Publications
Department of Medicine faculty members published more than 3,000 peer-reviewed articles in 2022.
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BACKGROUND
Plasma 25 hydroxycholecalciferol (vitamin D) deficiency has been associated with adverse cardiovascular outcomes in epidemiologic studies. Chronic kidney disease is associated with loss of 1α-hydroxylase and consequently vitamin D deficiency. We hypothesized that vitamin D deficiency was associated with increased mortality and increased vascular access failure in patients undergoing permanent vascular access for end-stage renal disease.
METHODS
This retrospective cohort study analyzed 128 patients undergoing permanent vascular access surgery between 2003 and 2012 for whom concurrent plasma vitamin D levels were also available. Levels were considered deficient at <20 ng/mL. Multivariable analysis was used to determine the association between vitamin D and mortality and vascular access outcomes.
RESULTS
The mean age was 66.7 years, 96.8% were male, 32.0% were African American, and 60.9% had diabetes mellitus. In the entire cohort, 55.5% were vitamin D-deficient, despite similar rates of repletion among the vitamin D-deficient and nondeficient groups. During a median follow-up of 2.73 years, there were 40 deaths (31%). Vitamin D-deficient patients tended to be younger (P = .01) and to have higher total cholesterol (P = .001) and lower albumin (P = .017) and calcium (P = .007) levels. Despite their younger age, mortality was significantly higher (P = .026) and vascular access failure was increased (P = .008) in the vitamin D-deficient group. Multivariate logistic regression analysis found vitamin D deficiency (odds ratio [OR], 3.64; 95% confidence interval [CI], 1.12-11.79; P = .031), hemodialysis through a central catheter (OR, 3.08; 95% CI, 1.04-9.12; P = .042), coronary artery disease (OR, 3.08; 95% CI, 1.06-8.94; P = .039), increased age (OR, 1.09; 95% CI, 1.03-1.15; P = .001), and albumin (OR, 0.27; 95% CI, 0.09-0.83; P = .023) remained independent predictors of mortality. Vitamin D deficiency (hazard ratio [HR], 2.34; 95% CI, 1.17-4.71; P = .02), a synthetic graft (HR, 3.50; 95% CI, 1.38-8.89; P = .009), and hyperlipidemia (HR, 0.42; 95% CI, 0.22-0.81; P = .01) were independent predictors of vascular access failure in a Cox proportional hazard model.
CONCLUSIONS
Vitamin D deficiency is highly prevalent in patients undergoing vascular access procedures. Patients who are deficient in vitamin D have worse survival and worse vascular access outcomes. Further study is warranted to assess whether aggressive vitamin D repletion will improve outcomes in this population.
View on PubMed2014
BACKGROUND
Human immunodeficiency virus (HIV) infection-induced indoleamine 2,3-dioxygenase-1 (IDO) expression in activated monocytes and dendritic cells catabolizes tryptophan to kynurenine and other downstream catabolites that inhibit T-cell proliferation and interleukin 17 (IL-17) production. The prognostic significance of this pathway in treated HIV disease is unknown.
METHODS
We measured systemic IDO activity (calculated as the ratio of plasma levels of kynurenine to tryptophan; hereafter, the "KT ratio") in HIV-infected Ugandans before and during antiretroviral therapy (ART)-mediated viral suppression and its association with the rate of subsequent CD4(+) T-cell count recovery and mortality.
RESULTS
Among 435 participants, a higher pre-ART KT ratio was associated with a higher plasma virus load (P < .001) and lipopolysaccharide level (P = .018), a lower CD4(+) T-cell count (P < .001), and female sex (P = .047). Through month 12 of ART-mediated viral suppression, the plasma KT ratio decreased by approximately 50% (P < .001). After adjustment for pre-ART CD4(+) T-cell count, virus load, age, and sex, a higher month 12 KT ratio predicted a slower rate of subsequent CD4(+) T-cell count recovery (P = .001). Thirty-nine participants died. After adjustment for pre-ART CD4(+) T-cell count, virus load, body mass index, sex, and age, a higher pre-ART and month 6 KT ratio predicted increased mortality (P ≤ .016).
CONCLUSIONS
The kynurenine pathway of tryptophan catabolism independently predicts poor CD4(+) T-cell count recovery and increased mortality among HIV-infected Ugandans initiating ART and may be an important target for interventions.
View on PubMed2014
BACKGROUND
Unlike cytomegalovirus (CMV) infection and aging, human immunodeficiency virus (HIV) decreases the proportion of CD28(-)CD8(+) T cells expressing CD57. Whether this abnormality predicts mortality in treated HIV infection and can be reversed by early antiretroviral therapy (ART) remains unknown.
METHODS
We sampled recently HIV-infected individuals (<6 months) and HIV-uninfected controls and compared longitudinal changes in the proportion of CD28(-)CD8(+) T cells expressing CD57 between those who initiated ART early (<6 months) vs later (≥2 years). We also assessed the relationship between this phenotype and mortality in a nested case-control study of ART-suppressed chronically infected individuals.
RESULTS
Compared to HIV-uninfected controls (n = 15), individuals who were recently infected with HIV had lower proportions of CD28(-)CD8(+) T cells expressing CD57 (P < .001), and these proportions increased during ART. The early ART group (n = 33) achieved normal levels, whereas the later ART group (n = 30) continued to have lower levels than HIV-uninfected controls (P = .02). Among 141 ART-suppressed participants in the SOCA study, those in the lowest quartile of CD28(-)CD8(+) T cells expressing CD57 had 5-fold higher odds of mortality than those in the highest quartile (95% CI, 1.6-15.9, P = .007).
CONCLUSIONS
Abnormally low proportions of CD28(-)CD8(+) T cells expressing CD57 predict increased mortality during treated HIV infection and may be reversed with early ART initiation.
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