The metabolic syndrome and renal function in an African cohort infected with Human Immunodeficiency Virus for at least 5 years
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Motivation The human immunodeficiency virus (HIV) is increasingly prevalent in South Africa, with approximately 6.12 million people living with HIV. As a result of the high infection rate, South Africa has the largest antiretroviral therapy (ART) roll-out programme, providing ART to approximately 3.1 million people. The introduction of ART has revolutionised the era of HIV in reducing the morbidity and mortality associated with HIV or acquired immunodeficiency syndrome (AIDS) opportunistic disease. However, after the introduction of ART, several studies reported metabolic derangements and renal disease with the use of ART. The metabolic syndrome (MetS) is frequently reported in HIV-infected individuals and this population may be at higher risk due to the combination of HIV infection, ART and traditional risk factors. Renal disease has also been highlighted in people living with HIV. HIV infection may directly infect the glomerular epithelial cells and podocytes, inducing renal injury. The ART is also potentially nephrotoxic and may augment the effect exerted by HIV and pre-existing kidney diseases. The MetS and kidney disease have been reported in HIV-infected individuals, however, it has not been fully elucidated how kidney function is affected by HIV, ART and the MetS. Apart from HIV, the MetS and kidney disease have important public health implications as both are associated with increased risk of cardiovascular disease. As a result, these comorbidities may complicate the progression and management of HIV. Studies reporting on the combined effects of HIV, the MetS and renal function among the African population are scant. Aim In this study, we therefore determined the prevalence of the MetS and the association thereof with renal function in an African cohort infected with HIV for at least five years. Methodology We included 114 HIV-infected and 114 HIV-free participants matched for age, sex and locality. This is a sub-study of the Prospective Urban and Rural Epidemiological study (PURE) in South Africa, as approved by the Health Research Ethics Committee of the North-West University (approval number: NWU-00035-16-S1 and NWU-00016-10- A1). Of the 114 HIV-infected participants, 87 were infected for 10 years and 27 for 5 years. The HIV-infected participants on ART were using first-line regimen, namely a fixed-dose combination of tenofovir, efavirenz and emtricitabine. Anthropometric measurements such as height, weight and waist circumference (WC) were measured according to standardised procedures prescribed by the International Society for the Advancement of Kinathropometry, while body mass index (BMI) was also calculated. Duplicate brachial blood pressure (BP) measurements were performed in a sitting position, at an interval of five minutes, using the validated OMRON M6 (Omron Healthcare, Kyoto, Japan). We also performed duplicate central systolic blood pressures (cSBP) with the Sphygmocor XCEL device (Atcor Medical Pty. Ltd., Sydney, Australia), with the participant in the supine position. Blood collection was done by a qualified nurse after an overnight fast. We performed biochemical analysis for serum glucose, total cholesterol, high-density lipoprotein cholesterol, low density lipoprotein cholesterol, γ-glutamyl transferase and C-reactive protein. Mid-stream spot urine was used to determine albumin and creatinine levels and we calculated creatinine clearance (CrCl), estimated glomerular filtration rate (eGFR), and calculated urinary albumin-creatinine ratio (uACR). HIV status was determined from whole blood, according to the South African Department of Health guidelines. We defined the MetS using the criteria of the International Diabetes Federation. Results The prevalence of the MetS was lower in the HIV-infected participants (77.3% of the HIV-infected were on ART) as compared to their uninfected counterparts (28% vs. 44%, p=0.0013). The HIV-infected group had lower BMI and WC (all p<0.001), as well as lower cSBP and branchial blood pressure (all p≤ 0.021). With regard to renal function, the CrCl was higher in the HIV-infected participants compared to their uninfected counterparts (p<0.001). There was no difference in eGFR and uACR in the two groups (p=0.99 and p=0.72 respectively). When adjustment was done for WC, the cSBP (p<0.001) and brachial blood pressure remained significant (p=0.05), and CrCl, eGFR and uACR were similar (p>0.27). With regard to the use of ART, the HIV-infected participants taking ART also presented with lower cSBP and brachial blood pressures (all p=0.01). CrCl was lower in the HIVinfected participants taking ART than the uninfected participants (p=0.002), whereas eGFR and uACR were similar between the two groups (all p>0.11). When we compared HIV-infected and uninfected participants with the MetS, the blood pressures were similar (all p>0.46). Of those with the MetS, 46% and 17% of the HIVinfected and the uninfected participants respectively had microalbuminuria. The HIVinfected participants and those with the MetS had 43% higher uACR compared to the uninfected participants with the MetS (p=0.032). CrCl was lower in the HIV-infected group with the MetS than the uninfected group with the MetS (p=0.05), but eGFR was not different between these two groups (p=0.21). General conclusion HIV-infected participants with the MetS had a twofold higher uACR compared to their uninfected counterparts, despite similar age and sex distribution and a lower prevalence of the MetS. These findings suggest that a combination of the MetS and HIV may alter glomerular permeability. The presence of the MetS and renal dysfunction may therefore increase the risk of cardiovascular disease in the HIVinfected population.
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