CKD Prognosis Consortium

Coresh, Josef

Gansevoort, Ron T

Jadoul, Michel

KDIGO

Levin, Adeera

English

ARTS repository - University of Groningen

   University of GroningenCurrent CKD Definition Takes into Account Both Relative and Absolute RiskCKD Prognosis Consortium; Coresh, Josef; Gansevoort, Ron T; Levin, Adeera; Jadoul,MichelPublished in:Journal of the American Society of NephrologyDOI:10.1681/ASN.2019101049IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2020Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):CKD Prognosis Consortium, Coresh, J., Gansevoort, R. T., Levin, A., & Jadoul, M. (2020). Current CKDDefinition Takes into Account Both Relative and Absolute Risk. Journal of the American Society ofNephrology, 31(2), 447-448. https://doi.org/10.1681/ASN.2019101049CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 10-09-2023LETTER TO THE EDITOR www.jasn.orgAge-Dependent Definition of CKDI read the online article by Delanaye et al.1 calling for age-dependent definitions of CKD and the two accompanyingeditorials2,3 with great interest. As a pediatric nephrologist,I do not have a stake in the details of the adult argument.However, as a nephrologist, I also recognize the impor-tance of clinically relevant definitions of CKD stages andI was struck by one of the arguments advanced by Chertowand Beddhu2 who advise caution before tampering withthe current scheme. They take exception to the claim byDelanaye et al. that overdiagnosis of CKD in the elderlycould lead to inappropriate care, including diagnostic evalu-ation and treatment of nonexistent kidney disease. Chertowand Beddhu assert that the elderly are less likely toget clinically indicated care for cardiac disease and otherconditions that require contrast-enhanced imaging. Infact, this well documented observation reinforces the callfor change by Delanaye et al. because inappropriate care isbidirectional—overzealous evaluation of patients who arehealthy and insufficient testing of patients who are pre-sumed sick, in this case with CKD. Rethinking the thresholdGFR to define CKDmay have the potential to be helpful, notonly in the geriatric population but across the life span ifthat includes the older end of the pediatric spectrum.DISCLOSURESNone.FUNDINGDr. Trachtman is supported by the National Institute of Diabetes and Di-gestive and Kidney Diseases (grant DK100307).REFERENCES1. Delanaye P, Jager KJ, Bökenkamp A, Christensson A, Dubourg L,Eriksen BO, et al.: CKD: A Call for an age-adapted definition. J Am SocNephrol 30: 1785–1805, 20192. Chertow GM, Beddhu S: Modification of eGFR-based CKD definitions:Perfect, or enemy of the good? J Am Soc Nephrol 30: 1807–1809, 20193. Wesson DE: Does eGFR by Any Number Mean the Same? J Am SocNephrol 30: 1806–1807, 2019Howard TrachtmanNew York University Langone Health, New York, New YorkJASN 31: 447, 2020.doi: https://doi.org/10.1681/ASN.2019090914Current CKD Definition Takesinto Account Both Relative andAbsolute RiskDelanaye et al.1 propose that GFR thresholds to define CKDshould depend on age. Specifically, people aged$65 years withGFR 45–59 ml/min per 1.73 m2 and albumin-creatinineratio,30 mg/g should not be classified as having CKD. Thisis not a new proposal. It has been discussed many times, in-cluding by the Kidney Disease Outcomes Quality Initiative in2002 and Kidney Disease Improving Global Outcomes(KDIGO) work groups in 2009 and 2012.2 Each time, theconsensus was that the GFR threshold for the definition ofCKD should be age-independent.Delanaye et al. now reopen the discussion, suggestingthat the GFR threshold for the CKD definition should bedetermined only by relative risks for mortality. They citedata from the CKD Prognosis Consortium, the largestmeta-analysis, showing that the relative hazard of mortal-ity for eGFR 45–59 versus 75–89 ml/min per 1.73 m2 withalbumin-creatinine ratio,30 mg/g was lower at olderage. However, they do not mention the higher absoluterisk of mortality (two to four times higher at the oldestcompared with youngest group).3 Absolute risk is more im-portant than relative risk to patients and providers. Thethreshold for CKD should also take into account outcomesbeyond mortality such as ESKD, AKI, heart failure, andhospitalization which are often more specific and sensitivePublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Dr. Howard Trachtman, New York University LangoneHealth, 403 E34th Street, Room 1-02, New York, NY 10016. Email: howard.trachtman@nyulangone.orgCopyright © 2020 by the American Society of NephrologyPublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Dr. Josef Coresh, 2024 E. Monument, Suite 2-600, Baltimore,MD 21287. Email: coresh@jhu.eduCopyright © 2020 by the American Society of NephrologyJASN 31: 447–449, 2020 ISSN : 1046-6673/3102-447 447LETTERTOTHEEDITORconsequences of CKD, and have substantial excess risk inolder age.Many other diseases, such as hypertension and diabetes,follow a similar pattern of higher prevalence at older agewith smaller relative risks but higher attributable risks of mor-tality and complications. Yet, the hypertension and diabetesguidelines define these diseases independently of age whilerecommending evaluation and management personalized toage and other factors. Similarly, the KDIGO guideline recom-mends an age-independent definition but personalized eval-uation and management.The CKD definition has been stable since 2002, enablinggreat progress in the field. The age-independent GFRthreshold has been widely accepted by nephrology societiesacross the world, endorsed by the World Health Organiza-tion, and incorporated into the International Classificationof Disease Coding System. At each deliberation, the ex-panding evidence base has supported the original defini-tion. We think that changing the GFR threshold at olderage on the basis solely of relative risk of mortality whileignoring the higher absolute risk for mortality and otheroutcomes is a narrow view that impedes progress. We be-lieve it is time, as a nephrology community, to move thediscussion to optimizing management and discoveringnew therapies.DISCLOSURESNone.REFERENCES1. Delanaye P, Jager KJ, BökenkampA, ChristenssonA, Dubourg L, EriksenBO, et al.: CKD: A call for an age-adapted definition. J Am Soc Nephrol30: 1785–1805, 20192. Kidney Disease: Improving Global Outcomes (KDIGO) CKD WorkGroup: KDIGO 2012 clinical practice guideline for the evaluation andmanagement of chronic kidney disease. Kidney Int Suppl 3: 1–150,20133. Hallan SI, Matsushita K, Sang Y, Mahmoodi BK, Black C, Ishani A, et al.;Chronic Kidney Disease Prognosis Consortium: Age and association ofkidney measures with mortality and end-stage renal disease. JAMA 308:2349–2360, 2012Josef Coresh 1, and Ron T. Gansevoort2 on behalfof the CKD Prognosis Consortium, Adeera Levin3,and Michel Jadoul4 on behalf of KDIGO1Epidemiology, Medicine, Biostatistics, and CKD PrognosisConsortium, The Johns Hopkins University, Baltimore, Maryland;2Nephrology, and CKD Prognosis Consortium, University ofGroningen, Groningen, Netherlands;3Nephrology, and KDIGO, St. Paul Hospital, Vancouver,Canada; and4Department of Nephrology, Cliniques Universitaires St-Luc, andKDIGO, Université Catholique de Louvain, Brussels, BelgiumJASN 31: 447–448, 2020.doi: https://doi.org/10.1681/ASN.2019101049Authors’ ReplyWe agree with Trachtman1 regarding the potential benefits forboth young and elderly with age-based eGFR thresholds. Wedisagree with the points raised by Coresh et al.2 First, despitethe cited guidelines, there is not widespread consensus amongpracticing nephrologists that elderly patients with an eGFR of45–59 ml/min per 1.73 m2 and no albuminuria have diseasedkidneys.3 Further, primary care guidelines fail to see clinicalbenefit with this classification.4 Second, although absoluterisks are often important, humans have a limited lifespanand it is not clear that an hazard ratio of 1.2 for risk translatesinto clinically meaningful life years lost.5 The statistical prog-nostic models relating eGFR to outcomes were on the basis ofrelative risk and the “heat maps” were on the basis of relativerisk. The eGFR level associated with lowest risk (absolute orrelative) declines with older age and this is not accounted forin the CKD definition. As with any epidemiologic study, asmall hazard ratio of 1.2 could easily be due to bias (high-risk rather than just general population cohorts were used inthe CKD prognosis consortium analyses) or residual con-founding (such as systemic microvascular disease or lowernephron endowment linked to other complications of lowerbirthweight). Third, a causal pathway linking the age-relateddecline in eGFR to an increased risk of nonrenal outcomes islacking.We concur that older patients with a low-normal GFRhave less renal reserves putting them at increased risk for kid-ney failure, but this is too rare of an event to justify a diseaselabel. High BP and glucose can be lowered with medicationswith a demonstrable clinical benefit, but there is no evidencethat eGFR can be increased for a clinical benefit. A fairer com-parison would be pulmonary function tests, which are report-ed with age-appropriate reference ranges due to the age-re-lated decline in pulmonary function.6 We hope that the CKDprognosis consortium and Kidney Disease Improving GlobalOutcomes will reconsider the age-related decline in eGFR forthe purposes of identifying persons with diseased kidneys.DISCLOSURESNone.REFERENCES1. Trachtman H: Age-dependent definition of CKD. J Am Soc Nephrol 31:447, 2020Authors are members of the European Kidney Function ConsortiumPublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Prof. Pierre Delanaye, Service de Dialyse, CHU Sart Tilman,4000 Liège, Belgium. Email: pierre_delanaye@yahoo.frCopyright © 2020 by the American Society of Nephrology448 JASN JASN 31: 447–449, 2020LETTER TO THE EDITOR www.jasn.org

Current CKD Definition Takes into Account Both Relative and Absolute Risk

University of Groningen

   University of GroningenCurrent CKD Definition Takes into Account Both Relative and Absolute RiskCKD Prognosis Consortium; Coresh, Josef; Gansevoort, Ron T; Levin, Adeera; Jadoul,MichelPublished in:Journal of the American Society of NephrologyDOI:10.1681/ASN.2019101049IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2020Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):CKD Prognosis Consortium, Coresh, J., Gansevoort, R. T., Levin, A., & Jadoul, M. (2020). Current CKDDefinition Takes into Account Both Relative and Absolute Risk. Journal of the American Society ofNephrology, 31(2), 447-448. https://doi.org/10.1681/ASN.2019101049CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 29-04-2023LETTER TO THE EDITOR www.jasn.orgAge-Dependent Definition of CKDI read the online article by Delanaye et al.1 calling for age-dependent definitions of CKD and the two accompanyingeditorials2,3 with great interest. As a pediatric nephrologist,I do not have a stake in the details of the adult argument.However, as a nephrologist, I also recognize the impor-tance of clinically relevant definitions of CKD stages andI was struck by one of the arguments advanced by Chertowand Beddhu2 who advise caution before tampering withthe current scheme. They take exception to the claim byDelanaye et al. that overdiagnosis of CKD in the elderlycould lead to inappropriate care, including diagnostic evalu-ation and treatment of nonexistent kidney disease. Chertowand Beddhu assert that the elderly are less likely toget clinically indicated care for cardiac disease and otherconditions that require contrast-enhanced imaging. Infact, this well documented observation reinforces the callfor change by Delanaye et al. because inappropriate care isbidirectional—overzealous evaluation of patients who arehealthy and insufficient testing of patients who are pre-sumed sick, in this case with CKD. Rethinking the thresholdGFR to define CKDmay have the potential to be helpful, notonly in the geriatric population but across the life span ifthat includes the older end of the pediatric spectrum.DISCLOSURESNone.FUNDINGDr. Trachtman is supported by the National Institute of Diabetes and Di-gestive and Kidney Diseases (grant DK100307).REFERENCES1. Delanaye P, Jager KJ, Bökenkamp A, Christensson A, Dubourg L,Eriksen BO, et al.: CKD: A Call for an age-adapted definition. J Am SocNephrol 30: 1785–1805, 20192. Chertow GM, Beddhu S: Modification of eGFR-based CKD definitions:Perfect, or enemy of the good? J Am Soc Nephrol 30: 1807–1809, 20193. Wesson DE: Does eGFR by Any Number Mean the Same? J Am SocNephrol 30: 1806–1807, 2019Howard TrachtmanNew York University Langone Health, New York, New YorkJASN 31: 447, 2020.doi: https://doi.org/10.1681/ASN.2019090914Current CKD Definition Takesinto Account Both Relative andAbsolute RiskDelanaye et al.1 propose that GFR thresholds to define CKDshould depend on age. Specifically, people aged$65 years withGFR 45–59 ml/min per 1.73 m2 and albumin-creatinineratio,30 mg/g should not be classified as having CKD. Thisis not a new proposal. It has been discussed many times, in-cluding by the Kidney Disease Outcomes Quality Initiative in2002 and Kidney Disease Improving Global Outcomes(KDIGO) work groups in 2009 and 2012.2 Each time, theconsensus was that the GFR threshold for the definition ofCKD should be age-independent.Delanaye et al. now reopen the discussion, suggestingthat the GFR threshold for the CKD definition should bedetermined only by relative risks for mortality. They citedata from the CKD Prognosis Consortium, the largestmeta-analysis, showing that the relative hazard of mortal-ity for eGFR 45–59 versus 75–89 ml/min per 1.73 m2 withalbumin-creatinine ratio,30 mg/g was lower at olderage. However, they do not mention the higher absoluterisk of mortality (two to four times higher at the oldestcompared with youngest group).3 Absolute risk is more im-portant than relative risk to patients and providers. Thethreshold for CKD should also take into account outcomesbeyond mortality such as ESKD, AKI, heart failure, andhospitalization which are often more specific and sensitivePublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Dr. Howard Trachtman, New York University LangoneHealth, 403 E34th Street, Room 1-02, New York, NY 10016. Email: howard.trachtman@nyulangone.orgCopyright © 2020 by the American Society of NephrologyPublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Dr. Josef Coresh, 2024 E. Monument, Suite 2-600, Baltimore,MD 21287. Email: coresh@jhu.eduCopyright © 2020 by the American Society of NephrologyJASN 31: 447–449, 2020 ISSN : 1046-6673/3102-447 447LETTERTOTHEEDITORconsequences of CKD, and have substantial excess risk inolder age.Many other diseases, such as hypertension and diabetes,follow a similar pattern of higher prevalence at older agewith smaller relative risks but higher attributable risks of mor-tality and complications. Yet, the hypertension and diabetesguidelines define these diseases independently of age whilerecommending evaluation and management personalized toage and other factors. Similarly, the KDIGO guideline recom-mends an age-independent definition but personalized eval-uation and management.The CKD definition has been stable since 2002, enablinggreat progress in the field. The age-independent GFRthreshold has been widely accepted by nephrology societiesacross the world, endorsed by the World Health Organiza-tion, and incorporated into the International Classificationof Disease Coding System. At each deliberation, the ex-panding evidence base has supported the original defini-tion. We think that changing the GFR threshold at olderage on the basis solely of relative risk of mortality whileignoring the higher absolute risk for mortality and otheroutcomes is a narrow view that impedes progress. We be-lieve it is time, as a nephrology community, to move thediscussion to optimizing management and discoveringnew therapies.DISCLOSURESNone.REFERENCES1. Delanaye P, Jager KJ, BökenkampA, ChristenssonA, Dubourg L, EriksenBO, et al.: CKD: A call for an age-adapted definition. J Am Soc Nephrol30: 1785–1805, 20192. Kidney Disease: Improving Global Outcomes (KDIGO) CKD WorkGroup: KDIGO 2012 clinical practice guideline for the evaluation andmanagement of chronic kidney disease. Kidney Int Suppl 3: 1–150,20133. Hallan SI, Matsushita K, Sang Y, Mahmoodi BK, Black C, Ishani A, et al.;Chronic Kidney Disease Prognosis Consortium: Age and association ofkidney measures with mortality and end-stage renal disease. JAMA 308:2349–2360, 2012Josef Coresh 1, and Ron T. Gansevoort2 on behalfof the CKD Prognosis Consortium, Adeera Levin3,and Michel Jadoul4 on behalf of KDIGO1Epidemiology, Medicine, Biostatistics, and CKD PrognosisConsortium, The Johns Hopkins University, Baltimore, Maryland;2Nephrology, and CKD Prognosis Consortium, University ofGroningen, Groningen, Netherlands;3Nephrology, and KDIGO, St. Paul Hospital, Vancouver,Canada; and4Department of Nephrology, Cliniques Universitaires St-Luc, andKDIGO, Université Catholique de Louvain, Brussels, BelgiumJASN 31: 447–448, 2020.doi: https://doi.org/10.1681/ASN.2019101049Authors’ ReplyWe agree with Trachtman1 regarding the potential benefits forboth young and elderly with age-based eGFR thresholds. Wedisagree with the points raised by Coresh et al.2 First, despitethe cited guidelines, there is not widespread consensus amongpracticing nephrologists that elderly patients with an eGFR of45–59 ml/min per 1.73 m2 and no albuminuria have diseasedkidneys.3 Further, primary care guidelines fail to see clinicalbenefit with this classification.4 Second, although absoluterisks are often important, humans have a limited lifespanand it is not clear that an hazard ratio of 1.2 for risk translatesinto clinically meaningful life years lost.5 The statistical prog-nostic models relating eGFR to outcomes were on the basis ofrelative risk and the “heat maps” were on the basis of relativerisk. The eGFR level associated with lowest risk (absolute orrelative) declines with older age and this is not accounted forin the CKD definition. As with any epidemiologic study, asmall hazard ratio of 1.2 could easily be due to bias (high-risk rather than just general population cohorts were used inthe CKD prognosis consortium analyses) or residual con-founding (such as systemic microvascular disease or lowernephron endowment linked to other complications of lowerbirthweight). Third, a causal pathway linking the age-relateddecline in eGFR to an increased risk of nonrenal outcomes islacking.We concur that older patients with a low-normal GFRhave less renal reserves putting them at increased risk for kid-ney failure, but this is too rare of an event to justify a diseaselabel. High BP and glucose can be lowered with medicationswith a demonstrable clinical benefit, but there is no evidencethat eGFR can be increased for a clinical benefit. A fairer com-parison would be pulmonary function tests, which are report-ed with age-appropriate reference ranges due to the age-re-lated decline in pulmonary function.6 We hope that the CKDprognosis consortium and Kidney Disease Improving GlobalOutcomes will reconsider the age-related decline in eGFR forthe purposes of identifying persons with diseased kidneys.DISCLOSURESNone.REFERENCES1. Trachtman H: Age-dependent definition of CKD. J Am Soc Nephrol 31:447, 2020Authors are members of the European Kidney Function ConsortiumPublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Prof. Pierre Delanaye, Service de Dialyse, CHU Sart Tilman,4000 Liège, Belgium. Email: pierre_delanaye@yahoo.frCopyright © 2020 by the American Society of Nephrology448 JASN JASN 31: 447–449, 2020LETTER TO THE EDITOR www.jasn.org

   University of GroningenCurrent CKD Definition Takes into Account Both Relative and Absolute RiskCKD Prognosis Consortium; Coresh, Josef; Gansevoort, Ron T; Levin, Adeera; Jadoul,MichelPublished in:Journal of the American Society of NephrologyDOI:10.1681/ASN.2019101049IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2020Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):CKD Prognosis Consortium, Coresh, J., Gansevoort, R. T., Levin, A., & Jadoul, M. (2020). Current CKDDefinition Takes into Account Both Relative and Absolute Risk. Journal of the American Society ofNephrology, 31(2), 447-448. https://doi.org/10.1681/ASN.2019101049CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 07-06-2022LETTER TO THE EDITOR www.jasn.orgAge-Dependent Definition of CKDI read the online article by Delanaye et al.1 calling for age-dependent definitions of CKD and the two accompanyingeditorials2,3 with great interest. As a pediatric nephrologist,I do not have a stake in the details of the adult argument.However, as a nephrologist, I also recognize the impor-tance of clinically relevant definitions of CKD stages andI was struck by one of the arguments advanced by Chertowand Beddhu2 who advise caution before tampering withthe current scheme. They take exception to the claim byDelanaye et al. that overdiagnosis of CKD in the elderlycould lead to inappropriate care, including diagnostic evalu-ation and treatment of nonexistent kidney disease. Chertowand Beddhu assert that the elderly are less likely toget clinically indicated care for cardiac disease and otherconditions that require contrast-enhanced imaging. Infact, this well documented observation reinforces the callfor change by Delanaye et al. because inappropriate care isbidirectional—overzealous evaluation of patients who arehealthy and insufficient testing of patients who are pre-sumed sick, in this case with CKD. Rethinking the thresholdGFR to define CKDmay have the potential to be helpful, notonly in the geriatric population but across the life span ifthat includes the older end of the pediatric spectrum.DISCLOSURESNone.FUNDINGDr. Trachtman is supported by the National Institute of Diabetes and Di-gestive and Kidney Diseases (grant DK100307).REFERENCES1. Delanaye P, Jager KJ, Bökenkamp A, Christensson A, Dubourg L,Eriksen BO, et al.: CKD: A Call for an age-adapted definition. J Am SocNephrol 30: 1785–1805, 20192. Chertow GM, Beddhu S: Modification of eGFR-based CKD definitions:Perfect, or enemy of the good? J Am Soc Nephrol 30: 1807–1809, 20193. Wesson DE: Does eGFR by Any Number Mean the Same? J Am SocNephrol 30: 1806–1807, 2019Howard TrachtmanNew York University Langone Health, New York, New YorkJASN 31: 447, 2020.doi: https://doi.org/10.1681/ASN.2019090914Current CKD Definition Takesinto Account Both Relative andAbsolute RiskDelanaye et al.1 propose that GFR thresholds to define CKDshould depend on age. Specifically, people aged$65 years withGFR 45–59 ml/min per 1.73 m2 and albumin-creatinineratio,30 mg/g should not be classified as having CKD. Thisis not a new proposal. It has been discussed many times, in-cluding by the Kidney Disease Outcomes Quality Initiative in2002 and Kidney Disease Improving Global Outcomes(KDIGO) work groups in 2009 and 2012.2 Each time, theconsensus was that the GFR threshold for the definition ofCKD should be age-independent.Delanaye et al. now reopen the discussion, suggestingthat the GFR threshold for the CKD definition should bedetermined only by relative risks for mortality. They citedata from the CKD Prognosis Consortium, the largestmeta-analysis, showing that the relative hazard of mortal-ity for eGFR 45–59 versus 75–89 ml/min per 1.73 m2 withalbumin-creatinine ratio,30 mg/g was lower at olderage. However, they do not mention the higher absoluterisk of mortality (two to four times higher at the oldestcompared with youngest group).3 Absolute risk is more im-portant than relative risk to patients and providers. Thethreshold for CKD should also take into account outcomesbeyond mortality such as ESKD, AKI, heart failure, andhospitalization which are often more specific and sensitivePublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Dr. Howard Trachtman, New York University LangoneHealth, 403 E34th Street, Room 1-02, New York, NY 10016. Email: howard.trachtman@nyulangone.orgCopyright © 2020 by the American Society of NephrologyPublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Dr. Josef Coresh, 2024 E. Monument, Suite 2-600, Baltimore,MD 21287. Email: coresh@jhu.eduCopyright © 2020 by the American Society of NephrologyJASN 31: 447–449, 2020 ISSN : 1046-6673/3102-447 447LETTERTOTHEEDITORconsequences of CKD, and have substantial excess risk inolder age.Many other diseases, such as hypertension and diabetes,follow a similar pattern of higher prevalence at older agewith smaller relative risks but higher attributable risks of mor-tality and complications. Yet, the hypertension and diabetesguidelines define these diseases independently of age whilerecommending evaluation and management personalized toage and other factors. Similarly, the KDIGO guideline recom-mends an age-independent definition but personalized eval-uation and management.The CKD definition has been stable since 2002, enablinggreat progress in the field. The age-independent GFRthreshold has been widely accepted by nephrology societiesacross the world, endorsed by the World Health Organiza-tion, and incorporated into the International Classificationof Disease Coding System. At each deliberation, the ex-panding evidence base has supported the original defini-tion. We think that changing the GFR threshold at olderage on the basis solely of relative risk of mortality whileignoring the higher absolute risk for mortality and otheroutcomes is a narrow view that impedes progress. We be-lieve it is time, as a nephrology community, to move thediscussion to optimizing management and discoveringnew therapies.DISCLOSURESNone.REFERENCES1. Delanaye P, Jager KJ, BökenkampA, ChristenssonA, Dubourg L, EriksenBO, et al.: CKD: A call for an age-adapted definition. J Am Soc Nephrol30: 1785–1805, 20192. Kidney Disease: Improving Global Outcomes (KDIGO) CKD WorkGroup: KDIGO 2012 clinical practice guideline for the evaluation andmanagement of chronic kidney disease. Kidney Int Suppl 3: 1–150,20133. Hallan SI, Matsushita K, Sang Y, Mahmoodi BK, Black C, Ishani A, et al.;Chronic Kidney Disease Prognosis Consortium: Age and association ofkidney measures with mortality and end-stage renal disease. JAMA 308:2349–2360, 2012Josef Coresh 1, and Ron T. Gansevoort2 on behalfof the CKD Prognosis Consortium, Adeera Levin3,and Michel Jadoul4 on behalf of KDIGO1Epidemiology, Medicine, Biostatistics, and CKD PrognosisConsortium, The Johns Hopkins University, Baltimore, Maryland;2Nephrology, and CKD Prognosis Consortium, University ofGroningen, Groningen, Netherlands;3Nephrology, and KDIGO, St. Paul Hospital, Vancouver,Canada; and4Department of Nephrology, Cliniques Universitaires St-Luc, andKDIGO, Université Catholique de Louvain, Brussels, BelgiumJASN 31: 447–448, 2020.doi: https://doi.org/10.1681/ASN.2019101049Authors’ ReplyWe agree with Trachtman1 regarding the potential benefits forboth young and elderly with age-based eGFR thresholds. Wedisagree with the points raised by Coresh et al.2 First, despitethe cited guidelines, there is not widespread consensus amongpracticing nephrologists that elderly patients with an eGFR of45–59 ml/min per 1.73 m2 and no albuminuria have diseasedkidneys.3 Further, primary care guidelines fail to see clinicalbenefit with this classification.4 Second, although absoluterisks are often important, humans have a limited lifespanand it is not clear that an hazard ratio of 1.2 for risk translatesinto clinically meaningful life years lost.5 The statistical prog-nostic models relating eGFR to outcomes were on the basis ofrelative risk and the “heat maps” were on the basis of relativerisk. The eGFR level associated with lowest risk (absolute orrelative) declines with older age and this is not accounted forin the CKD definition. As with any epidemiologic study, asmall hazard ratio of 1.2 could easily be due to bias (high-risk rather than just general population cohorts were used inthe CKD prognosis consortium analyses) or residual con-founding (such as systemic microvascular disease or lowernephron endowment linked to other complications of lowerbirthweight). Third, a causal pathway linking the age-relateddecline in eGFR to an increased risk of nonrenal outcomes islacking.We concur that older patients with a low-normal GFRhave less renal reserves putting them at increased risk for kid-ney failure, but this is too rare of an event to justify a diseaselabel. High BP and glucose can be lowered with medicationswith a demonstrable clinical benefit, but there is no evidencethat eGFR can be increased for a clinical benefit. A fairer com-parison would be pulmonary function tests, which are report-ed with age-appropriate reference ranges due to the age-re-lated decline in pulmonary function.6 We hope that the CKDprognosis consortium and Kidney Disease Improving GlobalOutcomes will reconsider the age-related decline in eGFR forthe purposes of identifying persons with diseased kidneys.DISCLOSURESNone.REFERENCES1. Trachtman H: Age-dependent definition of CKD. J Am Soc Nephrol 31:447, 2020Authors are members of the European Kidney Function ConsortiumPublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Prof. Pierre Delanaye, Service de Dialyse, CHU Sart Tilman,4000 Liège, Belgium. Email: pierre_delanaye@yahoo.frCopyright © 2020 by the American Society of Nephrology448 JASN JASN 31: 447–449, 2020LETTER TO THE EDITOR www.jasn.org

NARCIS 

   University of GroningenCurrent CKD Definition Takes into Account Both Relative and Absolute RiskCKD Prognosis Consortium; Coresh, Josef; Gansevoort, Ron T; Levin, Adeera; Jadoul,MichelPublished in:Journal of the American Society of NephrologyDOI:10.1681/ASN.2019101049IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2020Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):CKD Prognosis Consortium, Coresh, J., Gansevoort, R. T., Levin, A., & Jadoul, M. (2020). Current CKDDefinition Takes into Account Both Relative and Absolute Risk. Journal of the American Society ofNephrology, 31(2), 447-448. https://doi.org/10.1681/ASN.2019101049CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 19-11-2022LETTER TO THE EDITOR www.jasn.orgAge-Dependent Definition of CKDI read the online article by Delanaye et al.1 calling for age-dependent definitions of CKD and the two accompanyingeditorials2,3 with great interest. As a pediatric nephrologist,I do not have a stake in the details of the adult argument.However, as a nephrologist, I also recognize the impor-tance of clinically relevant definitions of CKD stages andI was struck by one of the arguments advanced by Chertowand Beddhu2 who advise caution before tampering withthe current scheme. They take exception to the claim byDelanaye et al. that overdiagnosis of CKD in the elderlycould lead to inappropriate care, including diagnostic evalu-ation and treatment of nonexistent kidney disease. Chertowand Beddhu assert that the elderly are less likely toget clinically indicated care for cardiac disease and otherconditions that require contrast-enhanced imaging. Infact, this well documented observation reinforces the callfor change by Delanaye et al. because inappropriate care isbidirectional—overzealous evaluation of patients who arehealthy and insufficient testing of patients who are pre-sumed sick, in this case with CKD. Rethinking the thresholdGFR to define CKDmay have the potential to be helpful, notonly in the geriatric population but across the life span ifthat includes the older end of the pediatric spectrum.DISCLOSURESNone.FUNDINGDr. Trachtman is supported by the National Institute of Diabetes and Di-gestive and Kidney Diseases (grant DK100307).REFERENCES1. Delanaye P, Jager KJ, Bökenkamp A, Christensson A, Dubourg L,Eriksen BO, et al.: CKD: A Call for an age-adapted definition. J Am SocNephrol 30: 1785–1805, 20192. Chertow GM, Beddhu S: Modification of eGFR-based CKD definitions:Perfect, or enemy of the good? J Am Soc Nephrol 30: 1807–1809, 20193. Wesson DE: Does eGFR by Any Number Mean the Same? J Am SocNephrol 30: 1806–1807, 2019Howard TrachtmanNew York University Langone Health, New York, New YorkJASN 31: 447, 2020.doi: https://doi.org/10.1681/ASN.2019090914Current CKD Definition Takesinto Account Both Relative andAbsolute RiskDelanaye et al.1 propose that GFR thresholds to define CKDshould depend on age. Specifically, people aged$65 years withGFR 45–59 ml/min per 1.73 m2 and albumin-creatinineratio,30 mg/g should not be classified as having CKD. Thisis not a new proposal. It has been discussed many times, in-cluding by the Kidney Disease Outcomes Quality Initiative in2002 and Kidney Disease Improving Global Outcomes(KDIGO) work groups in 2009 and 2012.2 Each time, theconsensus was that the GFR threshold for the definition ofCKD should be age-independent.Delanaye et al. now reopen the discussion, suggestingthat the GFR threshold for the CKD definition should bedetermined only by relative risks for mortality. They citedata from the CKD Prognosis Consortium, the largestmeta-analysis, showing that the relative hazard of mortal-ity for eGFR 45–59 versus 75–89 ml/min per 1.73 m2 withalbumin-creatinine ratio,30 mg/g was lower at olderage. However, they do not mention the higher absoluterisk of mortality (two to four times higher at the oldestcompared with youngest group).3 Absolute risk is more im-portant than relative risk to patients and providers. Thethreshold for CKD should also take into account outcomesbeyond mortality such as ESKD, AKI, heart failure, andhospitalization which are often more specific and sensitivePublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Dr. Howard Trachtman, New York University LangoneHealth, 403 E34th Street, Room 1-02, New York, NY 10016. Email: howard.trachtman@nyulangone.orgCopyright © 2020 by the American Society of NephrologyPublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Dr. Josef Coresh, 2024 E. Monument, Suite 2-600, Baltimore,MD 21287. Email: coresh@jhu.eduCopyright © 2020 by the American Society of NephrologyJASN 31: 447–449, 2020 ISSN : 1046-6673/3102-447 447LETTERTOTHEEDITORconsequences of CKD, and have substantial excess risk inolder age.Many other diseases, such as hypertension and diabetes,follow a similar pattern of higher prevalence at older agewith smaller relative risks but higher attributable risks of mor-tality and complications. Yet, the hypertension and diabetesguidelines define these diseases independently of age whilerecommending evaluation and management personalized toage and other factors. Similarly, the KDIGO guideline recom-mends an age-independent definition but personalized eval-uation and management.The CKD definition has been stable since 2002, enablinggreat progress in the field. The age-independent GFRthreshold has been widely accepted by nephrology societiesacross the world, endorsed by the World Health Organiza-tion, and incorporated into the International Classificationof Disease Coding System. At each deliberation, the ex-panding evidence base has supported the original defini-tion. We think that changing the GFR threshold at olderage on the basis solely of relative risk of mortality whileignoring the higher absolute risk for mortality and otheroutcomes is a narrow view that impedes progress. We be-lieve it is time, as a nephrology community, to move thediscussion to optimizing management and discoveringnew therapies.DISCLOSURESNone.REFERENCES1. Delanaye P, Jager KJ, BökenkampA, ChristenssonA, Dubourg L, EriksenBO, et al.: CKD: A call for an age-adapted definition. J Am Soc Nephrol30: 1785–1805, 20192. Kidney Disease: Improving Global Outcomes (KDIGO) CKD WorkGroup: KDIGO 2012 clinical practice guideline for the evaluation andmanagement of chronic kidney disease. Kidney Int Suppl 3: 1–150,20133. Hallan SI, Matsushita K, Sang Y, Mahmoodi BK, Black C, Ishani A, et al.;Chronic Kidney Disease Prognosis Consortium: Age and association ofkidney measures with mortality and end-stage renal disease. JAMA 308:2349–2360, 2012Josef Coresh 1, and Ron T. Gansevoort2 on behalfof the CKD Prognosis Consortium, Adeera Levin3,and Michel Jadoul4 on behalf of KDIGO1Epidemiology, Medicine, Biostatistics, and CKD PrognosisConsortium, The Johns Hopkins University, Baltimore, Maryland;2Nephrology, and CKD Prognosis Consortium, University ofGroningen, Groningen, Netherlands;3Nephrology, and KDIGO, St. Paul Hospital, Vancouver,Canada; and4Department of Nephrology, Cliniques Universitaires St-Luc, andKDIGO, Université Catholique de Louvain, Brussels, BelgiumJASN 31: 447–448, 2020.doi: https://doi.org/10.1681/ASN.2019101049Authors’ ReplyWe agree with Trachtman1 regarding the potential benefits forboth young and elderly with age-based eGFR thresholds. Wedisagree with the points raised by Coresh et al.2 First, despitethe cited guidelines, there is not widespread consensus amongpracticing nephrologists that elderly patients with an eGFR of45–59 ml/min per 1.73 m2 and no albuminuria have diseasedkidneys.3 Further, primary care guidelines fail to see clinicalbenefit with this classification.4 Second, although absoluterisks are often important, humans have a limited lifespanand it is not clear that an hazard ratio of 1.2 for risk translatesinto clinically meaningful life years lost.5 The statistical prog-nostic models relating eGFR to outcomes were on the basis ofrelative risk and the “heat maps” were on the basis of relativerisk. The eGFR level associated with lowest risk (absolute orrelative) declines with older age and this is not accounted forin the CKD definition. As with any epidemiologic study, asmall hazard ratio of 1.2 could easily be due to bias (high-risk rather than just general population cohorts were used inthe CKD prognosis consortium analyses) or residual con-founding (such as systemic microvascular disease or lowernephron endowment linked to other complications of lowerbirthweight). Third, a causal pathway linking the age-relateddecline in eGFR to an increased risk of nonrenal outcomes islacking.We concur that older patients with a low-normal GFRhave less renal reserves putting them at increased risk for kid-ney failure, but this is too rare of an event to justify a diseaselabel. High BP and glucose can be lowered with medicationswith a demonstrable clinical benefit, but there is no evidencethat eGFR can be increased for a clinical benefit. A fairer com-parison would be pulmonary function tests, which are report-ed with age-appropriate reference ranges due to the age-re-lated decline in pulmonary function.6 We hope that the CKDprognosis consortium and Kidney Disease Improving GlobalOutcomes will reconsider the age-related decline in eGFR forthe purposes of identifying persons with diseased kidneys.DISCLOSURESNone.REFERENCES1. Trachtman H: Age-dependent definition of CKD. J Am Soc Nephrol 31:447, 2020Authors are members of the European Kidney Function ConsortiumPublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Prof. Pierre Delanaye, Service de Dialyse, CHU Sart Tilman,4000 Liège, Belgium. Email: pierre_delanaye@yahoo.frCopyright © 2020 by the American Society of Nephrology448 JASN JASN 31: 447–449, 2020LETTER TO THE EDITOR www.jasn.org

Crossref

University of GroningenCurrent CKD Definition Takes into Account Both Relative and Absolute RiskCKD Prognosis Consortium; Coresh, Josef; Gansevoort, Ron T; Levin, Adeera; Jadoul,MichelPublished in:Journal of the American Society of NephrologyDOI:10.1681/ASN.2019101049IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2020Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):CKD Prognosis Consortium, Coresh, J., Gansevoort, R. T., Levin, A., & Jadoul, M. (2020). Current CKDDefinition Takes into Account Both Relative and Absolute Risk. Journal of the American Society ofNephrology, 31(2), 447-448. https://doi.org/10.1681/ASN.2019101049CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 31-12-2025LETTER TO THE EDITOR www.jasn.orgAge-Dependent Definition of CKDI read the online article by Delanaye et al.1 calling for age-dependent definitions of CKD and the two accompanyingeditorials2,3 with great interest. As a pediatric nephrologist,I do not have a stake in the details of the adult argument.However, as a nephrologist, I also recognize the impor-tance of clinically relevant definitions of CKD stages andI was struck by one of the arguments advanced by Chertowand Beddhu2 who advise caution before tampering withthe current scheme. They take exception to the claim byDelanaye et al. that overdiagnosis of CKD in the elderlycould lead to inappropriate care, including diagnostic evalu-ation and treatment of nonexistent kidney disease. Chertowand Beddhu assert that the elderly are less likely toget clinically indicated care for cardiac disease and otherconditions that require contrast-enhanced imaging. Infact, this well documented observation reinforces the callfor change by Delanaye et al. because inappropriate care isbidirectional—overzealous evaluation of patients who arehealthy and insufficient testing of patients who are pre-sumed sick, in this case with CKD. Rethinking the thresholdGFR to define CKDmay have the potential to be helpful, notonly in the geriatric population but across the life span ifthat includes the older end of the pediatric spectrum.DISCLOSURESNone.FUNDINGDr. Trachtman is supported by the National Institute of Diabetes and Di-gestive and Kidney Diseases (grant DK100307).REFERENCES1. Delanaye P, Jager KJ, Bökenkamp A, Christensson A, Dubourg L,Eriksen BO, et al.: CKD: A Call for an age-adapted definition. J Am SocNephrol 30: 1785–1805, 20192. Chertow GM, Beddhu S: Modification of eGFR-based CKD definitions:Perfect, or enemy of the good? J Am Soc Nephrol 30: 1807–1809, 20193. Wesson DE: Does eGFR by Any Number Mean the Same? J Am SocNephrol 30: 1806–1807, 2019Howard TrachtmanNew York University Langone Health, New York, New YorkJASN 31: 447, 2020.doi: https://doi.org/10.1681/ASN.2019090914Current CKD Definition Takesinto Account Both Relative andAbsolute RiskDelanaye et al.1 propose that GFR thresholds to define CKDshould depend on age. Specifically, people aged$65 years withGFR 45–59 ml/min per 1.73 m2 and albumin-creatinineratio,30 mg/g should not be classified as having CKD. Thisis not a new proposal. It has been discussed many times, in-cluding by the Kidney Disease Outcomes Quality Initiative in2002 and Kidney Disease Improving Global Outcomes(KDIGO) work groups in 2009 and 2012.2 Each time, theconsensus was that the GFR threshold for the definition ofCKD should be age-independent.Delanaye et al. now reopen the discussion, suggestingthat the GFR threshold for the CKD definition should bedetermined only by relative risks for mortality. They citedata from the CKD Prognosis Consortium, the largestmeta-analysis, showing that the relative hazard of mortal-ity for eGFR 45–59 versus 75–89 ml/min per 1.73 m2 withalbumin-creatinine ratio,30 mg/g was lower at olderage. However, they do not mention the higher absoluterisk of mortality (two to four times higher at the oldestcompared with youngest group).3 Absolute risk is more im-portant than relative risk to patients and providers. Thethreshold for CKD should also take into account outcomesbeyond mortality such as ESKD, AKI, heart failure, andhospitalization which are often more specific and sensitivePublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Dr. Howard Trachtman, New York University LangoneHealth, 403 E34th Street, Room 1-02, New York, NY 10016. Email: howard.trachtman@nyulangone.orgCopyright © 2020 by the American Society of NephrologyPublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Dr. Josef Coresh, 2024 E. Monument, Suite 2-600, Baltimore,MD 21287. Email: coresh@jhu.eduCopyright © 2020 by the American Society of NephrologyJASN 31: 447–449, 2020 ISSN : 1046-6673/3102-447 447LETTERTOTHEEDITORconsequences of CKD, and have substantial excess risk inolder age.Many other diseases, such as hypertension and diabetes,follow a similar pattern of higher prevalence at older agewith smaller relative risks but higher attributable risks of mor-tality and complications. Yet, the hypertension and diabetesguidelines define these diseases independently of age whilerecommending evaluation and management personalized toage and other factors. Similarly, the KDIGO guideline recom-mends an age-independent definition but personalized eval-uation and management.The CKD definition has been stable since 2002, enablinggreat progress in the field. The age-independent GFRthreshold has been widely accepted by nephrology societiesacross the world, endorsed by the World Health Organiza-tion, and incorporated into the International Classificationof Disease Coding System. At each deliberation, the ex-panding evidence base has supported the original defini-tion. We think that changing the GFR threshold at olderage on the basis solely of relative risk of mortality whileignoring the higher absolute risk for mortality and otheroutcomes is a narrow view that impedes progress. We be-lieve it is time, as a nephrology community, to move thediscussion to optimizing management and discoveringnew therapies.DISCLOSURESNone.REFERENCES1. Delanaye P, Jager KJ, BökenkampA, ChristenssonA, Dubourg L, EriksenBO, et al.: CKD: A call for an age-adapted definition. J Am Soc Nephrol30: 1785–1805, 20192. Kidney Disease: Improving Global Outcomes (KDIGO) CKD WorkGroup: KDIGO 2012 clinical practice guideline for the evaluation andmanagement of chronic kidney disease. Kidney Int Suppl 3: 1–150,20133. Hallan SI, Matsushita K, Sang Y, Mahmoodi BK, Black C, Ishani A, et al.;Chronic Kidney Disease Prognosis Consortium: Age and association ofkidney measures with mortality and end-stage renal disease. JAMA 308:2349–2360, 2012Josef Coresh 1, and Ron T. Gansevoort2 on behalfof the CKD Prognosis Consortium, Adeera Levin3,and Michel Jadoul4 on behalf of KDIGO1Epidemiology, Medicine, Biostatistics, and CKD PrognosisConsortium, The Johns Hopkins University, Baltimore, Maryland;2Nephrology, and CKD Prognosis Consortium, University ofGroningen, Groningen, Netherlands;3Nephrology, and KDIGO, St. Paul Hospital, Vancouver,Canada; and4Department of Nephrology, Cliniques Universitaires St-Luc, andKDIGO, Université Catholique de Louvain, Brussels, BelgiumJASN 31: 447–448, 2020.doi: https://doi.org/10.1681/ASN.2019101049Authors’ ReplyWe agree with Trachtman1 regarding the potential benefits forboth young and elderly with age-based eGFR thresholds. Wedisagree with the points raised by Coresh et al.2 First, despitethe cited guidelines, there is not widespread consensus amongpracticing nephrologists that elderly patients with an eGFR of45–59 ml/min per 1.73 m2 and no albuminuria have diseasedkidneys.3 Further, primary care guidelines fail to see clinicalbenefit with this classification.4 Second, although absoluterisks are often important, humans have a limited lifespanand it is not clear that an hazard ratio of 1.2 for risk translatesinto clinically meaningful life years lost.5 The statistical prog-nostic models relating eGFR to outcomes were on the basis ofrelative risk and the “heat maps” were on the basis of relativerisk. The eGFR level associated with lowest risk (absolute orrelative) declines with older age and this is not accounted forin the CKD definition. As with any epidemiologic study, asmall hazard ratio of 1.2 could easily be due to bias (high-risk rather than just general population cohorts were used inthe CKD prognosis consortium analyses) or residual con-founding (such as systemic microvascular disease or lowernephron endowment linked to other complications of lowerbirthweight). Third, a causal pathway linking the age-relateddecline in eGFR to an increased risk of nonrenal outcomes islacking.We concur that older patients with a low-normal GFRhave less renal reserves putting them at increased risk for kid-ney failure, but this is too rare of an event to justify a diseaselabel. High BP and glucose can be lowered with medicationswith a demonstrable clinical benefit, but there is no evidencethat eGFR can be increased for a clinical benefit. A fairer com-parison would be pulmonary function tests, which are report-ed with age-appropriate reference ranges due to the age-re-lated decline in pulmonary function.6 We hope that the CKDprognosis consortium and Kidney Disease Improving GlobalOutcomes will reconsider the age-related decline in eGFR forthe purposes of identifying persons with diseased kidneys.DISCLOSURESNone.REFERENCES1. Trachtman H: Age-dependent definition of CKD. J Am Soc Nephrol 31:447, 2020Authors are members of the European Kidney Function ConsortiumPublished online ahead of print. Publication date available at www.jasn.org.Correspondence: Prof. Pierre Delanaye, Service de Dialyse, CHU Sart Tilman,4000 Liège, Belgium. Email: pierre_delanaye@yahoo.frCopyright © 2020 by the American Society of Nephrology448 JASN JASN 31: 447–449, 2020LETTER TO THE EDITOR www.jasn.org

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Current CKD Definition Takes into Account Both Relative and Absolute Risk

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