Microalbuminuria—where low levels of a protein called albumin leak from the kidneys into urine—is associated with a much higher risk of death in HIV-positive women, according to a study published in the September 1 issue of the Journal of Acquired Immune Deficiency Syndromes. Proteinuria—the presence of any protein in urine—was also associated with increased mortality among women living with HIV in the study.

The kidneys are critical to filtering out toxins from the blood stream, while leaving in place blood proteins and other things that the body needs to remain healthy. Occasionally, when the filters in the kidneys become damaged, blood proteins can filter into the urine. Diabetes and high blood pressure are the most common culprits of kidney disease. People with a number of chronic diseases, including HIV and hepatitis, regularly have their urine tested for the presence of blood proteins. When proteins of any kind are present, this condition is called “proteinuria.”

Albumin is a specific blood protein that can leak into urine. When it does, it is often a sign of either cardiovascular disease or kidney disease. Microalbuminuria has been strongly associated with an increase in premature death in the general public. Though higher rates of the condition have been noted in people with HIV, researchers have never explored whether these higher rates are associated with an increased risk of death.

To examine this question, Christina Wyatt, MD, from the Mount Sinai School of Medicine in New York City, and her colleagues studied the results of two urine tests in 1,547 HIV-positive women enrolled in the Women's Interagency HIV Study (WIHS). Women were included if they had at least two eligible urine samples at least six months apart.

The women were tested for both proteinuria and microalbuminuria. Participants were classified as having “confirmed” microalbuminuria if they had either microalbuminuria at two study visits, or microalbuminuria at one visit and proteinuria at the other study visit. They were considered to have “unconfirmed” microalbuminuria if they had microalbuminuria at only one study visit, and they were considered to not have microalbuminuria if albumin could not be found in the urine at either study visit.

Of the more than 1,500 women, 1,261 had no microalbuminuria, 165 had unconfirmed microalbuminuria, 64 had confirmed microalbuminuria, and 57 had proteinuria. The demographics differed depending on the presence of protein in the kidneys. Women with no microalbuminuria were younger than the women in the other groups, more likely to be white, and less likely to have diabetes, high blood pressure or hepatitis B virus infection.

Wyatt and her colleagues found that the presence of protein in the urine was highly predictive of mortality. Women with unconfirmed microalbuminuria were 3.4 times as likely to die prematurely as women with no microalbuminuria. Women with confirmed microalbuminuria were 3.9 times as likely to die, and women with proteinuria had a death rate that was 5.9 times higher.

Though these numbers dropped when Wyatt's team accounted for factors such as race, CD4 count and previous AIDS-related illnesses, the increased death rate was still at least twice as high in women with protein in their urine. Systolic blood pressure was highly associated with microalbuminuria, but no other factors were, including whether or not a person was taking antiretroviral (ARV) therapy.

The authors acknowledge that their study only included women, most of whom were enrolled before the modern combination ARV era. Moreover, because most of the deaths were AIDS-related, it was difficult to tease out the individual contribution of microalbuminuria and also difficult to pinpoint the cause of this condition. Nevertheless, the authors concluded that testing for microalbuminuria could help predict which people with HIV are at increased risk for dying early and may be a good early warning sign of cardiovascular disease.

“Future studies should investigate whether microalbuminuria is associated with mortality in other HIV-infected populations and whether microalbuminuria testing is a cost-effective approach to identify patients who may benefit from earlier intervention,” the authors concluded.