Kidney toxicity including kidney stones (renal toxicity)

Associated drugs: Drugs cleared by the kidney with potential for renal toxicity include AZT, 3TC, FTC, tenofovir DF, Truvada, Atripla, atazanavir and maraviroc. Many combination pills contain tenofovir DF. Kidney stones can occur with atazanavir and efavirenz.

The kidney is a major organ with several important functions.

• Filtering salts and impurities from your blood to be cleared in urine.
• Regulating blood pressure.
• Regulating oxygen levels in blood.
• Helping bone health by processing vitamin D.

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

Kidney function 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

Monitoring kidney function

Routine tests monitor kidney function before and after treatment.

High levels of protein or a waste product called creatinine, indicate that the kidneys might not be working well.

Results from blood and urine tests calculate how well your kidneys are processing creatinine.

Dipstick urine tests

Urine tests can show abnormal levels of protein, blood, white blood cells, glucose and markers for diabetes.

Blood tests

Blood tests can measure protein and creatinine and are used to estimate glomerular filtration rate (eGFR).

eGFR

Estimated GFR is a common way to grade kidney function. It is measured in mL/min per 1.73 m2.

An eGFR less than 60 is defined as Chronic Kidney Disease (CKD).

End Stage Renal Disease (ESRD) inludes preparation for dialysis, transplant etc.

HIV drugs cleared by the kidneys

Several HIV drugs are cleared by the kidney. These include tenofovir DF, 3TC, FTC, AZT and ddI. The dose for these meds (and maraviroc in some combinations) might need to be changed depending on your eGFR level.

The prescribing information for each drug includes detailed guidance.

Tenofovir DF and kidney toxicity

Tenofovir DF (TDF) is a widely used HIV drugs and it is mainly processed by the kidneys. Although serious kidney related side effects (including Fanconi’s Syndrome) were reported in studies, these were rare. They also often reversed when TDF was stopped.

TDF also changes laboratory markers such as reducing creatinine clearance, low phosphate levels and increased protein levels in urine (called proteinuria). The importance of these changes in markers in the long-term is unknown, but it is likely to be more important if you already start with reduced kidney function.

Because TDF can also reduce eGFR compared to some other HIV drugs, it is not recommended in people who have eGFR below 75-80 if there are other HIV drugs to chose from.

Similarly, if you are using TDF and your eGFR drops to this level, then switching to a different drug is recommended.

If you are using TDF, there is a also a caution against using other drugs that are cleared by the kidney.

It is not recommended to use creatinine supplements with TDF, as this will affect the interpretation of your monitoring tests.

A new version of TDF called tenofovir alafenamide (TAF) is available in several combination pills.

TAF is less likely to cause kidney (or bone) side effects.

Kidney stones: atazanavir and efavirenz

Atazanavir and efavirenz

There have been several reports of kidney stones that contained high levels of atazanavir or efavirenz, showing that this can be a rare side effect with these and other drugs.

Indinavir

Kindey stones were also linked to to early protease inhibitor indinavir but this is now rarely used. The side effect of kidney stones was reduced by drinking an additional 1-2 litres of water daily.

Indinavir-related kidney stones

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

Indinavir is now a rarely used protease inhibitor. The information below is kept online in the rare case that some people are still using this drug.

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 might 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 might 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.

Last updated: 1 March 2023.