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Markers of renal disease and function are associated with systemic inflammation in HIV infection.

ABSTRACT: OBJECTIVES:Both renal disease and systemic inflammation predict non-AIDS-defining events and overall mortality in HIV-infected patients. Here, we sought to determine the relationships between renal disease and circulating inflammation markers. METHODS:We performed a secondary analysis of AIDS Clinical Trials Group Study A5224s to determine if markers of renal disease [urine protein:creatinine ratio (uPCR), urine albumin:creatinine ratio (uACR), and estimated glomerular filtration rate (eGFR), using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine and cystatin C-creatinine] were associated with markers of systemic inflammation [high-sensitivity C-reactive protein, interleukin-6, tumour necrosis factor (TNF)-?, soluble TNF-? receptor I (sTNFRI), sTNFRII, and soluble vascular cellular and intercellular adhesion molecules]. We correlated these renal and inflammatory markers prior to antiretroviral initiation and after 96 weeks of therapy. RESULTS:We found that eGFR (estimated using CKD-EPI cystatin C-creatinine), uPCR, and uACR were significantly correlated with most assessed markers of systemic inflammation prior to antiretroviral initiation. uPCR and eGFR (using CKD-EPI cystatin C-creatinine), but not uACR, remained significantly correlated with most of the assessed inflammatory markers after 96 weeks of antiretroviral therapy (ART). Most of these correlations, although statistically significant, were?

SUBMITTER: Gupta SK

PROVIDER: S-EPMC4620540 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Markers of renal disease and function are associated with systemic inflammation in HIV infection.

Gupta S K SK Kitch D D Tierney C C Melbourne K K Ha B B McComsey G A GA

HIV medicine 20150520 10

<h4>Objectives</h4>Both renal disease and systemic inflammation predict non-AIDS-defining events and overall mortality in HIV-infected patients. Here, we sought to determine the relationships between renal disease and circulating inflammation markers.<h4>Methods</h4>We performed a secondary analysis of AIDS Clinical Trials Group Study A5224s to determine if markers of renal disease [urine protein:creatinine ratio (uPCR), urine albumin:creatinine ratio (uACR), and estimated glomerular filtration ...[more]

PMID: 25990642

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Project description:BackgroundDespite effective antiretroviral therapy (ART), patients with chronic human immunodeficiency virus (HIV) infection have increased microbial translocation and systemic inflammation. Alterations in the intestinal microbiota may play a role in microbial translocation and inflammation.MethodsWe profiled the fecal microbiota by pyrosequencing the gene encoding 16S ribosomal RNA (rRNA) and measured markers of microbial translocation and systemic inflammation in 21 patients who had chronic HIV infection and were receiving suppressive ART (cases) and 16 HIV-uninfected controls.ResultsThe fecal microbial community composition was significantly different between cases and controls. The relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Erysipelotrichi, Erysipelotrichales, Erysipelotrichaceae, and Barnesiella was significantly enriched in cases, whereas that of Rikenellaceae and Alistipes was depleted. The plasma soluble CD14 level (sCD14) was significantly higher and the endotoxin core immunoglobulin M (IgM) level lower in cases, compared with controls. There were significant positive correlations between the relative abundances of Enterobacteriales and Enterobacteriaceae and the sCD14 level; the relative abundances of Gammaproteobacteria, Enterobacteriales, and Enterobacteriaceae and the interleukin 1β (IL-1β) level; the relative abundances of Enterobacteriales and Enterobacteriaceae and the interferon γ level; and the relative abundances of Erysipelotrichi and Barnesiella and the TNF-α level. There were negative correlations between endotoxin core IgM and IL-1β levels.ConclusionsPatients who have chronic HIV infection and are receiving suppressive ART display intestinal dysbiosis associated with increased microbial translocation and significant associations between specific taxa and markers of microbial translocation and systemic inflammation. This was an exploratory study, the findings of which need to be confirmed.

Project description:Despite antiretroviral therapy (ART), some HIV-infected persons maintain lower than normal CD4(+) T-cell counts in peripheral blood and in the gut mucosa. This incomplete immune restoration is associated with higher levels of immune activation manifested by high systemic levels of biomarkers, including sCD14 and D-dimer, that are independent predictors of morbidity and mortality in HIV infection. In this 12-week, single-arm, open-label study, we tested the efficacy of IL-7 adjunctive therapy on T-cell reconstitution in peripheral blood and gut mucosa in 23 ART suppressed HIV-infected patients with incomplete CD4(+) T-cell recovery, using one cycle (consisting of three subcutaneous injections) of recombinant human IL-7 (r-hIL-7) at 20 µg/kg. IL-7 administration led to increases of both CD4(+) and CD8(+) T-cells in peripheral blood, and importantly an expansion of T-cells expressing the gut homing integrin α4β7. Participants who underwent rectosigmoid biopsies at study baseline and after treatment had T-cell increases in the gut mucosa measured by both flow cytometry and immunohistochemistry. IL-7 therapy also resulted in apparent improvement in gut barrier integrity as measured by decreased neutrophil infiltration in the rectosigmoid lamina propria 12 weeks after IL-7 administration. This was also accompanied by decreased TNF and increased FOXP3 expression in the lamina propria. Plasma levels of sCD14 and D-dimer, indicative of systemic inflammation, decreased after r-hIL-7. Increases of colonic mucosal T-cells correlated strongly with the decreased systemic levels of sCD14, the LPS coreceptor - a marker of monocyte activation. Furthermore, the proportion of inflammatory monocytes expressing CCR2 was decreased, as was the basal IL-1β production of peripheral blood monocytes. These data suggest that administration of r-hIL-7 improves the gut mucosal abnormalities of chronic HIV infection and attenuates the systemic inflammatory and coagulation abnormalities that have been linked to it.

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Markers of renal disease and function are associated with systemic inflammation in HIV infection.

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Markers of renal disease and function are associated with systemic inflammation in HIV infection.

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