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: 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.
  
  
  RESULTS
  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 ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. 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.
authors.affiliation: Department of Infection and Population Health, University College London, London, United Kingdom.
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.affiliation: Copenhagen HIV Programme, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.affiliation: Division of Nephrology, Mount Sinai School of Medicine, New York, New York, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Ross
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.affiliation: Division of Infectious Diseases and Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.affiliation: Copenhagen HIV Programme, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Kirk
authors.affiliation: Department of Infection and Population Health, University College London, London, United Kingdom.
authors.forename: Colette
authors.initials: C
authors.lastname: Smith
authors.affiliation: University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Deborah
authors.initials: D
authors.lastname: Wentworth
authors.affiliation: University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Neuhaus
authors.affiliation: Clinic for Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Fux
authors.affiliation: Nephrology Department, Public Health Department, Centre Hospitalier Universitaire de Nice, Nice, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Moranne
authors.affiliation: Université de Bordeaux, INSERM U 897, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Phillipe
authors.initials: P
authors.lastname: Morlat
authors.affiliation: Department of HIV Medicine, Royal Free London NHS Foundation Trust, London, United Kingdom.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Johnson
authors.affiliation: Copenhagen HIV Programme, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Ryom
mesh_terms: D000328:Adult; D000367:Age Factors; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D000066491:Clinical Decision-Making; D015897:Comorbidity; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006679:HIV Seropositivity / Q000150:complications; D006801:Humans; D015994:Incidence; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology / Q000209:etiology*; D012306:Risk; D018570:Risk Assessment; D012737:Sex Factors
chemical_list: D019380:Anti-HIV Agents
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