Levels of albumin in urine higher in people with HIV, association with risk of heart and kidney disease

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HIV-positive individuals have a significantly higher risk of having small quantities of a protein in their urine that indicates an increased risk of both cardiovascular and kidney disease, according to American researchers writing in the May 11th edition of AIDS.

The investigators compared microalbuminuria – the presence of small amounts of the protein albumin in urine, a marker for both kidney and cardiovascular disease – in a cohort of HIV-positive patients and age-matched HIV-negative controls and found that the prevalence of elevated microalbuminuria was significantly higher in HIV-positive patients. The presence of microalbuminuria in HIV-positive patients was significantly associated with traditional risk factors for cardiovascular disease as well as HIV-related factors, most notably a weak immune system.

Kidney disease, involving symptoms such as protein in urine or elevated creatinine output, has been well described as a complication of HIV infection. Studies conducted before potent anti-HIV therapy became available suggested that between 19% - 34% of HIV-positive individuals had elevated levels of albumin in their urine.

Glossary

cardiovascular

Relating to the heart and blood vessels.

creatinine

Breakdown product of creatine phosphate in muscle, usually produced at a fairly constant rate by the body (depending on muscle mass). As a blood test, it is an important indicator of the health of the kidneys because it is an easily measured by-product of muscle metabolism that is excreted unchanged by the kidneys.

protein

A substance which forms the structure of most cells and enzymes.

cardiovascular disease

Disease of the heart or blood vessels, such as heart attack (myocardial infarction) and stroke.

glucose

A simple form of sugar found in the bloodstream. All sugars and starches are converted into glucose before they are absorbed. Cells use glucose as a source of energy. People with a constant high glucose level might have a disease called diabetes.

Investigators were interested in these observations because microalbuminuria has been associated with an increased risk of heart disease in the general population. As there is an increasingly robust body of evidence to show that antiretroviral therapy can increase the risk of cardiovascular disease, researchers wished to determine if microalbuminuria occurred with greater frequency in HIV-positive patients compared to age-matched HIV-negative controls. The researchers also wished to see if any factors predicted an increased risk of microalbuminuria in HIV-positive patients.

The study population consisted of individuals enrolled in the cross-sectional Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) cohort. The control population consisted of a population-based sample of healthy white and African-American men and women recruited to the CARDIA study.

Albumin and creatinine concentrations were measured in spot urine tests, and the investigators calculated the albumin to creatinine ratio (ACR), with an ACR of above 30mg/g defined as microalbuminuria. Data were also gathered on measures of cardiovascular risk, including blood pressure, insulin and glucose levels, family history of heart disease and smoking. For HIV-positive patients, the investigators obtained information on CD4 cell count and viral load.

Microalbuminuria was present in 11% of HIV-positive patients and 2% of controls, a statistically significant difference (p

Significant predictors of microalbuminuria in HIV-positive patients were older age (p = 0.02), and African American race (p = 0.001). Several factors associated with an increased risk of cardiovascular disease were also strongly associated with microalbuminuria in patients with HIV. These were higher systolic blood pressure (p = 0.01), a family history of hypertension (p = 0.03), and glucose in urine (p = 0.002). Smoking was not, however, significantly associated with microalbuminuria.

HIV-specific factors associated with microalbuminuria were a CD4 cell count below 200 cells/mm3 (p = 0.05), current viral load (p = 0.05), and treatment with an NNRTI (p

“This analysis demonstrated that HIV infection is a strong risk factor for the presence of microalbuminuria, independent of the risk factors for the presence of renal disease”, write the investigators.

The presence of markers for kidney or cardiovascular disease in HIV-positive patients with microalbuminuria, may be because of the increase in cardiovascular risk due to the metabolic complications caused by some antiretrovirals.

The investigators conclude, “the high prevalence of microalbuminuria among the HIV infected could be a harbinger of future increased risks of both kidney and cardiovascular disease. Further study defining the prognostic significance of microalbuminuria among HIV-infected persons will be essential."

References

Szczech LA et al. Microalbuminuria in HIV infection. AIDS 21: 1003 – 1009, 2007.