Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis
Identifieur interne : 002044 ( Pmc/Checkpoint ); précédent : 002043; suivant : 002045Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis
Auteurs : Bakhtawar K. Mahmoodi [États-Unis, Pays-Bas] ; Kunihiro Matsushita [États-Unis] ; Mark Woodward [États-Unis] ; Peter J. Blankestijn [Pays-Bas] ; Massimo Cirillo [Italie] ; Takayoshi Ohkubo [Japon] ; Peter Rossing [Danemark] ; Mark J. Sarnak [États-Unis] ; Bénédicte Stengel [France] ; Kazumasa Yamagishi [Japon] ; Kentaro Yamashita [Japon] ; Luxia Zhang [République populaire de Chine] ; Josef Coresh [États-Unis] ; Paul E. De Jong [Pays-Bas] ; Brad C. Astor [États-Unis]Source :
- Lancet [ 0140-6736 ] ; 2012.
Abstract
Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease (CKD). It is unknown, however, whether the association of the CKD measures, estimated glomerular filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status.
We performed a meta-analysis of 45 cohorts (25 general population, 7 high-risk and 13 CKD cohorts), including 1,127,656 participants (364,344 with hypertension). Adjusted hazard ratios (HRs) for all-cause mortality (84,078 deaths from 40 cohorts) and ESRD (7,587 events from 21 cohorts) by hypertensive status were obtained for each study and pooled using random-effects models.
Low eGFR and high albuminuria were associated with mortality in both non-hypertensive and hypertensive individuals in the general population and high-risk cohorts. Mortality risk was higher in hypertensives as compared to non-hypertensives at preserved eGFR but a steeper relative risk gradient among non-hypertensives than hypertensives at eGFR range 45-75 ml/min/1.73m2 led to similar mortality risk at lower eGFR. With a reference eGFR of 95 mL/min/1.73m2 in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min/1.73m2 was 1.77 (95% CI, 1.57-1.99) in non-hypertensives versus 1.24 (1.11-1.39) in hypertensives (P for overall interaction =0.0003). Similarly, for albumin-creatinine ratio (ACR) of 300 mg/g (vs. 5 mg/g), HRs were 2.30 (1.98-2.68) in non-hypertensives versus 2.08 (1.84-2.35) in hypertensives (P for overall interaction=0.019). Similar results were observed for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, did not differ by hypertensive status. Results in CKD cohorts were comparable to results in general and high-risk population cohorts.
Low eGFR and elevated albuminuria were more strongly associated with mortality among individuals without hypertension than in those with hypertension, but the associations with ESRD were similar. CKD should be considered at least an equally relevant risk factor for mortality and ESRD in non-hypertensive as it is in hypertensive individuals.
The US National Kidney Foundation (sources include Abbott and Amgen).
Url:
DOI: 10.1016/S0140-6736(12)61272-0
PubMed: 23013600
PubMed Central: 3993095
Affiliations:
- Danemark, France, Italie, Japon, Pays-Bas, République populaire de Chine, États-Unis
- Groningue (province), Maryland, Massachusetts, Wisconsin
- Groningue, Pékin
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<author><name sortKey="Stengel, Benedicte" sort="Stengel, Benedicte" uniqKey="Stengel B" first="Bénédicte" last="Stengel">Bénédicte Stengel</name>
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<author><name sortKey="Zhang, Luxia" sort="Zhang, Luxia" uniqKey="Zhang L" first="Luxia" last="Zhang">Luxia Zhang</name>
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<author><name sortKey="Coresh, Josef" sort="Coresh, Josef" uniqKey="Coresh J" first="Josef" last="Coresh">Josef Coresh</name>
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<affiliation wicri:level="2"><nlm:aff id="A18">Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA</nlm:aff>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis</title>
<author><name sortKey="Mahmoodi, Bakhtawar K" sort="Mahmoodi, Bakhtawar K" uniqKey="Mahmoodi B" first="Bakhtawar K." last="Mahmoodi">Bakhtawar K. Mahmoodi</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street (Rm W6017) Baltimore, MD 21205, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street (Rm W6017) Baltimore, MD 21205</wicri:regionArea>
<placeName><region type="state">Maryland</region>
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</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2">Department of Nephrology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Nephrology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen</wicri:regionArea>
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<author><name sortKey="Matsushita, Kunihiro" sort="Matsushita, Kunihiro" uniqKey="Matsushita K" first="Kunihiro" last="Matsushita">Kunihiro Matsushita</name>
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<author><name sortKey="Woodward, Mark" sort="Woodward, Mark" uniqKey="Woodward M" first="Mark" last="Woodward">Mark Woodward</name>
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<author><name sortKey="Blankestijn, Peter J" sort="Blankestijn, Peter J" uniqKey="Blankestijn P" first="Peter J." last="Blankestijn">Peter J. Blankestijn</name>
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<author><name sortKey="Cirillo, Massimo" sort="Cirillo, Massimo" uniqKey="Cirillo M" first="Massimo" last="Cirillo">Massimo Cirillo</name>
<affiliation wicri:level="1"><nlm:aff id="A5"> Department of Medicine, University of Salerno, Italy</nlm:aff>
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<author><name sortKey="Ohkubo, Takayoshi" sort="Ohkubo, Takayoshi" uniqKey="Ohkubo T" first="Takayoshi" last="Ohkubo">Takayoshi Ohkubo</name>
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<author><name sortKey="Rossing, Peter" sort="Rossing, Peter" uniqKey="Rossing P" first="Peter" last="Rossing">Peter Rossing</name>
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</affiliation>
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<author><name sortKey="Sarnak, Mark J" sort="Sarnak, Mark J" uniqKey="Sarnak M" first="Mark J." last="Sarnak">Mark J. Sarnak</name>
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</placeName>
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<author><name sortKey="Stengel, Benedicte" sort="Stengel, Benedicte" uniqKey="Stengel B" first="Bénédicte" last="Stengel">Bénédicte Stengel</name>
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<country xml:lang="fr">France</country>
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</affiliation>
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<country xml:lang="fr">France</country>
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<author><name sortKey="Yamagishi, Kazumasa" sort="Yamagishi, Kazumasa" uniqKey="Yamagishi K" first="Kazumasa" last="Yamagishi">Kazumasa Yamagishi</name>
<affiliation wicri:level="1"><nlm:aff id="A12">Department of Public Health Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tenodai, Tsukuba, 305-8575, Japan, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Public Health Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tenodai, Tsukuba, 305-8575, Japan</wicri:regionArea>
<wicri:noRegion>Japan</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A13">Ibaraki Health Plaza, Ibaraki Health Service Association, Mito, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Ibaraki Health Plaza, Ibaraki Health Service Association, Mito</wicri:regionArea>
<wicri:noRegion>Mito</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A14">Osaka Medical Center for Health Science and Promotion, Osaka, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Osaka Medical Center for Health Science and Promotion, Osaka</wicri:regionArea>
<wicri:noRegion>Osaka</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yamashita, Kentaro" sort="Yamashita, Kentaro" uniqKey="Yamashita K" first="Kentaro" last="Yamashita">Kentaro Yamashita</name>
<affiliation wicri:level="1"><nlm:aff id="A15">Department of Public Health and Health Systems, Nagoya University, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Public Health and Health Systems, Nagoya University, 65 Tsurumai, Showa, Nagoya, 466-8550</wicri:regionArea>
<wicri:noRegion>466-8550</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhang, Luxia" sort="Zhang, Luxia" uniqKey="Zhang L" first="Luxia" last="Zhang">Luxia Zhang</name>
<affiliation wicri:level="3"><nlm:aff id="A16">Renal Division, Peking University First Hospital, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Renal Division, Peking University First Hospital, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Coresh, Josef" sort="Coresh, Josef" uniqKey="Coresh J" first="Josef" last="Coresh">Josef Coresh</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street (Rm W6017) Baltimore, MD 21205, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street (Rm W6017) Baltimore, MD 21205</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="De Jong, Paul E" sort="De Jong, Paul E" uniqKey="De Jong P" first="Paul E." last="De Jong">Paul E. De Jong</name>
<affiliation wicri:level="3"><nlm:aff id="A2">Department of Nephrology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Nephrology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen</wicri:regionArea>
<placeName><settlement type="city">Groningue</settlement>
<region nuts="2" type="province">Groningue (province)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Astor, Brad C" sort="Astor, Brad C" uniqKey="Astor B" first="Brad C." last="Astor">Brad C. Astor</name>
<affiliation wicri:level="2"><nlm:aff id="A17">Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI</wicri:regionArea>
<placeName><region type="state">Wisconsin</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A18">Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI</wicri:regionArea>
<placeName><region type="state">Wisconsin</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Lancet</title>
<idno type="ISSN">0140-6736</idno>
<idno type="eISSN">1474-547X</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease (CKD). It is unknown, however, whether the association of the CKD measures, estimated glomerular filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">We performed a meta-analysis of 45 cohorts (25 general population, 7 high-risk and 13 CKD cohorts), including 1,127,656 participants (364,344 with hypertension). Adjusted hazard ratios (HRs) for all-cause mortality (84,078 deaths from 40 cohorts) and ESRD (7,587 events from 21 cohorts) by hypertensive status were obtained for each study and pooled using random-effects models.</p>
</sec>
<sec id="S3"><title>Findings</title>
<p id="P3">Low eGFR and high albuminuria were associated with mortality in both non-hypertensive and hypertensive individuals in the general population and high-risk cohorts. Mortality risk was higher in hypertensives as compared to non-hypertensives at preserved eGFR but a steeper relative risk gradient among non-hypertensives than hypertensives at eGFR range 45-75 ml/min/1.73m<sup>2</sup>
led to similar mortality risk at lower eGFR. With a reference eGFR of 95 mL/min/1.73m<sup>2</sup>
in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min/1.73m<sup>2</sup>
was 1.77 (95% CI, 1.57-1.99) in non-hypertensives versus 1.24 (1.11-1.39) in hypertensives (P for overall interaction =0.0003). Similarly, for albumin-creatinine ratio (ACR) of 300 mg/g (vs. 5 mg/g), HRs were 2.30 (1.98-2.68) in non-hypertensives versus 2.08 (1.84-2.35) in hypertensives (P for overall interaction=0.019). Similar results were observed for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, did not differ by hypertensive status. Results in CKD cohorts were comparable to results in general and high-risk population cohorts.</p>
</sec>
<sec id="S4"><title>Interpretation</title>
<p id="P4">Low eGFR and elevated albuminuria were more strongly associated with mortality among individuals without hypertension than in those with hypertension, but the associations with ESRD were similar. CKD should be considered at least an equally relevant risk factor for mortality and ESRD in non-hypertensive as it is in hypertensive individuals.</p>
</sec>
<sec id="S5"><title>Funding</title>
<p id="P5">The US National Kidney Foundation (sources include Abbott and Amgen).</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">2985213R</journal-id>
<journal-id journal-id-type="pubmed-jr-id">5470</journal-id>
<journal-id journal-id-type="nlm-ta">Lancet</journal-id>
<journal-id journal-id-type="iso-abbrev">Lancet</journal-id>
<journal-title-group><journal-title>Lancet</journal-title>
</journal-title-group>
<issn pub-type="ppub">0140-6736</issn>
<issn pub-type="epub">1474-547X</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23013600</article-id>
<article-id pub-id-type="pmc">3993095</article-id>
<article-id pub-id-type="doi">10.1016/S0140-6736(12)61272-0</article-id>
<article-id pub-id-type="manuscript">NIHMS550606</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Mahmoodi</surname>
<given-names>Bakhtawar K.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Matsushita</surname>
<given-names>Kunihiro</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Woodward</surname>
<given-names>Mark</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Blankestijn</surname>
<given-names>Peter J.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cirillo</surname>
<given-names>Massimo</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ohkubo</surname>
<given-names>Takayoshi</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A6">6</xref>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rossing</surname>
<given-names>Peter</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sarnak</surname>
<given-names>Mark J.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Stengel</surname>
<given-names>Bénédicte</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A10">10</xref>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yamagishi</surname>
<given-names>Kazumasa</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A12">12</xref>
<xref ref-type="aff" rid="A13">13</xref>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yamashita</surname>
<given-names>Kentaro</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Luxia</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Coresh</surname>
<given-names>Josef</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>de Jong</surname>
<given-names>Paul E.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Astor</surname>
<given-names>Brad C.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A17">17</xref>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author"><collab>for the Chronic Kidney Disease Prognosis Consortium</collab>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street (Rm W6017) Baltimore, MD 21205, USA</aff>
<aff id="A2"><label>2</label>
Department of Nephrology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands</aff>
<aff id="A3"><label>3</label>
Level 10, King George V Building, 83-117 Missenden Rd, PO Box M201, Camperdown NSW 2050 Australia</aff>
<aff id="A4"><label>4</label>
Department of Nephrology, University Medical Center, Room F03.226, PO BOX 85500, 3508 GA Utrecht, The Netherlands</aff>
<aff id="A5"><label>5</label>
Department of Medicine, University of Salerno, Italy</aff>
<aff id="A6"><label>6</label>
Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan</aff>
<aff id="A7"><label>7</label>
Department of Health Science, Shiga University of Medical Science, Setatsukinowa, Otsu, Shiga, 520-2192, Japan</aff>
<aff id="A8"><label>8</label>
Steno Diabetes Center, Niels Steensens Vej 2, DK 2820 Gentofte, Denmark</aff>
<aff id="A9"><label>9</label>
Division of Nephrology at Tufts Medical Center, 750 Washington Street, #391 Boston, MA 02111, USA</aff>
<aff id="A10"><label>10</label>
Inserm U1018, CESP Centre for Research in Epidemiology and Population Health, Villejuif, France</aff>
<aff id="A11"><label>11</label>
UMRS 1018, Paris-Sud University, Villejuif, France</aff>
<aff id="A12"><label>12</label>
Department of Public Health Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tenodai, Tsukuba, 305-8575, Japan, Japan</aff>
<aff id="A13"><label>13</label>
Ibaraki Health Plaza, Ibaraki Health Service Association, Mito, Japan</aff>
<aff id="A14"><label>14</label>
Osaka Medical Center for Health Science and Promotion, Osaka, Japan</aff>
<aff id="A15"><label>15</label>
Department of Public Health and Health Systems, Nagoya University, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan</aff>
<aff id="A16"><label>16</label>
Renal Division, Peking University First Hospital, Beijing, China</aff>
<aff id="A17"><label>17</label>
Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA</aff>
<aff id="A18"><label>18</label>
Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA</aff>
<author-notes><corresp id="FN1">Correspondence and requests for reprints: Chronic Kidney Disease Prognosis Consortium Data Coordinating Center (Principal Investigator, Josef Coresh, MD, PhD), 615 N. Wolfe Street (Rm W6017), Baltimore, MD 21205, USA. <email>ckdpc@jhmi.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>22</day>
<month>2</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>24</day>
<month>9</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="ppub"><day>10</day>
<month>11</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>21</day>
<month>4</month>
<year>2014</year>
</pub-date>
<volume>380</volume>
<issue>9854</issue>
<fpage>1649</fpage>
<lpage>1661</lpage>
<pmc-comment>elocation-id from pubmed: 10.1016/S0140-6736(12)61272-0</pmc-comment>
<abstract><sec id="S1"><title>Background</title>
<p id="P1">Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease (CKD). It is unknown, however, whether the association of the CKD measures, estimated glomerular filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">We performed a meta-analysis of 45 cohorts (25 general population, 7 high-risk and 13 CKD cohorts), including 1,127,656 participants (364,344 with hypertension). Adjusted hazard ratios (HRs) for all-cause mortality (84,078 deaths from 40 cohorts) and ESRD (7,587 events from 21 cohorts) by hypertensive status were obtained for each study and pooled using random-effects models.</p>
</sec>
<sec id="S3"><title>Findings</title>
<p id="P3">Low eGFR and high albuminuria were associated with mortality in both non-hypertensive and hypertensive individuals in the general population and high-risk cohorts. Mortality risk was higher in hypertensives as compared to non-hypertensives at preserved eGFR but a steeper relative risk gradient among non-hypertensives than hypertensives at eGFR range 45-75 ml/min/1.73m<sup>2</sup>
led to similar mortality risk at lower eGFR. With a reference eGFR of 95 mL/min/1.73m<sup>2</sup>
in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min/1.73m<sup>2</sup>
was 1.77 (95% CI, 1.57-1.99) in non-hypertensives versus 1.24 (1.11-1.39) in hypertensives (P for overall interaction =0.0003). Similarly, for albumin-creatinine ratio (ACR) of 300 mg/g (vs. 5 mg/g), HRs were 2.30 (1.98-2.68) in non-hypertensives versus 2.08 (1.84-2.35) in hypertensives (P for overall interaction=0.019). Similar results were observed for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, did not differ by hypertensive status. Results in CKD cohorts were comparable to results in general and high-risk population cohorts.</p>
</sec>
<sec id="S4"><title>Interpretation</title>
<p id="P4">Low eGFR and elevated albuminuria were more strongly associated with mortality among individuals without hypertension than in those with hypertension, but the associations with ESRD were similar. CKD should be considered at least an equally relevant risk factor for mortality and ESRD in non-hypertensive as it is in hypertensive individuals.</p>
</sec>
<sec id="S5"><title>Funding</title>
<p id="P5">The US National Kidney Foundation (sources include Abbott and Amgen).</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Danemark</li>
<li>France</li>
<li>Italie</li>
<li>Japon</li>
<li>Pays-Bas</li>
<li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Groningue (province)</li>
<li>Maryland</li>
<li>Massachusetts</li>
<li>Wisconsin</li>
</region>
<settlement><li>Groningue</li>
<li>Pékin</li>
</settlement>
</list>
<tree><country name="États-Unis"><region name="Maryland"><name sortKey="Mahmoodi, Bakhtawar K" sort="Mahmoodi, Bakhtawar K" uniqKey="Mahmoodi B" first="Bakhtawar K." last="Mahmoodi">Bakhtawar K. Mahmoodi</name>
</region>
<name sortKey="Astor, Brad C" sort="Astor, Brad C" uniqKey="Astor B" first="Brad C." last="Astor">Brad C. Astor</name>
<name sortKey="Astor, Brad C" sort="Astor, Brad C" uniqKey="Astor B" first="Brad C." last="Astor">Brad C. Astor</name>
<name sortKey="Coresh, Josef" sort="Coresh, Josef" uniqKey="Coresh J" first="Josef" last="Coresh">Josef Coresh</name>
<name sortKey="Matsushita, Kunihiro" sort="Matsushita, Kunihiro" uniqKey="Matsushita K" first="Kunihiro" last="Matsushita">Kunihiro Matsushita</name>
<name sortKey="Sarnak, Mark J" sort="Sarnak, Mark J" uniqKey="Sarnak M" first="Mark J." last="Sarnak">Mark J. Sarnak</name>
<name sortKey="Woodward, Mark" sort="Woodward, Mark" uniqKey="Woodward M" first="Mark" last="Woodward">Mark Woodward</name>
</country>
<country name="Pays-Bas"><region name="Groningue (province)"><name sortKey="Mahmoodi, Bakhtawar K" sort="Mahmoodi, Bakhtawar K" uniqKey="Mahmoodi B" first="Bakhtawar K." last="Mahmoodi">Bakhtawar K. Mahmoodi</name>
</region>
<name sortKey="Blankestijn, Peter J" sort="Blankestijn, Peter J" uniqKey="Blankestijn P" first="Peter J." last="Blankestijn">Peter J. Blankestijn</name>
<name sortKey="De Jong, Paul E" sort="De Jong, Paul E" uniqKey="De Jong P" first="Paul E." last="De Jong">Paul E. De Jong</name>
</country>
<country name="Italie"><noRegion><name sortKey="Cirillo, Massimo" sort="Cirillo, Massimo" uniqKey="Cirillo M" first="Massimo" last="Cirillo">Massimo Cirillo</name>
</noRegion>
</country>
<country name="Japon"><noRegion><name sortKey="Ohkubo, Takayoshi" sort="Ohkubo, Takayoshi" uniqKey="Ohkubo T" first="Takayoshi" last="Ohkubo">Takayoshi Ohkubo</name>
</noRegion>
<name sortKey="Ohkubo, Takayoshi" sort="Ohkubo, Takayoshi" uniqKey="Ohkubo T" first="Takayoshi" last="Ohkubo">Takayoshi Ohkubo</name>
<name sortKey="Yamagishi, Kazumasa" sort="Yamagishi, Kazumasa" uniqKey="Yamagishi K" first="Kazumasa" last="Yamagishi">Kazumasa Yamagishi</name>
<name sortKey="Yamagishi, Kazumasa" sort="Yamagishi, Kazumasa" uniqKey="Yamagishi K" first="Kazumasa" last="Yamagishi">Kazumasa Yamagishi</name>
<name sortKey="Yamagishi, Kazumasa" sort="Yamagishi, Kazumasa" uniqKey="Yamagishi K" first="Kazumasa" last="Yamagishi">Kazumasa Yamagishi</name>
<name sortKey="Yamashita, Kentaro" sort="Yamashita, Kentaro" uniqKey="Yamashita K" first="Kentaro" last="Yamashita">Kentaro Yamashita</name>
</country>
<country name="Danemark"><noRegion><name sortKey="Rossing, Peter" sort="Rossing, Peter" uniqKey="Rossing P" first="Peter" last="Rossing">Peter Rossing</name>
</noRegion>
</country>
<country name="France"><noRegion><name sortKey="Stengel, Benedicte" sort="Stengel, Benedicte" uniqKey="Stengel B" first="Bénédicte" last="Stengel">Bénédicte Stengel</name>
</noRegion>
<name sortKey="Stengel, Benedicte" sort="Stengel, Benedicte" uniqKey="Stengel B" first="Bénédicte" last="Stengel">Bénédicte Stengel</name>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="Zhang, Luxia" sort="Zhang, Luxia" uniqKey="Zhang L" first="Luxia" last="Zhang">Luxia Zhang</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
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