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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: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 ?4?7. 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-1? 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.

Project description:ObjectivesWe aimed to determine preoperative risk factors associated with pathologic T3a (pT3a) upstaging of clinical T1 (cT1) renal cell carcinomas (RCCs) and develop a novel model capable of accurately identifying those patients at high risk of harboring occult pT3a characteristics.MethodsA retrospective analysis of 1324 cT1 RCC patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) was performed. The study cohort was divided into training and testing datasets in a 70:30 ratio for further analysis. Univariable and multivariable logistic regression analyses were performed to identify predictors associated with cT1 to pT3a upstaging and subsequently, those significant risk factors were used to construct models. We used the area under the curve (AUC) to determine the model with the highest discrimination power. Decision curve analyses (DCAs) were applied to evaluate clinical net benefit associated with using the predictive models.ResultsThe rates of upstaging were 6.1% (n = 81), 5.8% (n = 54) and 6.8% (n = 27) in the total population, training cohort and validation cohort, respectively. Tumor size, clinical T stage, R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior) nephrometry score, lymphocyte to monocyte ratio (LMR), prognostic nutrition index (PNI) and albumin to globulin ratio (AGR) were significantly associated with pT3a upstaging. The model that consisted of R.E.N.A.L. score, LMR, AGR and PNI achieved the highest AUC of 0.70 in the validation cohort and yielded the highest net benefit. In the subpopulation with complete serum lipid profile, the inclusion of low-density lipoprotein cholesterol (LDL-C) and Castelli risk index-I (CRI-I) significantly improved the discrimination of model (AUC = 0.86).ConclusionsOur finding highlights the importance of systemic inflammation response markers and serum lipid parameters in predicting pT3a upstaging. Our model had relatively good discrimination in predicting occult pT3a disease among patients with cT1 renal lesions, and the use of the model may be greatly beneficial to urologists in risk stratification and management decisions.

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

Publications

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

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