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CATIE News - Long-term consequences of kidney injury in HIV

2010 June 23 - Acute kidney injury, formerly called acute renal failure, is a rapid decline in the functioning of the kidneys. Typically, acute kidney injury (AKI) develops when the concentration of the waste product creatinine in the blood increases significantly.  Compared to HIV-negative people, some studies have found that HIV-positive people are twice as likely to experience AKI.

Researchers at the University of California at San Francisco and Yale University have been studying the significance of AKI among a group of 17,000 HIV-positive people. Their findings suggest that AKI should be re-examined in the context of HIV infection. Specifically, they posit that AKI should be considered not merely a deeply troublesome event but a condition that makes the body vulnerable to a range of future crises.

Study details

The research team reviewed health-related information collected from 17,323 HIV-positive people (2% females, 98% males) who were former United States military personnel from the Veteran's Affairs Database. About 18% of these people developed AKI during the time they spent in the hospital.

People who developed AKI were significantly more likely to have one or more of the following features:

  • age - about 47 years
  • higher-than-normal blood pressure
  • diabetes
  • heart failure
  • cancer
  • elevated levels of protein in their urine

Only 25% of people with AKI were taking anti-HIV agents at the time they developed this complication. Furthermore, people with AKI tended to have less than 200 CD4+ cells. Yet 50% of people with AKI were hospitalized after 1995, which is when highly active antiretroviral therapy (HAART) became available.

Results

Participants were monitored for an average of six years and only health events that occurred 90 days or more after they left the hospital were assessed as part of the present study. During the study the following health outcomes occurred:

  • 1,006 cases of heart failure, stroke and other forms of cardiovascular illness
  • 348 cases of kidney failure
  • 8,405 deaths

The risk of heart failure, stroke and cardiovascular disease, kidney failure and death were all related to the initial severity of AKI. That is, the more severe the initial episode of AKI, the greater the eventual risk of death.

Having any degree of AKI was associated with an increased risk for death, even when researchers adjusted their calculations for the following factors:

  • CD4+ cell count
  • viral load
  • age
  • initial kidney function
  • co-existing health conditions
  • protein in urine

This finding surprised the study team because people who had minimal AKI and who did not experience heart or kidney failure were still at heightened risk for subsequent death.

Repercussions years later

The present study shows that AKI has repercussions for the health and survival of HIV-positive people years later. The study also provides a rationale for a new way of viewing AKI. The study team suspects that AKI "may be an inciting event that triggers a cascade of perturbations that never completely resolve."

And in animals

Animal experiments suggest that AKI causes permanent changes in the filtering apparatus and in the network of tubes and pipes in the kidneys. AKI also triggers changes in the lining of blood vessels, making them less healthy and increasing the release of inflammatory chemical messengers. These changes can increase the risk of the formation of unnecessary blood clots that can clog blood vessels and result in damage to the heart, lungs and brain. This damage may weaken these organs, making them less able to withstand future stressful events.

And in HIV

Similar processes have been found as a result of HIV infection. This infection is currently being reframed as a viral infection that causes inflammation, which degrades the immune, cardiovascular, nervous and other organ systems, including the kidneys.

The research team studying the impact of AKI speculates that AKI may intensify HIV-related inflammation through common pathways. However, this theory will require further research.

The current VA study is not perfect. Because researchers conducted a retrospective study, they may have inadvertently misinterpreted some of their findings. It is possible that rather than being a cause of subsequent serious events, AKI is merely a signifier of severe underlying illness.

However, in another study, a recent analysis ( in press ) of data from more than 100,000 HIV-negative people suggests that kidney disease, including AKI, is strongly associated with subsequent death, including death from cardiovascular complications, across North America, Europe, Asia and Oceania. This suggests that the VA study's findings with HIV-positive people are important and valid.

The present VA study with HIV-positive people sends an important warning signal: Acute kidney injury can have serious consequences. Maintaining kidney health is a goal that is likely to grow in importance in the years ahead, particularly as HIV-positive people age.

For tips about monitoring and maintaining kidney health see " Here's Lookin' at You, Kidneys " in The Positive Side magazine (fall/winter 2005):

http://www.positiveside.ca/e/v7i2/Kidneys_e.htm

-Sean R. Hosein

 

REFERENCES:

1. Choi AI, Li Y, Parikh C, et al. Long-term clinical consequences of acute kidney injury in the HIV-infected. Kidney International . 2010; in press .

2. Chronic Kidney Disease Prognosis Consortium. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet . 2010; in press .

 

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CATIE-News is written by Sean Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto.

From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at http://www.catie.ca

Source: CATIE: CANADIAN AIDS TREATMENT INFORMATION EXCHANGE


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