Kidneys Take Center Stage

Back in the early 2000s I faced some kidney problems, so, in my usual determined way, I set out to learn more about the kidneys and what I could do to protect them. I wrote about that experience in "Here's Lookin' at You, Kidneys" in the Fall/Winter 2005 issue of this magazine. During the past six years, much has changed for me and in our understanding of HIV and the kidneys, so it's time for an update.

The face of kidney disease in people with HIV is changing. Thanks to antiretroviral therapy (ART), we are surviving longer but we are also experiencing higher-than-normal rates of high blood pressure, diabetes and high cholesterol, which can all contribute to the development of kidney disease. People with HIV also have other risk factors that make us more susceptible: HIV can infect kidney cells and cause disease. Also, some medications taken by people with HIV (including certain antiretrovirals) can harm the kidneys.

Given all these factors, perhaps it shouldn't be surprising that about one-third of people with HIV in Canada have some kidney impairment. Because kidney function declines with age, this number will likely increase as more of us live longer. The good news is that we can do something about certain risk factors. But before we look at those risk factors and what we can do about them, let's take a moment to talk about the kidneys and what can go wrong with them.

Damaged Filters

Many people know that the kidneys -- two bean-shaped organs located on either side of your spine about midway up your back -- filter the blood and expel waste from our bodies, in the form of urine. But they do a lot more than that. The kidneys have four main functions:

1. They remove extra fluid from the blood.
2. They balance minerals in the blood.
3. They remove waste products.
4. They produce essential hormones that help us make red blood cells, regulate blood pressure and maintain calcium for our bones.

With kidney disease, it is usually the kidneys' filtering units -- the nephrons, which eliminate waste and excess fluid -- that are damaged. When this happens, dangerous levels of fluid and waste can accumulate over time in the body. Swollen hands and feet, fatigue, urinating more or less often than usual and cloudy or dark-coloured urine are some of the signals of possible problems, although there are often no obvious signs at first.

Kidney disease can be either acute or chronic. People with HIV are at higher risk for both. If we've had one, then we're more prone to develop the other.

When a person's kidney function declines quickly, this is called acute kidney injury. It can result from poisoning, infection or injury. A recent US study showed that in most cases of acute inflammation of the nephrons in people with HIV, drugs were to blame -- most commonly, nonsteroidal anti-inflammatory drugs (such as ibuprofen) and the antibiotic combo Septra/Bactrim. In only three out of the 21 cases of acute kidney injury due to medications, antiretrovirals were the culprit.

Chronic kidney disease involves a more gradual loss of kidney function and is defined as kidney damage that lasts for three months or more. The two most common causes of chronic kidney disease are diabetes and high blood pressure. Between two and 10 percent of people with HIV have chronic kidney disease.

When left untreated, kidney disease can be serious, even fatal, due to imbalances in blood levels of minerals and hormones or the build-up of fluid in the body. In extreme cases, dialysis or organ transplant is needed to replace the function that the kidneys normally perform. (People with HIV can now get kidney transplants in British Columbia, Ontario and Quebec.) Both acute and chronic kidney disease are associated with greater risk for cardiovascular disease and death among people with HIV than among HIV-negative people. Chronic kidney disease has also been linked to bone disease and cognitive impairment.

Yellow Lights

Who runs a higher risk of chronic kidney disease? People with HIV who can check off one or more of the following are at greater risk:

A low CD4 count or high viral load
People with HIV whose CD4 count is lower than 200 or whose viral load is greater than 4,000 are at increased risk.

African ancestry
Kidney failure due to HIV infection in the kidney cells (HIV-associated nephropathy, or HIVAN) is more common in people of African descent because of a genetic predisposition (though it is not more common in people of Ethiopian descent).

Hepatitis co-infection
Hepatitis can damage the kidneys as well as the liver.

Alcohol and drugs
Consuming large amounts of alcohol or street drugs, such as cocaine, heroin and amphetamines, can damage the kidneys.

High cholesterol, high blood pressure and diabetes
People on ART who have high cholesterol, high blood pressure or diabetes have a higher chance of seeing their kidney function decline.

Older age
Every year after the age of 30, the average person loses one percent of their kidney function. Since accelerated aging has been seen in people with HIV, we may be even more susceptible to chronic kidney disease as we age.

Inflammation
People with HIV, even those with an undetectable viral load, have higher markers of inflammation in their blood than HIV-negative people. Inflammation is associated with a greater risk of both cardiovascular and kidney disease. Aging and excess body fat can also cause chronic low-level inflammation.

Antiretrovirals
The antiretrovirals tenofovir (Viread, also in Truvada, Atripla and Complera), atazanavir (Reyataz) and indinavir (Crixivan) can cause kidney damage. Tenofovir can have acute and chronic effects on the kidneys. Fortunately, less than one percent of people who take tenofovir experience serious kidney injury. Atazanavir can cause kidney stones and interstitial nephritis, a condition in which the spaces between the nephrons swell. One study found that atazanavir was associated with a 22 percent increase in the incidence of chronic kidney disease per year of exposure; when taken with tenofovir, that rose to 41 percent. Indinavir, not used as much anymore, can cause crystals, kidney stones and interstitial nephritis to develop.

Transplant meds
Medications that are increasingly being used not only after a transplant but also to treat inflammation can be a risk factor as well.

Because most people have no symptoms in the early stages of chronic kidney disease, regular testing is critical. Your doctor may order one or more of the following simple tests:

• a urine test to look for protein in the urine, which can be a sign of kidney damage. Levels of protein, or albumin, that are higher than normal for three months or more indicate chronic kidney disease.
• a blood test to measure creatinine, a waste product from the muscles that shows up in the blood when the kidneys aren't able to get rid of it. The result from this test is used to estimate your GFR (glomerular filtration rate), which tells you and your doctor how well your kidneys are doing their job (see Getting to Know GFR, below).

Fortunately, these tests are usually part of the standard set that your doctor orders during checkups and physical exams.