HIV and Your Kidneys

Weighing a delicate six ounces each—that’s less than 0.5 percent of our total body weight—the kidneys play a number of vital roles. For those living with HIV, this includes breaking down some of the medications needed to keep the viral load low and CD4 counts high. Unfortunately, like other vital organs in the body, the kidneys are not immune to diseases that can impair their ability to function. About 20 million Americans—one in nine U.S. adults—have kidney disease, and another 20 million more are at risk. Studies also show that nearly one third of all HIV-positive people have abnormal amounts of protein in their urine—a sign of potential kidney trouble.

As people with HIV continue to live longer lives thanks to antiretroviral (ARV) therapy, experts reckon that kidney disease will remain a common and potentially serious health threat. Fortunately, much has been learned about HIV and kidney disease in recent years, including the best ways to screen for it, prevent it and treat it.

What do the kidneys do?
 
Most people have two of these bean-shaped organs (nearly one in 750 people are born with only one kidney). They’re about the size of a fist and are located halfway up the back on both sides of the spine. Often, the left kidney is positioned up to an inch higher than the right kidney.

The kidneys contain millions of nephrons, tiny units made up of blood vessels (glomeruli) and fluid-collecting tubes (tubules), sifting about 200 quarts of blood a day. Over a 24-hour period, they filter the entire volume of blood 30 to 40 times, extracting two quarts of waste products and extra water that’s removed in the form of urine.

In addition to acting as filters, the kidneys keep track of various substances in the blood and, if necessary, release hormones to help replenish missing stock. They produce erythropoietin (EPO) to stimulate red blood cell production, renin to help control blood pressure, and the active form of vitamin D (calcitriol) to maintain calcium levels for healthy bones

What is kidney disease?
 
When experts talk about kidney disease, they usually refer to "renal function." According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), people with two healthy kidneys have 100 percent renal function, which is actually more than you need. This is why people can survive just fine with one kidney.

If renal function falls below 25 percent, serious health problems can occur. And if it drops below 10 to 15 percent, a person will not live long without dialysis or a kidney transplant.

While reduced renal function has several different causes, there are generally three different types of kidney disease:

• Acute renal failure (ARF): This is when serious damage to the kidneys happens very quickly. An accident might cause this, as can some medications or poisons. In some cases, ARF can lead to permanent kidney damage.

• Chronic kidney disease (CKD): Most kidney problems, including those seen in HIV-positive people, happen slowly. CKD may be "silent" for many years, meaning that it doesn't cause any noticeable symptoms but may still be damaging the kidneys. CKD, left unchecked, can increase the risk of a heart attack or stroke. Routine laboratory testing can help detect CKD in the early stages, before it causes permanent kidney failure.

• End-stage renal disease (ESRD): This is total (or nearly total) kidney failure that cannot be reversed. Patients with ESRD require dialysis or a kidney transplant to stay alive. Of note, a study conducted by Johns Hopkins University in Baltimore suggests that the risk of ESRD among HIV-positive blacks is almost 12 times higher than in the HIV-negative black population—and that the risk may actually be increasing.

What causes kidney disease?
 
HIV-positive people may face a number of risk factors for kidney disease.

First, it’s important to recognize that some people are naturally at a higher risk for kidney disease. These include people with a family history of kidney disease (for example, if their mother, father or other immediate relative has certain types of kidney problems). Blacks, Latinos, Pacific Islanders and Native Americans also face an increased risk of kidney problems.

Some risk factors, however, can be modified or reduced. These include HIV-related causes of kidney disease, such as certain HIV medications as well as HIV infection of the kidneys. Other modifiable risk factors include high blood pressure and diabetes.

The following reviews the most important modifiable kidney disease risk factors HIV-positive people need to know about.

• Increased blood pressure (hypertension)
  Hypertension, or high blood pressure, is a leading cause of kidney disease. It can also be a sign that kidney health is already impaired. Hypertension can damage the small blood vessels in the kidneys and, in turn, prevent them from properly filtering waste.
  It's still not clear if HIV-positive people are more likely to suffer from high blood pressure than their HIV-negative counterparts. However, there's little data to suggest that they are less likely to experience it. And with HIV-positive people living longer, thanks to the widespread use of ARV treatment, non-HIV health problems like hypertension become increasingly likely.
  It's worth noting that blacks make up 49 percent of the HIV/AIDS cases in the United States And among blacks 20 and older, regardless of HIV status, about 43 percent of men and 47 percent of women have high blood pressure.
  Among Latinos, who make up 18 percent of the HIV/AIDS epidemic in the United States, one study documented high blood pressure in 29 percent of the men and 31 percent of the women of Mexican descent.

• Diabetes
  Diabetes is a disease that prevents the body from breaking down glucose (sugar) correctly. This causes glucose levels to remain high in the bloodstream and ultimately damage the nephrons in the kidneys. This can lead to a condition called diabetic nephropathy, a very common form of kidney disease.
  HIV-positive people, especially those on protease inhibitor therapy, are at an increased risk of glucose-related problems. In a 2004 report published by the Multicenter AIDS Cohort Study, HIV-positive men on ARV therapy were three times more likely to be diagnosed with diabetes over a four-year period, compared with HIV-negative men.
  It's also worth noting that blacks and Latinos are nearly two times more likely to have diabetes than whites of similar age. This increases their chance of developing complications like chronic kidney disease.

• HIV-associated nephropathy (HIVAN)
  A handful of diseases can attack the tiny blood vessels in the kidneys, a notable one being HIV-associated nephropathy (HIVAN). It's caused by HIV infection of the kidneys, which can damage the lining of the glomeruli and tubules. Left untreated, it can lead to ESRD in six to 12 months. HIV treatment can effectively prevent and treat HIVAN.
  While it's not really clear how many HIV-positive people suffer from HIVAN, it usually occurs among black men. Low CD4 cell counts and a family history of renal disease are also risk factors for HIVAN.

• Medications
  A small number of medications, including those used by HIV-positive people, list acute renal failure (ARF) as a possible side effect. Experts advise HIV-positive patients with a history of ARF or chronic kidney disease (CKD) to use these drugs with caution—and to have a health care provider adjust the doses.
  Medications for opportunistic infections (OIs). Some meds used to treat fungal infections, Pneumocystis pneumonia (PCP) and cytomegalovirus (CMV) are known to rapidly shut down the kidneys in some patients.
  HIV medications. The protease inhibitors Crixivan (indinavir) and less frequently Reyataz (atazanavir) can cause kidney stones. Nucleoside reverse transcriptase inhibitors (NRTIs), notably Zerit (stavudine) and Videx/Videx EC (didanosine), have been known to cause a buildup of acid (lactic acidosis) in the blood that can lead to kidney failure and other serious problems.
  Another member of the NRTI class that can cause kidney problems is tenofovir disoproxil fumarate (TDF), the active ingredient in Viread and one of the drugs in Truvada, Atripla, Complera and Stribild. TDF can accumulate in the kidney tubules, effectively blocking their function. Fortunately, rates of renal failure have been quite low, on the order of 0.5 to 1.5 percent of tenofovir takers.
  Pain medications. NSAIDS, such as over-the-counter Advil (ibuprofen) and Aleve (naproxen), are frequently recommended and used to relieve pain. In some people they can cause an allergic reaction known as interstitial nephritis, which can decrease blood flow inside the kidneys.
  Herbal therapies. Finally, some herbal therapies—notably those containing aristolochic acid (found in the flowering plant Dutchman's pipe, formally called Aristolochia)—have been shown to cause kidney damage and may be responsible for some cancers in the urinary tract. In fact, the U.S. Food and Drug Administration recommends that people do not take herbal therapies containing aristolochic acid—including products with the words "Aristolochia," "Bragantia" or "Asarum" listed as ingredients on the label. Click here for a partial list of products to avoid.

What are the symptoms of kidney disease and how is it diagnosed?
 
Symptoms of kidney disease include:

• The need to urinate more or less
• Foamy urine, caused by too much protein in the blood
• Pink or cola-colored urine, caused by blood in the urine
• Fatigue
• Swollen feet or hands
• Trouble concentrating
• Darkened skin
• Muscle cramps

It's important to remember that some people, especially those in the early stages of kidney disease, do not have any noticeable symptoms. In turn, it is important to conduct lab tests on a regular basis to look for certain abnormalities (these tests are also used to look for kidney disease in people with symptoms). These tests include:

• Urine testing (urinalysis): When kidneys stop working correctly, they start removing healthy protein from the blood, excreting it as waste. Your health-care provider, or the lab that tests your blood, can check for protein by using a dipstick in a small urine sample. Urinalysis is a very common and simple lab test and, depending on your health-care provider, a routine component of HIV care.

• Glomerular filtration rate (GFR) using creatinine measurements: Creatinine, found in the blood, is a waste product created by the normal breakdown of muscle cells. High levels of creatinine don't say much, as levels vary considerably and can be affected by diet. In turn, experts recommend calculations like GFR that use the creatinine measurement along with variables such as weight, age and values assigned for sex and race. The National Kidney Foundation and other expert groups consider GFR to be the best measurement of kidney function. 

• Blood urea nitrogen (BUN): After cells use protein, the waste is converted to urea, a compound that contains nitrogen. Healthy kidneys remove urea from the blood; diseased kidneys have a harder time performing this task. Another simple bood test may determine if levels of urea nitrogen are higher than normal in the blood, which may indicate renal problems.

It's also important to keep an eye out for signs and symptoms of high blood pressure and diabetes, the most common causes of kidney disease. Using a special cuff, your doc can keep an eye out for hypertension and, if necessary, recommend treatment or lifestyle modifications to keep your blood pressure below 130 over 80. Routine lab testing can also help you and your health-care provider keep an eye on your glucose levels in your blood.

Do I need to be checked for kidney problems?
 
The Infectious Disease Society of America (IDSA) recommends that all HIV-positive people be evaluated for kidney disease at the time of their diagnosis using urine and blood samples. Those at high risk for renal impairment—such as people with high blood pressure, diabetes, CD4 counts below 200, viral loads above 4,000 and hepatitis C virus (HCV) coinfection—should be checked by their health care providers every year, even if they appear to have normal kidney function. Twice-yearly checkups are recommended for high-risk patients who are taking medications that can potentially damage the kidneys, such as Crixivan and meds containing tenofovir DF (Viread, Truvada, Atripla, Complera and Stribild).

How is kidney disease treated?
 
The IDSA recommends that HIV-positive people who have signs or symptoms of kidney problems be referred to a kidney specialist (nephrologist) for care. Treatment options can vary considerably, depending on the cause (or causes) of a person's kidney disease and any other health issues. Some treatment possibilities include:

• Reduce blood pressure: Medications such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are frequently prescribed to bring blood pressure under control in people with kidney disease. Other medications, along with dietary and lifestyle changes (such as exercise), may be necessary as well.

• Manage diabetes: HIV-positive people with diabetes and kidney disease will need to rigorously watch their blood glucose levels and work closely with their health-care providers to keep these levels under control.

• Modify diet: Some parts of a normal diet may speed up kidney failure. It may be necessary to limit protein, cholesterol, sodium and potassium; working with a dietitian or nutritionist can be helpful.

• Stop smoking: Not only does smoking increase the risk of kidney disease, it contributes to deaths from strokes and heart attacks in people with kidney disease.

• Treat HIV: Kidney disease is climbing as one of the most common causes of illness and death among people living with HIV. Antiretroviral (ARV) treatment typically improves kidney function, and it may protect against HIV-related cellular inflammation in the kidneys. This is one of the reasons that the Department of Health and Human Services' HIV treatment guidelines recommends beginning ARV therapy before CD4 cell counts fall below 500.

• Treat HIVAN: IDSA stresses that people with HIV-associated nephropathy should be treated with ARV therapy, regardless of their CD4 count or viral load, once the disease is diagnosed.

• Check medications and their dosages:People with a history of kidney disease may need to avoid some medications, including certain HIV drugs. Doses of medications that are broken down (metabolized) by the kidneys may need to be altered to reduce the risk of side effects and further kidney damage.

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