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Inflammation Markers Tied to Worse Kidney Function in Men Taking Antiretroviral Therapy

October 20, 2015

Higher levels of inflammatory markers predicted worse kidney function in a comparison of HIV-positive men taking antiretroviral therapy and men without HIV infection. The findings could partly explain compromised kidney function in people with HIV.

Volumes of evidence confirm a higher risk of chronic kidney disease (CKD) in HIV populations than in the general population. Several factors (smoking, diabetes, hypertension, hepatitis C [HCV] infection) probably contribute to this heightened risk, including ongoing inflammation in people with otherwise well-controlled HIV infection. Although high levels of inflammatory markers predict future CKD in the general population, studies of these markers in relation to HIV-associated CKD generally assess single inflammatory markers.

To explore the impact of multiple inflammatory markers on CKD risk, Multicenter AIDS Cohort Study (MACS) investigators compared markers and renal variables in 434 HIV-positive men taking antiretroviral therapy and 200 HIV-negative men at risk of HIV infection. They measured glomerular filtration rate (GFR) directly by iohexol clearance and used logistic regression to identify factors associated with GFR at or below 90 mL/min. A GFR below 90 mL/min signifies stage 2 or worse CKD.

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Respectively, men with and without HIV had a median age of 51 and 53 years and a median GFR of 109 and 106 mL/min; 37% and 38% were black. Men with HIV had been infected for a median of 19 years and had taken antiretroviral therapy for 10 years. Their median CD4+ count stood at 544 cells/mm3, with 80% having a viral load below 50 copies/mL.

Levels of eight inflammatory markers were significantly higher in men with than without HIV: sTNFr22, sIL2rα, sgp130, sCD27, CXCL10, TNF-α, sCD14 and IL-10. Except for IL-10, levels of all these markers were significantly higher in men with compromised kidney function, indicated by a GFR ≤ 90 mL/min.

MACS investigators used a method called event factor analysis to identify sets of inflammatory markers that are highly correlated and therefore probably reflect the same process. In this way, they defined inflammatory process 1 (involving mainly sTNFr2, sIL2rα, sgp130, sCD27 and sCD14), inflammatory process 2 (IL-6, CXCL8 and TNF-α) and inflammatory process 3 (CXCL10 and CCL2). An analysis adjusted for age, race and HIV status determined the following associations in the entire study group:

Inflammatory process 1 (each standard deviation higher):

  • 2-fold higher odds of GFR ≤90 mL/min
  • 2.3-fold higher odds of urine protein > 200 mg/g
  • 1.6-fold higher odds of diabetes
  • 1.3-fold higher odds of hypertension
  • 1.9-fold higher odds of HCV infection
  • 0.5-fold lower odds of hyperfiltration

Inflammatory process 2 (each standard deviation higher):

  • 0.5-fold lower odds of HCV infection

Inflammatory process 3 (each standard deviation higher):

  • 7.4-fold higher odds of HCV infection

An analysis limited to HIV-positive men determined that inflammatory process 2 was associated with 1.5-fold higher odds of hyperfiltration. Treatment with tenofovir was not associated with any kidney outcomes.

The MACS team concludes that higher levels of immune activation markers in antiretroviral-treated men with HIV -- particularly markers clustered in inflammatory process 1 -- "may partially explain their higher burden of kidney dysfunction compared with uninfected men." The team suggests that other variables probably also contribute to renal problems in HIV populations, including behavioral factors such as substance use, and the toxic and metabolic effects of antiretroviral therapy. The authors also caution that this cross-sectional study cannot assign cause and effect, that is, "whether HIV infection is a driver of inflammation contributing to kidney damage or whether higher levels of immune activation markers result from decreased clearance due to kidney dysfunction."

Mark Mascolini writes about HIV infection.


Copyright © 2015 Remedy Health Media, LLC. All rights reserved.




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