM group. Relapse-free survival over the total follow-up was significantly longer in the TDM group (p=0.001, log-rank test) with an estimated relapse-free survival at six months of 73% for the TDM and 55% for the No-TDM group. After correcting for potential confounders, the association remained statistically significant (p<0.001). TDM patients also received lower doses of prednisone after MMF introduction. In the TDM group, children were more likely to modify their initial dose (90% vs 9%; p<0.001). While MMF dose was not associated with relapse (median 1186 vs 1298 mg/m2; p=0.14), MPA trough levels were significantly higher in children who did not relapse (4.0 vs 2.7 µg/ml, p=0.001). Among children maintaining mean MPA levels more than 2.9 µg/ml, relapse-free survival at 6 months was 86%. Reported side effects were similar in both groups.CONCLUSIONSMonitoring MPA trough levels was associated with an approximately 20% higher MMF effectiveness in maintaining remission at six months in children with SDNS/FRNS. Personalized MMF dosing, adjusted to maintain MPA levels more than 2.9 µg/ml, was both safe and effective. We recommend including MPA trough level monitoring in future studies comparing MMF with other steroid-sparing agents in SDNS/FRNS children.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"50 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeremy Puthumana,Justin M Belcher,Guadalupe Garcia-Tsao,Arun J Sanyal,Jesse C Seegmiller,Pranav S Garimella,Chirag R Parikh,Joachim H Ix
BACKGROUNDAcute kidney injury (AKI) is a common and severe complication among hospitalized patients with cirrhosis. The most common causes of AKI in cirrhosis are prerenal azotemia (PRA), hepatorenal syndrome (HRS), and acute tubular necrosis (ATN), and treatment depends upon its causes. Kidney proximal tubular secretion is an essential mechanism for elimination of many drugs and toxins and may be affected in AKI. We hypothesized that assessing secretion would help distinguish between structural tubular injury (ATN) and hemodynamic perturbations (PRA and HRS).METHODSWe collected paired plasma and spot urine specimens from 76 hospitalized patients with cirrhosis and AKI from four tertiary care centers in North America. A panel of endogenous metabolites known to be secreted was measured in blood and urine by tandem mass spectrometry, and a summary secretion score was calculated by averaging the standardized spot urine-to-plasma ratios of the endogenous secretion markers, with higher urine-to-plasma ratios reflecting greater tubular secretion. The summary secretion score was assessed for its ability to discriminate ATN from non-ATN.RESULTSAmong the 76 patients with cirrhosis and AKI, 39 (51%) had PRA, 13 (17%) had HRS, and 24 (32%) had ATN. Median secretion scores were significantly lower in ATN (50.3, 95% confidence intervals [CI] 42.2-61.2) compared with PRA (61.7, 95% CI 55.4-75.4) or HRS (62.5, 95% CI 55.6-66.5) (p=0.007). In models adjusted for clinical characteristics, baseline estimated glomerular filtration rate (eGFR), and Model for End Stage Liver Disease (MELD) score, higher summary secretion score was associated with lower odds of ATN (odds ratio per standard deviation higher secretion score: 0.34, 95% CI 0.15-0.67). The summary secretion score showed good discriminative ability in diagnosing ATN versus other causes of AKI (Area Under the Receiver Operating Curve 0.73, 95% CI 0.60-0.85).CONCLUSIONSIn patients with cirrhosis and AKI, substantially lower tubular secretion was observed among inpatients with ATN relative to those with PRA and HRS. These results support the use of tubular secretion for the differential diagnosis of AKI in cirrhosis and may have important therapeutic and prognostic implications.
背景：急性肾损伤（AKI）是肝硬化住院患者中一种常见且严重的并发症。肝硬化AKI最常见的原因是肾前氮质血症（PRA）、肝肾综合征（HRS）和急性肾小管坏死（ATN），治疗取决于其原因。肾近端小管分泌是消除许多药物和毒素的重要机制，并可能在AKI中受到影响。我们假设评估分泌将有助于区分结构性小管损伤（ATN）和血流动力学扰动（PRA和HRS）。方法：我们收集了来自北美4个三级医疗中心的76例肝硬化合并AKI住院患者的配对血浆和尿样。通过串联质谱法测量血液和尿液中已知分泌的内源性代谢物，并通过平均内源性分泌标记物的标准化点尿浆比来计算总分泌评分，较高的尿浆比反映了更多的小管分泌。总结分泌评分评估其区分ATN和非ATN的能力。结果76例肝硬化合并AKI患者中，39例（51%）有PRA， 13例（17%）有HRS， 24例（32%）有ATN。与PRA （61.7, 95% CI 55.4-75.4）或HRS （62.5, 95% CI 55.6-66.5）相比，ATN的中位分泌评分（50.3,95%可信区间[CI] 42.2-61.2）显著降低（p=0.007）。在调整了临床特征、基线估计肾小球滤过率（eGFR）和终末期肝病模型（MELD）评分的模型中，较高的总分泌评分与较低的ATN几率相关（每标准差较高的分泌评分的比值比：0.34,95% CI 0.15-0.67）。综合分泌评分在诊断ATN与其他原因AKI方面具有良好的鉴别能力（受试者工作曲线下面积0.73,95% CI 0.60-0.85）。结论在合并肝硬化和AKI的住院患者中，ATN患者的肾小管分泌明显低于PRA和HRS患者。这些结果支持将肾小管分泌用于肝硬化AKI的鉴别诊断，并可能具有重要的治疗和预后意义。
{"title":"Kidney Tubule Secretion Can Discriminate the Cause of Acute Kidney Injury in Cirrhosis.","authors":"Jeremy Puthumana,Justin M Belcher,Guadalupe Garcia-Tsao,Arun J Sanyal,Jesse C Seegmiller,Pranav S Garimella,Chirag R Parikh,Joachim H Ix","doi":"10.2215/cjn.0000000814","DOIUrl":"https://doi.org/10.2215/cjn.0000000814","url":null,"abstract":"BACKGROUNDAcute kidney injury (AKI) is a common and severe complication among hospitalized patients with cirrhosis. The most common causes of AKI in cirrhosis are prerenal azotemia (PRA), hepatorenal syndrome (HRS), and acute tubular necrosis (ATN), and treatment depends upon its causes. Kidney proximal tubular secretion is an essential mechanism for elimination of many drugs and toxins and may be affected in AKI. We hypothesized that assessing secretion would help distinguish between structural tubular injury (ATN) and hemodynamic perturbations (PRA and HRS).METHODSWe collected paired plasma and spot urine specimens from 76 hospitalized patients with cirrhosis and AKI from four tertiary care centers in North America. A panel of endogenous metabolites known to be secreted was measured in blood and urine by tandem mass spectrometry, and a summary secretion score was calculated by averaging the standardized spot urine-to-plasma ratios of the endogenous secretion markers, with higher urine-to-plasma ratios reflecting greater tubular secretion. The summary secretion score was assessed for its ability to discriminate ATN from non-ATN.RESULTSAmong the 76 patients with cirrhosis and AKI, 39 (51%) had PRA, 13 (17%) had HRS, and 24 (32%) had ATN. Median secretion scores were significantly lower in ATN (50.3, 95% confidence intervals [CI] 42.2-61.2) compared with PRA (61.7, 95% CI 55.4-75.4) or HRS (62.5, 95% CI 55.6-66.5) (p=0.007). In models adjusted for clinical characteristics, baseline estimated glomerular filtration rate (eGFR), and Model for End Stage Liver Disease (MELD) score, higher summary secretion score was associated with lower odds of ATN (odds ratio per standard deviation higher secretion score: 0.34, 95% CI 0.15-0.67). The summary secretion score showed good discriminative ability in diagnosing ATN versus other causes of AKI (Area Under the Receiver Operating Curve 0.73, 95% CI 0.60-0.85).CONCLUSIONSIn patients with cirrhosis and AKI, substantially lower tubular secretion was observed among inpatients with ATN relative to those with PRA and HRS. These results support the use of tubular secretion for the differential diagnosis of AKI in cirrhosis and may have important therapeutic and prognostic implications.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"35 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atlee Baker,Koyal Jain,Anna M Burgner,Bharvi Oza-Gajera,Sam Kant,Chyi Chyi Chong,Dalia Dawoud,Christopher R Ramos,Bharat Sachdeva,Adina Voiculescu,Jeffrey Hull,Kerry A Leigh,Joseph Kessler,Prabir Roy Chaudhury,Matthew A Sparks,Vandana Dua Niyyar
{"title":"Transforming Dialysis Access Together (TDAT) Dialysis Access Training: Recommendations for Nephrology Fellows.","authors":"Atlee Baker,Koyal Jain,Anna M Burgner,Bharvi Oza-Gajera,Sam Kant,Chyi Chyi Chong,Dalia Dawoud,Christopher R Ramos,Bharat Sachdeva,Adina Voiculescu,Jeffrey Hull,Kerry A Leigh,Joseph Kessler,Prabir Roy Chaudhury,Matthew A Sparks,Vandana Dua Niyyar","doi":"10.2215/cjn.0000000899","DOIUrl":"https://doi.org/10.2215/cjn.0000000899","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"64 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anuradha Wadhwa,Scott Reule,Kerri L Cavanaugh,Michael J Fischer,Karen Mackichan,Arjun D Sinha,Paul M Palevsky,Susan T Crowley,Linda F Fried,Ashutosh M Shukla
Peritoneal dialysis (PD) use among the United States (US) Veteran population is lower than in the non-Veteran kidney failure population. Enhancing access to PD within the Veteran Healthcare Administration (VHA) may be crucial for achieving the Advancing American Kidney Health Executive Order goals. The VHA Home Dialysis Committee conducted a nationwide survey of nephrology stakeholders to assess Veterans' access to PD across the VHA and identify barriers and opportunities for the growth of VHA-affiliated PD services. Participants were invited via email and completed an electronic questionnaire consisting of seventeen PD access items and fifteen respondent characteristic items. Of the 141 eligible centers, 117 (83%) responded, including 97 facilities that provide nephrology services. Respondents indicated that PD could ideally serve 25% (interquartile range IQR: 15%, 40%) of Veterans with kidney failure. Most (62%) of the nephrology service-providing centers offered outpatient hemodialysis; however, only 28% reported providing outpatient PD services, with a median census of 10 Veterans. Among those lacking, 30% expressed a desire to establish outpatient PD services. The availability of comprehensive kidney replacement therapy KRT-directed pre-kidney failure education, an inpatient PD program, or respondents' perceptions of Veteran interest in PD were positively associated (p<0.05) with their desire to establish outpatient PD services. System-related challenges, such as limited space and capital costs of establishing a program, alongside staff-related issues like insufficient availability of trained nurses and support staff, were frequently cited barriers to PD programs. Respondents commonly cited the need for formal VHA-specific policies and procedural standards, administrative guides to establish local PD and patient education programs, and VHA-based PD nurse training assistance as strategies to address PD underutilization. Our findings suggest that the Veterans' lack of access to VHA-based PD programs may be an underrecognized barrier to their PD utilization. VHA nephrology stakeholders have a high desire to establish PD services but require local and system-based support to address PD underuse across the VHA.
{"title":"Barriers and Opportunities in Access to Peritoneal Dialysis across Veterans Healthcare Administration.","authors":"Anuradha Wadhwa,Scott Reule,Kerri L Cavanaugh,Michael J Fischer,Karen Mackichan,Arjun D Sinha,Paul M Palevsky,Susan T Crowley,Linda F Fried,Ashutosh M Shukla","doi":"10.2215/cjn.0000000826","DOIUrl":"https://doi.org/10.2215/cjn.0000000826","url":null,"abstract":"Peritoneal dialysis (PD) use among the United States (US) Veteran population is lower than in the non-Veteran kidney failure population. Enhancing access to PD within the Veteran Healthcare Administration (VHA) may be crucial for achieving the Advancing American Kidney Health Executive Order goals. The VHA Home Dialysis Committee conducted a nationwide survey of nephrology stakeholders to assess Veterans' access to PD across the VHA and identify barriers and opportunities for the growth of VHA-affiliated PD services. Participants were invited via email and completed an electronic questionnaire consisting of seventeen PD access items and fifteen respondent characteristic items. Of the 141 eligible centers, 117 (83%) responded, including 97 facilities that provide nephrology services. Respondents indicated that PD could ideally serve 25% (interquartile range IQR: 15%, 40%) of Veterans with kidney failure. Most (62%) of the nephrology service-providing centers offered outpatient hemodialysis; however, only 28% reported providing outpatient PD services, with a median census of 10 Veterans. Among those lacking, 30% expressed a desire to establish outpatient PD services. The availability of comprehensive kidney replacement therapy KRT-directed pre-kidney failure education, an inpatient PD program, or respondents' perceptions of Veteran interest in PD were positively associated (p<0.05) with their desire to establish outpatient PD services. System-related challenges, such as limited space and capital costs of establishing a program, alongside staff-related issues like insufficient availability of trained nurses and support staff, were frequently cited barriers to PD programs. Respondents commonly cited the need for formal VHA-specific policies and procedural standards, administrative guides to establish local PD and patient education programs, and VHA-based PD nurse training assistance as strategies to address PD underutilization. Our findings suggest that the Veterans' lack of access to VHA-based PD programs may be an underrecognized barrier to their PD utilization. VHA nephrology stakeholders have a high desire to establish PD services but require local and system-based support to address PD underuse across the VHA.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"93 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Verônica T Costa E Silva,Meghan E Sise,Lesley A Inker,Lea Mantz Cand Med,Tianqi Ouyang,Fernando Louzada Strufaldi,Luiz A Gil-Jr,Renato A Caires,George Coura-Filho,Marcelo T Sapienza,Emmanuel A Burdmann,Florian J Fintelmann
BACKGROUNDSarcopenia and obesity are common in patients with cancer and may reduce the accuracy of estimated glomerular filtration rate (eGFR) equations. We evaluated the performance of recommended eGFR equations based on creatinine or cystatin C, and novel GFR markers β2-microglobulin (B2M) and β-trace protein (BTP) according to body composition derived from computed tomography (CT).METHODSProspective cohort study of adult patients with solid tumors recruited between May 2015 and October 2017 who had a CT scan within 90 days of measured GFR (mGFR) using plasma clearance of 51Cr-EDTA. eGFR was calculated with the CKD-EPI equations using either creatinine (eGFRCR); cystatin C (eGFRCYS); creatinine and cystatin (eGFRCR-CYS); creatinine and B2M (eGFRCR-B2M), cystatin, B2M, and BTP (eGFRCYS-B2M-BTP); or creatinine, cystatin, B2M, and BTP (eGFRCR-CYS-B2M-BTP). Bias was assessed as the median of the differences between mGFR and eGFR. Accuracy was assessed as the percentage of estimates that differed by more than 30% from the mGFR (1-P30). 1-P30 < 10%, 10-20%, and > 20% are considered optimal, acceptable, and poor accuracy, respectively. Skeletal muscle index (SMI) was quantified on CT and calculated by dividing the skeletal muscle cross-sectional area by the patient's height squared.RESULTSOf 465 patients included, 157 (34%) met criteria for sarcopenia. Bias varied by magnitude of SMI. In patients with sarcopenia, the accuracy of eGFRCR and eGFRCYS was poor (1-P30 42.0% [95% CI 34.4, 49.6] and 20.4% [95% CI 14.0, 26.8], respectively). eGFRCR-CYS had acceptable accuracy (1-P30: 14.0 [8.3, 19.1] %) whereas eGFRCYS-B2M-BTP and eGFRCR-CYS-B2M-BTP had optimal accuracy (1-P30: 7.0 [3.2, 10.8] % and 8.3 [3.8, 12.3] %, respectively). Obesity did not significantly affect bias or accuracy.CONCLUSIONSGFR estimates based on eGFRCR and eGFRCYS are not sufficiently accurate in patients with cancer and sarcopenia. Body composition analysis can identify patients in need of more accurate GFR assessment.
{"title":"Impact of CT-Derived Body Composition Analysis on the Performance of GFR Estimating Equations in Patients with Cancer.","authors":"Verônica T Costa E Silva,Meghan E Sise,Lesley A Inker,Lea Mantz Cand Med,Tianqi Ouyang,Fernando Louzada Strufaldi,Luiz A Gil-Jr,Renato A Caires,George Coura-Filho,Marcelo T Sapienza,Emmanuel A Burdmann,Florian J Fintelmann","doi":"10.2215/cjn.0000000878","DOIUrl":"https://doi.org/10.2215/cjn.0000000878","url":null,"abstract":"BACKGROUNDSarcopenia and obesity are common in patients with cancer and may reduce the accuracy of estimated glomerular filtration rate (eGFR) equations. We evaluated the performance of recommended eGFR equations based on creatinine or cystatin C, and novel GFR markers β2-microglobulin (B2M) and β-trace protein (BTP) according to body composition derived from computed tomography (CT).METHODSProspective cohort study of adult patients with solid tumors recruited between May 2015 and October 2017 who had a CT scan within 90 days of measured GFR (mGFR) using plasma clearance of 51Cr-EDTA. eGFR was calculated with the CKD-EPI equations using either creatinine (eGFRCR); cystatin C (eGFRCYS); creatinine and cystatin (eGFRCR-CYS); creatinine and B2M (eGFRCR-B2M), cystatin, B2M, and BTP (eGFRCYS-B2M-BTP); or creatinine, cystatin, B2M, and BTP (eGFRCR-CYS-B2M-BTP). Bias was assessed as the median of the differences between mGFR and eGFR. Accuracy was assessed as the percentage of estimates that differed by more than 30% from the mGFR (1-P30). 1-P30 < 10%, 10-20%, and > 20% are considered optimal, acceptable, and poor accuracy, respectively. Skeletal muscle index (SMI) was quantified on CT and calculated by dividing the skeletal muscle cross-sectional area by the patient's height squared.RESULTSOf 465 patients included, 157 (34%) met criteria for sarcopenia. Bias varied by magnitude of SMI. In patients with sarcopenia, the accuracy of eGFRCR and eGFRCYS was poor (1-P30 42.0% [95% CI 34.4, 49.6] and 20.4% [95% CI 14.0, 26.8], respectively). eGFRCR-CYS had acceptable accuracy (1-P30: 14.0 [8.3, 19.1] %) whereas eGFRCYS-B2M-BTP and eGFRCR-CYS-B2M-BTP had optimal accuracy (1-P30: 7.0 [3.2, 10.8] % and 8.3 [3.8, 12.3] %, respectively). Obesity did not significantly affect bias or accuracy.CONCLUSIONSGFR estimates based on eGFRCR and eGFRCYS are not sufficiently accurate in patients with cancer and sarcopenia. Body composition analysis can identify patients in need of more accurate GFR assessment.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"104 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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