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A clinically useful risk-score for chronic kidney disease in HIV infection

Identifieur interne : 001036 ( Pmc/Curation ); précédent : 001035; suivant : 001037

A clinically useful risk-score for chronic kidney disease in HIV infection

Auteurs : Amanda Mocroft [Royaume-Uni] ; Jens Lundgren [Danemark] ; Michael Ross [États-Unis] ; Matthew Law [Australie] ; Peter Reiss [Pays-Bas] ; Ole Kirk [Danemark] ; Colette Smith [Royaume-Uni] ; Debbie Wentworth [États-Unis] ; Jacquie Heuhaus [États-Unis] ; Christophe Fux [Suisse] ; Olivier Moranne [France] ; Phillipe Morlat [France] ; Margaret Johnson [Royaume-Uni] ; Lene Ryom [Danemark]

Source :

RBID : PMC:4224906

Abstract

Introduction

Development of a simple, widely applicable risk score for chronic kidney disease (CKD) allows comparisons of risks or benefits of starting potentially nephrotoxic antiretrovirals (ARVs) as part of a treatment regimen.

Materials and Methods

A total of 18,055 HIV-positive persons from the Data on Adverse Drugs (D:A:D) study with >3 estimated glomerular filtration rates (eGFRs) >1/1/2004 were included. Persons with use of tenofovir (TDF), atazanavir (ritonavir boosted (ATV/r) and unboosted (ATV)), lopinavir (LPV/r) and other boosted protease inhibitors (bPIs) before baseline (first eGFR >60 ml/min/1.73 m2 after 1/1/2004) were excluded. CKD was defined as confirmed (>3 months apart) eGFR <60. Poisson regression was used to develop a score predicting low (<0 points), medium (1–4 points) and high (>5 points) risk of developing CKD. Increased incidence of CKD associated with starting ARVs was modelled by including ARVs as time-updated variables. The risk score was externally validated on two independent cohorts.

Results

A total of 641 persons developed CKD during 103,278.5 PYFU (incidence 6.2/1000 PYFU, 95% CI 5.7–6.7). Older age, intravenous drug use, HCV+ antibody status, lower baseline eGFR, female gender, lower CD4 nadir, hypertension, diabetes and cardiovascular disease predicted CKD and were included in the risk score (Figure 1). The incidence of CKD in those at low, medium and high risk was 0.8/1000 PYFU (95% CI 0.6–1.0), 5.6 (95% CI 4.5–6.7) and 37.4 (95% CI 34.0–40.7) (Figure 1). The risk score showed good discrimination (Harrell's c statistic 0.92, 95% CI 0.90–0.93). The number needed to harm (NNTH) in patients starting ATV or LPV/r was 1395, 142 or 20, respectively, among those with low, medium or high risk. NNTH were 603, 61 and 9 for those with a low, medium or high risk starting TDF, ATV/r or bPIs. The risk score was externally validated on 2603 persons from the Royal Free Hospital clinic cohort (94 events, incidence 5.1/1000 PYFU; 95% CI 4.1–6.1) and 2013 persons from the control arms of SMART/ESPRIT (32 events, incidence 3.8/1000 PYFU; 95% CI 2.5–5.1). External validation showed consistent CKD rates across risk groups (Figure 2).

Interpretation

Traditional and HIV-related risk factors were predictive of CKD; all are routinely available, making the risk score easy to incorporate into clinical practise and of direct relevance for clinical decision making. NNTH in persons starting potentially nephrotoxic ARVs at high risk of CKD were low, and alternative ARVs may be more appropriate.


Url:
DOI: 10.7448/IAS.17.4.19514
PubMed: 25394023
PubMed Central: 4224906

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PMC:4224906

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<name sortKey="Moranne, Olivier" sort="Moranne, Olivier" uniqKey="Moranne O" first="Olivier" last="Moranne">Olivier Moranne</name>
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<nlm:aff id="AF0008_19514">INSERM U 897, CHU de Bordeaux, Université Bordeaux Segalen, Bordeaux, France</nlm:aff>
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<name sortKey="Morlat, Phillipe" sort="Morlat, Phillipe" uniqKey="Morlat P" first="Phillipe" last="Morlat">Phillipe Morlat</name>
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<nlm:aff id="AF0009_19514">Department of Nephrology, Public Health Department, CHU Nice, Nice, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Nephrology, Public Health Department, CHU Nice, Nice</wicri:regionArea>
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<name sortKey="Johnson, Margaret" sort="Johnson, Margaret" uniqKey="Johnson M" first="Margaret" last="Johnson">Margaret Johnson</name>
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<nlm:aff id="AF0010_19514">Thoracic Medicine, Royal Free Hospital NHS Trust, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Thoracic Medicine, Royal Free Hospital NHS Trust, London</wicri:regionArea>
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<name sortKey="Ryom, Lene" sort="Ryom, Lene" uniqKey="Ryom L" first="Lene" last="Ryom">Lene Ryom</name>
<affiliation wicri:level="1">
<nlm:aff id="AF0002_19514">Copenhagen HIV Programme, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Copenhagen HIV Programme, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen</wicri:regionArea>
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<series>
<title level="j">Journal of the International AIDS Society</title>
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<date when="2014">2014</date>
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<sec id="st1_19514">
<title>Introduction</title>
<p>Development of a simple, widely applicable risk score for chronic kidney disease (CKD) allows comparisons of risks or benefits of starting potentially nephrotoxic antiretrovirals (ARVs) as part of a treatment regimen.</p>
</sec>
<sec id="st2_19514">
<title>Materials and Methods</title>
<p>A total of 18,055 HIV-positive persons from the Data on Adverse Drugs (D:A:D) study with >3 estimated glomerular filtration rates (eGFRs) >1/1/2004 were included. Persons with use of tenofovir (TDF), atazanavir (ritonavir boosted (ATV/r) and unboosted (ATV)), lopinavir (LPV/r) and other boosted protease inhibitors (bPIs) before baseline (first eGFR >60 ml/min/1.73 m
<sup>2</sup>
after 1/1/2004) were excluded. CKD was defined as confirmed (>3 months apart) eGFR <60. Poisson regression was used to develop a score predicting low (<0 points), medium (1–4 points) and high (>5 points) risk of developing CKD. Increased incidence of CKD associated with starting ARVs was modelled by including ARVs as time-updated variables. The risk score was externally validated on two independent cohorts.</p>
</sec>
<sec id="st3_19514">
<title>Results</title>
<p>A total of 641 persons developed CKD during 103,278.5 PYFU (incidence 6.2/1000 PYFU, 95% CI 5.7–6.7). Older age, intravenous drug use, HCV+ antibody status, lower baseline eGFR, female gender, lower CD4 nadir, hypertension, diabetes and cardiovascular disease predicted CKD and were included in the risk score (
<xref ref-type="fig" rid="F0001_19514">Figure 1</xref>
). The incidence of CKD in those at low, medium and high risk was 0.8/1000 PYFU (95% CI 0.6–1.0), 5.6 (95% CI 4.5–6.7) and 37.4 (95% CI 34.0–40.7) (
<xref ref-type="fig" rid="F0001_19514">Figure 1</xref>
). The risk score showed good discrimination (Harrell's c statistic 0.92, 95% CI 0.90–0.93). The number needed to harm (NNTH) in patients starting ATV or LPV/r was 1395, 142 or 20, respectively, among those with low, medium or high risk. NNTH were 603, 61 and 9 for those with a low, medium or high risk starting TDF, ATV/r or bPIs. The risk score was externally validated on 2603 persons from the Royal Free Hospital clinic cohort (94 events, incidence 5.1/1000 PYFU; 95% CI 4.1–6.1) and 2013 persons from the control arms of SMART/ESPRIT (32 events, incidence 3.8/1000 PYFU; 95% CI 2.5–5.1). External validation showed consistent CKD rates across risk groups (
<xref ref-type="fig" rid="F0002_19514">Figure 2</xref>
). </p>
</sec>
<sec id="st4_19514">
<title>Interpretation</title>
<p>Traditional and HIV-related risk factors were predictive of CKD; all are routinely available, making the risk score easy to incorporate into clinical practise and of direct relevance for clinical decision making. NNTH in persons starting potentially nephrotoxic ARVs at high risk of CKD were low, and alternative ARVs may be more appropriate.</p>
</sec>
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<journal-id journal-id-type="nlm-ta">J Int AIDS Soc</journal-id>
<journal-id journal-id-type="iso-abbrev">J Int AIDS Soc</journal-id>
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<journal-title>Journal of the International AIDS Society</journal-title>
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<contrib contrib-type="author">
<name>
<surname>Mocroft</surname>
<given-names>Amanda</given-names>
</name>
<xref ref-type="aff" rid="AF0001_19514">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lundgren</surname>
<given-names>Jens</given-names>
</name>
<xref ref-type="aff" rid="AF0002_19514">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ross</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="AF0003_19514">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Law</surname>
<given-names>Matthew</given-names>
</name>
<xref ref-type="aff" rid="AF0004_19514">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Reiss</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="AF0005_19514">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kirk</surname>
<given-names>Ole</given-names>
</name>
<xref ref-type="aff" rid="AF0002_19514">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Smith</surname>
<given-names>Colette</given-names>
</name>
<xref ref-type="aff" rid="AF0001_19514">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wentworth</surname>
<given-names>Debbie</given-names>
</name>
<xref ref-type="aff" rid="AF0006_19514">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Heuhaus</surname>
<given-names>Jacquie</given-names>
</name>
<xref ref-type="aff" rid="AF0006_19514">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fux</surname>
<given-names>Christophe</given-names>
</name>
<xref ref-type="aff" rid="AF0007_19514">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Moranne</surname>
<given-names>Olivier</given-names>
</name>
<xref ref-type="aff" rid="AF0008_19514">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Morlat</surname>
<given-names>Phillipe</given-names>
</name>
<xref ref-type="aff" rid="AF0009_19514">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Johnson</surname>
<given-names>Margaret</given-names>
</name>
<xref ref-type="aff" rid="AF0010_19514">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ryom</surname>
<given-names>Lene</given-names>
</name>
<xref ref-type="aff" rid="AF0002_19514">2</xref>
</contrib>
<contrib contrib-type="author">
<collab>on behalf of the Data on Adverse Events (D:A:D) study group,the Royal Free Hospital Clinic Cohort and the INSIGHT study group</collab>
<xref ref-type="aff" rid="AF0008_19514">8</xref>
</contrib>
</contrib-group>
<aff id="AF0001_19514">
<label>1</label>
Department of Infection and Population Health, University College London, London, UK</aff>
<aff id="AF0002_19514">
<label>2</label>
Copenhagen HIV Programme, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark</aff>
<aff id="AF0003_19514">
<label>3</label>
Division of Nephrology, Mount Sinai School of Medicine, New York, USA</aff>
<aff id="AF0004_19514">
<label>4</label>
The Kirby Institute for Infection and Immunity, University of New South Wales, Sydney, Australia</aff>
<aff id="AF0005_19514">
<label>5</label>
Division of Infectious Diseases, Department of Global Health, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands</aff>
<aff id="AF0006_19514">
<label>6</label>
Division of Biostatistics, University of Minnesota, Minnesota, USA</aff>
<aff id="AF0007_19514">
<label>7</label>
Clinic for Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, Aarau, Switzerland</aff>
<aff id="AF0008_19514">
<label>8</label>
INSERM U 897, CHU de Bordeaux, Université Bordeaux Segalen, Bordeaux, France</aff>
<aff id="AF0009_19514">
<label>9</label>
Department of Nephrology, Public Health Department, CHU Nice, Nice, France</aff>
<aff id="AF0010_19514">
<label>10</label>
Thoracic Medicine, Royal Free Hospital NHS Trust, London, UK</aff>
<pub-date pub-type="epub">
<day>02</day>
<month>11</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="collection">
<year>2014</year>
</pub-date>
<volume>17</volume>
<issue>4Suppl 3</issue>
<elocation-id content-type="doi">19514</elocation-id>
<permissions>
<copyright-statement>© 2014 Mocroft A et al; licensee International AIDS Society</copyright-statement>
<copyright-year>2014</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0/">
<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract>
<sec id="st1_19514">
<title>Introduction</title>
<p>Development of a simple, widely applicable risk score for chronic kidney disease (CKD) allows comparisons of risks or benefits of starting potentially nephrotoxic antiretrovirals (ARVs) as part of a treatment regimen.</p>
</sec>
<sec id="st2_19514">
<title>Materials and Methods</title>
<p>A total of 18,055 HIV-positive persons from the Data on Adverse Drugs (D:A:D) study with >3 estimated glomerular filtration rates (eGFRs) >1/1/2004 were included. Persons with use of tenofovir (TDF), atazanavir (ritonavir boosted (ATV/r) and unboosted (ATV)), lopinavir (LPV/r) and other boosted protease inhibitors (bPIs) before baseline (first eGFR >60 ml/min/1.73 m
<sup>2</sup>
after 1/1/2004) were excluded. CKD was defined as confirmed (>3 months apart) eGFR <60. Poisson regression was used to develop a score predicting low (<0 points), medium (1–4 points) and high (>5 points) risk of developing CKD. Increased incidence of CKD associated with starting ARVs was modelled by including ARVs as time-updated variables. The risk score was externally validated on two independent cohorts.</p>
</sec>
<sec id="st3_19514">
<title>Results</title>
<p>A total of 641 persons developed CKD during 103,278.5 PYFU (incidence 6.2/1000 PYFU, 95% CI 5.7–6.7). Older age, intravenous drug use, HCV+ antibody status, lower baseline eGFR, female gender, lower CD4 nadir, hypertension, diabetes and cardiovascular disease predicted CKD and were included in the risk score (
<xref ref-type="fig" rid="F0001_19514">Figure 1</xref>
). The incidence of CKD in those at low, medium and high risk was 0.8/1000 PYFU (95% CI 0.6–1.0), 5.6 (95% CI 4.5–6.7) and 37.4 (95% CI 34.0–40.7) (
<xref ref-type="fig" rid="F0001_19514">Figure 1</xref>
). The risk score showed good discrimination (Harrell's c statistic 0.92, 95% CI 0.90–0.93). The number needed to harm (NNTH) in patients starting ATV or LPV/r was 1395, 142 or 20, respectively, among those with low, medium or high risk. NNTH were 603, 61 and 9 for those with a low, medium or high risk starting TDF, ATV/r or bPIs. The risk score was externally validated on 2603 persons from the Royal Free Hospital clinic cohort (94 events, incidence 5.1/1000 PYFU; 95% CI 4.1–6.1) and 2013 persons from the control arms of SMART/ESPRIT (32 events, incidence 3.8/1000 PYFU; 95% CI 2.5–5.1). External validation showed consistent CKD rates across risk groups (
<xref ref-type="fig" rid="F0002_19514">Figure 2</xref>
). </p>
</sec>
<sec id="st4_19514">
<title>Interpretation</title>
<p>Traditional and HIV-related risk factors were predictive of CKD; all are routinely available, making the risk score easy to incorporate into clinical practise and of direct relevance for clinical decision making. NNTH in persons starting potentially nephrotoxic ARVs at high risk of CKD were low, and alternative ARVs may be more appropriate.</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
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