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Higher risk of poor kidney function with versus without HIV in middle age.

HIV infection doubled chances of poor kidney function in a careful comparison of more than 1000 HIV-positive and negative people 45 years old or older. (1) The study also linked worsening kidney function to having HIV and staying with an antiretroviral combination that usually included tenofovir disoproxil fumarate (TDF). TDF, or Viread, is contained in Truvada and Atripla.

Studies show that kidney problems occur more often in people with HIV than in those without HIV (Figure 1). (2,3) Reasons for this higher rate of kidney trouble with HIV may involve traditional risk factors for chronic kidney disease (like smoking, hypertension, and diabetes), antiretroviral therapy, * and HIV infection itself. Much work has linked treatment with the antiretroviral TDF to worsening kidney function. Kidney function may improve if a person stops taking TDF. To get a better understanding of kidney function in middle-aged to older people with HIV, researchers in the Netherlands conducted this study.

How the study worked. Participants in the kidney analysis came from the AGEhIV cohort study, which includes more than 500 people with HIV and a matching group without HIV. (4) Everyone in both groups was at least 45 years old when they entered AGEhIV. People with HIV came from a large HIV clinic in Amsterdam, the Netherlands. People in the HIV-negative comparison group, matched to the HIV group by age and sex, were in care at a sexually transmitted infection (STI) clinic in Amsterdam. Signing up HIV-negative people at an STI clinic raised chances that they would have sexual behavior similar to the HIV group.

People in AGEhIV make regular study visits to get health check-ups, complete surveys, and give samples for testing. Researchers measured kidney-related markers in samples collected from each person's first study visit up to September 2016. They looked at three measures: ([dagger]) (1) kidney impairment calculated by a standard formula called estimated glomerular filtration rate (eGFR), (2) albuminuria--too much albumin protein in the urine (which may be an early sign of kidney disease), and (3) proximal renal tubular dysfunction (PRTD)--a problem with the kidney's blood-filtering system.

The researchers measured all of these kidney markers at least once in all study participants. They used an accepted statistical method to determine whether HIV itself--independently of other kidney risk factors--affected chances of kidney impairment, albuminuria, or PRTD.

In a subgroup of people, the researchers measured worsening kidney impairment and worsening albuminuria over time. ([double dagger]) In this subgroup they used a standard statistical method to compare worsening kidney impairment and worsening albuminuria in HIV-negative people versus HIV-positive people up to the time they changed their antiretroviral combination. The researchers stopped the analysis when people changed their antiretroviral combination to avoid complications in determining the kidney impact of several different antiretroviral combinations.

What the study found. The study focused on 596 people with HIV and 544 without HIV. Median (midpoint) age was similar in the HIV-positive and negative groups (52.7 and 52.1 years). About 85% of both groups were men. The HIV group included a higher proportion of people born in Africa (14.3% versus 6.4%) and a higher proportion of current smokers (32.1% versus 24.8%). (Both black race and smoking can raise chances of kidney problems.) Almost everyone was taking antiretroviral therapy and had an undetectable viral load. About three quarters of the HIV group currently used TDF (Viread, Truvada, Atripla) or used it in the past. Median time taking TDF was 4 years.

At the first study visit, significantly higher proportions of people with than without HIV had kidney impairment (4.7% versus 2.0%), albuminuria (24.4% versus 5.6%), or PRTD (40.1% versus 8.6%). (Here and below, "significantly" means a statistical test shows that chance is very unlikely to explain the noted difference.) Statistical analysis to assess the impact of HIV infection on these kidney signals accounted for the potential impact of age, sex, African descent, cigarette smoking, chronic hepatitis C virus (HCV) infection, high blood pressure, diabetes, and abnormal lipids (blood sugars). In this analysis, HIV itself--regardless of other risk factors--doubled the odds of kidney impairment, raised chances of albuminuria almost 6 times, and raised chances of PRTD 7 times (Figure 2).

Other factors linked to higher odds of one or more of these three kidney signals were older age, current smoking, higher blood pressure, taking blood pressure drugs, diabetes, cardiovascular (heart) disease, longer time since testing positive for HIV, and longer time taking TDF. Every additional year taking TDF was linked to 17% higher odds of PRTD.

The analysis of worsening kidney impairment or worsening albuminuria over time involved 377 people with HIV and 479 HIV-negative people. Researchers had data through about 4 years for both groups. Statistical analysis considering several kidney risk factors linked having HIV and staying on the same antiretroviral combination to worsening kidney impairment over time (eGFR -0.56 mL/min per year). Rapid kidney function decline affected a significantly higher proportion of people with than without HIV (5.8% versus 2.3%). Having HIV infection and staying on the same antiretroviral combination doubled the odds of worsening kidney impairment (Figure 3). Worsening albuminuria also affected a significantly higher proportion of people with than without HIV (11.6% versus 5.0%). Having HIV infection and staying on the same antiretroviral combination raised odds of worsening albuminuria 2.3 times. Current smoking almost tripled the odds of worsening albuminuria.

What the findings mean for you. The kidneys are two fist-sized organs that process up to 150 quarts of blood daily, producing 1 to 2 quarts of urine (Figure 1). (5) These hardworking organs prevent buildup of wastes and extra fluid in the body and make hormones that help control blood pressure and promote red blood cell production and healthy bones. The kidneys also play an important role in processing some drugs, including certain antiretrovirals. Keeping the kidneys healthy is crucial to people with and without HIV infection.

This comparison of middle-aged and older people with versus without HIV infection provides strong evidence that HIV infection itself may raise chances of poor kidney function and worsening kidney function over time. The study linked having HIV infection to higher odds of three signals of poor kidney function-regardless of whatever other kidney risk factors a person had. Other factors tied to higher odds of poor kidney function or worsening kidney function were taking TDF (which is in Truvada and Atripla) a longer time, smoking, high blood pressure, diabetes, and older age. (Truvada is also the pill taken by HIV-negative people to prevent HIV infection.)

You can't do anything about your age, but all of these other risk factors can be prevented or controlled. Because people with HIV run a higher risk of kidney problems, they should work closely with their providers to prevent or control kidney risk factors. Smoking damages not only the kidneys, but also the heart and lungs.

People with HIV should get tested regularly for kidney function. US HIV experts recommend urine testing for kidney function when people with HIV enter care, when they start antiretroviral therapy, every 6 months if they take TDF or tenofovir alafenamide (TAF or Vemlidy, contained in Descovy, Genvoya, and Odefsy), and every 12 months for everyone not taking TDF or TAF. (6)

REFERENCES

(1.) Kooij KW, Vogt L, Wit FWNM, et al. Higher prevalence and faster progression of chronic kidney disease in human immunodeficiency virus-infected middle-aged individuals compared with human immunodeficiency virus-uninfected controls. J Infect Dis. 2017;216:622-631.

(2.) Abraham AG, Althoff KN, Jing Y, et al. End-stage renal disease among HIV- infected adults in North America. Clin Infect Dis. 2015;60:941-949.

(3.) Rasmussen LD, May MT, Kronborg G, et al. Time trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark: a nationwide population-based cohort study. Lancet HIV. 2015;2:e288-e298.

(4.) Schouten J, Wit FW, Stolte IG, et al. Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV Cohort Study. Clin Infect Dis. 2014;59:1787-1797.

(5.) National Institute of Diabetes and Digestive and Kidney Diseases. Your kidneys and how they work. https://www.niddk.nih.gov/health-information/kidney-disease/kidneys-how-they- work

(6.) US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. October 17, 2017. https://aidsinfo.nih.gov/guidelines/html/1/adult-andadolescent-arv/0

* Words in boldface are explained in the Technical Word List at the end of this issue.

([dagger]) For providers: The researchers defined kidney impairment as estimated glomerular filtration rate (eGFR) less than 60 mL/ min; they defined albuminuria as an albumin/creatinine ratio at or above 3 mg/mmol; and they defined proximal renal tubular dysfunction as a retinol-binding protein/creatinine ratio above 2.93 pg/mmol and/or fractional phosphate excretion above 20% in a person with plasma phosphate below 0.8 mmol/L.

([double dagger]) For providers: The researchers defined worsening kidney impairment as an average yearly eGFR decline of at least 5 mL/min with the most recent eGFR below 90 mL/min. They defined worsening albuminuria as an average yearly increase in albumin/creatinine ratio of at least 10% plus a change in albuminuria category from <3 to [greater than or equal to] 3 mg/mmol or from [less than or equal to] 30 to >30 mg/mmol.

Caption: Figure 1. The kidneys play several important roles in maintaining health. Kidney problems are more frequent in people with than without HIV--especially in those with risk factors like smoking, high blood pressure, and diabetes. (Illustration from Servier PowerPoint Image Bank, http:// smart.servier.com/).
Figure 2. A comparison of more than 1000 adults with
versus without HIV infection linked HIV infection to higher
odds of three signals of poor kidney function--kidney
impairment (measured by estimated glomerular filtration
rate), albuminuria (excess albumin protein in the urine),
and PRTD (proximal renal tubular dysfunction, or damage
to the kidneys' ability to filter urine).

HIV impact on three signals of poor kidney function

Kidney impairment   2.1
Albuminuria         5.8
PRTD                7.1

Note: Table made from bar graph.

Figure 3. A comparison of older adults with and without
HIV infection linked having HIV infection and not changing
antiretroviral drugs to higher chances of worsening
kidney impairment and albuminuria.

HIV impact on chance of worsening kidney function

Kidney impairment    2.1
Albuminuria          2.3

Note: Table made from bar graph.
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Title Annotation:ARTICLE 6
Publication:HIV Treatment: ALERTS!
Date:May 1, 2018
Words:1741
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