Jose Perez,Jingbo Niu,Elliot Baerman,Wolfgang C Winkelmayer,Kerri L Cavanaugh,Monique R Pappadis,Kevin F Erickson
{"title":"Association between Access to Alternatives to Daytime In-Center Hemodialysis and Employment among Patients with Kidney Failure.","authors":"Jose Perez,Jingbo Niu,Elliot Baerman,Wolfgang C Winkelmayer,Kerri L Cavanaugh,Monique R Pappadis,Kevin F Erickson","doi":"10.2215/cjn.0000000819","DOIUrl":"https://doi.org/10.2215/cjn.0000000819","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"30 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247113","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}
John J Sim,Mercedes A Munis,Benjamin Lewing,Qiaoling Chen,Matthew Hill,Min Zhuo,Ancilla W Fernandes,Asher D Schachter
BACKGROUNDFocal segmental glomerulosclerosis (FSGS) has a variable response to immunosuppressive therapy (IS) and high relapse rates. Lack of Food and Drug Administration-approved therapies underscore the need for real-world evidence to better understand treatment patterns and outcomes. This study aimed to evaluate treatment response, relapse patterns, and kidney outcomes among patients with primary FSGS.METHODSA retrospective cohort study was performed within 14 medical centers of an integrated health system. Patients (≥18 years) with biopsy-confirmed primary FSGS treated with IS between 2010 and 2021 were included. Treatment response, assessed at up to eight months, was categorized as complete remission (CR): urine protein-to-creatinine ratio (UPCR) <0.3g/g; partial remission (PR): UPCR decline >50% from baseline and between 0.3-3.5g/g; and, no remission (NR). Relapse was defined as loss of remission within two years. Outcomes, including end-stage kidney disease (ESKD; treatment with dialysis or transplant) and mortality, were analyzed using Fine-Gray subdistribution hazard ratio (sHR) models.RESULTSAmong 228 patients treated with IS, 55% achieved remission (12% CR, 43% PR), with relapse rates of 63% and 75% by two years. Median follow-up was 4 years (interquartile range 2.0, 7.6), during which 88 (39%) progressed to ESKD. A total of 62 (27%) patients died, with 33 (15%) deaths occurring before reaching ESKD. Non-responders had a higher risk of ESKD compared to responders (sHR: 2.22; 95% CI: 1.41, 3.49). Baseline estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 was strongly associated with risk of ESKD (sHR for eGFR of <30 vs 60+: 4.74, 95% CI: 2.24, 10.05; p<0.001), while baseline proteinuria (UPCR >3.5 g/g) was not significant. Asian/Pacific Islander patients exhibited the highest ESKD risk among racial/ethnic groups (sHR: 2.03; 95% CI:1.07, 3.84).CONCLUSIONSApproximately half of FSGS patients achieved remission with IS, but relapse rates were high, and nearly 40% progressed to ESKD. Non-responders and low baseline eGFR had the highest risk. These findings underscore the need for novel therapies to achieve durable disease control, lower relapse rates, and improve outcomes in FSGS.
{"title":"Treatment Response Rates and Kidney Outcomes among Adults with Primary Focal Segmental Glomerulosclerosis.","authors":"John J Sim,Mercedes A Munis,Benjamin Lewing,Qiaoling Chen,Matthew Hill,Min Zhuo,Ancilla W Fernandes,Asher D Schachter","doi":"10.2215/cjn.0000000898","DOIUrl":"https://doi.org/10.2215/cjn.0000000898","url":null,"abstract":"BACKGROUNDFocal segmental glomerulosclerosis (FSGS) has a variable response to immunosuppressive therapy (IS) and high relapse rates. Lack of Food and Drug Administration-approved therapies underscore the need for real-world evidence to better understand treatment patterns and outcomes. This study aimed to evaluate treatment response, relapse patterns, and kidney outcomes among patients with primary FSGS.METHODSA retrospective cohort study was performed within 14 medical centers of an integrated health system. Patients (≥18 years) with biopsy-confirmed primary FSGS treated with IS between 2010 and 2021 were included. Treatment response, assessed at up to eight months, was categorized as complete remission (CR): urine protein-to-creatinine ratio (UPCR) <0.3g/g; partial remission (PR): UPCR decline >50% from baseline and between 0.3-3.5g/g; and, no remission (NR). Relapse was defined as loss of remission within two years. Outcomes, including end-stage kidney disease (ESKD; treatment with dialysis or transplant) and mortality, were analyzed using Fine-Gray subdistribution hazard ratio (sHR) models.RESULTSAmong 228 patients treated with IS, 55% achieved remission (12% CR, 43% PR), with relapse rates of 63% and 75% by two years. Median follow-up was 4 years (interquartile range 2.0, 7.6), during which 88 (39%) progressed to ESKD. A total of 62 (27%) patients died, with 33 (15%) deaths occurring before reaching ESKD. Non-responders had a higher risk of ESKD compared to responders (sHR: 2.22; 95% CI: 1.41, 3.49). Baseline estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 was strongly associated with risk of ESKD (sHR for eGFR of <30 vs 60+: 4.74, 95% CI: 2.24, 10.05; p<0.001), while baseline proteinuria (UPCR >3.5 g/g) was not significant. Asian/Pacific Islander patients exhibited the highest ESKD risk among racial/ethnic groups (sHR: 2.03; 95% CI:1.07, 3.84).CONCLUSIONSApproximately half of FSGS patients achieved remission with IS, but relapse rates were high, and nearly 40% progressed to ESKD. Non-responders and low baseline eGFR had the highest risk. These findings underscore the need for novel therapies to achieve durable disease control, lower relapse rates, and improve outcomes in FSGS.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"80 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240891","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}
Claudio Ronco,Francisco Maduell,Kamyar Kalantar-Zadeh,Magdalena Madero,Thiago Reis
Replacement of kidney function by dialysis maintains the lives of millions of patients. Clinical results however are still unsatisfactory with mortality rates and complications well above the matched control population. This has led to a continuous quest for more effective dialysis techniques and new biomaterials. In the 1980s, the production of synthetic membranes with higher water permeability (i.e., high-flux) leveraged the development of techniques such as hemodiafiltration (HDF) with improved solute removal thanks to combination of diffusion and convection. Efficacy trials have demonstrated the superiority of HDF over high-flux hemodialysis in terms of solute removal, hemodynamic tolerance, and survival. Consequently, the technique gained traction in Europe and Asia. In these trials, a minimum target convection volume (i.e., fluid replaced) of 23 L per session adjusted to body surface area (i.e., 23 L multiplied by ratio of individual body surface area normalized by 1.73 m2), was required to maximize the benefit of the therapy. In general, the replacement fluid is delivered in the post-filter site and to attain this target of 23 L adjusted to body surface area, blood flows must be ≥350 mL/min, requiring 14-15 Gauge needles or ≥14 French catheters to avoid excessive hemoconcentration and circuit pressure issues. In its early days, the replacement solution was provided with sterile bags (offline), making the therapy costly and cumbersome. Online (OL), that is, real-time preparation of ultrapure fluid for replacement has become the key to reduce cost and complexity, while making the technique (OL-HDF) safe and convenient. In the USA however, existing regulations and concerns about safety, prevented approval for clinical use. In 2025, OL-HDF has received approval by the Food and Drug Administration in the USA, and this opens new options and perspectives in the management of people living with kidney failure.
{"title":"The Role of Online Hemodiafiltration in Contemporary Kidney Care.","authors":"Claudio Ronco,Francisco Maduell,Kamyar Kalantar-Zadeh,Magdalena Madero,Thiago Reis","doi":"10.2215/cjn.0000000920","DOIUrl":"https://doi.org/10.2215/cjn.0000000920","url":null,"abstract":"Replacement of kidney function by dialysis maintains the lives of millions of patients. Clinical results however are still unsatisfactory with mortality rates and complications well above the matched control population. This has led to a continuous quest for more effective dialysis techniques and new biomaterials. In the 1980s, the production of synthetic membranes with higher water permeability (i.e., high-flux) leveraged the development of techniques such as hemodiafiltration (HDF) with improved solute removal thanks to combination of diffusion and convection. Efficacy trials have demonstrated the superiority of HDF over high-flux hemodialysis in terms of solute removal, hemodynamic tolerance, and survival. Consequently, the technique gained traction in Europe and Asia. In these trials, a minimum target convection volume (i.e., fluid replaced) of 23 L per session adjusted to body surface area (i.e., 23 L multiplied by ratio of individual body surface area normalized by 1.73 m2), was required to maximize the benefit of the therapy. In general, the replacement fluid is delivered in the post-filter site and to attain this target of 23 L adjusted to body surface area, blood flows must be ≥350 mL/min, requiring 14-15 Gauge needles or ≥14 French catheters to avoid excessive hemoconcentration and circuit pressure issues. In its early days, the replacement solution was provided with sterile bags (offline), making the therapy costly and cumbersome. Online (OL), that is, real-time preparation of ultrapure fluid for replacement has become the key to reduce cost and complexity, while making the technique (OL-HDF) safe and convenient. In the USA however, existing regulations and concerns about safety, prevented approval for clinical use. In 2025, OL-HDF has received approval by the Food and Drug Administration in the USA, and this opens new options and perspectives in the management of people living with kidney failure.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"98 3 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235863","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}
Heather Thiessen Philbrook,David G Hu,Sumit Mohan,Peter P Reese,Mona Doshi,Divyanshu Malhotra,Sherry G Mansour,Isaac E Hall,Kathleen F Kerr,Chirag R Parikh
BACKGROUNDThe identification of kidney transplant recipients at high risk of graft failure enables timely interventions to improve outcomes. We developed and validated a risk prediction model that utilizes changes in estimated glomerular filtration rate (eGFR) to dynamically predict three-year graft failure.METHODSThe risk prediction model was developed in a prospective multi-center cohort of deceased donor kidney transplant recipients (2010-2013) and validated in three independent cohorts (a registry cohort and two Electronic Medical Record (EMR) cohorts). The two-stage approach first estimated eGFR trends using a linear mixed-effects model and then utilized these trends in a logistic regression model to predict three-year graft failure. eGFR was calculated using race-free equation, and graft failure was defined as the return to dialysis or re-transplantation, censored for death. The model can be used at any time within the first three years after transplant, and the predicted risk is dynamically updated with each additional eGFR measurement.RESULTSIn the development cohort (N=1,114), 94 (8%) experienced graft failure within three years of transplant. The model's predictive accuracy improved over time with the increase in available eGFR measurements. The optimism-corrected area under the curve (AUC) was 0.70 (95% confidence interval [CI] 0.63, 0.77) at three months post-transplant and reached an AUC of 0.90 (95% CI 0.85, 0.95) at 30 months post-transplant. Performance was attenuated in the validation cohorts (AUC range 0.60-0.64 at three months to 0.72-0.78 at 30 months), likely due to differences in data collection approaches in ascertaining eGFR.CONCLUSIONThis risk prediction model has the potential to enhance post-transplant care by identifying high-risk recipients who may benefit from closer monitoring and personalized interventions.
背景：对肾移植受者移植物衰竭高危人群的识别有助于及时干预以改善预后。我们开发并验证了一个风险预测模型，该模型利用估计肾小球滤过率（eGFR）的变化来动态预测三年移植失败。方法在2010-2013年死亡肾移植受者的前瞻性多中心队列中建立风险预测模型，并在三个独立队列（一个注册队列和两个电子病历队列）中进行验证。两阶段方法首先使用线性混合效应模型估计eGFR趋势，然后在逻辑回归模型中利用这些趋势来预测三年移植失败。eGFR使用无种族方程计算，移植失败定义为再次透析或再次移植，以死亡为标准。该模型可以在移植后的前三年内的任何时间使用，并且预测的风险随着每次额外的eGFR测量而动态更新。结果在发展队列（N= 1114）中，94例（8%）在移植3年内发生移植失败。随着可用eGFR测量值的增加，该模型的预测精度随着时间的推移而提高。移植后3个月的乐观校正曲线下面积（AUC）为0.70(95%可信区间[CI] 0.63, 0.77)，移植后30个月的AUC为0.90 （95% CI 0.85, 0.95）。在验证队列中，效能下降（3个月时AUC范围为0.60-0.64,30个月时AUC范围为0.72-0.78），可能是由于确定eGFR的数据收集方法的差异。结论该风险预测模型通过识别高危受者，可从更密切的监测和个性化干预中获益，从而有可能加强移植后护理。
{"title":"Dynamic Risk Prediction of Graft Failure After Deceased Donor Kidney Transplant.","authors":"Heather Thiessen Philbrook,David G Hu,Sumit Mohan,Peter P Reese,Mona Doshi,Divyanshu Malhotra,Sherry G Mansour,Isaac E Hall,Kathleen F Kerr,Chirag R Parikh","doi":"10.2215/cjn.0000000883","DOIUrl":"https://doi.org/10.2215/cjn.0000000883","url":null,"abstract":"BACKGROUNDThe identification of kidney transplant recipients at high risk of graft failure enables timely interventions to improve outcomes. We developed and validated a risk prediction model that utilizes changes in estimated glomerular filtration rate (eGFR) to dynamically predict three-year graft failure.METHODSThe risk prediction model was developed in a prospective multi-center cohort of deceased donor kidney transplant recipients (2010-2013) and validated in three independent cohorts (a registry cohort and two Electronic Medical Record (EMR) cohorts). The two-stage approach first estimated eGFR trends using a linear mixed-effects model and then utilized these trends in a logistic regression model to predict three-year graft failure. eGFR was calculated using race-free equation, and graft failure was defined as the return to dialysis or re-transplantation, censored for death. The model can be used at any time within the first three years after transplant, and the predicted risk is dynamically updated with each additional eGFR measurement.RESULTSIn the development cohort (N=1,114), 94 (8%) experienced graft failure within three years of transplant. The model's predictive accuracy improved over time with the increase in available eGFR measurements. The optimism-corrected area under the curve (AUC) was 0.70 (95% confidence interval [CI] 0.63, 0.77) at three months post-transplant and reached an AUC of 0.90 (95% CI 0.85, 0.95) at 30 months post-transplant. Performance was attenuated in the validation cohorts (AUC range 0.60-0.64 at three months to 0.72-0.78 at 30 months), likely due to differences in data collection approaches in ascertaining eGFR.CONCLUSIONThis risk prediction model has the potential to enhance post-transplant care by identifying high-risk recipients who may benefit from closer monitoring and personalized interventions.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"123 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235861","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}
BACKGROUND AND OBJECTIVESThe combination of a low-protein diet supplemented with ketoacid analogs and amino acids (KA-AA) (sLPD)-which has been shown to be safe for patients with diabetic kidney disease (DKD) in some previous studies-and the anti-diabetic sodium-glucose cotransporter-2 inhibitors (SGLT2i)-known for their cardiovascular and kidney protective effects-may represent a treatment strategy for patients with advanced DKD. However, this combination has rarely been investigated in previous studies.METHODSThis retrospective cohort study included a total of 1729 adult type 2 diabetes mellitus patients with an estimated glomerular filtration rate (eGFR) equal or below 30 mL/min/1.73 m2 and newly received sLPD treatment. We then divided the patients into two groups based on whether they received a combination of KA-AA and SGLT2i (combination group) or KA-AA alone (KA-AA group). Inverse probability of treatment weighting was performed to balance baseline characteristics.RESULTSFor three-year follow-up, compared with KA-AA group, the combination group exhibited significantly lower risks of all-cause death (16% vs. 27%, hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.61-0.87), composite of all-cause death and End-stage kidney disease (ESKD) (54% vs. 63%, subdistribution HR [SHR]: 0.84, 95% CI: 0.75-0.93), and cardiovascular death (7% vs. 12%, SHR: 0.68, 95% CI: 0.52-0.89). The risk of new-onset ESKD requiring dialysis and heart failure related hospitalization did not significantly differ.CONCLUSIONSThese findings suggest that the addition of SGLT2 inhibitors to KA-AA sLPD are associated with lower all-cause and cardiovascular mortality.
{"title":"Combining Ketoacid Analog Supplemented Low-Protein Diets with Sodium-Glucose Cotransporter-2 Inhibitors for Patients with Diabetic Kidney Disease.","authors":"Chieh-Li Yen,Pei-Chun Fan,Cheng-Chia Lee,Jia-Jin Chen,Yueh-An Lu,Yi-Ran Tu,Pao-Hsien Chu,Ching-Chung Hsiao,Yung-Chang Chen,Chih-Hsiang Chang","doi":"10.2215/cjn.0000000846","DOIUrl":"https://doi.org/10.2215/cjn.0000000846","url":null,"abstract":"BACKGROUND AND OBJECTIVESThe combination of a low-protein diet supplemented with ketoacid analogs and amino acids (KA-AA) (sLPD)-which has been shown to be safe for patients with diabetic kidney disease (DKD) in some previous studies-and the anti-diabetic sodium-glucose cotransporter-2 inhibitors (SGLT2i)-known for their cardiovascular and kidney protective effects-may represent a treatment strategy for patients with advanced DKD. However, this combination has rarely been investigated in previous studies.METHODSThis retrospective cohort study included a total of 1729 adult type 2 diabetes mellitus patients with an estimated glomerular filtration rate (eGFR) equal or below 30 mL/min/1.73 m2 and newly received sLPD treatment. We then divided the patients into two groups based on whether they received a combination of KA-AA and SGLT2i (combination group) or KA-AA alone (KA-AA group). Inverse probability of treatment weighting was performed to balance baseline characteristics.RESULTSFor three-year follow-up, compared with KA-AA group, the combination group exhibited significantly lower risks of all-cause death (16% vs. 27%, hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.61-0.87), composite of all-cause death and End-stage kidney disease (ESKD) (54% vs. 63%, subdistribution HR [SHR]: 0.84, 95% CI: 0.75-0.93), and cardiovascular death (7% vs. 12%, SHR: 0.68, 95% CI: 0.52-0.89). The risk of new-onset ESKD requiring dialysis and heart failure related hospitalization did not significantly differ.CONCLUSIONSThese findings suggest that the addition of SGLT2 inhibitors to KA-AA sLPD are associated with lower all-cause and cardiovascular mortality.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"62 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203626","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}
Pub Date : 2025-10-01Epub Date: 2025-03-19DOI: 10.2215/CJN.0000000714
Raad B Chowdhury, Jessica L Ortega, Sophia L Wells, Marta Pirovano, Raphael Kim, Carolina S Lima, Mohit Madken, Sheikh B Khalid, Rania El Fekih, Firasat M Alikhan, Alexa C Peterkin, Gearoid M McMahon, David B Mount, Joseph V Bonventre, Shruti Gupta
{"title":"Innovating Kidney Care in Patients with Cancer: Development of an Inpatient Onconephrology Service.","authors":"Raad B Chowdhury, Jessica L Ortega, Sophia L Wells, Marta Pirovano, Raphael Kim, Carolina S Lima, Mohit Madken, Sheikh B Khalid, Rania El Fekih, Firasat M Alikhan, Alexa C Peterkin, Gearoid M McMahon, David B Mount, Joseph V Bonventre, Shruti Gupta","doi":"10.2215/CJN.0000000714","DOIUrl":"10.2215/CJN.0000000714","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":" ","pages":"1470-1473"},"PeriodicalIF":7.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Beyond Diffusion: Harnessing Physical Principles for Precision Kidney Replacement Therapy.","authors":"Franklin W Maddux,Ryan A Jimenez","doi":"10.2215/cjn.0000000917","DOIUrl":"https://doi.org/10.2215/cjn.0000000917","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"17 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203625","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}
This year commemorates the 75th anniversary of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), one of the 27 institutes and centers of the National Institutes of Health. A core mission of the NIDDK has been the advancement and support of biomedical research across a diverse spectrum of disciplines, including endocrine and metabolic diseases, digestive and nutritional disorders, obesity, urologic and benign hematologic conditions, and, notably, kidney diseases, which has been a major focus of the institute's strategic priorities. Through the years, the NIDDK has heavily invested in biomedical infrastructure, foundational studies, and cross-cutting basic science, clinical investigation, epidemiology, and health services research, which have fundamentally shaped the detection, management, and prevention of kidney diseases worldwide. Furthermore, the NIDDK has had a longstanding commitment to promoting workforce development, advancing equal access to kidney health care, and forging collaborative partnerships with academic centers, federal agencies, professional societies, patient advocacy organizations, community groups, and industry stakeholders toward the shared goal of improving kidney disease outcomes. In this review published across the three American Society of Nephrology journals, we celebrate the landmark achievements and profound effect of the NIDDK in improving the health and well-being of people living with kidney diseases.
{"title":"Commemorating the National Institute of Diabetes and Digestive and Kidney Diseases' Advances in Kidney Health: 75 Years of Discovery and Impact.","authors":"Connie M Rhee,Michael Allon,Rajnish Mehrotra","doi":"10.2215/cjn.0000000906","DOIUrl":"https://doi.org/10.2215/cjn.0000000906","url":null,"abstract":"This year commemorates the 75th anniversary of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), one of the 27 institutes and centers of the National Institutes of Health. A core mission of the NIDDK has been the advancement and support of biomedical research across a diverse spectrum of disciplines, including endocrine and metabolic diseases, digestive and nutritional disorders, obesity, urologic and benign hematologic conditions, and, notably, kidney diseases, which has been a major focus of the institute's strategic priorities. Through the years, the NIDDK has heavily invested in biomedical infrastructure, foundational studies, and cross-cutting basic science, clinical investigation, epidemiology, and health services research, which have fundamentally shaped the detection, management, and prevention of kidney diseases worldwide. Furthermore, the NIDDK has had a longstanding commitment to promoting workforce development, advancing equal access to kidney health care, and forging collaborative partnerships with academic centers, federal agencies, professional societies, patient advocacy organizations, community groups, and industry stakeholders toward the shared goal of improving kidney disease outcomes. In this review published across the three American Society of Nephrology journals, we celebrate the landmark achievements and profound effect of the NIDDK in improving the health and well-being of people living with kidney diseases.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"2 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194513","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}
Meng Wang,W H Wilson Tang,Xinmin S Li,Marcia C de Oliveira Otto,Rozenn N Lemaitre,Amanda Fretts,Ina Nemet,Nona Sotoodehnia,Colleen M Sitlani,Matthew Budoff,Joseph A DiDonato,Zeneng Wang,David S Siscovick,Mark J Sarnak,Dariush Mozaffarian,Stanley L Hazen
BACKGROUNDTrimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite of dietary phosphatidylcholine and carnitine. Mechanistically, TMAO raises urine albumin to creatinine ratio (UACR). However, little is known in humans about prospective associations between TMAO-related biomarkers and albuminuria, an early, sensitive marker of kidney damage.METHODSWe included 6,723 participants with TMAO-related biomarkers and UACR at baseline and follow-up data from July 2000 to May 2019 from a diverse cohort of community-based US adults. Plasma TMAO-related biomarkers (TMAO, γ-butyrobetaine, and crotonobetaine; and secondarily, carnitine, choline, and betaine) were measured using liquid chromatography tandem mass spectrometry at baseline and year five. UACR was measured at up to five visits. The co-primary outcomes were incident increased albuminuria, defined as at least two consecutive UACR measures ≥ 30mg/g during follow-up; and rate of UACR change over time. The secondary outcome was severely increased albuminuria, defined as a new UACR ≥ 300mg/g. Time-varying Cox models assessed associations of biomarkers with incident albuminuria; and linear mixed models with rate of UACR change; adjusting for sociodemographic, lifestyle, diet, and cardiovascular disease risk factors.RESULTSDuring a median follow-up of 15.7 years, 648 participants experienced increased albuminuria and 197 experienced severely increased albuminuria. TMAO levels positively associated with both outcomes (highest vs. lowest quintile HR [95%CI] = 1.41 [1.05-1.89] and 1.73 [0.99-3.00], respectively, P-trend<0.01 each). TMAO also associated with greater rate of UACR increase (adjusted percent change per 10-years = 22.1% in the lowest vs. 40.6% in the highest quintile, P-trend<0.001). Crotonobetaine and γ-butyrobetaine levels also associated with rate of UACR increase, as did carnitine, while choline levels positively associated with all three outcomes.CONCLUSIONSTMAO-related gut microbial metabolites may be a novel risk factor for albuminuria and its progression, raising the need to investigate the role of targeting the TMAO pathway on albuminuria.
{"title":"Associations of Plasma Trimethylamine N-Oxide-Related Metabolites with the Development and Progression of Albuminuria: The Multi-Ethnic Study of Atherosclerosis.","authors":"Meng Wang,W H Wilson Tang,Xinmin S Li,Marcia C de Oliveira Otto,Rozenn N Lemaitre,Amanda Fretts,Ina Nemet,Nona Sotoodehnia,Colleen M Sitlani,Matthew Budoff,Joseph A DiDonato,Zeneng Wang,David S Siscovick,Mark J Sarnak,Dariush Mozaffarian,Stanley L Hazen","doi":"10.2215/cjn.0000000812","DOIUrl":"https://doi.org/10.2215/cjn.0000000812","url":null,"abstract":"BACKGROUNDTrimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite of dietary phosphatidylcholine and carnitine. Mechanistically, TMAO raises urine albumin to creatinine ratio (UACR). However, little is known in humans about prospective associations between TMAO-related biomarkers and albuminuria, an early, sensitive marker of kidney damage.METHODSWe included 6,723 participants with TMAO-related biomarkers and UACR at baseline and follow-up data from July 2000 to May 2019 from a diverse cohort of community-based US adults. Plasma TMAO-related biomarkers (TMAO, γ-butyrobetaine, and crotonobetaine; and secondarily, carnitine, choline, and betaine) were measured using liquid chromatography tandem mass spectrometry at baseline and year five. UACR was measured at up to five visits. The co-primary outcomes were incident increased albuminuria, defined as at least two consecutive UACR measures ≥ 30mg/g during follow-up; and rate of UACR change over time. The secondary outcome was severely increased albuminuria, defined as a new UACR ≥ 300mg/g. Time-varying Cox models assessed associations of biomarkers with incident albuminuria; and linear mixed models with rate of UACR change; adjusting for sociodemographic, lifestyle, diet, and cardiovascular disease risk factors.RESULTSDuring a median follow-up of 15.7 years, 648 participants experienced increased albuminuria and 197 experienced severely increased albuminuria. TMAO levels positively associated with both outcomes (highest vs. lowest quintile HR [95%CI] = 1.41 [1.05-1.89] and 1.73 [0.99-3.00], respectively, P-trend<0.01 each). TMAO also associated with greater rate of UACR increase (adjusted percent change per 10-years = 22.1% in the lowest vs. 40.6% in the highest quintile, P-trend<0.001). Crotonobetaine and γ-butyrobetaine levels also associated with rate of UACR increase, as did carnitine, while choline levels positively associated with all three outcomes.CONCLUSIONSTMAO-related gut microbial metabolites may be a novel risk factor for albuminuria and its progression, raising the need to investigate the role of targeting the TMAO pathway on albuminuria.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"42 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140261","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}
{"title":"Gut Microbiota Metabolites and the Development of CKD.","authors":"Marie Evans,Peter Stenvinkel","doi":"10.2215/cjn.0000000887","DOIUrl":"https://doi.org/10.2215/cjn.0000000887","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"93 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140312","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：