As the kidneys perform their processing functions,
they can be exposed to harmful levels of drugs. Some drugs are more likely than
others to cause serious organ damage, and some people are more vulnerable than
others to drug toxicities. While cases of kidney damage thought to be caused by
several ARVs have been documented in the medical literature, only three of
those drugs have been consistently associated with adverse kidney-related
effects.
There is ample evidence that the protease inhibitor indinavir
(Crixivan) causes kidney stones in a
sizeable number of people – and this is one reason why this drug is very rarely
used now. (Waste products in the kidneys can sometimes form crystals and these
can accumulate to form hard lumps called ‘kidney stones’.)
Of more concern are case reports of kidney stones
associated with the protease inhibitor atazanavir (Reyataz). They appear to occur much more rarely than with indinavir,
but atazanavir is a frequently used drug. A French cohort study found that
about one in 100 patients developed atazanavir-related kidney stones after an
average of two years on the drug,4 30 cases were reported to the American Food and Drug Administration in
the first three years of its use,5 and one patient out of 121 in a trial comparing maraviroc with
tenofovir/FTC, both combined with atazanavir, had to pull out due to kidney
stones.6
The kidney stones associated with both these drugs, although
painful, may be avoidable by drinking plenty of water, and resolve if the drugs
are withdrawn.
If I were a patient, I would want to know that whoever is looking after me knows
about this potential problem, and has procedures in place to detect it.
John Connolly, University College London
The impact of tenofovir (Viread – also in Truvada and
Atripla) on the kidneys remains a
matter of greater concern. Since this drug’s approval almost ten years ago, a
number of studies have suggested that tenofovir may negatively affect renal
functioning in subtle ways. In some people it damages the upper portion of the
nephrons, resulting in symptoms similar to a condition called Fanconi’s
syndrome.
There is no clear consensus about the importance of
the findings, but many clinicians take them seriously.
An Australian study published in early 2010 found that
kidney functioning had failed to return to normal in almost half of 24 men with
tenofovir-induced renal toxicity more than a year after discontinuing the drug.7
In the EuroSIDA cohort, a group of nearly 7000 patients,
cumulative exposure to tenofovir or atazanavir was associated with a 16% and
21% increased risk, respectively, of chronic kidney disease, though the actual
proportion of people who developed CKD for any reason was relatively low, at
one case per 105 patients a year.8
On the other hand, a US group found no association
between tenofovir use and decline in kidney function in a prospective cohort
study involving 554 people,9 and a recent meta-analysis
of 17 studies involving 11,000 HIV-positive people concluded that from a
statistical standpoint, taking tenofovir was indeed associated with higher risk
of impaired kidney functioning, but that “the clinical magnitude of this effect
was modest”.10
What are we to make of the barrage of data about
tenofovir and kidney toxicity? Dr John Connolly of University College London’s
Centre for Nephrology encourages HIV-positive people to look at the big
picture.
“It’s important to be pragmatic, because tenofovir is
a very safe and very good drug overall,” he says.
Connolly characterises tenofovir-induced renal
toxicity as “a small problem for a significant minority of people”, and notes
that protocols for screening tenofovir users for renal damage are well
established.
“If I were a patient, I would want to know that
whoever is looking after me knows about this potential problem, and has
procedures in place to detect it,” he says. Patients at Connolly’s HIV
nephrology clinic provide blood and urine specimens for what he characterises
as “simple” screening tests every four to six months.
Antiretroviral toxicity is not the only kidney-related
HIV treatment concern. Because kidney damage impairs the body’s ability to
process drugs, dose reductions are required when prescribing certain
antiretrovirals to people with CKD.
A number of drugs used to treat and prevent
opportunistic infections are known to be hard on the kidneys, some to the point
of making them hard to use. These include amphotericin B, cidofovir, foscarnet,
pentamidine and sulfadiazine and to a lesser extent cotrimoxazole (Septrin) and the herpes drug aciclovir.11,12
Certain non-prescription substances such as most of
the over-the-counter pain relievers, herbal supplements (including yohimbe, a
component of ‘herbal Viagra’) and recreational drugs are potentially more
hazardous to HIV-positive people with existing kidney problems than they are to
the general population.