[Viva] Fwd: CATIE News - Increased risk for dialysis found with HIV infection

Denise Becker dbecker106 at gmail.com
Thu Sep 12 11:39:15 PDT 2013 

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From: CATIE <mailer at catie.ca>
Date: Thu, Sep 12, 2013 at 10:04 AM
Subject: CATIE News - Increased risk for dialysis found with HIV infection
To: dbecker106 at gmail.com


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    CATIE News - Bite-sized HIV and hepatitis C news bulletins
       CATIE News - Increased risk for dialysis found with HIV infection

In high-income countries such as Canada, Australia and the U.S. and in
regions such as Western Europe, the widespread availability of potent
combination anti-HIV therapy (commonly called ART or HAART) has greatly
reduced deaths due to AIDS-related infections. Furthermore, some
researchers are predicting that a young HIV-positive adult who begins ART
today and who does not have major co-morbidities—such as smoking,
co-infection with viral hepatitis, mental health issues, substance use—is
likely to live for several decades, perhaps, in some cases, even
experiencing a near-normal lifespan.
 Focus on the kidneys

Researchers conducting experiments in the lab have found that HIV can
infect some cells in the kidney. Studies in HIV-positive people have found
that they are at risk for increased kidney injury and, over time, in some
cases, impaired functioning of these vital organs. The kidneys perform many
important functions, including filtering the blood of wastes and producing
urine, regulating blood pressure, monitoring the level of oxygen in the
blood and helping convert vitamin D to its active form.
 The role of treatment

In cases where untreated HIV infection causes kidney dysfunction,
commencing ART generally results in improvement of overall health and
kidney health in particular.

There have been reports of an elevated risk of kidney injury and
dysfunction among some HIV-positive people who used the older anti-HIV drug
indinavir (Crixivan). However, this drug is seldom used in high-income
countries today. There have also been reports of kidney injury occurring
among some users of the newer anti-HIV medicines atazanavir (Reyataz) and
tenofovir (Viread, and found in Truvada, Atripla, Complera and Stribild).
More information about these issues appears later in this bulletin as well
as in the resources
section<http://www.catie.ca/en/catienews/2013-09-12/increased-risk-dialysis-found-hiv-infection#resources>
.
 New research

Researchers in Denmark have been monitoring the health of more than 5,000
HIV-positive people for up to 15 years. They compared data collected from
HIV-positive people to that collected from more than 50,000 HIV-negative
people of the same age and gender. Over the 15 years of the study the
researchers found that there was an increased risk (nearly five-fold) among
HIV-positive people of developing serious kidney injury—requiring temporary
or permanent dialysis—compared to HIV-negative people.

Further results from this study, including risk factors for serious kidney
injury and the possible impact of HIV treatment on kidney health, appear
later in this *CATIE News* bulletin.
 Study details

For some time now, Danish researchers have established a high-quality data
set containing health-related information from both HIV-positive and
HIV-negative people. This allows researchers to analyse the data for trends
in health-related issues.

In the present analysis, data from 5,300 HIV-positive people were compared
to data from 53,000 HIV-negative people. Specifically, data from each
HIV-positive person was compared to data from 10 HIV-negative people of the
same age and gender.

The average profile of the HIV-positive participants at the start of the
study was as follows:

   - gender – 76% men, 24% women
   - age – 37 years
   - race: white 79%; black 13%; other or unknown race 7% (numbers do not
   add up to 100 because of rounding)
   - CD4+ count – 290 cells

 Presence of co-morbidities that could impact kidney health:

   - diabetes – 2%
   - higher-than-normal blood pressure – 4%
   - hepatitis C virus (HCV) infection in people who did not inject street
   drugs – 7%
   - people who injected street drugs – 11% (most were likely HCV positive)

 Kidney function

Distribution of eGFR (estimated glomerular filtration rate—one method for
assessing kidney health) where an eGFR greater than 90 is considered
healthy and less than 60 is considered seriously abnormal:

   - eGFR greater than 90 – 34%
   - eGFR between 60 and 90 – 22%
   - eGFR less than 60 – 1%

 Note that eGFR for 43% of participants at the start of the study was not
available.
 Results

During the study, 68 HIV-positive participants required at least temporary
dialysis. Among HIV-negative participants, the figure was 182 people. This
suggests that HIV-positive people were at nearly five-fold increased risk
for serious kidney injury. This difference was statistically significant.

The need for dialysis was greatest in the 12 months after an HIV diagnosis.

Among the 68 HIV-positive people who required dialysis at least once, 28%
had kidney health that grew worse over time and ultimately required
dialysis on a regular basis.
 Results—Risk factors

Among HIV-positive people, the risk factors for serious kidney injury
requiring a round of dialysis were as follows:

   - injection of street drugs
   - higher-than-normal blood pressure
   - having an AIDS-related illness
   - older age

 Risk factors for needing chronic dialysis were as follows:

   - higher-than-normal blood pressure
   - eGFR less than 60

 Specific ART

In participants who used tenofovir, atazanavir or both drugs, there was no
significant impact on kidney health. This was the case even when
researchers restricted their analysis to the past decade, when atazanavir
and tenofovir became available.

Researchers explained that doctors who cared for patients in the study knew
about the potential for drugs such as atazanavir and tenofovir to cause
kidney injury and dysfunction. These doctors, the researchers argued, would
not have been likely to prescribe atazanavir or tenofovir (or both) to
patients with kidney dysfunction. Furthermore, should kidney dysfunction
have appeared, doctors would have discontinued these drugs. These practices
may have helped reduce the risk of kidney injury and the need for dialysis
among patients who took those medicines.
 Race, HIV and the kidneys

Several other studies have found a connection between an increased risk of
HIV-related kidney damage and being of African ancestry. This increased
risk has been linked to the gene called Apol1, which is more commonly found
in people of West and Central African ancestry.

In the Danish study, most (70%) of black people were of *East* African
descent. This could be one possible reason why the present study did not
find any significant link between being black and serious kidney disease.
 AIDS-related illnesses

The initial decrease in kidney function seen during the first year of an
HIV diagnosis may have been related to the poor health of participants when
they sought care. HIV infection causes inflammation, which can impair the
functioning of the kidneys (and other organ-systems). Also, participants
with an AIDS-related illness may have been weak, dehydrated and exposed to
certain medicines (antibiotics, antifungal agents and so on) that could
have injured the kidneys. All of these factors likely contributed to the
poor state of kidney health and the need for at least temporary dialysis
among some patients during their first year after an HIV diagnosis. After
this time, the risk of dialysis was generally reduced, likely because use
of ART improved overall health and kidney function.
 Bear in mind

Although this was a cohort study, some of the findings from the Danish
researchers have been seen in larger data sets in the European Union. Also,
the fact that Danish researchers were able to compare data from each
HIV-positive person to 10 HIV-negative people of the same age and gender
was one of the strengths of this study. The Danish study’s findings are
important and underscore factors that can be addressed to improve the
health of HIV-positive people and reduce the risk of developing serious
kidney injury. These factors include the following:

   - frequent testing for HIV (and other sexually transmitted infections)
   in sexually active adults so that this infection can be uncovered and
   treatment initiated before serious organ damage has developed and the
   immune system becomes weak
   - screening HIV-positive patients for mental health issues and providing
   the psycho-social support to assist recovery from depression, anxiety and
   other issues that can lead to substance use and addiction
   - screening HIV-positive patients for higher-than-normal blood pressure
   and treating this when found

 *Resources*

Risk factors for kidney
dysfunction<http://www.catie.ca/en/treatmentupdate/treatmentupdate-195/complications-and-side-effects/risk-factors-kidney-dysfunction>–
*TreatmentUpdate* 195

Ask the Experts: Kidney
Health<http://www.catie.ca/en/positiveside/winter-2012/ask-experts-kidney-health>–
*The Positive Side*

Here’s Lookin’ at You,
Kidneys<http://www.catie.ca/en/positiveside/fallwinter-2005/here-s-lookin-you-kidneys>–
*The Positive Side*

*—Sean R. Hosein*

REFERENCES:

   1. Fierer DS, Klotman ME. Kidney and central nervous system as
   reservoirs of HIV infection. *Current Opinion in HIV/AIDS*. 2006
   Mar;1(2):115-20.
   2. Marras D, Bruggeman LA, Gao F, et al. Replication and
   compartmentalization of HIV-1 in kidney epithelium of patients with
   HIV-associated nephropathy. *Nature Medicine*. 2002 May;8(5):522-6.
   3. Winston JA, Bruggeman LA, Ross MD, et al. Nephropathy and
   establishment of a renal reservoir of HIV type 1 during primary infection.
   *New England Journal of Medicine*. 2001 Jun 28;344(26):1979-84.
   4. Helleberg M, Afzal S, Kronborg G, et al. Mortality attributable to
   smoking among HIV-1-infected individuals: a nationwide, population-based
   cohort study*. Clinical Infectious Diseases*. 2013 Mar;56(5):727-34.
   5. Simmons R, Ciancio B, Kall M, et al. Ten-year mortality trends among
   persons diagnosed with HIV infection in England and Wales in the era of
   antiretroviral therapy: AIDS remains a silent killer. *HIV Medic*ine.
   2013; *in press*.
   6. Gustafson R, Montaner J, Sibbald B, et al. Seek and treat to optimize
   HIV and AIDS prevention. *Canadian Medical Association Journal*. 2012
   Dec 11;184(18):1971.
   7. Sabin C. Review of life expectancy in people with HIV in settings
   with optimal ART access: what we know and what we don’t. In: Program and
   abstracts of the *11th International Congress on Drug Therapy in HIV
   Infection*, 11–15 November 2012, Glasgow, UK. Abstract O131.
   8. May M, Gomples M, Sabin C, et al. Impact on life expectancy of late
   diagnosis and treatment of HIV-1 infected individuals: UK Collaborative HIV
   Cohort Study. In: Program and abstracts of the *11th International
   Congress on Drug Therapy in HIV Infection*, 11–15 November 2012,
   Glasgow, UK. Abstract O133.
   9. Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and
   without HIV infection in Denmark, 1995-2005. *Annals of Internal Medicine
   *. 2007 Jan 16;146(2):87-95.
   10. Lohse N, Hansen AB, Gerstoft J, et al. Improved survival in
   HIV-infected persons: consequences and perspectives. *Journal of
   Antimicrobial Chemot*herapy. 2007 Sep;60(3):461-3.
   11. Søgaard OS, Lohse N, Østergaard L, et al. Morbidity and risk of
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   identifying indicator diseases for HIV infection. *PLoS One*.
   2012;7(3):e32538.
   12. Rasch MG, Helleberg M, Feldt-Rasmussen B, et al. Increased risk of
   dialysis and end-stage renal disease among HIV patients in Denmark compared
   with background population. *Nephrology, Dialysis, Transplantation*.
   2013; *in press*.
   13. Harris RC, Neilson EG. Chapter 278. Adaption of the Kidney to Renal
   Injury. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo
   J, eds. *Harrison’s Principles of Internal Medicine*. 18th ed. New York:
   McGraw-Hill; 2012.
   14. Bargman JM, Skorecki K. Chapter 280. Chronic Kidney Disease. In:
   Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J,
eds. *Harrison’s
   Principles of Internal Medicine*. 18th ed. New York: McGraw-Hill; 2012.
   15. Waikar SS, Bonventre JV. Chapter 279. Acute Kidney Injury. In: Longo
   DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. *
   Harrison*’*s Principles of Internal Medicine*. 18th ed. New York:
   McGraw-Hill; 2012.
   16. Ryom L, Mocroft A, Kirk O, et al. Exposure to antiretrovirals (ARVs)
   and risk of renal impairment among HIV-positive persons with normal
   baseline renal function: the D:A:D study. *Journal of Infectious Diseases
   *. 2013 May 1;207(9):1359-69.
   17. Fine DM, Gallant JE. Nephrotoxicity of antiretroviral agents: Is the
   list getting longer? *Journal of Infectious Diseases*. 2013 May
   1;207(9):1349-51.
   18. Scherzer R, Estrella M, Li Y, et al. Association of tenofovir
   exposure with kidney disease risk in HIV infection. *AIDS.* 2012 Apr
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   19. Jaffe JA, Kimmel PL. Chronic nephropathies of cocaine and heroin
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   Nephrology*. 2006 Jul;1(4):655-67.

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-- 
www.denise-becker.com
Queen's Gold Jubilee Medal
Queen's Diamond Jubilee Medal
cell: 250-870-1714
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