Wednesday 29 June, 2016 13.00 EDT
Here’s Lookin’ at You, Kidneys
HIV and kidney disease — what you need to know
By Maggie Atkinson
FOR NINE YEARS, my motto was: “If it ain’t broke, don’t fix it.” That’s why, despite worsening lipodystrophy, I clung to the drug regimen that was keeping me alive. Why mess with success? Though my viral load was still below detection, my doctor was urging me to make a change. She wanted me to replace d4T (Zerit) with tenofovir (Viread) because of increasing evidence that d4T was responsible for my sunken cheeks and stick-like arms and legs. Even more sinister, it could be causing damage not apparent to the human eye.
So, why hadn’t I made the switch? I was concerned about safety. Tenofovir, a nucleotide analogue, is a member of a family of drugs known to cause kidney damage. A related drug, adefovir, was denied approval by the U.S. Food and Drug Administration (FDA) for treatment of HIV because of kidney problems. Although tenofovir was approved by the FDA and Health Canada based on clinical trials that showed no significant kidney problems, I am cautious about drugs.
I’ve had HIV since 1984 and have seen initial enthusiasms for drugs dissipate when adverse events, not apparent during clinical trials, appeared once the drug was approved and used by thousands of people. I remember in 1997 when we first discovered lipodystrophy in people with HIV/AIDS (PHAs) on protease inhibitors, a year after PHAs started using these drugs. So, until a drug has been on the market for a few years, I feel rather leery of it. But as the evidence mounted that tenofovir could be a safe replacement for d4T, I decided to make the switch. Many PHAs may now be on tenofovir because the latest treatment guidelines recommend it as part of the nuke backbone of antiretroviral therapy.
Before I began to take the new drug, I consulted my naturopath, Kenn Luby. He treats many PHAs in his Toronto practice and has helped me tremendously over the years. He made some changes to the supplements I take each day and, with that, I felt more confident starting tenofovir.
But only a few weeks later, I read an e-mail from NATAP, the National AIDS Treatment Advocacy Project, which concerned me. At the Conference on Retroviruses and Opportunistic Infections (CROI) in Boston last February, some researchers questioned how we measure kidney function and the rate of kidney dysfunction caused by HIV, tenofovir and other nukes. By only testing serum creatinine, as we currently do, we may be missing some PHAs — especially women and those over 50 — who are at risk for chronic kidney disease. I decided to find out what I could do to protect my kidneys.
The Urinary Tract
Every day the kidneys filter about 200 litres of blood. From this, about two litres of urine flow through the ureters to be stored in the bladder. The urine is ejected from the bladder and out of the body through the urethra. The male urethra ends at the tip of the penis; the female urethra ends just above the vaginal opening.
We have two kidneys — located in the back, one on either side of the spine, below the ribcage. They’re about the size of a fist and are shaped like kidney beans. Each kidney has about a million tiny blood-filtering units called nephrons. In each nephron, a network of tiny blood vessels called the glomerulus attaches to a small tubule. Blood is filtered in the glomerulus, and extra water and waste pass into the tubule and become urine.
I was under the impression that kidneys just cleaned the blood, but they do a lot more than that. The kidneys have four main functions:
- They balance body fluids.
- They balance body chemicals (ions or minerals), such as potassium, calcium, phosphorus and magnesium.
- They remove waste products, like urea (from the breakdown of protein from food) and creatinine (formed by normal muscle activity).
- They produce the following essential hormones:
- erythropoietin (EPO), which helps make red blood cells,
- renin, which regulates blood pressure, and
- the active form of vitamin D (D3), which helps maintain calcium for bones.
These are three different kidney-related problems that can affect PHAs. Their causes and treatments vary:
- Kidney stones result from the build-up of crystallized salts and minerals, such as calcium or drugs like indinavir (Crixivan), in the urinary tract. If kidney stones are large enough to block the kidney or ureter, they can cause severe abdominal and/or back pain. The stones usually pass through the urinary tract on their own, but in some cases they may need to be removed surgically. About 8% of people taking indinavir may get kidney stones. Fortunately they do not often cause kidney disease. Drinking lots of water can be helpful for preventing kidney stones and helping them to pass.
- Urinary tract infections (UTIs) occur in a part of or throughout the urinary tract, but mainly in the bladder and urethra. If left untreated or if they happen repeatedly, UTIs can travel up the ureters from the bladder and affect the kidneys. UTIs are usually caused by intestinal bacteria, such as E. coli, which are found in feces (poo). Women are more likely to get UTIs because they have shorter urethras than men. Sex, even with a condom, can transfer the feces to the urethra. Drinking lots of water and 8 ounces (240 ml) of cranberry juice cocktail a day (preferably at least 27% juice) and wiping from front to back after a bowel movement can help prevent UTIs.
- Fanconi’s Syndrome, sometimes caused by tenofovir, results in acidosis, loss of electrolytes, high creatinine levels and renal insufficiency. It can take months to recover, and, in some cases, kidney function may not return completely to its pre-treatment level. The best way to avoid it, according to Dr. Michelle Hladunewich, a kidney specialist from Sunnybrook Health Sciences Centre in Toronto, is to ensure that the dosage of tenofovir is adjusted appropriately before starting the drug. She says that kidney function, electrolytes, calcium profile and a urinalysis should be monitored every 3–4 months. “The key is to better judge renal dysfunction at the outset at least by utilizing one of the equations to estimate GFR (glomerular filtration rate) or by obtaining a creatinine clearance on a 24-hour urine collection.”
All of these kidney problems can lead to kidney disease.
Kidney diseases usually damage the nephrons and cause them to lose their filtering capacity. Kidney disease can be acute or chronic. Acute kidney failure can result suddenly from poisoning, infection or trauma. A gradual loss of kidney function, over years or decades, is called chronic kidney disease (CKD). If left untreated, kidney disease can result in impaired kidney function and, ultimately, kidney failure.
The rest of this article deals with chronic kidney disease, which is becoming increasingly more prevalent among PHAs.
Causes of CKD
Chronic kidney disease is defined as kidney damage (as evidenced by protein in the urine) or decreased kidney function (as evidenced by reduced GFR) for a period of three months or more. It is a condition caused by various diseases. According to the Kidney Foundation of Canada, as many as 1.9 million Canadians may have CKD but most are unaware of it.
The two most common causes of CKD are diabetes and high blood pressure. Some other causes are listed below:
- The third most common type of kidney disease is glomerulonephritis (inflammation of the glomeruli and the kidney) — a group of diseases in which the immune system mistakenly attacks the glomeruli.
- Inherited diseases, such as polycystic kidney disease, which causes large cysts to form in the kidneys.
- Reflux nephropathy. Some people are born with an abnormal junction of the bladder and the ureter, which causes urine to flow back up to the kidney. This causes infections and scarring of the kidneys, which can lead to kidney failure.
- HIV and other diseases that affect the body’s immune system. HIV-associated nephropathy usually begins with heavy proteinuria (large amounts of protein in the urine) and progresses rapidly (within a year of detection) to end-stage renal disease if left untreated.
- Obstructions caused by kidney stones, tumours or an enlarged prostate gland.
- Repeated urinary tract infections.
- Unresolved acute kidney failure.
- Drugs. Long-term or heavy use of painkillers and anti-inflammatories, such as acetaminophen (Tylenol), acetylsalicylic acid (Aspirin), ibuprofen (Advil, Motrin) and naproxen (Aleve, Anaprox). Combining these meds with caffeine can further damage your kidneys. Street drugs such as heroin, cocaine and amphetamines can also cause kidney damage.
Diagnosis of CKD
In the later stages of kidney disease, people may have some of the following symptoms:
- more fatigue
- less energy
- trouble thinking clearly
- poor appetite
- trouble sleeping
- dry, itchy skin
- muscle cramps at night
- swollen feet and ankles
- puffiness around the eyes, especially in the morning
- a need to urinate more often, especially at night
However, there are usually no symptoms of kidney disease until the damage is severe. That is why it’s important to be tested.
Testing for CKD
According to Dr. Hladunewich, everyone with HIV/AIDS should be screened yearly for kidney disease because PHAs are “proving to be a fairly high-risk group.” The first step is a blood test for serum creatinine and a urine test to measure protein (for the albumin:creatinine ratio). These tests are used to assess both kidney damage and kidney function.
Kidney damage is measured by the amount of protein in the urine, because when the kidneys are damaged, protein leaks into the urine.
Measuring kidney function is more controversial. Doctors and researchers normally use the serum creatinine test to measure kidney function indirectly, but a study presented at CROI suggested that this test alone might not be sufficient. Instead, the creatinine test result should be used in a mathematical equation, along with age, race and gender, to calculate the estimated glomerular filtration rate (estGFR) — an estimate of how well the glomeruli are filtering. Sometimes you also read about the creatinine clearance rate, a similar test of kidney function.
There are two well-known equations used to calculate estGFR in adults — Cockroft-Gault and the MDRD Study. San Francisco researchers compared serum creatinine to estGFR (using the MDRD Study equation) in more than 1,600 patients in CHORUS, a large, observational U.S. cohort. Using the serum creatinine test, none of the 136 women in the study showed kidney dysfunction, but using the estGFR equation, 10 (7%) of them had moderate kidney disease. Also, among the 307 people over 50 years old, the creatinine test results indicated that 12 (4%) had moderate kidney disease — the estGFR showed that 66 (21%) did. Overall, using the creatinine test, 1.9% of patients showed moderate kidney dysfunction, while that figure increased to 13.8% with estGFR. The take-home message: Perhaps we should be using the estGFR measurement in studies and in the clinic.
If these initial lab tests indicate kidney damage or reduced kidney function, the doctor may recommend an ultrasound or X-ray to see whether the shape or size of the kidneys is abnormal. A CT-scan or MRI might also be done. These tests are called renal imaging. The doctor may also do a kidney biopsy — a procedure in which a needle is used to extract small pieces of tissue from the kidneys for examination under a microscope.
Certain people may need additional testing, such as a 24-hour urine collection, if they’re over 70, very thin, obese or vegetarian, or if they take certain drugs, like Bactrim / Septra or cimetidine (Tagamet) because these drugs can affect your serum creatinine levels. Excessive exercise or taking creatine supplements may also increase serum creatinine levels.
In the final stage — end-stage renal disease — the kidneys stop working and dialysis or a transplant is needed. Dialysis involves using a machine or other artificial device to remove the excess water and wastes from the body. Organ transplants are rarely performed on PHAs in Canada, although they are done in the U.S.
Treatment of CKD
Medication, diet, supplements, exercise and drug dosage adjustments may help prevent or delay kidney failure. The treatment will depend on the stage of kidney disease, the cause, symptoms and other health problems.
There isn’t a medication for CKD. You can only treat the causes and the symptoms. For example:
- If you have high blood pressure, one of the causes of CKD, your doctor may recommend blood pressure medication.
- If you have anemia, which can be brought on by kidney disease, you may need synthetic epoetin (EPO) or iron.
According to Diana Johansen, dietician at the Oak Tree Clinic, the Women and Family HIV Centre for British Columbia, when a person has normal kidney function their diet is generally not adjusted to prevent kidney disease.
When the kidneys are unable to function properly, various substances build up in the blood to undesirable levels. Dietary changes aim to reduce the intake of foods that create more of these substances. In the early stages, you may need to reduce the amount of protein, phosphorus and sodium in your diet. Later on, in advanced kidney disease, you may also need to reduce potassium and fluids.
Speak with your doctor or a renal dietician before making any changes to your diet.
- Protein is found in meats, dairy products, dried beans, soy products and nuts.
- Dairy products, dried beans and peas, nuts, soft drinks, cocoa and beer are high in phosphorus.
- Since sodium can raise your blood pressure, you may need to cut down on salt and canned, pickled or processed foods. Avoid salt-substitutes that contain potassium.
- High sources of potassium are bananas, dried fruits, orange juice, melons, dried beans, nuts, potatoes and tomato sauces. In advanced kidney disease, high potassium levels can affect the heart rhythm.
- High blood cholesterol levels can also be associated with kidney failure. A low-fat diet, exercise and lipid-lowering medications can help reduce cholesterol levels.
I wondered about water intake. Dr. Hladunewich warned that too much water could be dangerous for someone with significant kidney disease. It’s best to determine your kidney function through the appropriate testing measures. If you have reduced kidney function, you may need to consult a renal dietician as well as a nephrologist for advice about your diet. Even something that might normally seem harmless, like drinking water, can potentially pose problems if your kidneys aren’t working properly. That said, as long as your kidneys are functioning normally, you should make sure to get enough water every day.
Lark Lands, a medical journalist and longtime AIDS treatment educator and advocate, says there isn’t any “magic bullet” for supporting the kidneys but there are some basics that can help. Here are her recommendations:
- The very minimum that every PHA should take is a multivitamin, an antioxidant formula and anti-inflammatory fish oil.
Take plenty of antioxidants. All the things that protect you against heart disease also help protect the blood vessels in the kidneys. Examples of antioxidants: vitamin E, vitamin C, bioflavonoid complex, carotenoid complex, selenium,
N-acetyl-cysteine (NAC), coenzyme Q10, alpha-lipoic acid.
- Take plenty of natural anti-inflammatories. Inflammation plays a key role in the artery-damaging and -blocking process. By countering that, you may also help prevent kidney problems due to scarring and blocking of the tiny blood vessels. Avoid fats that promote inflammation, such as partially hydrogenated oils (“trans fats”) and polyunsaturated vegetable oils. Here are some examples of naturally anti-inflammatory foods and seasonings: garlic, ginger, curcumin, bioflavonoid-rich fruits like dark berries, and omega-3 fatty acid–rich foods like fatty fish, flaxseed and walnuts. (Garlic may interact with some drugs, so speak with your doctor about possible interactions with your meds.)
- Protect yourself against the blood sugar effects of HIV and HAART because elevated blood sugar can damage the kidneys over time. Nutrients that help maintain normal cellular insulin sensitivity and improve glucose tolerance may help, such as alpha-lipoic acid, the B vitamins (especially B6) and the minerals chromium and zinc.
With your doctor’s permission, start a regular exercise program that includes strength, flexibility and cardiovascular training. Exercise is important, especially when you’re HIV positive and on antiretroviral therapy, for many reasons, including:
- It may prevent or help with diabetes, high blood pressure, heart disease, chronic kidney disease, cancer, osteoporosis and arthritis.
- It can help ease restless leg syndrome, sometimes associated with kidney disease.
- It will help to get rid of excess fluid and toxins through the skin.
Drug Dosage Adjustments
You may need to change your drug dosages. Septra / Bactrim, tenofovir and the nucleoside drugs (except abacavir / Ziagen) might need to be reduced. Oddly enough, although indinavir can affect the kidneys, it is not metabolized through the kidneys, so dosage adjustments are not required.
Some drugs that may harm the kidneys:
- tenofovir (Viread) – for treating HIV; there is some early evidence that combining tenofovir with ddI (Videx) may be related to more kidney damage than tenofovir alone
- Hepsera – for hepatitis B
- cidofovir (Vistide) and foscarnet (Foscavir) – for CMV retinitis
- IV pentamidine – for PCP treatment
- aminoglycosides – a class of antibiotics for serious infections (includes Amikacin, Gentamicin)
- rifampin – for tuberculosis
- acyclovir (Zovirax) and valacyclovir (Valtrex) – for herpes and shingles
- NSAIDs (non-steroidal anti-inflammatory drugs), such as acetylsalicylic acid (Aspirin), ibuprofen (Advil, Motrin), acetaminophen (Tylenol)
- Septra/Bactrim – for PCP prevention or treatment
If you are taking more than one of these drugs at a time, it’s a good idea to have your kidney function monitored more often.
The Kidneys are All Right
After learning about what can go wrong with the kidneys, I was nervous about my first checkup three months after starting tenofovir. But everything was fine. My creatinine level was slightly higher than when I started, and when I took that result and calculated my estGFR it was 89, which is only a mild decrease in kidney function. There’s no protein in my urine, so I don’t have kidney damage. I don’t have kidney disease but I’ll need to be checked every few months. In the meantime, I’ll do what I can to prevent diabetes, high blood pressure and high cholesterol, and to protect my kidneys. Here are some things you can do to protect yours:
- Have your blood pressure, urine and blood (including creatinine and cholesterol) checked regularly.
- Control high blood pressure (it should usually be less than 130/80).
- Try to quit or cut down on smoking.
- Exercise regularly.
- Maintain a healthy weight.
- Avoid excess alcohol (more than one drink a day).
- Avoid street or recreational drugs.
- Get enough sleep.
- Avoid heavy or long-term use of painkillers (low-dose Aspirin for heart disease is OK).
- If you have diabetes, maintain good control of your blood sugar.
Stages of Chronic Kidney Disease
Based on the kidney damage and kidney function tests, CKD is divided into five stages. Not all people progress from Stage 1 to Stage 5. If you have any of the risk factors below, you may be at increased risk of developing chronic kidney disease and should be tested for it.
|At increased risk||Risk factors for kidney disease: diabetes; high blood pressure; family history; age over 50; ethnic origin Aboriginal, Asian, South Asian, Pacific Island, Caribbean, African or Hispanic; being HIV positive||More than 90|
|1||Kidney damage (protein in the urine) with normal kidney function (estGFR)||More than 90|
|2||Kidney damage (protein in the urine) with mild decrease in kidney function (estGFR)||60 to 89|
|3||Moderate decrease in kidney function (estGFR) with or without kidney damage (protein in the urine)||30 to 59|
|4||Severe decrease in kidney function (estGFR)||15 to 29|
|5||Kidney failure or end-stage renal disease (dialysis or kidney transplant needed)||Less than 15|
(adapted with permission from the National Kidney Foundation)
Learn the Lingo
Doctors who specialize in kidney problems are called nephrologists (from the Greek word for kidney, nephron).
Doctors who specialize in problems of the organs and tubes that transport urine from the kidneys to outside the body are called urologists.
Anything related to the kidneys may be called renal, from Latin renes, meaning kidneys.
Screen Your Beans
The National Kidney Foundation is concerned that many people may be in the early stages of chronic kidney disease (CKD) and not know it. It recommends that adults who are at risk for kidney disease use the calculator on its website to determine their estGFR. This calculator is a screening tool to inexpensively identify people at risk for CKD. estGFR is not an absolute lab test result; it’s only an estimate of kidney function.
Unless you live in B.C., where the labs now provide the GFR result, you can ask your doctor to calculate your estimated GFR. Or, if you know your creatinine level, you can use the GFR calculator (www.kidney.org/professionals/kdoqi/GFR_calculator.cfm). It uses an abbreviated form of the MDRD equation. Fill in your creatinine test result, age, sex and race to estimate your GFR. Check the box for “umols/l” when inputting your creatinine level because that’s the international system unit used in Canada to measure creatinine.
If your estGFR measures less than 60, discuss your results with your doctor.
The Kidney Connection
The National Kidney Foundation www.kidney.org
The Kidney Foundation of Canada www.kidney.ca
The National Kidney Disease Education Program www.nkdep.nih.gov/index.htm
Life Options www.lifeoptions.org (sponsored by Amgen Inc., which markets a number of products in the field of nephrology)
Kidney School www.kidneyschool.org (also sponsored by Amgen Inc.)
HIV InSite www.hivinsite.com(search for “renal”)
Lark Lands’ Positively Well www.larklands.net (see Treatment Fact Sheets)
CATIE Fact Sheet on tenofovir (Viread) http://www.catie.ca/en/fact-sheets/nukes/tenofovir-viread