Kidney toxicity including kidney stones (renal toxicity)

Associated drugs: Drugs cleared by the kidney with potential for renal toxicity include AZT, 3TC, FTC, tenofovir, Truvada, Atripla, atazanavir and maraviroc. Kidney stones have been commonly reported with indinavir (Crixivan) and rarely with atazanavir and efavirenz.

The kidney is a major organ that:

• Filters salts and impurities from your blood to be excreted in urine.
• Regulates blood pressure.
• Regulates oxygen levels in blood.
• Helps bone health by processing vitamin D.

Kidney function can be affected by HIV and other illnesses, including diabetes.

It generally reduces as we get older.

Starting HIV treatment can improve reduced kidney function that is related to HIV. However, several HIV drugs can affect your kidneys and these need to be considered individually.

Symptoms

Symptoms of reduced kidney function include:

• Needing to urinate more often or less often
• Nausea and/or vomiting
• Feeling tired
• Itchy skin
• Muscle cramps
• Loss of appetite
• Swollen hands or feet or numbness

Tenofovir-related toxicity

Concerns about kidney-related side effects mainly relate to tenofovir (Viread) and the combinations that include tenofovir (Truvada and Atripla).

This is because tenofovir is now one of the most widely used HIV drugs and because it is mainly processed by the kidneys.

With so many people using tenofovir-based combinations, the research supports this being a safe and well-tolerated drug. Side effects, if they occur, are usually short-term and reversible.

Some studies clearly link tenofovir to an increased risk of kidney-related side effects. These include changes in laboratory test results such as reduced creatinine clearance, low phosphate levels and increased proteinuria (high protein levels in urine). The importance of these changes in markers in the long-term is unknown.

Side effects also include clinical complications including Fanconi’s Syndrome that are usually quickly reversible when tenofovir is discontinued.

These risks are likely to be more important for people who already have reduced kidney function.

HIV-related kidney disease (including HIVAN) improves after starting combination therapy, even when this includes tenofovir. Howewer, markers of kidney function drop slightly in people who have normal kidney function when they start treatment.

The risk of kidney toxicity may be higher if you are using other drugs cleared by the kidney, or if you have used these drugs in the past. There is a caution against using other such drugs with tenofovir.

This concern includes using tenofovir and ddI together in combination with a boodted-PI. Until this interaction is understood, these two drugs are not recommended in the same combination.

Tenofovir is included in the combination pills Truvada (tenofovir+FTC) and Atripla (efavirenz+tenofovir+FTC).

In people who have HIV-related kidney disease, HIV treatment is recommended and is likely to improve kidney function.

Drugs that are metabolised by the kidneys (including AZT, 3TC, FTC tenofovir and maraviroc) include recommendations for using reduced doses in people whose kidney function is reduced (usually indicated by creatinine clearance less than 60 mL/min).

See the individual prescribing information provided with each of these drugs.

Kidney stones

Indinavir used to be a widely used protease inhibitor, but hag several side effects including blocked kidneys. In 2007 there were several case reports of kidney stones that contained high levels of atazanavir or efavirenz, showing that this can be a rare side effect with other HIV drugs.

The detailed information relating to kidney stones and indinavir is only available in this online edition.

Indinavir-related kidney stones

Crystalluria = crystals in urine; nephrolithiasis: nephro = kidney, lithiasis = stone formation.

Indinavir is now a rarely used protease inhibitor.

Better newer and easier to tolerate protease inhibitors have replaced indinavir. It is strongly recommended that if you are currently taking indinavir you should talk to your doctor about changing to an alternative drug.

One side effect included kidney stones – largely avoided by drinking an additional 1-2 litres of water daily.

Indinavir originally was taken three times a day on an empty stomach, but now it is mainly prescribed with ritonavir. Ritonavir boosts the levels of indinavir so that it can be taken twice daily, with or without food.

Indinavir is mainly processed through the kidneys (most drugs are cleared through the liver) and one of the side effects is a build up of indinavir crystals in the kidneys.

About 20% of people will have indinavir crystals, and 4– 10% of people will show symptoms of kidney blockage. This is why you need to drink at least 1.5 litres of water a day (about three pints or six large glasses), especially just after taking your medications. This helps the tiny crystals of indinavir flush cleanly through your kidneys.

The risk of a blockage is related to the peak levels of indinavir. If the drug levels are too high, or if you don’t drink sufficient water, then a blockage can be caused because the crystals can accumulate as a sludge.

This is not the same as a real kidney stone, but the symptoms are still very similar: stomach cramps, bladder pain and, most predictably, a dull pain or ache which can quickly develop into an extremely sharp pain in your lower back. Dark urine, or urine containing blood can indicate kidney stones.

A kidney blockage is very painful and very serious and requires immediate attention. If untreated a blocked kidney can lead to irreversible damage.

A family history of kidney stones may increase the risk of this side effect – and require additional fluid intake.

If you use higher indinavir doses (usually 800 mg or 600 mg) with smaller doses of ritonavir (100 mg or 200 mg) then you will have a higher peak level of indinavir and greater hydration may be important.

In hot weather, and after exercise, increase your water intake even more. Tea, coffee and alcohol will cause you to dehydrate, so do not include these when adding up your fluid intake.

Treatment for indinavir-related kidney stones

If you have these symptoms, try to drink as much water as you can (and sit upright or stand up to try to help any blockage to clear).

Acidic drinks like orange juice and cranberry juice can help as indinavir is more soluble in acidic conditions. If the pain gets worse seek medical advice at your hospital or Accident and Emergency Unit. When you get to hospital, tell the doctor that you are on a medication that can cause this. A regular x-ray, which is routine for kidney stones, won’t show indinavir blockage.

The blockage can be diagnosed by an ‘IVU’ x-ray – where you are given a small amount of iodine solution injected into your blood, which is then followed by an x-ray every hour to check how well your body processes this fluid.

With an indinavir-related blockage, treatment is through increasing fluid intake (by intravenous drip and drinking) together with pain killers to control the pain.

Using indinavir again

Once you have cleared the problem it is safe to continue to take indinavir again – especially if it was working well for you – but make sure you keep drinking sufficient fluid.

Having the levels of indinavir checked with a blood test, especially if you are using indinavir with ritonavir (see therapeutic drug monitoring) is strongly recommended.