Short-term heat exposure has been linked with increased risks of acute kidney injury and chronic kidney disease (CKD), but the impact on the incidence or prevalence of CKD is unknown. This study examines the association of high temperatures with CKD prevalence and end-stage kidney disease (ESKD) incidence at county level in the US. County-level diagnosed CKD prevalence data (2005-2019) among Medicare enrollees aged ≥65 years from the US Kidney Disease Surveillance System and ESKD incidence data (2010-2019) from the United States Renal Data System were analyzed. County-specific heat exposure measurements included annual average temperature (AAT) and annual heat wave days (HWD) from nClimGrid-Daily dataset (US National Centers for Environmental Information). We used a linear mixed model to assess associations between heat exposure and diagnosed CKD prevalence as well as ESKD incidence, while geographically weighted regression assessed spatial variations, adjusting for time-trend, county-specific factors and demographics. Stratified analysis compared associations across socioeconomic subgroups. AAT had significantly positive associations with diagnosed CKD prevalence and ESKD incidence. Each 1°C increase in AAT was associated with a 0.23 (95% CI: 0.20-0.27) percentage point increase in the prevalence of diagnosed CKD. Similarly, each 1°C increase in AAT was associated with an additional 1.37 (95% CI: 1.08-1.65) ESKD cases/100,000 population. HWDs were positively associated with both kidney outcomes, and the strength of these associations increased with higher temperature thresholds and longer duration. Stronger associations between heat exposure and both kidney outcomes were observed in high poverty and nonmetropolitan counties (P<0.05). The strength of associations was greater in counties in southern and northwestern regions. The associations between ambient temperature and kidney health, with socioeconomic and regional differences, may have implications for interventions aimed at reducing the potential effects of high temperatures on kidney health, particularly in vulnerable populations.
{"title":"The Association of High Ambient Temperatures and Kidney Disease: A Kidney Disease Surveillance System (KDSS) Ecological Study.","authors":"Fulin Wang,Fengyu Wen,Yun Han,Jennifer Bragg-Gresham,Arun Agrawal,Sola Han,Meda E Pavkov,Chao Yang,Luxia Zhang,Rajiv Saran","doi":"10.2215/cjn.0000000935","DOIUrl":"https://doi.org/10.2215/cjn.0000000935","url":null,"abstract":"Short-term heat exposure has been linked with increased risks of acute kidney injury and chronic kidney disease (CKD), but the impact on the incidence or prevalence of CKD is unknown. This study examines the association of high temperatures with CKD prevalence and end-stage kidney disease (ESKD) incidence at county level in the US. County-level diagnosed CKD prevalence data (2005-2019) among Medicare enrollees aged ≥65 years from the US Kidney Disease Surveillance System and ESKD incidence data (2010-2019) from the United States Renal Data System were analyzed. County-specific heat exposure measurements included annual average temperature (AAT) and annual heat wave days (HWD) from nClimGrid-Daily dataset (US National Centers for Environmental Information). We used a linear mixed model to assess associations between heat exposure and diagnosed CKD prevalence as well as ESKD incidence, while geographically weighted regression assessed spatial variations, adjusting for time-trend, county-specific factors and demographics. Stratified analysis compared associations across socioeconomic subgroups. AAT had significantly positive associations with diagnosed CKD prevalence and ESKD incidence. Each 1°C increase in AAT was associated with a 0.23 (95% CI: 0.20-0.27) percentage point increase in the prevalence of diagnosed CKD. Similarly, each 1°C increase in AAT was associated with an additional 1.37 (95% CI: 1.08-1.65) ESKD cases/100,000 population. HWDs were positively associated with both kidney outcomes, and the strength of these associations increased with higher temperature thresholds and longer duration. Stronger associations between heat exposure and both kidney outcomes were observed in high poverty and nonmetropolitan counties (P<0.05). The strength of associations was greater in counties in southern and northwestern regions. The associations between ambient temperature and kidney health, with socioeconomic and regional differences, may have implications for interventions aimed at reducing the potential effects of high temperatures on kidney health, particularly in vulnerable populations.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"66 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937696","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}
Megan E Astley,Alberto Ortiz,Stein Hallan,Giovanni Gambaro,Juan-Jesus Carrero,Natalie Ebert,Bjørn Odvar Eriksen,Anne-Laure Faucon,Pietro Manuel Ferraro,Till Ittermann,Olafur S Indridason,Knut Asbjørn Rise Langlo,Toralf Melsom,Andrew D Rule,Elke Schaeffner,Sylvia Stracke,Runolfur Palsson,Kitty J Jager,Vianda S Stel,Nicholas C Chesnaye
The extent to which estimated glomerular filtration rate (eGFR) varies across populations, in the absence of risk factors and comorbidities associated with kidney disease, remains uncertain. We aimed to develop eGFR reference values in healthy American adults and to compare them with previously described European eGFR reference values. This cross-sectional study compared newly described age- and sex-specific creatinine-based eGFR reference values from over 9,000 healthy Americans from National Health and Nutrition Examination Survey (NHANES) with previously described eGFR reference values from over 1.5 million healthy individuals in the European Chronic Kidney Disease (CKD) Burden Consortium. Health status was based on 14 criteria related to comorbidities, lifestyle factors and medication use. eGFR was calculated using the European Kidney Function Consortium equation and modelled over the age span and by sex using a generalized additive model. Median eGFR in both 20-year-old American and European men was 98 mL/min/1.73 m2. In both 20-year-old American and European women, median eGFR was 101 mL/min/1.73 m2. eGFR started to decrease at the age of 40 years, a result of the structure of the EKFC equation. By age 79 years, median eGFR in American and European men was 68 mL/min/1.73 m2 and 67 mL/min/1.73 m2, respectively. Median eGFR in 79-year-old American and European women was 63 mL/min/1.73 m2 and 64 mL/min/1.73 m2, respectively. When removing the effect of comorbidities, lifestyle factors and medication use associated with kidney function, achieved by restricting the analyses to individuals who did not have a presence or history of certain criteria, the distribution of eGFR was similar between healthy Americans and Europeans. This supports the notion that eGFR reference values may be generalizable to populations they were not derived from.
{"title":"Comparing Age and Sex Specific Reference Values of Estimated Glomerular Filtration Rate between the United States and Europe.","authors":"Megan E Astley,Alberto Ortiz,Stein Hallan,Giovanni Gambaro,Juan-Jesus Carrero,Natalie Ebert,Bjørn Odvar Eriksen,Anne-Laure Faucon,Pietro Manuel Ferraro,Till Ittermann,Olafur S Indridason,Knut Asbjørn Rise Langlo,Toralf Melsom,Andrew D Rule,Elke Schaeffner,Sylvia Stracke,Runolfur Palsson,Kitty J Jager,Vianda S Stel,Nicholas C Chesnaye","doi":"10.2215/cjn.0000000956","DOIUrl":"https://doi.org/10.2215/cjn.0000000956","url":null,"abstract":"The extent to which estimated glomerular filtration rate (eGFR) varies across populations, in the absence of risk factors and comorbidities associated with kidney disease, remains uncertain. We aimed to develop eGFR reference values in healthy American adults and to compare them with previously described European eGFR reference values. This cross-sectional study compared newly described age- and sex-specific creatinine-based eGFR reference values from over 9,000 healthy Americans from National Health and Nutrition Examination Survey (NHANES) with previously described eGFR reference values from over 1.5 million healthy individuals in the European Chronic Kidney Disease (CKD) Burden Consortium. Health status was based on 14 criteria related to comorbidities, lifestyle factors and medication use. eGFR was calculated using the European Kidney Function Consortium equation and modelled over the age span and by sex using a generalized additive model. Median eGFR in both 20-year-old American and European men was 98 mL/min/1.73 m2. In both 20-year-old American and European women, median eGFR was 101 mL/min/1.73 m2. eGFR started to decrease at the age of 40 years, a result of the structure of the EKFC equation. By age 79 years, median eGFR in American and European men was 68 mL/min/1.73 m2 and 67 mL/min/1.73 m2, respectively. Median eGFR in 79-year-old American and European women was 63 mL/min/1.73 m2 and 64 mL/min/1.73 m2, respectively. When removing the effect of comorbidities, lifestyle factors and medication use associated with kidney function, achieved by restricting the analyses to individuals who did not have a presence or history of certain criteria, the distribution of eGFR was similar between healthy Americans and Europeans. This supports the notion that eGFR reference values may be generalizable to populations they were not derived from.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"25 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836220","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}
Johannes Wedel,Ying Tang,Bayan Alsairafi,Vicki Do,Madeline Maslyar,Ryan Fleming,Marc A Schwartz,Ulrike Gerdemann,Alexandre Albanese,Vanessa Mitsialis,Lauren V Collen,Miki Nishitani,Mairead Bresnahan,Gwen Saccocia,Richelle Bearup,Ibeawuchi Okoroafor,Steven J Siegel,Franziska Wachter,Katherine Waters,Nina Weichert-Leahey,Nigel J Clarke,Kenneth D Mandl,Leslie S Kean,Scott B Snapper,David M Briscoe,Bruce H Horwitz
BACKGROUNDImmunosuppressive therapy following solid organ transplantation inhibits protective immunity to pathogens and vaccines. However, the specific cell states associated with failure to generate responsiveness to vaccination are not known.METHODSWe evaluated a broad spectrum of immune cell states within peripheral blood of twelve pediatric solid organ transplant recipients (SOTR) and eight healthy children immediately prior to receiving SARS-CoV-2 vaccination, by performing single cell RNA-sequencing, T cell receptor sequencing and Cytometry by Time-Of-Flight. We then evaluated associations between the identified cell states and the development of anti-SARS-CoV-2 S-protein specific antibody and CD4+ T cell activation following an initial series of SARS-CoV-2 vaccinations.RESULTSWe found clonal expansion of a subset of CD8+ effector T cells and a polyclonal expansion of CD4+ effector T cell populations in SOTR compared to healthy controls. Responses to vaccination included normal SARS-CoV-2 specific T cell and antibody responses, intact T cell but impaired antibody responses, and absence of T cell and antibody responses. Comparison among the pre-vaccination cell states and responsiveness revealed a higher frequency of atypical B cells in SOTR with intact T cell, but impaired antibody responses compared to healthy controls. Also, T cell only SOTR responders had lower numbers of immature γδ T cells compared to SOTR non-responders. In contrast, there was no definitive cell state that identified an absent immune response in SOTR, but interactome analysis suggested that robust cellular interactions between myeloid, T cells and B cells are required for successful responses to vaccination.CONCLUSIONSOur findings in this exploratory observational study suggest that higher frequencies of atypical B cells in the peripheral blood of pediatric SOTR may identify intact cellular but absent humoral responsiveness to vaccination. Intact T cell responsiveness to antigen may be sufficient to monitor protective immunity following vaccination in SOTR.
{"title":"Multiomic Immune Profiling of Pediatric Transplant Recipients Identifies Cell States Associated with Vaccine Response.","authors":"Johannes Wedel,Ying Tang,Bayan Alsairafi,Vicki Do,Madeline Maslyar,Ryan Fleming,Marc A Schwartz,Ulrike Gerdemann,Alexandre Albanese,Vanessa Mitsialis,Lauren V Collen,Miki Nishitani,Mairead Bresnahan,Gwen Saccocia,Richelle Bearup,Ibeawuchi Okoroafor,Steven J Siegel,Franziska Wachter,Katherine Waters,Nina Weichert-Leahey,Nigel J Clarke,Kenneth D Mandl,Leslie S Kean,Scott B Snapper,David M Briscoe,Bruce H Horwitz","doi":"10.2215/cjn.0000000949","DOIUrl":"https://doi.org/10.2215/cjn.0000000949","url":null,"abstract":"BACKGROUNDImmunosuppressive therapy following solid organ transplantation inhibits protective immunity to pathogens and vaccines. However, the specific cell states associated with failure to generate responsiveness to vaccination are not known.METHODSWe evaluated a broad spectrum of immune cell states within peripheral blood of twelve pediatric solid organ transplant recipients (SOTR) and eight healthy children immediately prior to receiving SARS-CoV-2 vaccination, by performing single cell RNA-sequencing, T cell receptor sequencing and Cytometry by Time-Of-Flight. We then evaluated associations between the identified cell states and the development of anti-SARS-CoV-2 S-protein specific antibody and CD4+ T cell activation following an initial series of SARS-CoV-2 vaccinations.RESULTSWe found clonal expansion of a subset of CD8+ effector T cells and a polyclonal expansion of CD4+ effector T cell populations in SOTR compared to healthy controls. Responses to vaccination included normal SARS-CoV-2 specific T cell and antibody responses, intact T cell but impaired antibody responses, and absence of T cell and antibody responses. Comparison among the pre-vaccination cell states and responsiveness revealed a higher frequency of atypical B cells in SOTR with intact T cell, but impaired antibody responses compared to healthy controls. Also, T cell only SOTR responders had lower numbers of immature γδ T cells compared to SOTR non-responders. In contrast, there was no definitive cell state that identified an absent immune response in SOTR, but interactome analysis suggested that robust cellular interactions between myeloid, T cells and B cells are required for successful responses to vaccination.CONCLUSIONSOur findings in this exploratory observational study suggest that higher frequencies of atypical B cells in the peripheral blood of pediatric SOTR may identify intact cellular but absent humoral responsiveness to vaccination. Intact T cell responsiveness to antigen may be sufficient to monitor protective immunity following vaccination in SOTR.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"22 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145823874","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":"A Global Health Perspective on the ASN Guidance for Outpatient Management of Dialysis-Requiring AKI.","authors":"Vivek Kumar,Vivekanand Jha","doi":"10.2215/cjn.0000000988","DOIUrl":"https://doi.org/10.2215/cjn.0000000988","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"34 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145813503","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}
BACKGROUNDMembranoproliferative glomerulonephritides (MPGNs) are defined by a typical glomerular histopathological pattern including C3 glomerulopathy (C3G) and immune complex-mediated MPGN (IC-MPGN). The overall prognosis is poor and the treatment options remain limited. Outcome predictors and reliable surrogate endpoints are critically needed for interventional trials. Herein, we described the natural history and analyzed clinical, histological and biochemical data from a large cohort of patients with primary C3G/IC-MPGN.METHODSThis is a retrospective analysis of patients with biopsy-proven primary C3G or IC-MPGN from the Italian Registry of MPGN. Demographic, clinical and histopathological data, molecular complement profiles, treatment patterns, and outcomes were collected. We performed univariable and multivariable Cox regressions and Kaplan-Meier survival analyses to assess risk associations with kidney disease progression. The composite endpoint included end-stage kidney disease (ESKD, defined by either eGFR <15 ml/min/1.73m2, initiation of chronic dialysis or kidney transplantation), doubling of serum creatinine at the last available follow-up, or death by kidney-related causes.RESULTSOf the 349 patients identified, 208 had C3G and 141 IC-MPGN. Females were 41%, and over half were younger than 18 years old at time of biopsy. C3G and IC-MPGN patients shared most baseline and longitudinal features, with IC-MPGN patients presenting with higher baseline proteinuria (median 4.0 vs. 2.3 grams/24hours, p<0.001). Median estimated Glomerular Filtration Rate (eGFR) at presentation was 83 ml/minute/1.73m2. Twenty-six % of patients progressed to ESKD over a median follow-up of 5 years from diagnosis. Higher proteinuria levels at one year from biopsy, particularly ≥1gram/24hours, were significantly associated with a higher risk of adverse kidney outcomes. Pediatric onset was associated with better kidney survival, whereas kidney survival at 10 years did not statistically differ across histological subtypes. Complement dysregulation and rare functional variants in complement genes did were not associated with outcomes.CONCLUSIONSOur findings from a large and well-characterized cohort of individuals with primary C3G/IC-MPGN identify age at onset and proteinuria levels as associations with kidney survival, a finding that should inform future interventional trials.
{"title":"Natural History and Clinical Associations with Long-Term Outcomes in Primary C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis.","authors":"Giliane Nanchen,Maddalena Marasà,Matteo Breno,Carolina Martinatto,Miriam Rigoldi,Marina Noris,Elena Bresin,Sara Gamba,Laura Bottanelli,Zahra Imanifard,Rossella Piras,Roberta Donadelli,Matias Trillini,Francesco Emma,Marina Vivarelli,Luca Antonucci,Camillo Carrara,Piero Ruggenenti,Gaetano La Manna,Giorgia Comai,Enrico Vidal,Valeria Silecchia,Andrea Pasini,Andrea Ranghino,Alessandra Cingolani,Gabriele Donati,Silvia Giovanella,Luigi Biancone,Laura Valenza,Enrico Verrina,Andrea Angeletti,Giuliano Brunori,Laura Sottini,Mario Giordano,Diletta Domenica Torres,Federico Alberici,Federica Mescia,Umberto Maggiore,Micaela Gentile,Ariela Benigni,Giuseppe Remuzzi,Erica Daina, ","doi":"10.2215/cjn.0000000953","DOIUrl":"https://doi.org/10.2215/cjn.0000000953","url":null,"abstract":"BACKGROUNDMembranoproliferative glomerulonephritides (MPGNs) are defined by a typical glomerular histopathological pattern including C3 glomerulopathy (C3G) and immune complex-mediated MPGN (IC-MPGN). The overall prognosis is poor and the treatment options remain limited. Outcome predictors and reliable surrogate endpoints are critically needed for interventional trials. Herein, we described the natural history and analyzed clinical, histological and biochemical data from a large cohort of patients with primary C3G/IC-MPGN.METHODSThis is a retrospective analysis of patients with biopsy-proven primary C3G or IC-MPGN from the Italian Registry of MPGN. Demographic, clinical and histopathological data, molecular complement profiles, treatment patterns, and outcomes were collected. We performed univariable and multivariable Cox regressions and Kaplan-Meier survival analyses to assess risk associations with kidney disease progression. The composite endpoint included end-stage kidney disease (ESKD, defined by either eGFR <15 ml/min/1.73m2, initiation of chronic dialysis or kidney transplantation), doubling of serum creatinine at the last available follow-up, or death by kidney-related causes.RESULTSOf the 349 patients identified, 208 had C3G and 141 IC-MPGN. Females were 41%, and over half were younger than 18 years old at time of biopsy. C3G and IC-MPGN patients shared most baseline and longitudinal features, with IC-MPGN patients presenting with higher baseline proteinuria (median 4.0 vs. 2.3 grams/24hours, p<0.001). Median estimated Glomerular Filtration Rate (eGFR) at presentation was 83 ml/minute/1.73m2. Twenty-six % of patients progressed to ESKD over a median follow-up of 5 years from diagnosis. Higher proteinuria levels at one year from biopsy, particularly ≥1gram/24hours, were significantly associated with a higher risk of adverse kidney outcomes. Pediatric onset was associated with better kidney survival, whereas kidney survival at 10 years did not statistically differ across histological subtypes. Complement dysregulation and rare functional variants in complement genes did were not associated with outcomes.CONCLUSIONSOur findings from a large and well-characterized cohort of individuals with primary C3G/IC-MPGN identify age at onset and proteinuria levels as associations with kidney survival, a finding that should inform future interventional trials.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"2 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145813474","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}
Yan Zhang,Anke Winter,Linda H Ficociello,Belén Alejos Ferreras,Paola Carioni,Christian Apel,Otto Arkossy,Michael Anger,Robert Kossmann,Len A Usvyat,Stefano Stuard
BACKGROUNDPatients with end stage kidney disease undergoing hemodialysis (HD) experience high rates of hospitalizations and mortality, partly due to the incomplete removal of some toxic uremic molecules. To improve outcomes, multiple modalities of kidney replacement therapy have been developed, including high-flux HD and on-line hemodiafiltration (HDF). Notably, on-line high-volume HDF (HV-HDF) has demonstrated mortality benefits over high-flux HD in some randomized trials.METHODSThis retrospective cohort study evaluated hospitalization outcomes among in-center dialysis patients treated with HV-HDF and high-flux HD at Fresenius Medical Care NephroCare centers across Europe, the Middle East, and Africa between January 2019 and December 2022. Data were extracted from the European Clinical Database. The primary outcome was all-cause hospitalization; secondary outcomes included cause-specific hospitalizations. Negative binomial regression was used to estimate incidence rate ratio (IRR) for hospital outcomes, incorporating inverse probability of treatment weighting (IPTW) to adjust for baseline differences between treatment groups.RESULTSA total of 71,669 patients were included, with 45% receiving HD and 55% receiving HDF. During the follow-up period, patients in the HDF group underwent a total of 12,741,453 HDF treatments, with a mean convection volume of 25.8L. Compared to HD, treatment with HDF was associated with a lower incidence of both hospital admissions (adjusted IRR, 0.80; 95% confidence interval [CI], 0.79-0.82) and days spent in the hospital (adjusted IRR, 0.80; 95% CI, 0.78-0.82). These reductions were consistent across subgroups analyzed and across most major causes of hospitalization, including cardiovascular disease, infections, and fluid-related complications.CONCLUSIONSIn this large, real-world cohort spanning multiple regions and dialysis centers, HV-HDF was associated with significantly lower rates of both hospital admissions and days spent in the hospital compared to treatment with high-flux HD. These findings suggest that HV-HDF may have the potential to reduce morbidity in patients with ESKD.
{"title":"Real-World Hospitalization Outcomes with On-Line Hemodiafiltration versus High-Flux Hemodialysis: A Retrospective, International Cohort Study.","authors":"Yan Zhang,Anke Winter,Linda H Ficociello,Belén Alejos Ferreras,Paola Carioni,Christian Apel,Otto Arkossy,Michael Anger,Robert Kossmann,Len A Usvyat,Stefano Stuard","doi":"10.2215/cjn.0000000955","DOIUrl":"https://doi.org/10.2215/cjn.0000000955","url":null,"abstract":"BACKGROUNDPatients with end stage kidney disease undergoing hemodialysis (HD) experience high rates of hospitalizations and mortality, partly due to the incomplete removal of some toxic uremic molecules. To improve outcomes, multiple modalities of kidney replacement therapy have been developed, including high-flux HD and on-line hemodiafiltration (HDF). Notably, on-line high-volume HDF (HV-HDF) has demonstrated mortality benefits over high-flux HD in some randomized trials.METHODSThis retrospective cohort study evaluated hospitalization outcomes among in-center dialysis patients treated with HV-HDF and high-flux HD at Fresenius Medical Care NephroCare centers across Europe, the Middle East, and Africa between January 2019 and December 2022. Data were extracted from the European Clinical Database. The primary outcome was all-cause hospitalization; secondary outcomes included cause-specific hospitalizations. Negative binomial regression was used to estimate incidence rate ratio (IRR) for hospital outcomes, incorporating inverse probability of treatment weighting (IPTW) to adjust for baseline differences between treatment groups.RESULTSA total of 71,669 patients were included, with 45% receiving HD and 55% receiving HDF. During the follow-up period, patients in the HDF group underwent a total of 12,741,453 HDF treatments, with a mean convection volume of 25.8L. Compared to HD, treatment with HDF was associated with a lower incidence of both hospital admissions (adjusted IRR, 0.80; 95% confidence interval [CI], 0.79-0.82) and days spent in the hospital (adjusted IRR, 0.80; 95% CI, 0.78-0.82). These reductions were consistent across subgroups analyzed and across most major causes of hospitalization, including cardiovascular disease, infections, and fluid-related complications.CONCLUSIONSIn this large, real-world cohort spanning multiple regions and dialysis centers, HV-HDF was associated with significantly lower rates of both hospital admissions and days spent in the hospital compared to treatment with high-flux HD. These findings suggest that HV-HDF may have the potential to reduce morbidity in patients with ESKD.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"8 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145813501","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}
Jennifer Yee,Wu Gong,Jula Inrig,Michelle N Rheault,Angela J Gruber,Patricia W Bedard,Radko Komers,Howard Trachtman
BACKGROUNDFocal segmental glomerulosclerosis (FSGS) is a podocytopathy that is diagnosed based on characteristic histopathological lesions. Certain forms of FSGS with underlying genetic variants associated with the disease, including variants in podocyte proteins, as well as apolipoprotein L1 (APOL1) risk alleles, and variants in collagen type IV (COL4) α3, α4, and α5 (COL4A3-5) proteins, are typically resistant to current treatments.METHODSThe DUPLEX clinical trial assessed the efficacy and safety of sparsentan, a dual endothelin angiotensin receptor antagonist (DEARA), in patients with biopsy-proven or genetic FSGS and demonstrated a greater antiproteinuric effect over 108 weeks compared to the active control irbesartan. This post hoc, exploratory analysis assessed the efficacy of sparsentan in the subset of patients enrolled in DUPLEX who had pathogenic variants in genes coding for podocyte proteins, COL4A3-5 variants, and APOL1 high-risk genotypes, altogether referred to as genetic FSGS (gFSGS).RESULTSNext-generation sequencing identified 31 patients with podocyte gene variants, 25 with COL4A3-5 gene variants, and 14 with APOL1 high-risk genotypes. Baseline characteristics varied between genetic subgroups, with slightly younger patients, on average, in the podocyte gene variant group, and more African American patients in the APOL1 high-risk genotype group. In this exploratory analysis, sparsentan treatment resulted in substantial and sustained proteinuria reductions and numerically more frequent complete remission of proteinuria compared with irbesartan, consistent with observations in the full DUPLEX study population. Moreover, a lower proportion of sparsentan- vs irbesartan-treated patients reached composite kidney endpoints.CONCLUSIONSThese findings support sparsentan's antiproteinuric benefit in patients with gFSGS, a subgroup that is often resistant to other therapeutic interventions.
{"title":"Antiproteinuric Effect of Sparsentan in Patients with Genetic-Associated Focal Segmental Glomerulosclerosis Enrolled in the DUPLEX Trial.","authors":"Jennifer Yee,Wu Gong,Jula Inrig,Michelle N Rheault,Angela J Gruber,Patricia W Bedard,Radko Komers,Howard Trachtman","doi":"10.2215/cjn.0000000948","DOIUrl":"https://doi.org/10.2215/cjn.0000000948","url":null,"abstract":"BACKGROUNDFocal segmental glomerulosclerosis (FSGS) is a podocytopathy that is diagnosed based on characteristic histopathological lesions. Certain forms of FSGS with underlying genetic variants associated with the disease, including variants in podocyte proteins, as well as apolipoprotein L1 (APOL1) risk alleles, and variants in collagen type IV (COL4) α3, α4, and α5 (COL4A3-5) proteins, are typically resistant to current treatments.METHODSThe DUPLEX clinical trial assessed the efficacy and safety of sparsentan, a dual endothelin angiotensin receptor antagonist (DEARA), in patients with biopsy-proven or genetic FSGS and demonstrated a greater antiproteinuric effect over 108 weeks compared to the active control irbesartan. This post hoc, exploratory analysis assessed the efficacy of sparsentan in the subset of patients enrolled in DUPLEX who had pathogenic variants in genes coding for podocyte proteins, COL4A3-5 variants, and APOL1 high-risk genotypes, altogether referred to as genetic FSGS (gFSGS).RESULTSNext-generation sequencing identified 31 patients with podocyte gene variants, 25 with COL4A3-5 gene variants, and 14 with APOL1 high-risk genotypes. Baseline characteristics varied between genetic subgroups, with slightly younger patients, on average, in the podocyte gene variant group, and more African American patients in the APOL1 high-risk genotype group. In this exploratory analysis, sparsentan treatment resulted in substantial and sustained proteinuria reductions and numerically more frequent complete remission of proteinuria compared with irbesartan, consistent with observations in the full DUPLEX study population. Moreover, a lower proportion of sparsentan- vs irbesartan-treated patients reached composite kidney endpoints.CONCLUSIONSThese findings support sparsentan's antiproteinuric benefit in patients with gFSGS, a subgroup that is often resistant to other therapeutic interventions.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"118 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145813502","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}
BACKGROUNDIn the phase 3, randomized, double-blind PROTECT (NCT03762850) trial, sparsentan, a single-molecule dual endothelin angiotensin receptor antagonist (DEARA), reduced proteinuria and preserved kidney function compared to maximum labeled dose irbesartan in adults with immunoglobulin A nephropathy. In this post hoc analysis of PROTECT, we assessed the association between complete remission of proteinuria (CR) and preservation of kidney function.METHODSThis analysis compared kidney function in patients who achieved CR (urine protein excretion <0.3 g/day) by Week 36 (CR36) or at any time up to Week 110 (CR110) vs. those who did not (non-CR), regardless of original treatment allocation. Endpoints assessed by CR status were change in proteinuria, estimated glomerular filtration rate (eGFR), and blood pressure, rate of eGFR decline, a composite kidney endpoint, and safety.RESULTSOf 404 patients who were randomized and received study drug, 43 (11%) achieved CR36 and 85 (21%) achieved CR110. CR patients demonstrated greater and more rapid reductions in proteinuria compared with non-CR patients. CR110 patients had a smaller absolute change in eGFR vs. non-CR patients (-4.0 vs. -8.6 mL/min/1.73 m2) and a slower rate of eGFR decline (Day 1-Week 110; -0.7 vs. -4.2 mL/min/1.73 m2/year). Fewer CR110 patients (1%) reached the composite kidney endpoint vs. non-CR patients (14%). CR110 patients were more likely to experience treatment-emergent adverse events (TEAEs) associated with hypotension (hypotension, orthostatic hypotension, or blood pressure systolic decreased) and less likely to experience TEAEs of hypertension than non-CR patients. More non-CR patients vs. CR110 patients discontinued treatment due to adverse events (11% vs. 4%, respectively) or patient decision (8% vs. 2%, respectively).CONCLUSIONSParticipants in PROTECT who achieved CR36 or CR110 showed greater eGFR preservation, fewer kidney failure events, and similar safety profiles compared to non-CR participants. These data reinforce recommendations to maintain proteinuria levels ideally <0.3 g/day and underscore its relationship with kidney function preservation.
背景：在3期随机双盲PROTECT （NCT03762850）试验中，与最大标记剂量厄贝沙坦相比，单分子双内皮素血管紧张素受体拮抗剂（DEARA） sparsentan可减少成人免疫球蛋白a肾病患者的蛋白尿并保持肾功能。在PROTECT的事后分析中，我们评估了蛋白尿（CR）完全缓解与肾功能保存之间的关系。该分析比较了在第36周（CR36）或直到第110周（CR110）的任何时间达到CR（尿蛋白排泄<0.3 g/天）的患者与未达到CR（非CR）的患者的肾功能，无论最初的治疗分配如何。CR状态评估的终点是蛋白尿的变化、估计的肾小球滤过率（eGFR）和血压、eGFR下降率、复合肾脏终点和安全性。结果404例随机接受研究药物的患者中，43例（11%）达到CR36, 85例（21%）达到CR110。与非CR患者相比，CR患者表现出更大、更快的蛋白尿减少。与非cr患者相比，CR110患者eGFR的绝对变化较小（-4.0 vs -8.6 mL/min/1.73 m2）， eGFR下降速度较慢（第1-周110天；-0.7 vs -4.2 mL/min/1.73 m2/年）。达到复合肾脏终点的CR110患者（1%）少于非cr患者（14%）。与非cr患者相比，CR110患者更有可能经历与低血压（低血压、体位性低血压或收缩压降低）相关的治疗突发不良事件（teae），并且更不可能经历高血压的teae。更多的非cr患者与CR110患者因不良事件而停止治疗（分别为11%和4%）或患者决定（分别为8%和2%）。与非cr参与者相比，达到CR36或CR110的PROTECT参与者表现出更高的eGFR保存，更少的肾功能衰竭事件和相似的安全性。这些数据强化了维持理想的蛋白尿水平<0.3 g/天的建议，并强调了其与肾功能保护的关系。
{"title":"Association between Complete Proteinuria Remission and Kidney Function in the Phase 3 PROTECT Trial of Sparsentan in IgA Nephropathy.","authors":"Hiddo Jl Heerspink,Brad H Rovin,Radko Komers,Bruce Hendry,Alex Mercer,Priscila Preciado,Edward Murphy,Vladimir Tesar","doi":"10.2215/cjn.0000000961","DOIUrl":"https://doi.org/10.2215/cjn.0000000961","url":null,"abstract":"BACKGROUNDIn the phase 3, randomized, double-blind PROTECT (NCT03762850) trial, sparsentan, a single-molecule dual endothelin angiotensin receptor antagonist (DEARA), reduced proteinuria and preserved kidney function compared to maximum labeled dose irbesartan in adults with immunoglobulin A nephropathy. In this post hoc analysis of PROTECT, we assessed the association between complete remission of proteinuria (CR) and preservation of kidney function.METHODSThis analysis compared kidney function in patients who achieved CR (urine protein excretion <0.3 g/day) by Week 36 (CR36) or at any time up to Week 110 (CR110) vs. those who did not (non-CR), regardless of original treatment allocation. Endpoints assessed by CR status were change in proteinuria, estimated glomerular filtration rate (eGFR), and blood pressure, rate of eGFR decline, a composite kidney endpoint, and safety.RESULTSOf 404 patients who were randomized and received study drug, 43 (11%) achieved CR36 and 85 (21%) achieved CR110. CR patients demonstrated greater and more rapid reductions in proteinuria compared with non-CR patients. CR110 patients had a smaller absolute change in eGFR vs. non-CR patients (-4.0 vs. -8.6 mL/min/1.73 m2) and a slower rate of eGFR decline (Day 1-Week 110; -0.7 vs. -4.2 mL/min/1.73 m2/year). Fewer CR110 patients (1%) reached the composite kidney endpoint vs. non-CR patients (14%). CR110 patients were more likely to experience treatment-emergent adverse events (TEAEs) associated with hypotension (hypotension, orthostatic hypotension, or blood pressure systolic decreased) and less likely to experience TEAEs of hypertension than non-CR patients. More non-CR patients vs. CR110 patients discontinued treatment due to adverse events (11% vs. 4%, respectively) or patient decision (8% vs. 2%, respectively).CONCLUSIONSParticipants in PROTECT who achieved CR36 or CR110 showed greater eGFR preservation, fewer kidney failure events, and similar safety profiles compared to non-CR participants. These data reinforce recommendations to maintain proteinuria levels ideally <0.3 g/day and underscore its relationship with kidney function preservation.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"6 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807586","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":"The Saving Young Lives Program, Real World Solutions to Real World Problems.","authors":"Brett Cullis,Agatha Chan,Fredric Finkelstein,Annabel Boyer,Simon Davies,Melvin Bonilla-Felix,Guillermo Hidalgo,Mignon McCulloch,Monica Moorthy,William E Smoyer","doi":"10.2215/cjn.0000000983","DOIUrl":"https://doi.org/10.2215/cjn.0000000983","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"29 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732823","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":"Sodium-Glucose Cotransporter-2 Inhibitors and Ketoacid Diets for Diabetic Kidney Disease.","authors":"Joel D Kopple","doi":"10.2215/cjn.0000000958","DOIUrl":"https://doi.org/10.2215/cjn.0000000958","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"231 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732821","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：