The association of adiposity with kidney function decline among HIV-infected adults: findings from the Fat Redistribution and Metabolic Changes in HIV Infection (FRAM) study.

OBJECTIVES: The aim of the study was to investigate the association of adiposity with longitudinal kidney function change in 544 HIV-infected persons in the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) cohort over 5 years of follow-up. METHODS: The regional distribution of muscle and adipose tissue was quantified by whole-body magnetic resonance imaging (MRI), and total adiponectin and leptin levels were measured in serum. Kidney function was assessed using the estimated glomerular filtration rate from serum cystatin C (eGFRCys), obtained at baseline and follow-up. Rapid kidney function decline was defined as annual loss of eGFRCys ≥ 3 mL/min/1.73 m(2) , and incident chronic kidney disease (CKD) was defined as eGFRCys <60 mL/min/1.73 m(2) . Multivariate regression analysis was adjusted for age, race, gender, glucose, antihypertensive use, serum albumin, baseline and change in HIV viral load. RESULTS: At baseline, mean age was 43 years, mean eGFRCys was 86 mL/min/1.73 m(2) , and 21% of patients had albuminuria. The mean (± standard deviation) eGFRCys decline was -0.11 ± 4.87 mL/min/1.73 m(2) per year; 23% of participants had rapid kidney function decline, and 10% developed incident CKD. The lowest tertile of visceral adipose tissue and the highest tertile of adiponectin were both marginally associated with annual kidney function decline of -0.5 mL/min/1.73 m(2) each, but these associations were not statistically significant after adjustment. We found no statistically significant associations of MRI-measured regional adiposity or serum adipokines with rapid kidney function decline or incident CKD (all P-values>0.1 in adjusted models). CONCLUSIONS: Contrary to findings in the general population, adiposity did not have a substantial association with longitudinal change in kidney function among HIV-infected persons.

Fat distribution is altered in HIV-infected men without clinical evidence of the HIV lipodystrophy syndrome.

OBJECTIVE: To determine if fat distribution is altered in HIV-infected men without clinical evidence of lipodystrophy. METHODS: In a cross-sectional design, 14 protease inhibitor (PI)-treated men with lipodystrophy and 12 PI-treated and five PI-naive men without clinical evidence of lipodystrophy underwent body composition and fat distribution analysis by dual-energy X-ray absorptiometry and computed tomography. Their fat distribution was compared to 43 uninfected male controls matched for age and BMI. RESULTS: The percent of body fat in the trunk of men with HIV lipodystrophy was significantly greater compared to both HIV-infected and healthy controls. The percentage of body fat in the extremities was significantly lower in men with HIV lipodystrophy compared to both HIV-infected and healthy controls. HIV-infected men without clinical evidence of lipodystrophy also had a significantly greater percentage of total body fat in the trunk and a significantly lower percent of body fat in the extremities compared to healthy controls. Among the HIV-infected men, age was an independent predictor of truncal and extremity adiposity. CONCLUSION: This study suggests that a continuum of change is present in the adipose organ of HIV-infected men on antiretroviral therapy. Physical examination alone can miss significant changes in body fat distribution in HIV-infected patients.

Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome.

OBJECTIVE: To examine the relationships between protease inhibitor (PI) therapy, body fat distribution and metabolic disturbances in the HIV lipodystrophy syndrome. DESIGN: Cross-sectional study. SETTING: HIV primary care practices. PATIENTS: PI-treated patients with lipodystrophy (n= 14) and PI-treated (n= 13) and PI-naive (n= 5) patients without lipodystrophy. MAIN OUTCOME MEASURES: Body composition was assessed by physical examination, dual-energy X-ray absorptiometry and computed tomography. Insulin sensitivity (SI) was measured using the insulin-modified frequently sampled intravenous glucose tolerance test. Lipid profiles, other metabolic parameters, duration of HIV infection, CD4 lymphocyte counts, HIV-1 RNA load and resting energy expenditure (REE) were also assessed. RESULTS: PI-treated patients with lipodystrophy were significantly less insulin sensitive than PI-treated patients and PI-naive patients without any changes in fat distribution (SI(22) x 10(-4) (min(-1)/microU/ml) versus 3.2 x 10(-4) and 4.6 x 10(-4) (min(-1)/microU/ml), respectively; P < 0.001). Visceral adipose tissue area and other measures of central adiposity correlated strongly with metabolic disturbances as did the percent of total body fat present in the extremities; visceral adipose tissue was an independent predictor of insulin sensitivity and high density lipoprotein cholesterol levels. REE per kg lean body mass was significantly higher in the group with lipodystrophy compared to the groups without lipodystrophy (36.9 versus 31.5 and 29.4 kcal/kg lean body mass; P < 0.001), and SI was strongly correlated with and was an independent predictor of REE in this population. CONCLUSIONS: Body fat distribution and metabolic disturbances are strongly correlated in the HIV lipodystrophy syndrome and REE is increased.

Drugs causing dyslipoproteinemia.

Diuretics and beta-blockers have a strong tendency to affect serum lipids adversely, whereas the peripherally acting alpha-blocking agents consistently result in beneficial effects. Most of the other antihypertensive agents (calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists, and drugs that act centrally) are lipid neutral. The effect of steroid hormones varies with the drug, dose, and route of administration. In general, androgens lower HDL-C and have a variable effect on LDL-C. The effects of progestins vary greatly depending on their androgenicity, and estrogens are beneficial except when hypertriglyceridemia occurs with oral estrogens. Glucocorticoids raise HDL-C and may also increase triglycerides and LDL-C. Retinoids increase triglycerides and LDL-C and also reduce HDL-C. Interferons can cause hypertriglyceridemia. Following organ transplantation, a dyslipidemia often ensues. This is caused in part by the medications used to prevent rejection (glucocorticoids, cyclosporine, and FK-506) and requires close attention and, in some patients, drug therapy to prevent coronary artery disease.