Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

A. Mocroft, J.D. Lundgren, M. Ross, M. Law, P. Reiss, O. Kirk, C. Smith, D. Wentworth, J. Neuhaus, C.A. Fux, O. Moranne, P. Morlat, M.A. Johnson, the D:A:D Study Group, the Royal Free Hospital Clinic Cohort, the INSIGHT Study Group, the SMART Study Group, the ESPRIT Study Group, A. Oude Lashof, D. PosthouwerP.H.M. Savelkoul, L. Ryom

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Abstract

Background

Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.

Methods and Findings

A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR

In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score <0, 33 events), rising to 1: 47 and 1: 6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score >= 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor.

The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria.

Conclusions

Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.

Original languageEnglish
Article numbere1001809
Number of pages31
JournalPLoS Medicine
Volume12
Issue number3
DOIs
Publication statusPublished - Mar 2015

Keywords

  • GLOMERULAR-FILTRATION-RATE
  • STAGE RENAL-DISEASE
  • POSITIVE PERSONS
  • ANTIRETROVIRAL THERAPY
  • LIFE EXPECTANCY
  • ASSOCIATION
  • PREDICTION
  • INDIVIDUALS
  • EXPOSURE
  • PROTEINURIA

Cite this

Mocroft, A. ; Lundgren, J.D. ; Ross, M. ; Law, M. ; Reiss, P. ; Kirk, O. ; Smith, C. ; Wentworth, D. ; Neuhaus, J. ; Fux, C.A. ; Moranne, O. ; Morlat, P. ; Johnson, M.A. ; D:A:D Study Group, the ; Royal Free Hospital Clinic Cohort, the ; INSIGHT Study Group, the ; SMART Study Group, the ; ESPRIT Study Group, the ; Oude Lashof, A. ; Posthouwer, D. ; Savelkoul, P.H.M. ; Ryom, L. / Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study. In: PLoS Medicine. 2015 ; Vol. 12, No. 3.
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title = "Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study",
abstract = "BackgroundChronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.Methods and FindingsA total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFRIn the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95{\%} CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score <0, 33 events), rising to 1: 47 and 1: 6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score >= 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95{\%} CI 1,166-3,367); NNTH was 202 (95{\%} CI 159-278) and 21 (95{\%} CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95{\%} CI 506-1462), 88 (95{\%} CI 69-121), and 9 (95{\%} CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor.The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7{\%}) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6{\%}) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria.ConclusionsBoth traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.",
keywords = "GLOMERULAR-FILTRATION-RATE, STAGE RENAL-DISEASE, POSITIVE PERSONS, ANTIRETROVIRAL THERAPY, LIFE EXPECTANCY, ASSOCIATION, PREDICTION, INDIVIDUALS, EXPOSURE, PROTEINURIA",
author = "A. Mocroft and J.D. Lundgren and M. Ross and M. Law and P. Reiss and O. Kirk and C. Smith and D. Wentworth and J. Neuhaus and C.A. Fux and O. Moranne and P. Morlat and M.A. Johnson and {D:A:D Study Group}, the and {Royal Free Hospital Clinic Cohort}, the and {INSIGHT Study Group}, the and {SMART Study Group}, the and {ESPRIT Study Group}, the and {Oude Lashof}, A. and D. Posthouwer and P.H.M. Savelkoul and L. Ryom",
year = "2015",
month = "3",
doi = "10.1371/journal.pmed.1001809",
language = "English",
volume = "12",
journal = "PLoS Medicine",
issn = "1549-1277",
publisher = "Public Library of Science",
number = "3",

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Mocroft, A, Lundgren, JD, Ross, M, Law, M, Reiss, P, Kirk, O, Smith, C, Wentworth, D, Neuhaus, J, Fux, CA, Moranne, O, Morlat, P, Johnson, MA, D:A:D Study Group, T, Royal Free Hospital Clinic Cohort, T, INSIGHT Study Group, T, SMART Study Group, T, ESPRIT Study Group, T, Oude Lashof, A, Posthouwer, D, Savelkoul, PHM & Ryom, L 2015, 'Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study', PLoS Medicine, vol. 12, no. 3, e1001809. https://doi.org/10.1371/journal.pmed.1001809

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study. / Mocroft, A.; Lundgren, J.D.; Ross, M.; Law, M.; Reiss, P.; Kirk, O.; Smith, C.; Wentworth, D.; Neuhaus, J.; Fux, C.A.; Moranne, O.; Morlat, P.; Johnson, M.A.; D:A:D Study Group, the; Royal Free Hospital Clinic Cohort, the; INSIGHT Study Group, the; SMART Study Group, the; ESPRIT Study Group, the; Oude Lashof, A.; Posthouwer, D.; Savelkoul, P.H.M.; Ryom, L.

In: PLoS Medicine, Vol. 12, No. 3, e1001809, 03.2015.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

AU - Mocroft, A.

AU - Lundgren, J.D.

AU - Ross, M.

AU - Law, M.

AU - Reiss, P.

AU - Kirk, O.

AU - Smith, C.

AU - Wentworth, D.

AU - Neuhaus, J.

AU - Fux, C.A.

AU - Moranne, O.

AU - Morlat, P.

AU - Johnson, M.A.

AU - D:A:D Study Group, the

AU - Royal Free Hospital Clinic Cohort, the

AU - INSIGHT Study Group, the

AU - SMART Study Group, the

AU - ESPRIT Study Group, the

AU - Oude Lashof, A.

AU - Posthouwer, D.

AU - Savelkoul, P.H.M.

AU - Ryom, L.

PY - 2015/3

Y1 - 2015/3

N2 - BackgroundChronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.Methods and FindingsA total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFRIn the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score <0, 33 events), rising to 1: 47 and 1: 6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score >= 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor.The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria.ConclusionsBoth traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.

AB - BackgroundChronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.Methods and FindingsA total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFRIn the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score <0, 33 events), rising to 1: 47 and 1: 6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score >= 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor.The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria.ConclusionsBoth traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.

KW - GLOMERULAR-FILTRATION-RATE

KW - STAGE RENAL-DISEASE

KW - POSITIVE PERSONS

KW - ANTIRETROVIRAL THERAPY

KW - LIFE EXPECTANCY

KW - ASSOCIATION

KW - PREDICTION

KW - INDIVIDUALS

KW - EXPOSURE

KW - PROTEINURIA

U2 - 10.1371/journal.pmed.1001809

DO - 10.1371/journal.pmed.1001809

M3 - Article

VL - 12

JO - PLoS Medicine

JF - PLoS Medicine

SN - 1549-1277

IS - 3

M1 - e1001809

ER -