Kidney toxicity including kidney stones

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

Tenofovir-related toxicity
Indinavir-related kidney stones

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

Tenofovir-related toxicity

Tenofovir is mainly cleared from body by your kidneys and side effects reported with tenofovir include kidney toxicity. This includes reduced creatinine clearance, low phosphate levels and renal tubular complications including Fanconi’s Syndrome. These side effects are usually quickly reversible when tenofovir is discontinued.

Routine blood tests (including urinalysis and estimated GFR - glomerular filtration rate) should be used before starting tenofovir and for montioring when on 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.

Recently there has been concern that tenofovir-related toxicity may be greater when tenofovir is used with ddI. Until this interaction is understood, these two drugs are generally not recommended to be used 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 reduced creatinine clearance less than 60 ml/min).

See the individaul prescibing information provided with each of these drugs for details.

Indinavir-related kidney stones

Indinavir used to be a widely used protease inhibitor, especially when boosted with ritonavir. One side effect included kidney stones - largely avoided by drinking an additional 1-2 litres of water daily.

It is now rarely used and so the detailed information relating to kidney stones and indinavir is only available in the online edition of this guide.

In 2007 there were several case reports of kidney stones that contained high levels of atazanavir or efavirenz, cautioning that this may be a rare side effect with other drugs. Kidney stone passing through the bladder (ow!)

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.

Avoiding stones

Maintain fluid intake to 1.5 litres a day – higher if you have a family history of kidney stones.
Increase fluid acidity – drink more cranberry or orange juice.
Check indinavir levels with TDM.
Have routine urine checks with your regular blood tests to see if you are at higher risk.

Treatment

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.