Usha Kumari,Zhongji Han,Yamini Mallisetty,Chi-Yang Chiu,Guillem Castro-Bono,Pandurang Kolekar,Swapna Thota,D Neil Hayes,Csaba P Kovesdy,Xiaotu Ma,Esther A Obeng,Keiichi Sumida
{"title":"Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Mortality in Patients with End-Stage Kidney Disease: A Pilot Case-Control Study.","authors":"Usha Kumari,Zhongji Han,Yamini Mallisetty,Chi-Yang Chiu,Guillem Castro-Bono,Pandurang Kolekar,Swapna Thota,D Neil Hayes,Csaba P Kovesdy,Xiaotu Ma,Esther A Obeng,Keiichi Sumida","doi":"10.2215/cjn.0000000888","DOIUrl":"https://doi.org/10.2215/cjn.0000000888","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"40 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599700","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}
Dana V Rizk,Bradley P Dixon,Melvin Chan,H Terence Cook,Ashley Frazer-Abel,Sydney C W Tang
Pharmacologic complement inhibition offers a promising therapeutic strategy for several complement-mediated kidney diseases. Yet, at present, nephrologists must rely on an incomplete toolkit of histopathologic and circulating biomarkers to assess complement activity in complement-mediated kidney diseases. Our clinical capacity to characterize and monitor pathologically dysregulated complement for disease prognosis, to inform patient selection, and to evaluate therapeutic efficacy severely lags behind the growing number of complement inhibitors under development. Reliable, sensitive complement biomarkers that are suitable for clinical assessment are needed for the timely and optimal implementation of existing and upcoming therapeutics. Despite this urgent need and growing research efforts, the repertoire of clinically available complement biomarker assays has proven refractory to expansion. This is, in part, due to a myriad of practical challenges limiting the information reliably interpreted from existing complement biomarkers and hindering the translation of novel biomarkers from research settings into the clinical pathology laboratory. In this article, the authors review commonly evaluated complement biomarkers within the context of an evolving therapeutic landscape, as well as the practical challenges related to their effective application. Noteworthy, emerging biomarkers are also discussed, along with the challenges in translating robust markers of complement activity from research settings into clinical practice.
{"title":"Biomarkers in the Management of Complement-Mediated Kidney Diseases in the Era of Complement Therapeutics.","authors":"Dana V Rizk,Bradley P Dixon,Melvin Chan,H Terence Cook,Ashley Frazer-Abel,Sydney C W Tang","doi":"10.2215/cjn.0000000967","DOIUrl":"https://doi.org/10.2215/cjn.0000000967","url":null,"abstract":"Pharmacologic complement inhibition offers a promising therapeutic strategy for several complement-mediated kidney diseases. Yet, at present, nephrologists must rely on an incomplete toolkit of histopathologic and circulating biomarkers to assess complement activity in complement-mediated kidney diseases. Our clinical capacity to characterize and monitor pathologically dysregulated complement for disease prognosis, to inform patient selection, and to evaluate therapeutic efficacy severely lags behind the growing number of complement inhibitors under development. Reliable, sensitive complement biomarkers that are suitable for clinical assessment are needed for the timely and optimal implementation of existing and upcoming therapeutics. Despite this urgent need and growing research efforts, the repertoire of clinically available complement biomarker assays has proven refractory to expansion. This is, in part, due to a myriad of practical challenges limiting the information reliably interpreted from existing complement biomarkers and hindering the translation of novel biomarkers from research settings into the clinical pathology laboratory. In this article, the authors review commonly evaluated complement biomarkers within the context of an evolving therapeutic landscape, as well as the practical challenges related to their effective application. Noteworthy, emerging biomarkers are also discussed, along with the challenges in translating robust markers of complement activity from research settings into clinical practice.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"23 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765481","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":"Shared Family Experiences with Kidney Disease.","authors":"Patrick O Gee,Quenton Turner-Gee","doi":"10.2215/cjn.0000000962","DOIUrl":"https://doi.org/10.2215/cjn.0000000962","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"24 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765483","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":"When is Genetic Testing Needed in Glomerular Diseases?","authors":"Francesca Becherucci,Benedetta Mazzinghi,Lugi Cirillo,Valentina Raglianti,Viviana Palazzo,Samuela Landini,Paola Romagnani","doi":"10.2215/cjn.0000000964","DOIUrl":"https://doi.org/10.2215/cjn.0000000964","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"85 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568144","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}
Meghana Eswarappa,Ronit Katz,Dan E Arking,Wen Shi,Charles Newcomb,Gregory J Tranah,Joachim H Ix,Chirag R Parikh,Steve Cummings,Sushrut S Waikar,Samir M Parikh,Mark J Sarnak,Michael G Shlipak,Vasantha Jotwani
BACKGROUNDBlood-based measures of mitochondrial DNA (mtDNA), including lower copy number and inherited mutations, have been associated with higher incidence of chronic kidney disease (CKD). However, the effect of mtDNA heteroplasmy, the age-associated accumulation of somatic mutations, is not well elucidated. We evaluated associations of mtDNA heteroplasmy and copy number (mtDNA-CN) with risk of kidney function decline.METHODSWe conducted a case-cohort study among community-living participants of the Health, Aging, and Body Composition study. A random subcohort of 502 participants was selected at baseline. One hundred and fifty-seven cases with a ≥40% estimated glomerular filtration rate (eGFR) decline to less than 60 ml/min/1.73m2 over 10 years of follow-up were identified, including 30 cases from the subcohort. Additional analyses evaluated ≥30% eGFR decline, present in 207 participants, including 80 within the subcohort. MtDNA heteroplasmy and mtDNA-CN were quantified from peripheral blood buffy coat specimens at baseline. A modified mitochondrial local constraint score sum (mMSS) was utilized to capture predicted deleterious consequences of mtDNA mutations. Modified Cox regression evaluated associations of each mtDNA exposure variable with the kidney outcomes.RESULTSAmong participants in the random subcohort, the mean age was 74±3, 49% were female, and the mean baseline eGFR was 73±18 mL/min/1.73m2. In analyses adjusted for CKD risk factors, higher mMSS was associated with a higher risk of ≥40% eGFR decline to less than 60 ml/min/1.73m2 (hazard ratio (HR) 1.23 [95% confidence interval (CI): 1.02, 1.48] per standard deviation (SD) higher; HR 2.60 [95% CI: 1.21, 5.56] for mMSS >0.5 versus 0). Higher mtDNA-CN was associated with a lower risk of ≥30% eGFR decline (HR 0.79 [95% CI: 0.63, 0.98] per SD higher; HR 0.55 [95% CI: 0.32, 0.95] for highest versus lowest tertile) in adjusted analyses.CONCLUSIONSIn older community-dwelling adults, higher mtDNA heteroplasmy was associated with a higher risk of kidney function decline, while higher mtDNA-CN was associated with a lower risk of kidney function decline. These findings expand the measures of mitochondrial health that may provide insight into kidney disease progression and warrant exploration in higher-risk populations.
{"title":"Associations of Blood Mitochondrial DNA Quality and Quantity with Risk of Kidney Function Decline.","authors":"Meghana Eswarappa,Ronit Katz,Dan E Arking,Wen Shi,Charles Newcomb,Gregory J Tranah,Joachim H Ix,Chirag R Parikh,Steve Cummings,Sushrut S Waikar,Samir M Parikh,Mark J Sarnak,Michael G Shlipak,Vasantha Jotwani","doi":"10.2215/cjn.0000000893","DOIUrl":"https://doi.org/10.2215/cjn.0000000893","url":null,"abstract":"BACKGROUNDBlood-based measures of mitochondrial DNA (mtDNA), including lower copy number and inherited mutations, have been associated with higher incidence of chronic kidney disease (CKD). However, the effect of mtDNA heteroplasmy, the age-associated accumulation of somatic mutations, is not well elucidated. We evaluated associations of mtDNA heteroplasmy and copy number (mtDNA-CN) with risk of kidney function decline.METHODSWe conducted a case-cohort study among community-living participants of the Health, Aging, and Body Composition study. A random subcohort of 502 participants was selected at baseline. One hundred and fifty-seven cases with a ≥40% estimated glomerular filtration rate (eGFR) decline to less than 60 ml/min/1.73m2 over 10 years of follow-up were identified, including 30 cases from the subcohort. Additional analyses evaluated ≥30% eGFR decline, present in 207 participants, including 80 within the subcohort. MtDNA heteroplasmy and mtDNA-CN were quantified from peripheral blood buffy coat specimens at baseline. A modified mitochondrial local constraint score sum (mMSS) was utilized to capture predicted deleterious consequences of mtDNA mutations. Modified Cox regression evaluated associations of each mtDNA exposure variable with the kidney outcomes.RESULTSAmong participants in the random subcohort, the mean age was 74±3, 49% were female, and the mean baseline eGFR was 73±18 mL/min/1.73m2. In analyses adjusted for CKD risk factors, higher mMSS was associated with a higher risk of ≥40% eGFR decline to less than 60 ml/min/1.73m2 (hazard ratio (HR) 1.23 [95% confidence interval (CI): 1.02, 1.48] per standard deviation (SD) higher; HR 2.60 [95% CI: 1.21, 5.56] for mMSS >0.5 versus 0). Higher mtDNA-CN was associated with a lower risk of ≥30% eGFR decline (HR 0.79 [95% CI: 0.63, 0.98] per SD higher; HR 0.55 [95% CI: 0.32, 0.95] for highest versus lowest tertile) in adjusted analyses.CONCLUSIONSIn older community-dwelling adults, higher mtDNA heteroplasmy was associated with a higher risk of kidney function decline, while higher mtDNA-CN was associated with a lower risk of kidney function decline. These findings expand the measures of mitochondrial health that may provide insight into kidney disease progression and warrant exploration in higher-risk populations.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"138 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568142","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":"How I Treat Anticoagulation for Atrial Fibrillation in CKD and ESKD.","authors":"Shubham Dixit,John Sy","doi":"10.2215/cjn.0000000963","DOIUrl":"https://doi.org/10.2215/cjn.0000000963","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"51 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710984","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}
Ester S Oh,Gilda Opoku,Sanna Darvish,Daniel H Craighead,Anna Ostrow,Matthew J Rossman,Cortney N Steele,Taylor Struemph,Zhiying You,Douglas R Seals,Michel Chonchol,Kristen L Nowak
BACKGROUNDWomen face higher risk of dementia than men in the general population, with some studies also reporting female sex is associated with higher dementia risk in patients receiving hemodialysis. However, it is unclear whether this sex-specific pattern extends to non-dialysis CKD, in whom the pathophysiology of cognitive impairment may differ due to absence of dialysis-related factors. Accordingly, we examined sex differences in older adults with and without non-dialysis CKD, who participated in Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension (SPRINT MIND). Using pooled data from our clinical studies, we further explored mechanisms underlying sex-specific cognitive decline by cross-sectionally comparing cerebrovascular and cognitive measures between sexes, separately for adults with and without non-dialysis CKD.METHODSSPRINT MIND analyses used Cox proportional hazard models to compare sex differences in the risk of cognitive outcomes (probable dementia [PD], mild cognitive impairment [MCI], and their composite) in men and propensity score-matched women, separately for CKD and non-CKD. A total of 681 men with CKD were propensity score-matched to 681 women with CKD, and 1,253 men without CKD to 1,253 women without CKD. In physiological clinical study, including participants with CKD (81 men, 34 women) and without CKD (35 men, 64 women), we compared middle cerebral artery pulsatility index (MCA PI; measure of cerebrovascular stiffness assessed by transcranial Doppler) and cognitive function (trails A and B times) by sex, separately for CKD and non-CKD.RESULTSIn SPRINT MIND, men with CKD had higher risk of PD/MCI composite (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.10-2.02) and PD alone (HR 1.98, 95% CI 1.23-3.17) than women, with no sex differences in non-CKD. In the physiological clinical study, men with CKD exhibited higher MCA PI and slower trails A and B times than women, with no sex differences in non-CKD. Across all participants, lower eGFR was associated with greater MCA PI more strongly in men (r=-0.34; P<0.001) than women (r=-0.23; P=0.03), and with slower trails B time (r=-0.22; P=0.02) in men only.CONCLUSIONSMen with non-dialysis CKD may have higher dementia risk than women, potentially associated with greater cerebrovascular stiffness.
{"title":"Sex Differences in Probable Dementia and Mild Cognitive Impairment Risk, and Cerebrovascular and Cognitive Function in Non-Dialysis CKD.","authors":"Ester S Oh,Gilda Opoku,Sanna Darvish,Daniel H Craighead,Anna Ostrow,Matthew J Rossman,Cortney N Steele,Taylor Struemph,Zhiying You,Douglas R Seals,Michel Chonchol,Kristen L Nowak","doi":"10.2215/cjn.0000000922","DOIUrl":"https://doi.org/10.2215/cjn.0000000922","url":null,"abstract":"BACKGROUNDWomen face higher risk of dementia than men in the general population, with some studies also reporting female sex is associated with higher dementia risk in patients receiving hemodialysis. However, it is unclear whether this sex-specific pattern extends to non-dialysis CKD, in whom the pathophysiology of cognitive impairment may differ due to absence of dialysis-related factors. Accordingly, we examined sex differences in older adults with and without non-dialysis CKD, who participated in Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension (SPRINT MIND). Using pooled data from our clinical studies, we further explored mechanisms underlying sex-specific cognitive decline by cross-sectionally comparing cerebrovascular and cognitive measures between sexes, separately for adults with and without non-dialysis CKD.METHODSSPRINT MIND analyses used Cox proportional hazard models to compare sex differences in the risk of cognitive outcomes (probable dementia [PD], mild cognitive impairment [MCI], and their composite) in men and propensity score-matched women, separately for CKD and non-CKD. A total of 681 men with CKD were propensity score-matched to 681 women with CKD, and 1,253 men without CKD to 1,253 women without CKD. In physiological clinical study, including participants with CKD (81 men, 34 women) and without CKD (35 men, 64 women), we compared middle cerebral artery pulsatility index (MCA PI; measure of cerebrovascular stiffness assessed by transcranial Doppler) and cognitive function (trails A and B times) by sex, separately for CKD and non-CKD.RESULTSIn SPRINT MIND, men with CKD had higher risk of PD/MCI composite (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.10-2.02) and PD alone (HR 1.98, 95% CI 1.23-3.17) than women, with no sex differences in non-CKD. In the physiological clinical study, men with CKD exhibited higher MCA PI and slower trails A and B times than women, with no sex differences in non-CKD. Across all participants, lower eGFR was associated with greater MCA PI more strongly in men (r=-0.34; P<0.001) than women (r=-0.23; P=0.03), and with slower trails B time (r=-0.22; P=0.02) in men only.CONCLUSIONSMen with non-dialysis CKD may have higher dementia risk than women, potentially associated with greater cerebrovascular stiffness.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"184 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559048","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}
Byounghwi Ko,Chan-Young Jung,Ye Eun Ko,Dong Hoon Kang,Ga Young Heo,Hee Byung Koh,Cheol Ho Park,Hyung Woo Kim,Jung Tak Park,Tae Ik Chang,Tae-Hyun Yoo,Shin-Wook Kang,Sue Kyung Park,Ji Yong Jung,Jong Cheol Jeong,Yaeni Kim,Kook Hwan Oh,Amanda H Anderson,Wei Yang,Jordana B Cohen,Mahboob Rahman,Seung Hyeok Han,
BACKGROUNDEthnic differences in chronic kidney disease (CKD) progression remain understudied, particularly between Asian and Western populations. Therefore, we aimed to investigate ethnic disparities in CKD progression by comparing nationwide cohorts from South Korea (the Korean cohort study for Outcomes in Patients With CKD [KNOW-CKD]) and the United States (the US Chronic Renal Insufficiency Cohort [CRIC]).METHODSA total of 4,953 participants were included (69% from CRIC and 31% from KNOW-CKD). The primary outcome was CKD progression, defined as a 50% or greater decline of estimated glomerular filtration rate (eGFR) or kidney failure requiring kidney replacement therapy. In the secondary outcome analysis, we compared eGFR decline rates and all-cause mortality.RESULTSOf the 4,953 participants, CKD progression occurred in 1,285 and 570 in the KNOW-CKD and CRIC cohorts, with incidence rates of 67.9 and 41.7 per 1,000 person-years, respectively. The hazard ratio for the KNOW-CKD compared to CRIC was 1.66 (95% confidence interval [CI], 1.45-1.89). The annual eGFR decline was steeper in KNOW-CKD participants than in CRIC participants (-2.51 vs. -1.14 mL/min/1.73 m2). Asian participants from the CRIC cohort exhibited a similar eGFR slope (95% CIs) (-2.10 [-2.69 to -1.52]) to those from KNOW-CKD (-2.50 [-2.67 to -1.52]), while the slope was -1.47 (-1.61 to -1.33), and -0.81 (-0.92 to -0.70) mL/min/1.73 m2 per year for Black and White participants, respectively. However, the risk of mortality was significantly lower in KNOW-CKD participants compared with CRIC participants (hazard ratio, 0.51; 95% CI, 0.38-0.68).CONCLUSIONSCKD progression was faster in the Korean cohort than in the US cohort, with Asian participants in both cohorts showing similar eGFR decline rates. However, the Korean cohort had a lower risk of mortality, indicating potential ethnic or regional differences in disease progression and survival.
{"title":"Ethnic Disparities in Chronic Kidney Disease Progression: A Comparative Study of CRIC and KNOW-CKD Cohorts.","authors":"Byounghwi Ko,Chan-Young Jung,Ye Eun Ko,Dong Hoon Kang,Ga Young Heo,Hee Byung Koh,Cheol Ho Park,Hyung Woo Kim,Jung Tak Park,Tae Ik Chang,Tae-Hyun Yoo,Shin-Wook Kang,Sue Kyung Park,Ji Yong Jung,Jong Cheol Jeong,Yaeni Kim,Kook Hwan Oh,Amanda H Anderson,Wei Yang,Jordana B Cohen,Mahboob Rahman,Seung Hyeok Han, ","doi":"10.2215/cjn.0000000884","DOIUrl":"https://doi.org/10.2215/cjn.0000000884","url":null,"abstract":"BACKGROUNDEthnic differences in chronic kidney disease (CKD) progression remain understudied, particularly between Asian and Western populations. Therefore, we aimed to investigate ethnic disparities in CKD progression by comparing nationwide cohorts from South Korea (the Korean cohort study for Outcomes in Patients With CKD [KNOW-CKD]) and the United States (the US Chronic Renal Insufficiency Cohort [CRIC]).METHODSA total of 4,953 participants were included (69% from CRIC and 31% from KNOW-CKD). The primary outcome was CKD progression, defined as a 50% or greater decline of estimated glomerular filtration rate (eGFR) or kidney failure requiring kidney replacement therapy. In the secondary outcome analysis, we compared eGFR decline rates and all-cause mortality.RESULTSOf the 4,953 participants, CKD progression occurred in 1,285 and 570 in the KNOW-CKD and CRIC cohorts, with incidence rates of 67.9 and 41.7 per 1,000 person-years, respectively. The hazard ratio for the KNOW-CKD compared to CRIC was 1.66 (95% confidence interval [CI], 1.45-1.89). The annual eGFR decline was steeper in KNOW-CKD participants than in CRIC participants (-2.51 vs. -1.14 mL/min/1.73 m2). Asian participants from the CRIC cohort exhibited a similar eGFR slope (95% CIs) (-2.10 [-2.69 to -1.52]) to those from KNOW-CKD (-2.50 [-2.67 to -1.52]), while the slope was -1.47 (-1.61 to -1.33), and -0.81 (-0.92 to -0.70) mL/min/1.73 m2 per year for Black and White participants, respectively. However, the risk of mortality was significantly lower in KNOW-CKD participants compared with CRIC participants (hazard ratio, 0.51; 95% CI, 0.38-0.68).CONCLUSIONSCKD progression was faster in the Korean cohort than in the US cohort, with Asian participants in both cohorts showing similar eGFR decline rates. However, the Korean cohort had a lower risk of mortality, indicating potential ethnic or regional differences in disease progression and survival.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"46 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491725","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}
Cardiac biomarkers can provide an easily accessible and non-invasive method of assessing aspects of a patients' underlying cardiovascular health. In doing so, they can serve both as a screening tool for evaluating patients' risk for cardiovascular events and a management tool for evaluating response to directed treatment. Biomarkers serve as surrogates for mechanistic pathways that are relevant for cardiovascular pathophysiology, and as such, have even been utilized as clinical trial endpoints. The overall utility of a biomarker is dependent on the reliability and consistency of the assay, the content of the represented information, and its ability to affect clinical care. Several cardiac biomarkers are widely available and routinely used in clinical practice. However, despite significant research into cardiac biomarkers, many have not been translated into routine clinical care of persons with chronic kidney disease (CKD). Interpretation of cardiac biomarkers can be challenging given the possible effects of reduced kidney clearance as well as the contribution of kidney-specific risk facts on circulating levels of the biomarkers. Here we will provide an overview of the current state of cardiac biomarkers in CKD; and whether the biomarker meets the above criteria specifically in persons with CKD. We will focus on several widely used cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin) as well as select newer promising cardiac biomarkers (soluble suppression of tumorigenicity 2,, galectin-3, and growth differentiation factor-15).
{"title":"Cardiac Biomarkers in Chronic Kidney Disease: Signal or Noise?","authors":"Karen de Wolski,Nisha Bansal","doi":"10.2215/cjn.0000000947","DOIUrl":"https://doi.org/10.2215/cjn.0000000947","url":null,"abstract":"Cardiac biomarkers can provide an easily accessible and non-invasive method of assessing aspects of a patients' underlying cardiovascular health. In doing so, they can serve both as a screening tool for evaluating patients' risk for cardiovascular events and a management tool for evaluating response to directed treatment. Biomarkers serve as surrogates for mechanistic pathways that are relevant for cardiovascular pathophysiology, and as such, have even been utilized as clinical trial endpoints. The overall utility of a biomarker is dependent on the reliability and consistency of the assay, the content of the represented information, and its ability to affect clinical care. Several cardiac biomarkers are widely available and routinely used in clinical practice. However, despite significant research into cardiac biomarkers, many have not been translated into routine clinical care of persons with chronic kidney disease (CKD). Interpretation of cardiac biomarkers can be challenging given the possible effects of reduced kidney clearance as well as the contribution of kidney-specific risk facts on circulating levels of the biomarkers. Here we will provide an overview of the current state of cardiac biomarkers in CKD; and whether the biomarker meets the above criteria specifically in persons with CKD. We will focus on several widely used cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin) as well as select newer promising cardiac biomarkers (soluble suppression of tumorigenicity 2,, galectin-3, and growth differentiation factor-15).","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"226 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411521","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}
Complement activation occurs in most glomerular diseases. Complement activation on the kidney biopsy is evidenced by deposition of C3c and C1q on the kidney biopsy. The kidney biopsy provides only limited information as other complement proteins and complement-regulating proteins are not typically studied. Furthermore, kidney biopsy does not distinguish between activated versus inactive complement proteins. Laser microdissection and mass spectrometry (LMD/MS) is a relatively new methodology that can provide an in-depth evaluation of the proteomic profile of complement proteins, complement regulating proteins, complement pathways, and can also determine whether active complement fragments are present in the kidney biopsy sample. A semiquantitative burden of complement can be determined. Furthermore, proteins of a disease can be analyzed using principal component analysis, volcano plots and heatmaps. In this review, the complement proteomic profile of diseases representing the spectrum of glomerular diseases are shown. The proteomic complement profile of membranous nephropathy associated with various antigens, immunoglobulin-associated glomerulonephritis such as proliferative glomerulonephritis with monoclonal immunoglobulin deposits and fibrillary glomerulonephritis, C3 glomerulopathy, and IgA nephropathy, are shown. The findings show important differences in the complement profile including pathways of complement in each disease, and even within the disease, such as altered complement burden and profile between different antigens associated with membranous nephropathy. In conclusion, LMD/MS is a valuable tool for determining the complement proteins, complement-regulating proteins, complement pathways, and determining the burden of complement in each individual case of glomerular disease. In the era of new anti-complement drugs, it will become essential to accurately determine the complement profile in each kidney biopsy for a personalized approach to treating the glomerular disease. LMD/MS is a methodology that can help provide such answers.
{"title":"Complement Profiling in Glomerular Disease: Insights from Laser Microdissection and Mass Spectrometry.","authors":"Sanjeev Sethi","doi":"10.2215/cjn.0000000943","DOIUrl":"https://doi.org/10.2215/cjn.0000000943","url":null,"abstract":"Complement activation occurs in most glomerular diseases. Complement activation on the kidney biopsy is evidenced by deposition of C3c and C1q on the kidney biopsy. The kidney biopsy provides only limited information as other complement proteins and complement-regulating proteins are not typically studied. Furthermore, kidney biopsy does not distinguish between activated versus inactive complement proteins. Laser microdissection and mass spectrometry (LMD/MS) is a relatively new methodology that can provide an in-depth evaluation of the proteomic profile of complement proteins, complement regulating proteins, complement pathways, and can also determine whether active complement fragments are present in the kidney biopsy sample. A semiquantitative burden of complement can be determined. Furthermore, proteins of a disease can be analyzed using principal component analysis, volcano plots and heatmaps. In this review, the complement proteomic profile of diseases representing the spectrum of glomerular diseases are shown. The proteomic complement profile of membranous nephropathy associated with various antigens, immunoglobulin-associated glomerulonephritis such as proliferative glomerulonephritis with monoclonal immunoglobulin deposits and fibrillary glomerulonephritis, C3 glomerulopathy, and IgA nephropathy, are shown. The findings show important differences in the complement profile including pathways of complement in each disease, and even within the disease, such as altered complement burden and profile between different antigens associated with membranous nephropathy. In conclusion, LMD/MS is a valuable tool for determining the complement proteins, complement-regulating proteins, complement pathways, and determining the burden of complement in each individual case of glomerular disease. In the era of new anti-complement drugs, it will become essential to accurately determine the complement profile in each kidney biopsy for a personalized approach to treating the glomerular disease. LMD/MS is a methodology that can help provide such answers.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"21 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381153","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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