The Kidney Failure Risk Equation for prediction of end stage renal disease in UK primary care: An external validation and clinical impact projection cohort study
The Kidney Failure Risk Equation (KFRE) uses the 4 variables of age, sex, urine albumin-to-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) in individuals with chronic kidney disease (CKD) to predict the risk of end stage renal disease (ESRD), i.e., the need for dialysis or a...
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| description | The Kidney Failure Risk Equation (KFRE) uses the 4 variables of age, sex, urine albumin-to-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) in individuals with chronic kidney disease (CKD) to predict the risk of end stage renal disease (ESRD), i.e., the need for dialysis or a kidney transplant, within 2 and 5 years. Currently, national guideline writers in the UK and other countries are evaluating the role of the KFRE in renal referrals from primary care to secondary care, but the KFRE has had limited external validation in primary care. The study's objectives were therefore to externally validate the KFRE's prediction of ESRD events in primary care, perform model recalibration if necessary, and assess its projected impact on referral rates to secondary care renal services.
Individuals with 2 or more Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR values < 60 ml/min/1.73 m2 more than 90 days apart and a urine ACR or protein-to-creatinine ratio measurement between 1 December 2004 and 1 November 2016 were included in the cohort. The cohort included 35,539 (5.6%) individuals (57.5% female, mean age 75.9 years, median CKD-EPI eGFR 51 ml/min/1.73 m2, median ACR 3.2 mg/mmol) from a total adult practice population of 630,504. Overall, 176 (0.50%) and 429 (1.21%) ESRD events occurred within 2 and 5 years, respectively. Median length of follow-up was 4.7 years (IQR 2.8 to 6.6). Model discrimination was excellent for both 2-year (C-statistic 0.932, 95% CI 0.909 to 0.954) and 5-year (C-statistic 0.924, 95% 0.909 to 0.938) ESRD prediction. The KFRE overpredicted risk in lower ( |
| doi_str_mv | 10.1371/journal.pmed.1002955 |
| format | Article |
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Individuals with 2 or more Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR values < 60 ml/min/1.73 m2 more than 90 days apart and a urine ACR or protein-to-creatinine ratio measurement between 1 December 2004 and 1 November 2016 were included in the cohort. The cohort included 35,539 (5.6%) individuals (57.5% female, mean age 75.9 years, median CKD-EPI eGFR 51 ml/min/1.73 m2, median ACR 3.2 mg/mmol) from a total adult practice population of 630,504. Overall, 176 (0.50%) and 429 (1.21%) ESRD events occurred within 2 and 5 years, respectively. Median length of follow-up was 4.7 years (IQR 2.8 to 6.6). Model discrimination was excellent for both 2-year (C-statistic 0.932, 95% CI 0.909 to 0.954) and 5-year (C-statistic 0.924, 95% 0.909 to 0.938) ESRD prediction. The KFRE overpredicted risk in lower (<20%) risk groups. Reducing the model's baseline risk improved calibration for both 2- and 5-year risk for lower risk groups, but led to some underprediction of risk in higher risk groups. Compared to current criteria, using referral criteria based on a KFRE-calculated 5-year ESRD risk of ≥5% and/or an ACR of ≥70 mg/mmol reduced the number of individuals eligible for referral who did not develop ESRD, increased the likelihood of referral eligibility in those who did develop ESRD, and referred the latter at a younger age and with a higher eGFR. The main limitation of the current study is that the cohort is from one region of the UK and therefore may not be representative of primary care CKD care in other countries.
In this cohort, the recalibrated KFRE accurately predicted the risk of ESRD at 2 and 5 years in primary care. Its introduction into primary care for referrals to secondary care renal services may lead to a reduction in unnecessary referrals, and earlier referrals in those who go on to develop ESRD. However, further validation studies in more diverse cohorts of the clinical impact projections and suggested referral criteria are required before the latter can be clinically implemented.</description><identifier>ISSN: 1549-1676</identifier><identifier>ISSN: 1549-1277</identifier><identifier>EISSN: 1549-1676</identifier><identifier>DOI: 10.1371/journal.pmed.1002955</identifier><identifier>PMID: 31693662</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Age Factors ; Aged ; Aged, 80 and over ; Albumin ; Albuminuria - urine ; Algorithms ; Biology and Life Sciences ; Calibration ; Cardiovascular disease ; Chronic kidney failure ; Clinical medicine ; Cohort analysis ; Cohort Studies ; Creatinine ; Creatinine - urine ; Criteria ; Dialysis ; Disease Progression ; Epidemiology ; Epidermal growth factor receptors ; Female ; Forecasting ; Funding ; Glomerular Filtration Rate ; Health sciences ; Hilario, Maybyner (Nene) ; Humans ; Kidney diseases ; Kidney failure ; Kidney Failure, Chronic - etiology ; Kidney Failure, Chronic - mortality ; Kidney Function Tests ; Kidney transplantation ; Kidneys ; Male ; Median (statistics) ; Medical research ; Medicine and Health Sciences ; Middle Aged ; Organ transplantation ; Patients ; Physical Sciences ; Population ; Predictions ; Primary care ; Primary Health Care ; Prognosis ; Renal failure ; Renal Insufficiency - mortality ; Renal Insufficiency - physiopathology ; Renal Insufficiency, Chronic ; Reproducibility of Results ; Research and Analysis Methods ; Risk Assessment - methods ; Risk Factors ; Risk groups ; Sex ratio ; Software ; United Kingdom - epidemiology ; Urine</subject><ispartof>PLoS medicine, 2019-11, Vol.16 (11), p.e1002955-e1002955</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Major et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Major et al 2019 Major et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c764t-fa441cba07e54150a021ad2813242e1e7850a1bc3e4003e863781c91b212a0a03</citedby><cites>FETCH-LOGICAL-c764t-fa441cba07e54150a021ad2813242e1e7850a1bc3e4003e863781c91b212a0a03</cites><orcidid>0000-0002-7109-7108 ; 0000-0003-4920-623X ; 0000-0002-9284-9321 ; 0000-0002-8991-3660 ; 0000-0001-8364-3041</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834237/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834237/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31693662$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Major, Rupert W</creatorcontrib><creatorcontrib>Shepherd, David</creatorcontrib><creatorcontrib>Medcalf, James F</creatorcontrib><creatorcontrib>Xu, Gang</creatorcontrib><creatorcontrib>Gray, Laura J</creatorcontrib><creatorcontrib>Brunskill, Nigel J</creatorcontrib><title>The Kidney Failure Risk Equation for prediction of end stage renal disease in UK primary care: An external validation and clinical impact projection cohort study</title><title>PLoS medicine</title><addtitle>PLoS Med</addtitle><description>The Kidney Failure Risk Equation (KFRE) uses the 4 variables of age, sex, urine albumin-to-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) in individuals with chronic kidney disease (CKD) to predict the risk of end stage renal disease (ESRD), i.e., the need for dialysis or a kidney transplant, within 2 and 5 years. Currently, national guideline writers in the UK and other countries are evaluating the role of the KFRE in renal referrals from primary care to secondary care, but the KFRE has had limited external validation in primary care. The study's objectives were therefore to externally validate the KFRE's prediction of ESRD events in primary care, perform model recalibration if necessary, and assess its projected impact on referral rates to secondary care renal services.
Individuals with 2 or more Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR values < 60 ml/min/1.73 m2 more than 90 days apart and a urine ACR or protein-to-creatinine ratio measurement between 1 December 2004 and 1 November 2016 were included in the cohort. The cohort included 35,539 (5.6%) individuals (57.5% female, mean age 75.9 years, median CKD-EPI eGFR 51 ml/min/1.73 m2, median ACR 3.2 mg/mmol) from a total adult practice population of 630,504. Overall, 176 (0.50%) and 429 (1.21%) ESRD events occurred within 2 and 5 years, respectively. Median length of follow-up was 4.7 years (IQR 2.8 to 6.6). Model discrimination was excellent for both 2-year (C-statistic 0.932, 95% CI 0.909 to 0.954) and 5-year (C-statistic 0.924, 95% 0.909 to 0.938) ESRD prediction. The KFRE overpredicted risk in lower (<20%) risk groups. Reducing the model's baseline risk improved calibration for both 2- and 5-year risk for lower risk groups, but led to some underprediction of risk in higher risk groups. Compared to current criteria, using referral criteria based on a KFRE-calculated 5-year ESRD risk of ≥5% and/or an ACR of ≥70 mg/mmol reduced the number of individuals eligible for referral who did not develop ESRD, increased the likelihood of referral eligibility in those who did develop ESRD, and referred the latter at a younger age and with a higher eGFR. The main limitation of the current study is that the cohort is from one region of the UK and therefore may not be representative of primary care CKD care in other countries.
In this cohort, the recalibrated KFRE accurately predicted the risk of ESRD at 2 and 5 years in primary care. Its introduction into primary care for referrals to secondary care renal services may lead to a reduction in unnecessary referrals, and earlier referrals in those who go on to develop ESRD. However, further validation studies in more diverse cohorts of the clinical impact projections and suggested referral criteria are required before the latter can be clinically implemented.</description><subject>Age</subject><subject>Age Factors</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Albumin</subject><subject>Albuminuria - urine</subject><subject>Algorithms</subject><subject>Biology and Life Sciences</subject><subject>Calibration</subject><subject>Cardiovascular disease</subject><subject>Chronic kidney failure</subject><subject>Clinical medicine</subject><subject>Cohort analysis</subject><subject>Cohort Studies</subject><subject>Creatinine</subject><subject>Creatinine - urine</subject><subject>Criteria</subject><subject>Dialysis</subject><subject>Disease Progression</subject><subject>Epidemiology</subject><subject>Epidermal growth factor receptors</subject><subject>Female</subject><subject>Forecasting</subject><subject>Funding</subject><subject>Glomerular Filtration Rate</subject><subject>Health sciences</subject><subject>Hilario, Maybyner (Nene)</subject><subject>Humans</subject><subject>Kidney diseases</subject><subject>Kidney failure</subject><subject>Kidney Failure, Chronic - etiology</subject><subject>Kidney Failure, Chronic - mortality</subject><subject>Kidney Function Tests</subject><subject>Kidney transplantation</subject><subject>Kidneys</subject><subject>Male</subject><subject>Median (statistics)</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Organ transplantation</subject><subject>Patients</subject><subject>Physical Sciences</subject><subject>Population</subject><subject>Predictions</subject><subject>Primary care</subject><subject>Primary Health Care</subject><subject>Prognosis</subject><subject>Renal failure</subject><subject>Renal Insufficiency - mortality</subject><subject>Renal Insufficiency - physiopathology</subject><subject>Renal Insufficiency, Chronic</subject><subject>Reproducibility of Results</subject><subject>Research and Analysis Methods</subject><subject>Risk Assessment - methods</subject><subject>Risk Factors</subject><subject>Risk groups</subject><subject>Sex ratio</subject><subject>Software</subject><subject>United Kingdom - 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mortality</topic><topic>Renal Insufficiency - physiopathology</topic><topic>Renal Insufficiency, Chronic</topic><topic>Reproducibility of Results</topic><topic>Research and Analysis Methods</topic><topic>Risk Assessment - methods</topic><topic>Risk Factors</topic><topic>Risk groups</topic><topic>Sex ratio</topic><topic>Software</topic><topic>United Kingdom - epidemiology</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Major, Rupert W</creatorcontrib><creatorcontrib>Shepherd, David</creatorcontrib><creatorcontrib>Medcalf, James F</creatorcontrib><creatorcontrib>Xu, Gang</creatorcontrib><creatorcontrib>Gray, Laura J</creatorcontrib><creatorcontrib>Brunskill, Nigel J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Medicine</collection><jtitle>PLoS medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Major, Rupert W</au><au>Shepherd, David</au><au>Medcalf, James F</au><au>Xu, Gang</au><au>Gray, Laura J</au><au>Brunskill, Nigel J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Kidney Failure Risk Equation for prediction of end stage renal disease in UK primary care: An external validation and clinical impact projection cohort study</atitle><jtitle>PLoS medicine</jtitle><addtitle>PLoS Med</addtitle><date>2019-11-06</date><risdate>2019</risdate><volume>16</volume><issue>11</issue><spage>e1002955</spage><epage>e1002955</epage><pages>e1002955-e1002955</pages><issn>1549-1676</issn><issn>1549-1277</issn><eissn>1549-1676</eissn><abstract>The Kidney Failure Risk Equation (KFRE) uses the 4 variables of age, sex, urine albumin-to-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) in individuals with chronic kidney disease (CKD) to predict the risk of end stage renal disease (ESRD), i.e., the need for dialysis or a kidney transplant, within 2 and 5 years. Currently, national guideline writers in the UK and other countries are evaluating the role of the KFRE in renal referrals from primary care to secondary care, but the KFRE has had limited external validation in primary care. The study's objectives were therefore to externally validate the KFRE's prediction of ESRD events in primary care, perform model recalibration if necessary, and assess its projected impact on referral rates to secondary care renal services.
Individuals with 2 or more Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR values < 60 ml/min/1.73 m2 more than 90 days apart and a urine ACR or protein-to-creatinine ratio measurement between 1 December 2004 and 1 November 2016 were included in the cohort. The cohort included 35,539 (5.6%) individuals (57.5% female, mean age 75.9 years, median CKD-EPI eGFR 51 ml/min/1.73 m2, median ACR 3.2 mg/mmol) from a total adult practice population of 630,504. Overall, 176 (0.50%) and 429 (1.21%) ESRD events occurred within 2 and 5 years, respectively. Median length of follow-up was 4.7 years (IQR 2.8 to 6.6). Model discrimination was excellent for both 2-year (C-statistic 0.932, 95% CI 0.909 to 0.954) and 5-year (C-statistic 0.924, 95% 0.909 to 0.938) ESRD prediction. The KFRE overpredicted risk in lower (<20%) risk groups. Reducing the model's baseline risk improved calibration for both 2- and 5-year risk for lower risk groups, but led to some underprediction of risk in higher risk groups. Compared to current criteria, using referral criteria based on a KFRE-calculated 5-year ESRD risk of ≥5% and/or an ACR of ≥70 mg/mmol reduced the number of individuals eligible for referral who did not develop ESRD, increased the likelihood of referral eligibility in those who did develop ESRD, and referred the latter at a younger age and with a higher eGFR. The main limitation of the current study is that the cohort is from one region of the UK and therefore may not be representative of primary care CKD care in other countries.
In this cohort, the recalibrated KFRE accurately predicted the risk of ESRD at 2 and 5 years in primary care. Its introduction into primary care for referrals to secondary care renal services may lead to a reduction in unnecessary referrals, and earlier referrals in those who go on to develop ESRD. However, further validation studies in more diverse cohorts of the clinical impact projections and suggested referral criteria are required before the latter can be clinically implemented.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31693662</pmid><doi>10.1371/journal.pmed.1002955</doi><orcidid>https://orcid.org/0000-0002-7109-7108</orcidid><orcidid>https://orcid.org/0000-0003-4920-623X</orcidid><orcidid>https://orcid.org/0000-0002-9284-9321</orcidid><orcidid>https://orcid.org/0000-0002-8991-3660</orcidid><orcidid>https://orcid.org/0000-0001-8364-3041</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1549-1676 |
| ispartof | PLoS medicine, 2019-11, Vol.16 (11), p.e1002955-e1002955 |
| issn | 1549-1676 1549-1277 1549-1676 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Public Library of Science (PLoS) |
| subjects | Age Age Factors Aged Aged, 80 and over Albumin Albuminuria - urine Algorithms Biology and Life Sciences Calibration Cardiovascular disease Chronic kidney failure Clinical medicine Cohort analysis Cohort Studies Creatinine Creatinine - urine Criteria Dialysis Disease Progression Epidemiology Epidermal growth factor receptors Female Forecasting Funding Glomerular Filtration Rate Health sciences Hilario, Maybyner (Nene) Humans Kidney diseases Kidney failure Kidney Failure, Chronic - etiology Kidney Failure, Chronic - mortality Kidney Function Tests Kidney transplantation Kidneys Male Median (statistics) Medical research Medicine and Health Sciences Middle Aged Organ transplantation Patients Physical Sciences Population Predictions Primary care Primary Health Care Prognosis Renal failure Renal Insufficiency - mortality Renal Insufficiency - physiopathology Renal Insufficiency, Chronic Reproducibility of Results Research and Analysis Methods Risk Assessment - methods Risk Factors Risk groups Sex ratio Software United Kingdom - epidemiology Urine |
| title | The Kidney Failure Risk Equation for prediction of end stage renal disease in UK primary care: An external validation and clinical impact projection cohort study |
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