Assessment of Cystatin C Level for Risk Stratification in Adults With Chronic Kidney Disease
Kidney function is usually estimated from serum creatinine level, whereas an alternative glomerular filtration marker (cystatin C level) associates more closely with future risk of cardiovascular disease (CVD) and mortality. To evaluate whether testing concordance between estimated glomerular filtra...
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| Vydané v: | JAMA network open Ročník 5; číslo 10; s. e2238300 |
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United States
American Medical Association
25.10.2022
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| Abstract | Kidney function is usually estimated from serum creatinine level, whereas an alternative glomerular filtration marker (cystatin C level) associates more closely with future risk of cardiovascular disease (CVD) and mortality.
To evaluate whether testing concordance between estimated glomerular filtration rates based on cystatin C (eGFRcys) and creatinine (eGFRcr) levels would improve risk stratification for future outcomes and whether estimations differ by age.
A prospective population-based cohort study (UK Biobank), with participants recruited between 2006-2010 with median follow-up of 11.5 (IQR, 10.8-12.2) years; data were collected until August 31, 2020. Participants had eGFRcr greater than or equal to 45 mL/min/1.73 m2, albuminuria (albumin <30 mg/g), and no preexisting CVD or kidney failure.
Chronic kidney disease status was categorized by concordance between eGFRcr and eGFRcys across the threshold for hronic kidney disease (CKD) diagnosis (60 mL/min/1.73 m2).
Ten-year probabilities of CVD, mortality, and kidney failure were assessed according to CKD status. Multivariable-adjusted Cox proportional hazards models tested associations between CVD and mortality. Area under the receiving operating curve tested discrimination of eGFRcr and eGFRcys for CVD and mortality. The Net Reclassification Index assessed the usefulness of eGFRcr and eGFRcys for CVD risk stratification. Analyses were stratified by older (age 65-73 years) and younger (age <65 years) age.
There were 428 402 participants: median age was 57 (IQR, 50-63) years and 237 173 (55.4%) were women. Among 76 629 older participants, there were 9335 deaths and 5205 CVD events. Among 351 773 younger participants, there were 14 776 deaths and 9328 CVD events. The 10-year probability of kidney failure was less than 0.1%. Regardless of the eGFRcr, the 10-year probabilities of CVD and mortality were low when eGFRcys was greater than or equal to 60 mL/min/1.73 m2; conversely, with eGFRcys less than 60 mL/min/1.73 m2, 10-year risks were nearly doubled in older adults and more than doubled in younger adults. Use of eGFRcys better discriminated CVD and mortality risk than eGFRcr. Across a 7.5% 10-year risk threshold for CVD, eGFRcys improved case Net Reclassification Index by 0.7% (95% CI, 0.6%-0.8%) in older people and 0.7% (95% CI, 0.7%-0.8%) in younger people; eGFRcr did not add to CVD risk estimation.
The findings of this study suggest that eGFRcr 45 to 59 mL/min/1.73 m2 includes a proportion of individuals at low risk and fails to capture a substantial proportion of individuals at high-risk for CVD and mortality. The eGFRcys appears to be more sensitive and specific for CVD and mortality risks in mild CKD. |
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| AbstractList | Kidney function is usually estimated from serum creatinine level, whereas an alternative glomerular filtration marker (cystatin C level) associates more closely with future risk of cardiovascular disease (CVD) and mortality.ImportanceKidney function is usually estimated from serum creatinine level, whereas an alternative glomerular filtration marker (cystatin C level) associates more closely with future risk of cardiovascular disease (CVD) and mortality.To evaluate whether testing concordance between estimated glomerular filtration rates based on cystatin C (eGFRcys) and creatinine (eGFRcr) levels would improve risk stratification for future outcomes and whether estimations differ by age.ObjectivesTo evaluate whether testing concordance between estimated glomerular filtration rates based on cystatin C (eGFRcys) and creatinine (eGFRcr) levels would improve risk stratification for future outcomes and whether estimations differ by age.A prospective population-based cohort study (UK Biobank), with participants recruited between 2006-2010 with median follow-up of 11.5 (IQR, 10.8-12.2) years; data were collected until August 31, 2020. Participants had eGFRcr greater than or equal to 45 mL/min/1.73 m2, albuminuria (albumin <30 mg/g), and no preexisting CVD or kidney failure.Design, Setting, and ParticipantsA prospective population-based cohort study (UK Biobank), with participants recruited between 2006-2010 with median follow-up of 11.5 (IQR, 10.8-12.2) years; data were collected until August 31, 2020. Participants had eGFRcr greater than or equal to 45 mL/min/1.73 m2, albuminuria (albumin <30 mg/g), and no preexisting CVD or kidney failure.Chronic kidney disease status was categorized by concordance between eGFRcr and eGFRcys across the threshold for hronic kidney disease (CKD) diagnosis (60 mL/min/1.73 m2).ExposuresChronic kidney disease status was categorized by concordance between eGFRcr and eGFRcys across the threshold for hronic kidney disease (CKD) diagnosis (60 mL/min/1.73 m2).Ten-year probabilities of CVD, mortality, and kidney failure were assessed according to CKD status. Multivariable-adjusted Cox proportional hazards models tested associations between CVD and mortality. Area under the receiving operating curve tested discrimination of eGFRcr and eGFRcys for CVD and mortality. The Net Reclassification Index assessed the usefulness of eGFRcr and eGFRcys for CVD risk stratification. Analyses were stratified by older (age 65-73 years) and younger (age <65 years) age.Main Outcomes and MeasuresTen-year probabilities of CVD, mortality, and kidney failure were assessed according to CKD status. Multivariable-adjusted Cox proportional hazards models tested associations between CVD and mortality. Area under the receiving operating curve tested discrimination of eGFRcr and eGFRcys for CVD and mortality. The Net Reclassification Index assessed the usefulness of eGFRcr and eGFRcys for CVD risk stratification. Analyses were stratified by older (age 65-73 years) and younger (age <65 years) age.There were 428 402 participants: median age was 57 (IQR, 50-63) years and 237 173 (55.4%) were women. Among 76 629 older participants, there were 9335 deaths and 5205 CVD events. Among 351 773 younger participants, there were 14 776 deaths and 9328 CVD events. The 10-year probability of kidney failure was less than 0.1%. Regardless of the eGFRcr, the 10-year probabilities of CVD and mortality were low when eGFRcys was greater than or equal to 60 mL/min/1.73 m2; conversely, with eGFRcys less than 60 mL/min/1.73 m2, 10-year risks were nearly doubled in older adults and more than doubled in younger adults. Use of eGFRcys better discriminated CVD and mortality risk than eGFRcr. Across a 7.5% 10-year risk threshold for CVD, eGFRcys improved case Net Reclassification Index by 0.7% (95% CI, 0.6%-0.8%) in older people and 0.7% (95% CI, 0.7%-0.8%) in younger people; eGFRcr did not add to CVD risk estimation.ResultsThere were 428 402 participants: median age was 57 (IQR, 50-63) years and 237 173 (55.4%) were women. Among 76 629 older participants, there were 9335 deaths and 5205 CVD events. Among 351 773 younger participants, there were 14 776 deaths and 9328 CVD events. The 10-year probability of kidney failure was less than 0.1%. Regardless of the eGFRcr, the 10-year probabilities of CVD and mortality were low when eGFRcys was greater than or equal to 60 mL/min/1.73 m2; conversely, with eGFRcys less than 60 mL/min/1.73 m2, 10-year risks were nearly doubled in older adults and more than doubled in younger adults. Use of eGFRcys better discriminated CVD and mortality risk than eGFRcr. Across a 7.5% 10-year risk threshold for CVD, eGFRcys improved case Net Reclassification Index by 0.7% (95% CI, 0.6%-0.8%) in older people and 0.7% (95% CI, 0.7%-0.8%) in younger people; eGFRcr did not add to CVD risk estimation.The findings of this study suggest that eGFRcr 45 to 59 mL/min/1.73 m2 includes a proportion of individuals at low risk and fails to capture a substantial proportion of individuals at high-risk for CVD and mortality. The eGFRcys appears to be more sensitive and specific for CVD and mortality risks in mild CKD.Conclusions and RelevanceThe findings of this study suggest that eGFRcr 45 to 59 mL/min/1.73 m2 includes a proportion of individuals at low risk and fails to capture a substantial proportion of individuals at high-risk for CVD and mortality. The eGFRcys appears to be more sensitive and specific for CVD and mortality risks in mild CKD. Importance Kidney function is usually estimated from serum creatinine level, whereas an alternative glomerular filtration marker (cystatin C level) associates more closely with future risk of cardiovascular disease (CVD) and mortality. Objectives To evaluate whether testing concordance between estimated glomerular filtration rates based on cystatin C (eGFRcys) and creatinine (eGFRcr) levels would improve risk stratification for future outcomes and whether estimations differ by age. Design, Setting, and Participants A prospective population-based cohort study (UK Biobank), with participants recruited between 2006-2010 with median follow-up of 11.5 (IQR, 10.8-12.2) years; data were collected until August 31, 2020. Participants had eGFRcr greater than or equal to 45 mL/min/1.73 m2, albuminuria (albumin <30 mg/g), and no preexisting CVD or kidney failure. Exposures Chronic kidney disease status was categorized by concordance between eGFRcr and eGFRcys across the threshold for hronic kidney disease (CKD) diagnosis (60 mL/min/1.73 m2). Main Outcomes and Measures Ten-year probabilities of CVD, mortality, and kidney failure were assessed according to CKD status. Multivariable-adjusted Cox proportional hazards models tested associations between CVD and mortality. Area under the receiving operating curve tested discrimination of eGFRcr and eGFRcys for CVD and mortality. The Net Reclassification Index assessed the usefulness of eGFRcr and eGFRcys for CVD risk stratification. Analyses were stratified by older (age 65-73 years) and younger (age <65 years) age. Results There were 428 402 participants: median age was 57 (IQR, 50-63) years and 237 173 (55.4%) were women. Among 76 629 older participants, there were 9335 deaths and 5205 CVD events. Among 351 773 younger participants, there were 14 776 deaths and 9328 CVD events. The 10-year probability of kidney failure was less than 0.1%. Regardless of the eGFRcr, the 10-year probabilities of CVD and mortality were low when eGFRcys was greater than or equal to 60 mL/min/1.73 m2; conversely, with eGFRcys less than 60 mL/min/1.73 m2, 10-year risks were nearly doubled in older adults and more than doubled in younger adults. Use of eGFRcys better discriminated CVD and mortality risk than eGFRcr. Across a 7.5% 10-year risk threshold for CVD, eGFRcys improved case Net Reclassification Index by 0.7% (95% CI, 0.6%-0.8%) in older people and 0.7% (95% CI, 0.7%-0.8%) in younger people; eGFRcr did not add to CVD risk estimation. Conclusions and Relevance The findings of this study suggest that eGFRcr 45 to 59 mL/min/1.73 m2includes a proportion of individuals at low risk and fails to capture a substantial proportion of individuals at high-risk for CVD and mortality. The eGFRcys appears to be more sensitive and specific for CVD and mortality risks in mild CKD. This cohort study compares the use of cystatin C vs creatinine level for detection of high-risk chronic kidney disease. Kidney function is usually estimated from serum creatinine level, whereas an alternative glomerular filtration marker (cystatin C level) associates more closely with future risk of cardiovascular disease (CVD) and mortality. To evaluate whether testing concordance between estimated glomerular filtration rates based on cystatin C (eGFRcys) and creatinine (eGFRcr) levels would improve risk stratification for future outcomes and whether estimations differ by age. A prospective population-based cohort study (UK Biobank), with participants recruited between 2006-2010 with median follow-up of 11.5 (IQR, 10.8-12.2) years; data were collected until August 31, 2020. Participants had eGFRcr greater than or equal to 45 mL/min/1.73 m2, albuminuria (albumin <30 mg/g), and no preexisting CVD or kidney failure. Chronic kidney disease status was categorized by concordance between eGFRcr and eGFRcys across the threshold for hronic kidney disease (CKD) diagnosis (60 mL/min/1.73 m2). Ten-year probabilities of CVD, mortality, and kidney failure were assessed according to CKD status. Multivariable-adjusted Cox proportional hazards models tested associations between CVD and mortality. Area under the receiving operating curve tested discrimination of eGFRcr and eGFRcys for CVD and mortality. The Net Reclassification Index assessed the usefulness of eGFRcr and eGFRcys for CVD risk stratification. Analyses were stratified by older (age 65-73 years) and younger (age <65 years) age. There were 428 402 participants: median age was 57 (IQR, 50-63) years and 237 173 (55.4%) were women. Among 76 629 older participants, there were 9335 deaths and 5205 CVD events. Among 351 773 younger participants, there were 14 776 deaths and 9328 CVD events. The 10-year probability of kidney failure was less than 0.1%. Regardless of the eGFRcr, the 10-year probabilities of CVD and mortality were low when eGFRcys was greater than or equal to 60 mL/min/1.73 m2; conversely, with eGFRcys less than 60 mL/min/1.73 m2, 10-year risks were nearly doubled in older adults and more than doubled in younger adults. Use of eGFRcys better discriminated CVD and mortality risk than eGFRcr. Across a 7.5% 10-year risk threshold for CVD, eGFRcys improved case Net Reclassification Index by 0.7% (95% CI, 0.6%-0.8%) in older people and 0.7% (95% CI, 0.7%-0.8%) in younger people; eGFRcr did not add to CVD risk estimation. The findings of this study suggest that eGFRcr 45 to 59 mL/min/1.73 m2 includes a proportion of individuals at low risk and fails to capture a substantial proportion of individuals at high-risk for CVD and mortality. The eGFRcys appears to be more sensitive and specific for CVD and mortality risks in mild CKD. |
| Author | Scherzer, Rebecca Ebert, Natalie Mark, Patrick B. Estrella, Michelle M. Stevens, Kathryn I. Rutherford, Elaine Sullivan, Michael K. Shlipak, Michael G. Lees, Jennifer S. Chen, Debbie C. |
| AuthorAffiliation | 6 Institute of Public Health, Charité University Hospital, Berlin, Germany 3 Renal Unit, Mountainhall Treatment Centre, NHS Dumfries and Galloway, Dumfries, United Kingdom 1 School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom 4 Kidney Health Research Collaborative, Department of Medicine, University of California San Francisco and San Francisco VA Health Care System, San Francisco 2 Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, United Kingdom 5 Genentech/Roche, South San Francisco, California |
| AuthorAffiliation_xml | – name: 2 Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, United Kingdom – name: 3 Renal Unit, Mountainhall Treatment Centre, NHS Dumfries and Galloway, Dumfries, United Kingdom – name: 1 School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom – name: 6 Institute of Public Health, Charité University Hospital, Berlin, Germany – name: 4 Kidney Health Research Collaborative, Department of Medicine, University of California San Francisco and San Francisco VA Health Care System, San Francisco – name: 5 Genentech/Roche, South San Francisco, California |
| Author_xml | – sequence: 1 givenname: Jennifer S. surname: Lees fullname: Lees, Jennifer S. organization: School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom, Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, United Kingdom – sequence: 2 givenname: Elaine surname: Rutherford fullname: Rutherford, Elaine organization: School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom, Renal Unit, Mountainhall Treatment Centre, NHS Dumfries and Galloway, Dumfries, United Kingdom – sequence: 3 givenname: Kathryn I. surname: Stevens fullname: Stevens, Kathryn I. organization: School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom, Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, United Kingdom – sequence: 4 givenname: Debbie C. surname: Chen fullname: Chen, Debbie C. organization: Kidney Health Research Collaborative, Department of Medicine, University of California San Francisco and San Francisco VA Health Care System, San Francisco, Genentech/Roche, South San Francisco, California – sequence: 5 givenname: Rebecca surname: Scherzer fullname: Scherzer, Rebecca organization: Kidney Health Research Collaborative, Department of Medicine, University of California San Francisco and San Francisco VA Health Care System, San Francisco – sequence: 6 givenname: Michelle M. surname: Estrella fullname: Estrella, Michelle M. organization: Kidney Health Research Collaborative, Department of Medicine, University of California San Francisco and San Francisco VA Health Care System, San Francisco – sequence: 7 givenname: Michael K. surname: Sullivan fullname: Sullivan, Michael K. organization: School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom, Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, United Kingdom – sequence: 8 givenname: Natalie surname: Ebert fullname: Ebert, Natalie organization: Institute of Public Health, Charité University Hospital, Berlin, Germany – sequence: 9 givenname: Patrick B. surname: Mark fullname: Mark, Patrick B. organization: School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom, Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, United Kingdom – sequence: 10 givenname: Michael G. surname: Shlipak fullname: Shlipak, Michael G. organization: Kidney Health Research Collaborative, Department of Medicine, University of California San Francisco and San Francisco VA Health Care System, San Francisco |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36282503$$D View this record in MEDLINE/PubMed |
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| References | Goede (zoi221084r36) 2009; 139 Allen (zoi221084r8) 2012; 1 zoi221084r9 Suetta (zoi221084r4) 2019; 10 Inker (zoi221084r14) 2012; 367 Goff (zoi221084r16) 2014; 129 Kang (zoi221084r30) 2021; 3 Rule (zoi221084r37) 2013; 83 Inker (zoi221084r13) 2021; 385 Bundy (zoi221084r34) 2022; 175 Liu (zoi221084r24) 2021; 181 Delanaye (zoi221084r42) 2022 Panaich (zoi221084r35) 2013; 61 Anderson (zoi221084r38) 2012; 60 Matsushita (zoi221084r26) 2020; 27 zoi221084r41 zoi221084r25 Elliott (zoi221084r10) 2008; 37 Baxmann (zoi221084r40) 2008; 3 Lasserson (zoi221084r7) 2017; 67 Herrington (zoi221084r27) 2016; 4 Whitlock (zoi221084r33) 2017; 4 Batty (zoi221084r44) 2020; 368 Major (zoi221084r31) 2019; 16 Hsu (zoi221084r15) 2021; 385 Kühn (zoi221084r23) 2021; 77 Tangri (zoi221084r32) 2016; 315 Peralta (zoi221084r20) 2011; 305 Hallan (zoi221084r21) 2012; 308 Shlipak (zoi221084r6) 2013; 369 Kidney Disease Working Group (zoi221084r1) 2013; 3 Matsushita (zoi221084r22) 2010; 375 Patel (zoi221084r39) 2013; 4 zoi221084r11 Schaeffner (zoi221084r2) 2022 Vogt (zoi221084r29) 2021; 384 zoi221084r12 Lees (zoi221084r5) 2019; 25 zoi221084r18 Delanaye (zoi221084r19) 2019; 30 Kohli-Lynch (zoi221084r28) 2022; 145 zoi221084r17 Nankivell (zoi221084r3) 2020; 29-30 Fry (zoi221084r43) 2017; 186 |
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| Snippet | Kidney function is usually estimated from serum creatinine level, whereas an alternative glomerular filtration marker (cystatin C level) associates more... Importance Kidney function is usually estimated from serum creatinine level, whereas an alternative glomerular filtration marker (cystatin C level) associates... This cohort study compares the use of cystatin C vs creatinine level for detection of high-risk chronic kidney disease. |
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| SubjectTerms | Age Aged Albumins Cardiovascular Diseases - epidemiology Cohort Studies Creatinine Cystatin C Female Humans Kidney diseases Male Middle Aged Mortality Nephrology Older people Online Only Original Investigation Prospective Studies Renal Insufficiency, Chronic Risk Assessment |
| Title | Assessment of Cystatin C Level for Risk Stratification in Adults With Chronic Kidney Disease |
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