CATIE News

People with HIV infection are at increased risk for kidney injury. This problem of injured kidneys arises for one main reason: HIV infects key cells in the kidneys, causing inflammation. Inflamed kidneys are less efficient at doing their main job of filtering waste products from the blood. Taking anti-HIV therapy (ART) and achieving and maintaining an undetectable viral load in the blood greatly reduces but does not eliminate this inflammation, as small amounts of HIV continue to be produced by infected cells.

Other factors that play a role in kidney dysfunction include the following:

• As HIV-positive people age, their kidneys, like everyone else’s, become gradually less efficient at filtering waste material.
• Some HIV-positive people have co-existing complications (called comorbidities), such as type 2 diabetes and/or higher-than-normal blood pressure, which weaken the health of the kidneys.
• Some HIV-positive people have used the drug tenofovir DF (sold as Viread and found in many fixed-dose formulations of drugs sold under the brand names Truvada, Atripla, Complera and Stribild). A small proportion of people who have used ART that contains tenofovir DF have developed a degree of kidney injury as a side effect. The new formulation of tenofovir, called TAF (tenofovir alafenamide), does not cause kidney injury.

Exploring a possible association with hepatitis C virus

Hepatitis C virus (HCV) is another virus that has been associated with kidney injury in some studies. In high-income countries such as Canada, the most common way that HCV is spread today is by sharing equipment for substance use, including needles, syringes, straws, glass pipes and rolled currency notes. Among gay and bisexual and other men who have sex with men (MSM), particularly those with HIV, condomless sex can be another route of HCV infection.

It is possible that the association between HCV infection and kidney injury seen in some people may arise not because of this virus but because of exposure to street drugs. Other researchers have found that among HIV-negative people, use of cocaine is associated with kidney injury and dysfunction.

A Canadian study

Researchers in Canada have enrolled people co-infected with HIV and HCV into a study called the Canadian Coinfection Cohort (CCC). The latest analysis from the CCC has focused on assessing factors that influence the kidney health of participants. Researchers found that people who used cocaine frequently (three or more times a week) were more likely to develop a rapid deterioration in kidney health compared to people who did not use cocaine. Furthermore, in some participants, this decline in kidney health was irreversible; that is, they were never able to return to a normal level of kidney functioning. The route of getting cocaine into the body (injected or inhaled) did not result in any difference in the injury this substance caused to the kidneys. The researchers did not find a link between HCV infection and an increased risk for chronic kidney disease.

About assessing kidney health

A common assessment of kidney health is based on a calculation called eGFR (estimated glomerular filtration rate). This requires a test to measure the level of the waste product creatinine in the blood. Once this value is obtained it is put into a formula, along with a person’s age, gender and race. For more about eGFR see Kidneys Take Centre Stage from CATIE’s Positive Side magazine.

Study details

In the report by the Canadian Coinfection Cohort, researchers defined chronic kidney dysfunction (also called chronic renal impairment) as having an eGFR below 70 mL/minute when participants made their first clinic visit. Such visits occurred between January 2003 and October 2014. Researchers obtained additional health information from participants’ medical charts.

Researchers performed several analyses but we will only report on a few of these. One analysis focused on 1,061 participants co-infected with HIV and HCV. Their average profile when they entered the study was as follows:

• age – 45 years
• 75% men, 25% women
• eGFR – 104 mL/minute
• CD4+ cell count – 400 cells/mm³
• 37% had an HIV viral load greater than 50 copies/mL
• 41% used tenofovir DF
• 27% had been diagnosed with AIDS
• 10% had higher-than-normal blood pressure
• 8% had extensive liver injury
• 4% had type 2 diabetes

HCV viral load testing was done on a regular basis. This testing allowed researchers to see if there was any statistical relationship between HCV viral load and eGFR.

Results—Chronic renal impairment and more

A total of 126 participants (12%) developed chronic renal impairment. At the time participants developed chronic renal impairment, their average eGFR was 63 mL/minute.  It is noteworthy that once the majority (83%) of these participants developed chronic renal impairment, they never had a subsequent sustained improvement in eGFR. That is, eGFR levels in the majority of people who developed chronic renal impairment never rose above 70 mL/min. Furthermore, 42% of participants who developed chronic renal impairment subsequently developed more serious kidney injury as their eGFR fell below the 60 mL/min mark. People who have an eGFR less than 60 mL/min have chronic kidney disease.

Impact of cocaine on the kidneys

Researchers found that people who currently injected cocaine increased their risk of developing chronic renal impairment by 26%. Furthermore, participants who injected cocaine at least three days each week had “more than a two-fold greater risk of developing chronic renal injury” compared to people who had not used cocaine in the past six months.

The impact of cocaine was not affected by the following factors:

• ART, including specific drugs such as tenofovir DF, atazanavir (Reyataz) or lopinavir (in Kaletra)
• smoking
• type 2 diabetes
• HCV infection

Injecting or inhaling cocaine

The route through which cocaine entered the body—injected or inhaled—did not have a statistically significant impact on this substance’s ability to injure the kidneys.

How cocaine can injure the kidneys

Previous research has found that, in general, cocaine can injure different organ-systems. It can affect the functioning of the heart and the health of blood vessels, and consequently can cause heart attack and stroke. As the kidneys are rich in blood vessels, cocaine likely raises blood pressure within the blood vessels in the kidneys and restricts the flow of blood within these vital organs. Cocaine can also directly harm kidney cells by reducing the level of an important antioxidant molecule called glutathione. The purity of cocaine is sometimes reduced with fillers, which may also cause injury to the kidneys.

Screening kidney injury—don’t forget to ask about substance use

Based on their results, the CCC researchers note that “cocaine use may represent an important modifiable risk factor for chronic kidney disease among co-infected patients.” They state that their findings support doctors and nurses asking their patients about substance use, particularly cocaine, as part of screening for kidney injury and dysfunction.

CATIE resources

Kidney health

• Kidney Health – A Practical Guide to a Healthy Body for People Living with HIV
• Ask the Experts: Kidney Health – The Positive Side (Winter 2012)
• Kidneys Take Centre Stage – The Positive Side (Winter 2012)

Substance use and mental health

• Pre-fix: A guide for people with Hep C or HIV who inject drugs
• Study finds sustained-release dexamfetamine is promising for reducing cocaine use – CATIE News
• Profile: Back from the Brink – The Positive Side (Fall 2016)
• Ask the Experts: Addictions – The Positive Side (Fall 2016)
• HIV and emotional wellness

Hepatitis C

CATIE’s hepatitis C information

—Sean R. Hosein

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