Pub Date : 2024-10-21DOI: 10.2215/CJN.0000000000000559
Laura Pyle, Ye Ji Choi, Phoom Narongkiatikhun, Kumar Sharma, Sushrut Waikar, Anita Layton, Kalie L Tommerdahl, Ian de Boer, Timothy Vigers, Robert G Nelson, Jane Lynch, Frank Brosius, Pierre J Saulnier, Jesse A Goodrich, Jeanie B Tryggestad, Elvira Isganaitis, Fida Bacha, Kristen J Nadeau, Daniel van Raalte, Matthias Kretzler, Hiddo Heerspink, Petter Bjornstad
Background: The onset of diabetic kidney disease (DKD) in youth with type 2 diabetes mellitus often occurs early, leading to complications in young adulthood. Risk biomarkers associated with the early onset of DKD are urgently needed in youth with type 2 diabetes.
Methods: We conducted an in-depth analysis of 6596 proteins (SomaScan 7K) in 374 baseline plasma samples from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study to identify multi-protein signatures associated with the onset of albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g), a rapid decline in estimated glomerular filtration rate (eGFR) [annual eGFR decline >3 mL/min/1.73m2 and/or ≥3.3% at two consecutive visits], and hyperfiltration (≥135 mL/min/1.73m2 at two consecutive visits). Elastic net Cox regression with 10-fold cross-validation was applied to the top 100 proteins (ranked by p-value) to identify multi-protein signatures of time to development of DKD outcomes.
Results: Participants in the TODAY study (14±2 years old, 63% female, 7±6 months diabetes duration) experienced high rates of early DKD: 43% developed albuminuria, 48% hyperfiltration, and 16% rapid eGFR decline. Increased levels of seven and three proteins were predictive of shorter time to develop albuminuria and rapid eGFR decline, respectively; 118 proteins predicted time to development of hyperfiltration. Elastic net Cox proportional hazards model identified multi-protein signatures of time to incident early DKD with concordance for models with clinical covariates and selected proteins between 0.81 and 0.96, while the concordance for models with clinical covariates only was between 0.56 and 0.63.
Conclusions: Our research sheds new light on proteomic changes early in the course of youth-onset type 2 diabetes that associate with DKD. Proteomic analyses identified promising risk factors that predict DKD risk in youth with type 2 diabetes and could deepen our understanding of DKD mechanisms and potential interventions.
{"title":"Proteomic Analysis Uncovers Multi-Protein Signatures Associated with Early Diabetic Kidney Disease in Youth with Type 2 Diabetes Mellitus.","authors":"Laura Pyle, Ye Ji Choi, Phoom Narongkiatikhun, Kumar Sharma, Sushrut Waikar, Anita Layton, Kalie L Tommerdahl, Ian de Boer, Timothy Vigers, Robert G Nelson, Jane Lynch, Frank Brosius, Pierre J Saulnier, Jesse A Goodrich, Jeanie B Tryggestad, Elvira Isganaitis, Fida Bacha, Kristen J Nadeau, Daniel van Raalte, Matthias Kretzler, Hiddo Heerspink, Petter Bjornstad","doi":"10.2215/CJN.0000000000000559","DOIUrl":"10.2215/CJN.0000000000000559","url":null,"abstract":"<p><strong>Background: </strong>The onset of diabetic kidney disease (DKD) in youth with type 2 diabetes mellitus often occurs early, leading to complications in young adulthood. Risk biomarkers associated with the early onset of DKD are urgently needed in youth with type 2 diabetes.</p><p><strong>Methods: </strong>We conducted an in-depth analysis of 6596 proteins (SomaScan 7K) in 374 baseline plasma samples from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study to identify multi-protein signatures associated with the onset of albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g), a rapid decline in estimated glomerular filtration rate (eGFR) [annual eGFR decline >3 mL/min/1.73m2 and/or ≥3.3% at two consecutive visits], and hyperfiltration (≥135 mL/min/1.73m2 at two consecutive visits). Elastic net Cox regression with 10-fold cross-validation was applied to the top 100 proteins (ranked by p-value) to identify multi-protein signatures of time to development of DKD outcomes.</p><p><strong>Results: </strong>Participants in the TODAY study (14±2 years old, 63% female, 7±6 months diabetes duration) experienced high rates of early DKD: 43% developed albuminuria, 48% hyperfiltration, and 16% rapid eGFR decline. Increased levels of seven and three proteins were predictive of shorter time to develop albuminuria and rapid eGFR decline, respectively; 118 proteins predicted time to development of hyperfiltration. Elastic net Cox proportional hazards model identified multi-protein signatures of time to incident early DKD with concordance for models with clinical covariates and selected proteins between 0.81 and 0.96, while the concordance for models with clinical covariates only was between 0.56 and 0.63.</p><p><strong>Conclusions: </strong>Our research sheds new light on proteomic changes early in the course of youth-onset type 2 diabetes that associate with DKD. Proteomic analyses identified promising risk factors that predict DKD risk in youth with type 2 diabetes and could deepen our understanding of DKD mechanisms and potential interventions.</p>","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479854","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 : 2024-10-18DOI: 10.2215/cjn.0000000000000567
Youngshin Keum,Maria Luiza Caramori,David Z Cherney,Jill P Crandall,Ian H de Boer,Ildiko Lingvay,Janet B McGill,Sarit Polsky,Rodica Pop-Busui,Peter Rossing,Ronald J Sigal,Michael Mauer,Alessandro Doria
BACKGROUNDThe optimal criteria to select individuals with type 1 diabetes mellitus (T1D) and albuminuric or normoalbuminuric diabetic kidney disease (DKD), who are at risk of rapid kidney function decline, for clinical trials are unclear.METHODSThis study analyzed data from the Preventing Early Renal Loss in Diabetes (PERL) clinical trial, which investigated whether allopurinol slowed kidney function decline in persons with T1D and early-to-moderate DKD. Rates of iohexol GFR (iGFR) and estimated GFR (eGFR) decline during the three-year study were compared by linear mixed effect regression between participants enrolled based on a history of moderately or severely increased albuminuria (N=394) and those enrolled based on a recent history of rapid kidney function decline (≥3 ml/min/1.73 m2/year) in the absence of a history of albuminuria (N=124). The association between baseline albuminuria and iGFR/eGFR decline during the trial was also evaluated.RESULTSRates of eGFR decline during the trial were higher in participants with a history of albuminuria than in those with a history of rapid kidney function decline (-3.56 [95% confidence intervals {CI} -3.17, -3.95] versus -2.35 [95% CI: -1.86, -2.84] ml/min/1.73 m2/year, p=0.001). Results were similar for iGFR decline, although the difference was not significant (p=0.07). Within the history of albuminuria group, the rate of eGFR decline was -5.30 (95% CI -4.52, -6.08) ml/min/1.73m2/year in participants with severely increased albuminuria as compared to -2.97 (95% CI 2.44, -3.50) and -2.32 (95% CI -1.61, -3.03) ml/min/1.73m2/year in those with moderately increased or normal/mildly increased albuminuria at baseline (p<0.001).CONCLUSIONSSeverely increased albuminuria at screening is a powerful criterion for selecting persons with T1D at high risk of kidney function decline. A history of rapid eGFR decline without a history of albuminuria is less effective for this purpose but it can still identify individuals with T1D who will lose kidney function more rapidly than expected from physiological aging.CLINICAL TRAIL REGISTRATIONClinicalTrials.gov, NCT02017171.
背景选择1型糖尿病（T1D）和白蛋白尿或正常白蛋白尿型糖尿病肾病（DKD）患者进行临床试验的最佳标准尚不清楚，因为这些患者有肾功能快速下降的风险。方法本研究分析了预防糖尿病早期肾功能丧失（PERL）临床试验的数据，该试验研究了别嘌醇是否能减缓T1D和早期至中度DKD患者的肾功能下降。通过线性混合效应回归比较了三年研究期间异嘌呤醇 GFR (iGFR) 和估计 GFR (eGFR) 下降率，比较对象为有中度或重度白蛋白尿增高病史的入选者（394 人）和近期肾功能快速下降（≥3 毫升/分钟/1.73 平方米/年）且无白蛋白尿病史的入选者（124 人）。结果试验期间，有白蛋白尿史的参与者的 eGFR 下降率高于有肾功能快速下降史的参与者（-3.56 [95% 置信区间 {CI} -3.17, -3.95]对 -2.35 [95% CI: -1.86, -2.84]毫升/分钟/1.73平方米/年，P=0.001）。iGFR 下降的结果类似，但差异不显著（P=0.07）。在白蛋白尿病史组中，白蛋白尿严重增高者的 eGFR 下降率为-5.30（95% CI -4.52，-6.08）毫升/分钟/1.73 米2/年，而白蛋白尿中度增高者的 eGFR 下降率分别为-2.97（95% CI 2.44，-3.50）毫升/分钟/1.73 米2/年和-2.32（95% CI -1.61，-3.03）毫升/分钟/1.73 米2/年。结论筛查时白蛋白尿严重增加是选择肾功能衰退高风险 T1D 患者的有力标准。没有白蛋白尿的 eGFR 快速下降史在这方面的效果较差，但仍能识别出肾功能下降速度比生理衰老预期速度更快的 T1D 患者。
{"title":"Albuminuria and Rapid Kidney Function Decline as Selection Criteria for Kidney Clinical Trials in Type 1 Diabetes Mellitus.","authors":"Youngshin Keum,Maria Luiza Caramori,David Z Cherney,Jill P Crandall,Ian H de Boer,Ildiko Lingvay,Janet B McGill,Sarit Polsky,Rodica Pop-Busui,Peter Rossing,Ronald J Sigal,Michael Mauer,Alessandro Doria","doi":"10.2215/cjn.0000000000000567","DOIUrl":"https://doi.org/10.2215/cjn.0000000000000567","url":null,"abstract":"BACKGROUNDThe optimal criteria to select individuals with type 1 diabetes mellitus (T1D) and albuminuric or normoalbuminuric diabetic kidney disease (DKD), who are at risk of rapid kidney function decline, for clinical trials are unclear.METHODSThis study analyzed data from the Preventing Early Renal Loss in Diabetes (PERL) clinical trial, which investigated whether allopurinol slowed kidney function decline in persons with T1D and early-to-moderate DKD. Rates of iohexol GFR (iGFR) and estimated GFR (eGFR) decline during the three-year study were compared by linear mixed effect regression between participants enrolled based on a history of moderately or severely increased albuminuria (N=394) and those enrolled based on a recent history of rapid kidney function decline (≥3 ml/min/1.73 m2/year) in the absence of a history of albuminuria (N=124). The association between baseline albuminuria and iGFR/eGFR decline during the trial was also evaluated.RESULTSRates of eGFR decline during the trial were higher in participants with a history of albuminuria than in those with a history of rapid kidney function decline (-3.56 [95% confidence intervals {CI} -3.17, -3.95] versus -2.35 [95% CI: -1.86, -2.84] ml/min/1.73 m2/year, p=0.001). Results were similar for iGFR decline, although the difference was not significant (p=0.07). Within the history of albuminuria group, the rate of eGFR decline was -5.30 (95% CI -4.52, -6.08) ml/min/1.73m2/year in participants with severely increased albuminuria as compared to -2.97 (95% CI 2.44, -3.50) and -2.32 (95% CI -1.61, -3.03) ml/min/1.73m2/year in those with moderately increased or normal/mildly increased albuminuria at baseline (p<0.001).CONCLUSIONSSeverely increased albuminuria at screening is a powerful criterion for selecting persons with T1D at high risk of kidney function decline. A history of rapid eGFR decline without a history of albuminuria is less effective for this purpose but it can still identify individuals with T1D who will lose kidney function more rapidly than expected from physiological aging.CLINICAL TRAIL REGISTRATIONClinicalTrials.gov, NCT02017171.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451442","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 : 2024-10-17DOI: 10.2215/cjn.0000000000000550
Dominique van Mil, Priya Vart, Glenn M. Chertow, Ron T. Gansevoort, Peter Rossing, Robert D. Toto, Ricardo Correa-Rotter, Anna Maria Langkilde, C. David Sjöström, David C. Wheeler, Hiddo J.L. Heerspink
Pub Date : 2024-10-15DOI: 10.2215/cjn.0000000000000560
Yoshitsugu Obi,Anna Xu,Jonathan A Wilson,Patti L Ephraim,Daniel E Weiner,Julia J Scialla,Bernard G Jaar,L Ebony Boulware,Benjamin Goldstein,Tariq Shafi
BACKGROUNDCause-specific mortality data from the United States Renal Data System (USRDS) form the basis for identifying cardiovascular disease (CVD), specifically sudden cardiac death (SCD), as the leading cause of death for patients on dialysis. Death certificate data from the National Death Index (NDI) is the epidemiological standard for assessing causes of death for the United States population. The cause of death has not been compared between the USRDS and the NDI.METHODSAmong 39,507 adults starting dialysis in the US, we identified 6436 patients who died between 2003-2009. We classified the cause of death as SCD, non-SCD CVD, cancer, infection, and others; and compared the USRDS to the NDI.RESULTSMedian age at the time of death was 70 years, 44% were female, and 30% were non-Hispanic Black individuals. The median time from dialysis initiation to death was 1.2 years. Most deaths occurred in-hospital (N=4681, 73%). The overall concordance in cause of death between the two national registries was 42% (κ=0.23, 95% confidence interval 0.22 to 0.24). CVD, including SCD and non-SCD CVD, accounted for 67% of deaths per the USRDS but only 52% per the NDI; this difference was mainly driven by the larger proportion of SCD in the USRDS (42%) versus the NDI (22%). Of the 2962 deaths reported as SCD by the USRDS, only 35% were also classified as SCD by the NDI. Out-of-hospital deaths were more likely to be classified as SCD in the USRDS (60%) versus the NDI (29%), compared to in-hospital deaths (41% in the USRDS; 25% in the NDI).CONCLUSIONSSignificant discordance exists in the causes of death for patients on dialysis reported by the USRDS and the NDI. Our findings underscore the urgent need to integrate NDI data into the USRDS registry and enhance the accuracy of cause-of-death reporting.
{"title":"Sudden Cardiac Death Reporting in US Dialysis Patients: Comparison of USRDS and National Death Index Data.","authors":"Yoshitsugu Obi,Anna Xu,Jonathan A Wilson,Patti L Ephraim,Daniel E Weiner,Julia J Scialla,Bernard G Jaar,L Ebony Boulware,Benjamin Goldstein,Tariq Shafi","doi":"10.2215/cjn.0000000000000560","DOIUrl":"https://doi.org/10.2215/cjn.0000000000000560","url":null,"abstract":"BACKGROUNDCause-specific mortality data from the United States Renal Data System (USRDS) form the basis for identifying cardiovascular disease (CVD), specifically sudden cardiac death (SCD), as the leading cause of death for patients on dialysis. Death certificate data from the National Death Index (NDI) is the epidemiological standard for assessing causes of death for the United States population. The cause of death has not been compared between the USRDS and the NDI.METHODSAmong 39,507 adults starting dialysis in the US, we identified 6436 patients who died between 2003-2009. We classified the cause of death as SCD, non-SCD CVD, cancer, infection, and others; and compared the USRDS to the NDI.RESULTSMedian age at the time of death was 70 years, 44% were female, and 30% were non-Hispanic Black individuals. The median time from dialysis initiation to death was 1.2 years. Most deaths occurred in-hospital (N=4681, 73%). The overall concordance in cause of death between the two national registries was 42% (κ=0.23, 95% confidence interval 0.22 to 0.24). CVD, including SCD and non-SCD CVD, accounted for 67% of deaths per the USRDS but only 52% per the NDI; this difference was mainly driven by the larger proportion of SCD in the USRDS (42%) versus the NDI (22%). Of the 2962 deaths reported as SCD by the USRDS, only 35% were also classified as SCD by the NDI. Out-of-hospital deaths were more likely to be classified as SCD in the USRDS (60%) versus the NDI (29%), compared to in-hospital deaths (41% in the USRDS; 25% in the NDI).CONCLUSIONSSignificant discordance exists in the causes of death for patients on dialysis reported by the USRDS and the NDI. Our findings underscore the urgent need to integrate NDI data into the USRDS registry and enhance the accuracy of cause-of-death reporting.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443751","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 : 2024-10-15DOI: 10.2215/cjn.0000000000000547
Sunita K. Singh, Allison Jaure, Natasha Caton, Olwyn Johnson, Camilla S. Hanson, Amanda Dominello, Maia P. Gill, Linnea Young, Kathy Yetzer, Sarah Chritchley, Doris Chang, John S. Gill
{"title":"Meat Your Veggies:: Could Plant-Based Meat Alternatives Help Improve Outcomes in Chronic Kidney Disease and Urinary Stone Disease?","authors":"Annabel Biruete,Nooshan Mirmohammadali","doi":"10.2215/cjn.0000000594","DOIUrl":"https://doi.org/10.2215/cjn.0000000594","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439237","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}
Steven Fishbane,Candice Halinski,Alla Alaiev,Ellen Porzelt,Vipul Sakhiya,Noreen McGroarty
{"title":"Challenges and Opportunities in Advanced Chronic Kidney Disease.","authors":"Steven Fishbane,Candice Halinski,Alla Alaiev,Ellen Porzelt,Vipul Sakhiya,Noreen McGroarty","doi":"10.2215/cjn.0000000609","DOIUrl":"https://doi.org/10.2215/cjn.0000000609","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443752","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 : 2024-10-14DOI: 10.2215/cjn.0000000000000548
Kenneth Lim,Matthew Nayor,Eliott Arroyo,Heather N Burney,Xiaochun Li,Yang Li,Ravi Shah,Joseph Campain,Douglas Wan,Stephen Ting,Thomas F Hiemstra,Ravi Thadhani,Sharon Moe,Daniel Zehnder,Martin G Larson,Ramachandran S Vasan,Gregory D Lewis
BACKGROUNDTraditional diagnostic tools that assess resting cardiac function and structure fail to accurately reflect cardiovascular alterations in patients with chronic kidney disease (CKD). This study sought to determine whether multidimensional exercise response patterns related to cardiovascular functional capacity can detect abnormalities in mild-to-moderate CKD.METHODSIn a cross-sectional study, we examined 3,075 participants from the Framingham Heart Study (FHS) and 451 participants from the Massachusetts General Hospital Exercise Study (MGH-ExS) who underwent cardiopulmonary exercise testing (CPET). Participants were stratified by estimated glomerular filtration rate (eGFR): eGFR ≥90; eGFR 60-89; eGFR 30-59. Our primary outcomes of interest were peak oxygen uptake (VO2Peak),VO2 at anaerobic threshold (VO2AT), and the ratio of minute ventilation to carbon dioxide production (VE/VCO2). Multiple linear regression models were fitted to evaluate the associations between eGFR group and each outcome variable adjusted for covariates.RESULTSIn the FHS cohort, N=1,712 (56%) had an eGFR ≥90 ml/min/1.73m2, N=1,271 (41%) had an eGFR 60-89 ml/min/1.73m2, and N=92 (3%) had an eGFR 30-59 ml/min/1.73m2. In the MGH-ExS cohort, N=247 (55%) had an eGFR ≥90 ml/min/1.73m2, N=154 (34%) had an eGFR 60-89 ml/min/1.73m2, and N=50 (11%) had an eGFR 30-59 ml/min/1.73m2. In FHS, VO2Peak and VO2AT were incrementally impaired with declining kidney function (p<0.001); however this pattern was attenuated following adjustment for age. Percent-predicted VO2Peak at AT was higher in the lower eGFR groups (p<0.001). In MGH-ExS, VO2Peak and VO2AT were incrementally impaired with declining kidney function in unadjusted and adjusted models (p<0.05). VO2Peak was associated with eGFR (p<0.05) in all models even after adjusting for age. On further mechanistic analysis, we directly measured cardiac output (CO) at peak exercise via right heart catheterization and found impaired CO in the lower eGFR groups (p≤0.007).CONCLUSIONCPET-derived indices may detect impairment in cardiovascular functional capacity and track cardiac output declines in mild to moderate CKD.
{"title":"Impairment of Cardiovascular Functional Capacity in Mild to Moderate Kidney Dysfunction.","authors":"Kenneth Lim,Matthew Nayor,Eliott Arroyo,Heather N Burney,Xiaochun Li,Yang Li,Ravi Shah,Joseph Campain,Douglas Wan,Stephen Ting,Thomas F Hiemstra,Ravi Thadhani,Sharon Moe,Daniel Zehnder,Martin G Larson,Ramachandran S Vasan,Gregory D Lewis","doi":"10.2215/cjn.0000000000000548","DOIUrl":"https://doi.org/10.2215/cjn.0000000000000548","url":null,"abstract":"BACKGROUNDTraditional diagnostic tools that assess resting cardiac function and structure fail to accurately reflect cardiovascular alterations in patients with chronic kidney disease (CKD). This study sought to determine whether multidimensional exercise response patterns related to cardiovascular functional capacity can detect abnormalities in mild-to-moderate CKD.METHODSIn a cross-sectional study, we examined 3,075 participants from the Framingham Heart Study (FHS) and 451 participants from the Massachusetts General Hospital Exercise Study (MGH-ExS) who underwent cardiopulmonary exercise testing (CPET). Participants were stratified by estimated glomerular filtration rate (eGFR): eGFR ≥90; eGFR 60-89; eGFR 30-59. Our primary outcomes of interest were peak oxygen uptake (VO2Peak),VO2 at anaerobic threshold (VO2AT), and the ratio of minute ventilation to carbon dioxide production (VE/VCO2). Multiple linear regression models were fitted to evaluate the associations between eGFR group and each outcome variable adjusted for covariates.RESULTSIn the FHS cohort, N=1,712 (56%) had an eGFR ≥90 ml/min/1.73m2, N=1,271 (41%) had an eGFR 60-89 ml/min/1.73m2, and N=92 (3%) had an eGFR 30-59 ml/min/1.73m2. In the MGH-ExS cohort, N=247 (55%) had an eGFR ≥90 ml/min/1.73m2, N=154 (34%) had an eGFR 60-89 ml/min/1.73m2, and N=50 (11%) had an eGFR 30-59 ml/min/1.73m2. In FHS, VO2Peak and VO2AT were incrementally impaired with declining kidney function (p<0.001); however this pattern was attenuated following adjustment for age. Percent-predicted VO2Peak at AT was higher in the lower eGFR groups (p<0.001). In MGH-ExS, VO2Peak and VO2AT were incrementally impaired with declining kidney function in unadjusted and adjusted models (p<0.05). VO2Peak was associated with eGFR (p<0.05) in all models even after adjusting for age. On further mechanistic analysis, we directly measured cardiac output (CO) at peak exercise via right heart catheterization and found impaired CO in the lower eGFR groups (p≤0.007).CONCLUSIONCPET-derived indices may detect impairment in cardiovascular functional capacity and track cardiac output declines in mild to moderate CKD.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439362","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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