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      Microalbuminuria associated with indicators of inflammatory activity in an HIV-positive population

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          Abstract

          Background. The survival of human immunodeficiency virus (HIV)-infected patients has increased significantly since the introduction of combination antiretroviral therapy, leading to the development of important long-term complications including cardiovascular disease (CVD) and renal disease. Microalbuminuria, an indicator of glomerular injury, is associated with an increased risk of progressive renal deterioration, CVD and mortality. However, the prevalence of microalbuminuria has barely been investigated in HIV-infected individuals.

          Methods. Based on three prospective urine samples in an unselected nonhypertensive, nondiabetic HIV-positive cohort ( n = 495), we analysed the prevalence of microalbuminuria and compared the Caucasian share with that of a nonhypertensive, nondiabetic population-based control group ( n = 2091). Significant predictors for microalbuminuria were analysed within the HIV-positive cohort.

          Results. The prevalence of microalbuminuria was 8.7% in the HIV-infected cohort, which is three to five times higher than that in the general population. HIV-infected patients with microalbuminuria were older, and had higher blood pressure, longer duration of HIV infection, higher serum beta 2-microglobulin, higher serum creatinine and a reduced glomerular filtration rate of ≤90 mL/min, compared with those with normal albumin excretion. In multivariate analysis, systolic blood pressure, serum beta 2-microglobulin and duration of HIV infection were found to be independent predictors of microalbuminuria.

          Conclusions. Our findings indicate that in addition to haemodynamic effects, inflammatory activity may be implicated as a cause of the development of microalbuminuria. With respect to the increasing risk of developing CVD or renal diseases and mortality, the high prevalence of microalbuminuria in HIV-infected individuals warrants special attention.

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          Most cited references41

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          Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes.

          The aim of this study was to assess the level of urinary albumin excretion (microalbuminuria), which is associated with increased risk of coronary heart disease and death, in the population. Microalbuminuria has been suggested as an atherosclerotic risk factor. However, the lower cutoff level of urinary albumin excretion is unknown. It is also unknown whether impaired renal function confounds the association. In the Third Copenhagen City Heart Study in 1992 to 1994, 2762 men and women 30 to 70 years of age underwent a detailed cardiovascular investigation program, including a timed overnight urine sample. The participants were then followed up prospectively by registers until 1999 with respect to coronary heart disease and until 2001 with respect to death. During follow-up, 109 incident cases of coronary heart disease and 276 deaths were traced. A urinary albumin excretion above the upper quartile, ie, 4.8 microg/min, was associated with increased risk of coronary heart disease (RR, 2.0; 95% CI, 1.4 to 3.0; P 4.8 microg/min (corresponding to approximately 6.4 microg/min during daytime), is a strong and independent determinant of coronary heart disease and death. Our suggestion is to redefine microalbuminuria accordingly and perform intervention studies.
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            Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population.

            The distribution of risk factors for cardiovascular disease in patients aged 35-44 years who were treated for human immunodeficiency virus type 1 (HIV-1) infection was compared with that for a population-based cohort. HIV-1-infected men treated with a protease inhibitor-containing regimen (n=223), compared with HIV-1-uninfected men (n=527), were characterized by a lower prevalence of hypertension, a lower mean high-density lipoprotein cholesterol level, a higher prevalence of smoking, a higher mean waist-to-hip ratio, and a higher mean triglyceride level. No difference was found for total plasma or low-density cholesterol levels, nor for the prevalence of diabetes. Similar trends were observed among female subjects. The predicted risk of coronary heart disease was greater among HIV-1-infected men (relative risk [RR], 1.20) and women (RR, 1.59; P<10(-6) for both), compared with the HIV-1-uninfected cohort. The estimated attributable risks due to smoking were 65% and 29% for HIV-1-infected men and women, respectively. Because most HIV-1-infected people will ultimately need antiretroviral therapy, risk factors for cardiovascular disease should be determined at the initiation of treatment, and interventions should be considered for all patients who have them.
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              Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection.

              Metabolic abnormalities associated with human immunodeficiency virus (HIV) infection, including dysglycemia and hyperlipidemia, are increasingly prevalent, and there is concern about the possibility of an association with accelerated cardiovascular and cerebrovascular disease. We conducted a retrospective study of the risk of cardiovascular and cerebrovascular disease among the 36,766 patients who received care for HIV infection at Veterans Affairs facilities between January 1993 and June 2001. For antiretroviral therapy, 70.2 percent of the patients received nucleoside analogues, 41.6 percent received protease inhibitors, and 25.6 percent received nonnucleoside reverse-transcriptase inhibitors for a median of 17 months, 16 months, and 9 months, respectively. Approximately 1000 patients received combination therapy with a protease inhibitor for at least 48 months, and approximately 1000 patients received combination therapy with a nonnucleoside reverse-transcriptase inhibitor for at least 24 months. Between 1995 and 2001, the rate of admissions for cardiovascular or cerebrovascular disease decreased from 1.7 to 0.9 per 100 patient-years, and the rate of death from any cause decreased from 21.3 to 5.0 deaths per 100 patient-years. Patient-level regression analyses indicated that there was no relation between the use of nucleoside analogues, protease inhibitors, or nonnucleoside reverse-transcriptase inhibitors and the hazard of cardiovascular or cerebrovascular events, but the use of antiretroviral drugs was associated with a decreased hazard of death from any cause. Use of newer therapies for HIV was associated with a large benefit in terms of mortality that was not diminished by any increase in the rate of cardiovascular or cerebrovascular events or related mortality. Fear of accelerated vascular disease need not compromise antiretroviral therapy over the short term. However, prolonged survival among HIV infected patients means that longer-term observation and analysis are required. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Journal
                Nephrol Dial Transplant
                ndt
                ndt
                Nephrology Dialysis Transplantation
                Oxford University Press
                0931-0509
                1460-2385
                October 2008
                9 May 2008
                9 May 2008
                : 23
                : 10
                : 3130-3137
                Affiliations
                [1 ]Department of Infectious Diseases, Ullevaal University Hospital
                [2 ]Faculty of Medicine, University of Oslo
                [3 ]Department of Nephrology
                [4 ]Center of Clinical Research, Ullevaal University Hospital , Oslo, Norway
                Author notes
                Morten Baekken, Department of Infectious Diseases, Ullevaal University Hospital, 0407 Oslo, Norway. Tel: +472-211-9101; Fax: +472-211-9181; E-mail: morten.baekken@ 123456medisin.uio.no ; olok@ 123456ulleval.no
                Article
                gfn236
                10.1093/ndt/gfn236
                2542409
                18469311
                9ce659a2-4a31-43fc-9aa7-c3f851486e42
                © The Author [2008].

                The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

                History
                : 11 January 2008
                : 28 March 2008
                Categories
                Clinical Nephrology

                Nephrology
                hiv,combination antiretroviral treatment,microalbuminuria,beta 2-microglobulin,blood pressure

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