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Activation and Senescence Markers in HIV Patients with Chronic Kidney Disease
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CROI 2016
Reported by Jules Levin
The proportion of all comorbidities was higher among patients with an eGFR <60 (p<0.01), except
for hypertension and degenerative CNS disorders. Patients with an eGFR <60 were also more
likely to present two or more comorbidities (57% vs. 29%, p<0.01).
• an increase of the CIADIS score was
significantly associated with an eGFR<60, (OR=1.2; 95% CI
1.0-1.5; P=0.04)(Figure 2,3 and 4) and eGFR <90 (OR=1.1;
95% CI 1.0-1.2; P<0.01) (Data not shown).
• The CIADIS score remained significantly associated with an
eGFR <60 after adjustement for the number of comorbidities
(OR=1.2; 95% CI 1.0-1.5; P=0.04) (Figure 2), diabetes
(OR=1.5; 95% CI 1.0-2.2; P=0.04) (Figure 3) or for
cardiovascular events (OR=1.5; 95% CI 1.0-2.3; P=0.04)
(Figure 4) but not for the other comorbidities.
The CIADIS score was determined with CD4 and CD8 activation (DR+), maturation (T naive, memory) and senescence (CD57+CD28-) markers (Duffau et al. AIDS in press)
program abstract
ART-treated HIV-infected individuals remain at higher risk for chronic kidney disease (CKD) than the general population and multiple causes are hypothesized. We evaluated the association between T cell immune activation (IA) and -senescence (IS), and CKD in these patients.
Patients with undetectable viral load and an estimated Glomerular Filtration Rate (eGFR) measurement were part of the cross-sectional CIADIS substudy (2011-2013) of the ANRS CO3 Aquitaine cohort. The CIADIS score was determined with CD4 and CD8 activation (DR+), maturation (T naive, memory) and senescence (CD57+CD28-) markers (Duffau et al. AIDS in press): positive values represent a phenotype with high IA and IS, negative values a profile with low IA/IS and with high proportion of naive T cells. The association between the CIADIS score and CKD was evaluated for two separate outcomes: i) eGFR <60 mL/min/1.73m2 and ii) eGFR<90 mL/min/1.73m2. Logistic regression models adjusted for age, sex, tenofovir (TDF) use and non-HIV related comorbidities (diabetes, cardiovascular events, dyslipidemias, hypertension and cancer) were constructed. In a sub-group analysis, urine protein-creatinine ratio (uPCr) >30 mg/mmol was combined with eGFR≥90 to define early kidney dysfunction.
We included 849 patients with a median age of 51 years; 74% were men, 23% at CDC stage C; they were on ART for a median of 13 years, 85% of patients had an ongoing or previous TDF-containing regimen. eGFR was ≥90, 60-89 and <60 in 68 %, 28% and 4% of patients, respectively. The median CIADIS score was -0.1 (IQR -1.5;1.5) and increased significantly with decreasing kidney function (Figure). In univariable analysis: an increase of the CIADIS score was significantly associated with an eGFR<60, (OR=1.2; 95% CI 1.0-1.5; P=0.04) and eGFR<90 (OR=1.1; 95% CI 1.0-1.2; P<0.01). After adjustment, the CIADIS score remained significantly associated with an eGFR<60 (OR=1.3; 95% CI 1.0-1.6; P=0.03) only. Among 221 patients with an eGFR ≥90 and available uPCr, 9% had an early kidney dysfunction. No difference in the score was found whether uPCr was ≤30 or >30 (P=0.46).
Higher IA and IS levels were independently associated with advanced CKD. Although other factors may contribute to kidney damage, persisting T-cells activation and senescence could induce inflammation and thus play a direct role even in successfully treated patients. Follow-up continues; longitudinal analysis will allow studying the development of CKD according to IA/IS profiles.
References:
1. Winston JA. et al. HIV and CKD epidemiology. Adv Chronic Kidney Dis. 2010 Jan;17(1):19-25
2. Lucas GM. et al. End-stage renal disease and chronic kidney disease in a cohort of African-American HIV-infected and at-risk HIV-seronegative participants followed between 1988 and 2004. AIDS. 2007 Nov;21(18):2435-43
3, Longenecker et al. Rosuvastatin Preserves Renal Function and Lowers Cystatin C in HIV-Infected Subjects on Antiretroviral Therapy: The SATURN-HIV Trial. Clin. Inf. Dis. 2014. Oct;59(8):1148-56
4. Duffau P. , Wittkop L. et al. Association of immune-activation and senescence markers with non-AIDS-defining comorbidities in HIV-suppressed patients. AIDS. 2015 Oct;29(16):2099-108
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