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Activation, senescence and inflammation markers in HIV patients: association with renal function
Alexandra Ozanne1, Pierre Duffau, Frédéric-Antoine Dauchy
1aUniversity Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, Team MORPH3EUS, UMR 1219, CIC-EC 1401 bCNRS-UMR 5164 Immuno ConcEpT, Bordeaux University and Bordeaux Hospital cCHU de Bordeaux, Service de médecine interne et immunologie clinique dCHU de Bordeaux, Service de Maladies infectieuses et Tropicales eCHU de Bordeaux, Service de néphrologie, transplantation et dialyse fCHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, University Bordeaux, Bordeaux gCHU de Bordeaux, Service de Médecine Interne, Hôpital Haut-Lévêque, Pessac hCHU de Bordeaux, Pôle de santé publique iCHU de Bordeaux, service de Médecine Interne et Maladies Infectieuses, Bordeaux, France. *Alexandra Ozanne, Pierre Duffau, Linda Wittkop and Isabelle Pellegrin contributed equally to the article.
Insights
Inflammation biomarkers, measured by the soluble-CIADIS score, are linked to reduced kidney function (eGFR < 60) in HIV patients with undetectable viral load. Higher inflammation predicted faster eGFR decline in those with existing kidney issues.
Area of Science:
- Immunology
- Nephrology
- Virology
Background:
- HIV infection is associated with immune activation, senescence, and inflammation.
- These factors may impact renal function, particularly in patients with suppressed viral loads.
- Understanding these associations is crucial for managing long-term health in HIV-positive individuals.
Purpose of the Study:
- To investigate the relationship between immune activation, senescence, inflammation biomarkers, and kidney function (eGFR) in HIV-infected patients.
- To assess how these biomarkers influence the evolution of renal function over a 3-year period.
- To determine if immune markers predict reduced eGFR in patients with undetectable viral load.
Main Methods:
- The Chronic Immune Activation and Senescence (CIADIS) substudy included HIV patients with undetectable viral load.
- Principal component analysis created weighted scores for cellular (T-cell) and soluble (inflammation) biomarkers.
- Logistic and linear mixed models analyzed associations with confirmed eGFR < 60 ml/min/1.73m² and eGFR change over 3 years.
Main Results:
- The soluble-CIADIS score (inflammation) was independently associated with a confirmed eGFR < 60 ml/min/1.73m² at baseline (OR=1.4).
- The cellular-CIADIS score (T-cell activation/senescence) showed a weaker, non-significant association with reduced eGFR.
- In patients with eGFR < 60 ml/min/1.73m² at baseline, higher inflammation was linked to a faster annual decline in eGFR (-2.3 ml/min/1.73m²/year).
Conclusions:
- Inflammation biomarkers (soluble-CIADIS score) are significantly associated with reduced kidney function in HIV patients with undetectable viral load.
- Inflammation exacerbates kidney function decline over time, particularly in those with pre-existing renal impairment.
- Targeting inflammation may be a key strategy to preserve renal function in this population.
Objectives:
To assess the association among immune activation, immune senescence, inflammation biomarkers and renal function measured by estimated glomerular filtration rate (eGFR) at inclusion and its evolution over a 3-year follow-up in HIV-infected patients with undetectable viral load.
Design:
The Chronic Immune Activation and Senescence (CIADIS) substudy consecutively included patients between October 2011 and May 2013 enrolled in the ANRS CO3 Aquitaine observational cohort.
Methods:
Biomarkers of T-cell activation, differentiation and senescence were summarized in a cellular-CIADIS weighted score and inflammation biomarkers in a soluble-CIADIS weighted score using principal component analysis. Logistic regression and linear mixed models were used to determine the association between the CIADIS weighted scores and confirmed eGFR less than 60 ml/min per 1.73 m, and evolution of eGFR, respectively.
Results:
Of 756 patients with an undetectable viral load, 76% were men, and median age was 51 years (Interquartile range: 45-57 years). In multivariable analysis, the soluble-CIADIS weighted score was independently associated with a confirmed eGFR less than 60 [odds ratio = 1.4; 95% confidence interval (CI) 1.1-1.8] but the cellular-CIADIS weighted score was not (odds ratio = 1.2; 95% CI 1.0-1.5). Only in patients with a confirmed eGFR less than 60 ml/min per 1.73 m at inclusion, a higher soluble-CIADIS weighted score (increased inflammation) was associated with a steeper decrease of renal function of -2.3 (ml/min per 1.73 m) per year (95% CI -3.6 to -1.0).
Conclusion:
At inclusion, soluble-CIADIS weighted score was independently associated with a confirmed eGFR less than 60 ml/min per 1.73 m. The soluble-CIADIS weighted score was associated with a decrease of eGFR evolution during a 3-year follow-up only in patients with a confirmed eGFR less than 60 ml/min per 1.73 m.
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